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1.
Am J Transplant ; 24(4): 564-576, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37918482

RESUMEN

Intestinal transplantation (IT) is the final treatment option for intestinal failure. Static cold storage (CS) is the standard preservation method used for intestinal allografts. However, CS and subsequent transplantation induce ischemia-reperfusion injury (IRI). Severe IRI impairs epithelial barrier function, including loss of intestinal stem cells (ISC), critical to epithelial regeneration. Normothermic machine perfusion (NMP) preservation of kidney and liver allografts minimizes CS-associated IRI; however, it has not been used clinically for IT. We hypothesized that intestine NMP would induce less epithelial injury and better protect the intestine's regenerative ability when compared with CS. Full-length porcine jejunum and ileum were procured, stored at 4 °C, or perfused at 34 °C for 6 hours (T6), and transplanted. Histology was assessed following procurement (T0), T6, and 1 hour after reperfusion. Real-time quantitative reverse transcription polymerase chain reaction, immunofluorescence, and crypt culture measured ISC viability and proliferative potential. A greater number of NMP-preserved intestine recipients survived posttransplant, which correlated with significantly decreased tissue injury following 1-hour reperfusion in NMP compared with CS samples. Additionally, ISC gene expression, spheroid area, and cellular proliferation were significantly increased in NMP-T6 compared with CS-T6 intestine. NMP appears to reduce IRI and improve graft regeneration with improved ISC viability and proliferation.


Asunto(s)
Trasplante de Hígado , Daño por Reperfusión , Porcinos , Animales , Trasplante de Hígado/métodos , Preservación de Órganos/métodos , Hígado/patología , Perfusión/métodos , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & control , Daño por Reperfusión/patología , Aloinjertos/patología , Intestinos
2.
Nitric Oxide ; 149: 1-6, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38806106

RESUMEN

Intestinal transplantation is a complex technical procedure that provides patients suffering from end-stage intestinal failure an opportunity to enjoy improved quality of life, nutrition and survival. Compared to other types of organ transplants, it is a relatively new advancement in the field of organ transplantation. Nevertheless, great advances have been made over the past few decades to the present era, including the use of ischemic preconditioning, gene therapy, and addition of pharmacological supplements to preservation solutions. However, despite these strides, intestinal transplantation is still a challenging endeavor due to several factors. Notable among them is ischemia-reperfusion injury (IRI), which results in loss of cellular integrity and mucosal barrier function. In addition, IRI causes graft failure, delayed graft function, and decreased graft and recipient survival. This has necessitated the search for novel therapeutic avenues and improved transplantation protocols to prevent or attenuate intestinal IRI. Among the many candidate agents that are being investigated to combat IRI and its associated complications, nitric oxide (NO). NO is an endogenously produced gaseous signaling molecule with several therapeutic properties. The purpose of this mini-review is to discuss IRI and its related complications in intestinal transplantation, and NO as an emerging pharmacological tool against this challenging pathological condition. i.


Asunto(s)
Rechazo de Injerto , Mucosa Intestinal , Óxido Nítrico , Humanos , Óxido Nítrico/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Rechazo de Injerto/prevención & control , Animales , Intestinos/efectos de los fármacos , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Funcion de la Barrera Intestinal
3.
Clin Transplant ; 38(1): e15213, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38064299

RESUMEN

BACKGROUND: Outcomes of intestinal transplantation with colon allograft (ICTx) remain controversial. We aimed to assess the outcomes of ICTx in comparison to intestinal transplantation without colon (ITx) using the UNOS/OPTN registry database. METHODS: We retrospectively reviewed 2612 patients who received primary intestinal transplants from 1998 to 2020. The rates of acute rejection (AR) within 6 months after transplant were compared between ICTx and ITx. Risk factors of 6-month AR were examined using logistic regression model by era. Furthermore, conditional graft survival was analyzed to determine long-term outcomes of ICTx. RESULTS: Of 2612 recipients, 506 (19.4%) received ICTx. Graft and patient survival in ICTx recipients were comparable to those in ITx recipients. White ICTx recipients had a higher incidence of AR within 6 months compared to ITx during the entire study period (p = .002), colonic inclusion did not increase the risk of 6-month AR in the past decade. ICTx recipients who experienced 6-month AR had worse graft and patient survival compared to those who did not (p <.001 and p = .004, respectively). Among patients who did not develop 6-month AR, Cox proportional hazard model analysis revealed that colonic inclusion was independently associated with improved conditional graft survival. CONCLUSIONS: In the recent transplant era, colonic inclusion is no longer associated with a heightened risk of 6-month AR and may provide better long-term survival compared to ITx when AR is absent. Risk adjustment for rejection and proper immunosuppressive therapy are crucial to maximize the benefits of colonic inclusion.


