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1.
Clin Transplant ; 38(1): e15228, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38289880

RESUMO

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.


Assuntos
Falência Renal Crônica , Transplante de Rim , Insuficiência Renal Crônica , Adulto , Humanos , Pessoa de Meia-Idade , Lactente , Tacrolimo/efeitos adversos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Fatores de Risco , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/etiologia , Falência Renal Crônica/etiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Estudos Retrospectivos
2.
Clin Transplant ; 38(5): e15336, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38762783

RESUMO

BACKGROUND: Individual events during donation after circulatory death (DCD) procurement, such as hypotensive or hypoxic warm ischemia, or circulatory arrest are all a part of donor warm ischemia time (dWIT), and may have differing effects on the outcome of the liver graft. This study aimed to identify risk factors for postreperfusion syndrome (PRS), a state of severe hemodynamic derangement following graft reperfusion, and its impact on DCD liver transplantation (LT) outcomes. METHODS: This was a retrospective analysis using 106 DCD LT. Detailed information for events during procurement (withdrawal of life support; systolic blood pressure < 80 mmHg; oxygen saturation < 80%; circulatory arrest; aortic cold perfusion) and their association with the development of PRS were examined using logistic regression. RESULTS: The overall incidence of PRS was 26.4%, occurring in 28 patients. Independent risk factors for PRS were asystolic dWIT (odds ratio (OR) 3.65, 95% confidence interval (CI) 1.38-9.66) and MELD score (OR 1.06, 95% CI 1.01-1.10). Total bilirubin was significantly higher in the PRS group at postoperative day (POD) 1 (p = .02; 5.2 mg/dL vs. 3.4 mg/dL), POD 3 (p = .049; 4.5 mg/dL vs. 2.8 mg/dL), and POD 7 (p = .04; 3.1 mg/dL vs. 1.9 mg/dL). Renal replacement therapy after LT was more likely to be required in the PRS group (p = .01; 48.2% vs. 23.1%). CONCLUSION: Asystolic dWIT is a risk factor for the development of PRS in DCD LT. Our results suggest that asystolic dWIT should be considered when selecting DCD liver donors.


Assuntos
Transplante de Fígado , Doadores de Tecidos , Isquemia Quente , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Isquemia Quente/efeitos adversos , Pessoa de Meia-Idade , Fatores de Risco , Prognóstico , Seguimentos , Sobrevivência de Enxerto , Adulto , Obtenção de Tecidos e Órgãos , Complicações Pós-Operatórias/etiologia , Traumatismo por Reperfusão/etiologia , Reperfusão/efeitos adversos , Síndrome , Coleta de Tecidos e Órgãos/efeitos adversos
3.
Antimicrob Agents Chemother ; 66(7): e0005322, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35770999

RESUMO

Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity > 0.9996; Aligned Percentage > 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1Δ33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checkerboard, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.


Assuntos
Antifúngicos , Farmacorresistência Fúngica , Antifúngicos/farmacologia , Candida auris , Farmacorresistência Fúngica/genética , Humanos , Testes de Sensibilidade Microbiana , Filogenia
4.
Clin Transplant ; 36(4): e14587, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34997798

RESUMO

BACKGROUND: This study aimed to identify risk factors for postreperfusion syndrome (PRS) and its impact on LT outcomes. METHODS: Data analysis was performed in 1021 adult patients undergoing donation after brain death (DBD) LT to identify PRS incidence, the risk factors for PRS development, and its impact on LT outcomes. RESULTS: The overall incidence of PRS was 16.1%. Independent risk factors for PRS included donor age (odds ratio (OR) 1.01, P = .02), donor body mass index (BMI) (OR 1.04, P = .003), moderate macrosteatosis (OR 2.48, P = .02), and cold ischemia time (CIT) (OR 1.06, P = .02). On multivariable analysis for 30-day graft failure, PRS (hazard ratio (HR) 3.49; P < .001) and Model for End-stage Liver Disease (MELD) score (HR 1.01; P = .05) were independent risk factors. Patients were categorized into four distinct groups based on PRS risk groups and MELD groups, which showed different 1-year graft survival (P < .001). There were comparable outcomes between low PRS risk - high MELD and high PRS risk - low MELD group (P = .33). CONCLUSIONS: Donor age, donor BMI, moderate macrosteatosis, and CIT were identified as risk factors for the development of PRS in LT using DBD grafts. PRS risk evaluation may improve donor-to-recipient matching based on their MELD scores.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Adulto , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Doadores de Tecidos , Resultado do Tratamento
5.
HPB (Oxford) ; 24(6): 817-824, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742650

RESUMO

BACKGROUND: Outcomes of left lateral segment (LLS) grafts in pediatric recipients were compared between living (LD-LLS) and deceased donor (DD-LLS) grafts. METHODS: 195 LLS grafts (99DD-LLS-96LD-LLS) were analyzed with a median follow-up of 9.1years. The primary endpoints were overall patient/graft survival. RESULTS: LD-LLS grafts were younger (0.9vs.1.4years, p = 0.039), more likely to have a fulminant liver failure (17.9%vs.5.3%,p = 0.002), less likely to have a metabolic disorder (6.3%vs.25.5%,p = 0.002), and less likely to be undergoing retransplantation (5.3% vs.16.2%,p = 0.015). There was a trend toward decreased hepatic artery thrombosis in LD-LLS grafts (6.6% vs. 15.5%,p = 0.054). No differences in the overall biliary complications occurred. The LD-LLS group had prolonged survival compared to the DD-LLS group with 10-year survival rates of 81%, and 74% (p = 0.005), respectively. LD-LLS grafts had longer graft survival compared to DD-LLS grafts (10-year graft survival 85%vs.67%,p = 0.005). Recipient age >1year (HR 2.39,p = 0.026), aortic reconstruction (HR 2.12,p = 0.046) and vascular complication (HR 3.12,p < 0.001) were independent predictors of poor patient survival. Non-biliary liver disease (HR 2.17,p = 0.015), DD-LLS (HR 2.06,p = 0.034) and vascular complication (HR 4.61,p < 0.001) were independent predictors of poor graft survival. CONCLUSION: The use of SLT remains a viable option with excellent long-term outcomes. We show improved graft and