Asunto(s)
Trasplante de Riñón , Humanos , Estudios Retrospectivos , Rechazo de Injerto/etiología , Trasplante Homólogo , Supervivencia de Injerto , Aloinjertos
4.
Clin Transplant ; 38(1): e15228, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38289880

RESUMEN

INTRODUCTION: Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined. METHODS: This was a single-center retrospective review of isolated adult intestinal allograft recipients from 2011 to 2019. Patients who died or experienced graft loss within 1-year or had a prior transplant were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation at 0-, 6- and 12-months post-transplant, and multivariable linear regression was performed to identify variables associated with adjusted eGFR at 1-year. Independent variables included age, ethnicity, BMI, history of diabetes/hypertension, vasopressor use, TPN and stoma days, urinary or bloodstream infections, intravenous contrast exposure, rejection, concomitant immunosuppression, and time above the therapeutic range of tacrolimus. Variables with a p < .1 in univariate analysis were considered for multivariable modeling. RESULTS: Thirty-three patients were included with a mean age of 43.9 ± 13.0. A mean 42.3% decline in eGFR was observed at 1-year post-transplant, with 15.2% of patients developing new stage 4/5 CKD. Factors associated with a greater decline in adjusted eGFR in the univariate model included increasing age, decreased BMI, stoma days, and vasopressor use. In the adjusted multivariable model patient age (ß = -.77, p < .01) and stoma days (ß = -.06, p < .01) remained significant. Tacrolimus and sirolimus exposure were not associated with decline in eGFR at 1 year. CONCLUSIONS: Renal dysfunction is common following intestinal transplantation. The need for stoma creation should be carefully considered, and reversal should be performed when feasible for renal protection.


Asunto(s)
Fallo Renal Crónico , Trasplante de Riñón , Insuficiencia Renal Crónica , Adulto , Humanos , Persona de Mediana Edad , Lactante , Tacrolimus/efectos adversos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Factores de Riesgo , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/etiología , Fallo Renal Crónico/etiología , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Estudios Retrospectivos
5.
Pediatr Transplant ; 28(3): e14756, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38623905

RESUMEN

INTRODUCTION: Intestinal failure, defined as the loss of gastrointestinal function to the point where nutrition cannot be maintained by enteral intake alone, presents numerous challenges in children, not least the timing of consideration of intestine transplantation. OBJECTIVES: To describe the evolution of care of infants and children with intestinal failure including parenteral nutrition, intestine transplantation, and contemporary intestinal failure care. METHODS: The review is based on the authors' experience supported by an in-depth review of the published literature. RESULTS: The history of parenteral nutrition, including out-patient (home) administration, and intestine transplantation are reviewed along with the complications of intestinal failure that may become indications for consideration of intestine transplantation. Current management strategies for children with intestinal failure are discussed along with changes in need for intestine transplantation, recognizing the difficulty in generalizing recommendations due to the high level of heterogeneity of intestinal pathology and residual bowel anatomy and function. DISCUSSION: Advances in the medical and surgical care of children with intestinal failure have resulted in improved transplant-free survival and a significant fall in demand for transplantation. Despite these improvements a number of children continue to fail rehabilitative care and require intestine transplantation as life-saving therapy or when the burden on ongoing parenteral nutrition becomes too great to bear.


Asunto(s)
Enfermedades Intestinales , Insuficiencia Intestinal , Síndrome del Intestino Corto , Trasplantes , Niño , Lactante , Humanos , Intestinos , Intestino Delgado , Nutrición Parenteral , Enfermedades Intestinales/cirugía , Síndrome del Intestino Corto/cirugía
6.
Pediatr Transplant ; 28(1): e14638, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37942670

RESUMEN

BACKGROUND: The study purpose was to add to limited literature assessing anti-HLA donor-specific antibody (DSA) appearance, clearance, specificity, and impact in intestinal/multivisceral (MV) transplant as well as the value of serial monitoring following an institutional protocol shift implementing serial monitoring. METHODS: This single-center retrospective review included intestinal/MV recipients transplanted 1/1/15-9/31/17 with completed DSA testing. Patients were divided into groups based on DSA presence post-transplant. The primary outcome was biopsy-proven acute rejection (BPAR). Secondary outcomes included graft loss and death. Descriptive analysis of DSA was completed. RESULTS: Of the 35 intestinal/MV recipients (60% pediatric) with DSA testing, 24 patients had post-transplant DSA. Fifteen patients in the DSA(+) group had T-cell-mediated BPAR versus five in the DSA(-) group (63% vs 45%, p = .47). Days to BPAR were 25 [IQR 19-165] (DSA(+) group) versus 232 [IQR 25.5-632.5] (DSA(-) group) (p = .066). There were no differences between groups for graft loss or death. One hundred and five DSA were identified in the DSA(+) group with 63% being class II, and 54% cleared during follow-up. DSA were directed against 50 different HLA alleles, with the most common being directed against HLA- DQ (35%). Time to first DSA and to clearance did not differ between class I and II. CONCLUSION: Findings confirm previous data that suggest post-transplant DSA in this population may lead to increased BPAR or shorter time to BPAR, although not statistically significant. Most DSA were identified within the first month after transplant, and ahead of rejection identification on biopsy. DSA therefore may have utility as an early rejection biomarker and use may be considered in place of early protocol biopsies, particularly in pediatric patients. We identified novel findings of DSA directed against a large breadth of HLA in intestinal/MV patients.


Asunto(s)
Trasplante de Riñón , Receptores de Trasplantes , Adulto , Humanos , Niño , Antígenos HLA , Anticuerpos , Donantes de Tejidos , Estudios Retrospectivos , Suero Antilinfocítico , Rechazo de Injerto/diagnóstico , Supervivencia de Injerto , Isoanticuerpos
7.
Acta Paediatr ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949557

RESUMEN

AIM: Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms. METHODS: A retrospective cohort of HD patients (2012-2023) from two institutions. Three HD forms were compared: short-segment HD (SSHD, n = 19), long-segment HD or total colonic aganglionosis (LS/TCA, n = 9) and ETCA (n = 7). RESULTS: Normally innervated segments in ETCA patients ranged 0-70 cm. Median times to first surgery were; ETCA = 3 days versus TCA = 21 days (p = 0.017) and SSHD = 95 days (p < 0.001), respectively. Median number of surgeries were; ETCA = 4, versus TCA = 2 (p = 0.17) and SSHD = 1 (p = 0.002), respectively. All the patients underwent a definitive pull-through procedure, except four ETCA patients with a permanent jejunostomy and residual aganglionic segment of 57-130 cm. ETCA patients had 92% lower odds of enterocolitis (14%) compared to TCA patients (67%, p = 0.054), and comparable odds to SSHD patients (16%, p = 0.92). ETCA mortality was 14%. CONCLUSION: Extended total colonic aganglionosis patients require earlier and multiple interventions. Leaving an aganglionic segment may be advantageous, without increasing risk for enterocolitis. Tailored surgical treatment and rehabilitation programmes may prevent mortality and need for transplantation.

8.
Clin Transplant ; 37(3): e14865, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36416299

RESUMEN

INTRODUCTION: Sensitization to human leukocyte antigen (HLA) creates an immunological barrier to intestinal transplantation (ITx). Current desensitization therapies are limited and ineffective in the most highly sensitized patients. A co-transplanted whole liver transplant can protect a kidney, heart, or intestinal allograft from antibody-mediated injury. Whether an auxiliary partial liver allograft provides effective protection for highly sensitized intestinal transplant recipients is unknown. METHODS: Two patients with strong HLA donor-specific antibody at high titer against their deceased donors underwent combined auxiliary partial liver and ITx across a positive cross-match. The left lateral lobes from the combined-graft recipients and the right liver lobes from the deceased donors were transplanted as a domino procedure to other four patients. RESULTS: Two combined-graft recipients have had an uneventful postoperative course without major complications at a 12- and 24-month follow-up, respectively. Intestinal graft function has been excellent with no evidence of humoral or cellular rejection. While a positive cross-match turned negative, titers of donor-specific HLA antibodies gradually declined over time after transplant. The left liver lobes procured from the combined-graft recipients were successfully transplanted into two pediatric patients (age 1.9, 2.4 years) and the right lobes from two deceased donors were successfully transplanted into two adult patients. All transplant procedures went well, without post-operative complications related to the splitting technique. CONCLUSION: Our results indicate that an auxiliary liver transplant can effectively protect a co-transplanted intestinal allograft against rejection and suggest that this combined procedure may serve as a useful therapeutic adjunct for a highly sensitized intestinal transplant candidate.


Asunto(s)
Trasplante de Riñón , Adulto , Humanos , Niño , Trasplante de Riñón/métodos , Riñón , Anticuerpos , Hígado , Trasplante Homólogo
9.
Transpl Int ; 36: 11371, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37671117

RESUMEN

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.


Asunto(s)
Donantes de Tejidos , Trasplantes , Humanos , Estudios Retrospectivos , Supervivencia de Injerto , Intestinos
10.
Transpl Int ; 36: 10803, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36713114

RESUMEN

There is an urgent need to address the shortage of potential multivisceral grafts in order to reduce the average time in waiting list. Since donation after circulatory death (DCD) has been successfully employed for other solid organs, a thorough evaluation of the use of intestinal grafts from DCD is warranted. Here, we have generated a model of Maastricht III DCD in rodents, focusing on the viability of intestinal and multivisceral grafts at five (DCD5) and twenty (DCD20) minutes of cardiac arrest compared to living and brain death donors. DCD groups exhibited time-dependent damage. DCD20 generated substantial intestinal mucosal injury and decreased number of Goblet cells whereas grafts from DCD5 closely resemble those of brain death and living donors groups in terms intestinal morphology, expression of tight junction proteins and number of Paneth and Globet cells. Upon transplantation, intestines from DCD5 showed increased ischemia/reperfusion damage compared to living donor grafts, however mucosal integrity was recovered 48 h after transplantation. No differences in terms of graft rejection, gene expression and absorptive function between DCD5 and living donor were observed at 7 post-transplant days. Collectively, our results highlight DCD as a possible strategy to increase multivisceral donation and transplantation procedures.


Asunto(s)
Trasplante de Hígado , Obtención de Tejidos y Órganos , Humanos , Muerte Encefálica , Donantes de Tejidos , Trasplante de Hígado/métodos , Intestinos , Muerte , Supervivencia de Injerto , Estudios Retrospectivos
11.
Transpl Int ; 36: 11518, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37745640

RESUMEN

Considering recent clinical and experimental evidence, expectations for using DCD-derived intestines have increased considerably. However, more knowledge about DCD procedure and long-term results after intestinal transplantation (ITx) is needed. We aimed to describe in detail a DCD procedure for ITx using normothermic regional perfusion (NRP) in a preclinical model. Small bowel was obtained from pigs donors after 1 h of NRP and transplanted to the recipients. Graft Intestinal samples were obtained during the procedure and after transplantation. Ischemia-reperfusion injury (Park-Chiu score), graft rejection and transplanted intestines absorptive function were evaluated. Seven of 8 DCD procedures with NRP and ITx were successful (87.5%), with a good graft reperfusion and an excellent recovery of the recipient. The architecture of grafts was well conserved during NRP. After an initial damage of Park-chiu score of 4, all grafts recovered from ischemia-reperfusion, with no or very subtle alterations 2 days after ITx. Most recipients (71.5%) did not show signs of rejection. Only two cases demonstrated histologic signs of mild rejection 7 days after ITx. Interestingly intestinal grafts showed good absorptive capacity. The study's results support the viability of intestinal grafts from DCD using NRP, contributing more evidence for the use of DCD for ITx.


Asunto(s)
Daño por Reperfusión , Donantes de Tejidos , Animales , Porcinos , Humanos , Perfusión , Reperfusión , Rechazo de Injerto
12.
Transpl Int ; 36: 11568, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37779512

RESUMEN

In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV (p < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) (p = 0.002) and Received Induction (p = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.


Asunto(s)
Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Donadores Vivos , Hígado , Trasplante Homólogo , Intestinos/trasplante , Rechazo de Injerto/prevención & control , Supervivencia de Injerto
13.
Pediatr Transplant ; 27(5): e14528, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37334497

RESUMEN

BACKGROUND: Bench liver reduction, with or without intestinal length reduction (LR) (coupled with delayed closure and abdominal wall prostheses), has been a strategy adopted by our program for small children due to the limited availability of size-matched donors. This report describes the short, medium, and long-term outcomes of this graft reduction strategy. METHODS: A single-center, retrospective analysis of children that underwent intestinal transplantation (April 1993 to December 2020) was performed. Patients were grouped according to whether they received an intestinal graft of full length (FL) or following LR. RESULTS: Overall, 105 intestinal transplants were performed. The LR group (n = 10) was younger (14.5 months vs. 40.0 months, p = .012) and smaller (8.7 kg vs. 13.0 kg, p = .032) compared to the FL group (n = 95). Similar abdominal closure rates were achieved after LR, without any increase in abdominal compartment syndrome (1/10 vs. 7/95, p = .806). The 90-day graft and patient survival were similar (9/10, 90% vs. 83/95, 86%; p = .810). Medium and long-term graft survival at 1 year (8/10, 80% vs. 65/90, 71%; p = .599), and 5 years (5/10, 50% vs. 42/84, 50%; p = 1.00) was similar. CONCLUSION: LR of intestinal grafts appears to be a safe strategy for infants and small children requiring intestinal transplantation. This technique should be considered in the situation of significant size mismatch of intestine containing grafts.


Asunto(s)
Trasplante de Hígado , Lactante , Niño , Humanos , Trasplante de Hígado/métodos , Estudios Retrospectivos , Intestinos/trasplante , Hígado , Donantes de Tejidos , Supervivencia de Injerto
14.
Dig Dis Sci ; 68(1): 29-37, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36434372

RESUMEN

Short bowel syndrome (SBS) is a chronic disease whose natural history requires a changing array of management strategies over time. Chief amongst these is the chronic use of parenteral nutrition (PN) to ensure adequate nutritional intake. With time and appropriate management, approximately half of all SBS patients will successfully regain a functional, baseline level of intrinsic bowel function that will allow for them to achieve PN independence. However, the other half of SBS patients will progress into chronic intestinal failure which warrants a change in therapy to include more aggressive medical and potentially surgical measures. This review examines the evolving treatment strategies involved in the management of SBS as well as intestinal failure.


Asunto(s)
Enfermedades Intestinales , Insuficiencia Intestinal , Síndrome del Intestino Corto , Humanos , Síndrome del Intestino Corto/terapia , Péptidos/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Intestinales/terapia , Enfermedad Crónica
15.
Eur Surg Res ; 64(2): 201-210, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35926441

RESUMEN

INTRODUCTION: Intestinal cold ischemia and subsequent reperfusion during transplantation result in various degrees of mucosal injury ranging from mild edema to extensive mucosal loss. Mucosal barrier impairment favors bacterial translocation and fluid loss and raises nutritional challenges. The injured intestine also releases proinflammatory mediators and upregulates various epitopes toward an inflammatory phenotype. We studied the process of mucosal injury and repair during the early period after intestinal transplantation from a histological and molecular standpoint. MATERIALS AND METHODS: Adult Sprague-Dawley rats were used as donors and recipients. Donor intestines were perfused and stored in saline for 3 h, then transplanted heterotopically using microvascular anastomoses. Intestinal graft segments were obtained after 20 min, 6 h, 12 h, and 24 h after reperfusion. Histology studies (goblet cell count, morphometry), immunofluorescence, and western blot for several tight junction proteins, apoptosis, and inflammation-related proteins were performed. RESULTS: Cold storage led to extensive epithelial detachment, whereas reperfusion resulted in extensive villus loss (about 60% of the initial length), and goblet cell numbers were drastically reduced. Over the first 24 h, gradual morphologic and molecular recovery was noted, although several molecular alterations persisted (increased apoptosis and inflammation, altered expression of several tight junctions). CONCLUSIONS: The current data suggest that a near-complete morphologic recovery from a moderate mucosal injury occurs within the first 24 h after intestinal transplantation. However, several molecular alterations persist and need to be considered when designing intestinal transplant experiments and choosing sampling and endpoints.


Asunto(s)
Daño por Reperfusión , Ratas , Animales , Ratas Sprague-Dawley , Intestinos/patología , Mucosa Intestinal , Inflamación/metabolismo , Inflamación/patología
16.
Int J Mol Sci ; 24(5)2023 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-36901975

RESUMEN

Intestinal transplantation (ITx) remains a lifesaving option for patients suffering from irreversible intestinal failure and complications from total parenteral nutrition. Since its inception, it became obvious that intestinal grafts are highly immunogenic, due to their high lymphoid load, the abundance in epithelial cells and constant exposure to external antigens and microbiota. This combination of factors and several redundant effector pathways makes ITx immunobiology unique. To this complex immunologic situation, which leads to the highest rate of rejection among solid organs (>40%), there is added the lack of reliable non-invasive biomarkers, which would allow for frequent, convenient and reliable rejection surveillance. Numerous assays, of which several were previously used in inflammatory bowel disease, have been tested after ITx, but none have shown sufficient sensibility and/or specificity to be used alone for diagnosing acute rejection. Herein, we review and integrate the mechanistic aspects of graft rejection with the current knowledge of ITx immunobiology and summarize the quest for a noninvasive biomarker of rejection.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Trasplante de Hígado , Humanos , Rechazo de Injerto/etiología , Intestinos , Nutrición Parenteral Total
17.
Am J Transplant ; 22(12): 3053-3060, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36066568

RESUMEN

Intestinal transplantation from deceased donors is the established procedure for patients with irreversible intestinal failure. However, a living-donor intestinal transplant has not been routinely performed yet because of undefined surgical risks to the donor. In this report, we reviewed our experience with living-donor ileal resection from May 1999 to December 2021. A total of 40 living-donor ileal resections were performed for 40 intestinal transplant recipients. Clinical data were prospectively collected and analyzed for postoperative complications after ileal procurement. None of the donors experienced life-threatening complications or mortality. Six (15%) of 40 donors experienced minor operative complications. Transit intestinal graft inadequacy including weight loss, diarrhea, and vitamin B12 deficiency was common early following surgery, but was manageable and disappeared in most cases within a year. All donors had significant reductions in total plasma cholesterol and low-density lipoprotein cholesterol concentrations after donation as compared with the baseline levels. With an average follow-up of 67.8 months, bilateral kidney stones occurred in one donor and gallstones in the other. All the donors have regained their normal capacity for work. Living-donor ileal resection is associated with minimal short- and long-term morbidity and remains an attractive alternative for potential recipients when suitable deceased donors are unavailable.


Asunto(s)
Trasplante de Riñón , Donadores Vivos , Humanos , Colesterol , Supervivencia de Injerto , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/etiología , Receptores de Trasplantes
18.
Clin Transplant ; 36(2): e14535, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34783062

RESUMEN

Difficulty in obtaining adequate abdominal wall closure due to loss of the abdominal domain is a frequent complication of multivisceral, isolated intestinal transplantation and in some cases of liver transplantation. Various methods for primary closure have been proposed, including the use of synthetic and biological meshes, as well as full-thickness abdominal wall and non-vascularized rectus fascia grafts. We describe a novel technique for abdominal wall procurement in which the graft is perfused synchronously with the abdominal organs and can be transplanted as a full-thickness wall or as a non-vascularized rectus fascia graft. We performed six transplants of non-vascularized rectus fascia in three intestinal transplants, one multivisceral transplant, and two liver transplants. The size of the covered abdominal wall defects ranged from 17 cm × 7 cm to 25 cm × 20 cm. Only one patient developed graft infection secondary to enterocutaneous fistula requiring surgical correction and removal of the fascia graft. This patient, as well as two other patients, died due to sepsis. Our procurement technique allows removal of the rectus fascia graft to cover the abdominal wall defect, providing a feasible solution for treatment of abdominal wall defects in recipients after abdominal organ transplantation.


Asunto(s)
Pared Abdominal , Trasplante de Hígado , Trasplante de Órganos , Músculos Abdominales , Pared Abdominal/cirugía , Fascia/trasplante , Humanos , Trasplante de Hígado/métodos
19.
Transpl Infect Dis ; 24(6): e13929, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35980220

RESUMEN

West Nile virus (WNv) is a major cause of viral encephalitis in the United States. WNv infection is usually asymptomatic or a limited febrile illness in the immunocompetent hosts, although a small percentage can develop neuroinvasive disease. Neuroinvasive disease due to WNv in solid organ transplant recipients occurs at higher rates than observed in the general population and can have long term neurological sequalae. METHODS: We retrospectively reviewed medical records of all solid organ transplant recipients at our institution who tested positive for WNv from 2010 to 2018. Two reviewers performed electronic searches of Medline, Embase, Cochrane Library of literature of WNv infections in SOT. Descriptive statistics were performed on key variables. RESULTS: Eight recipients (mean age 54, five males) were diagnosed with neuroinvasive WNv infection at our institution. Distribution of infection was as follows: five kidney transplants, one in each kidney-pancreas, liver, and lung. Diagnoses included meningitis (3), encephalitis (1), meningo-encephalitis (4). Median time from transplant to infection was 49.8 months (2.7-175.4). No infections were considered donor-derived. Five patients received treatment with IVIG. Six patients were alive at median follow-up of 49.5 months (21.7-116.8). We identified 29 studies published from 2002 to 2019. Median time from transplant to infection was 14.2 months, with similar allograft distribution; 53% were donor-derived infections. CONCLUSION: WNv infections in solid organ transplant recipients can be a consequence of organ donation or can be acquired via the community. Infections can be more severe in SOT recipients and lead to neuroinvasive disease.


Asunto(s)
Trasplante de Riñón , Trasplante de Órganos , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Riñón/efectos adversos , Trasplante de Órganos/efectos adversos , Estudios Retrospectivos , Estados Unidos , Fiebre del Nilo Occidental/epidemiología
20.
Pediatr Transplant ; 26(4): e14257, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35195934

RESUMEN

BACKGROUND: The aim of the study was to analyze the long-term outcomes of transplants utilizing ITx donors <1 year and to compare these results with older donors. METHODS: Between January 2007 and December 2019, the primary ITx donors in the Children's Hospital of Pittsburgh of UPMC were retrospectively reviewed. Short- and long-term outcomes of recipients receiving a deceased donor organ from donors <1 year were compared with those found in all other recipients. RESULTS: During the study period, there were 89 primary ITx donors, using 30 donors (33.7%) aged <1 year. The mean age of their recipients was 1.6 ± 0.7 (0.7-3.2) years. The 30 graft types were isolated intestine (n = 3, 10.0%), liver bowel (n = 20, 66.7%), and multivisceral (n = 7, 23.3%). Technical complications occurred in 12 (40.0%) recipients. Candidates transplanted with intestine allografts from donors <1 year of age had shorter wait times (p < .001), more liver-inclusive grafts (p < .001), and less donor-specific antibodies (DSA) (p = .014). During follow-up, the recipients had less graft loss (p = .018), and more remained alive with graft in place (p = .011). Among children transplanted with such donors, 3-year and graft survival rates were 86.7% and 82.9% compared to 62.8% and 49.9% in the cohort of donors >1 year (p = .032 and .011). CONCLUSIONS: Donor age <1 year was associated with improved graft survival. Optimal utilization of this population for toddler candidates would increase intestine availability, reduce time to transplantation, and potentially improve long-term outcome.


Asunto(s)
Trasplante de Riñón , Donantes de Tejidos , Preescolar , Supervivencia de Injerto , Humanos , Lactante , Intestinos , Estudios Retrospectivos , Resultado del Tratamiento
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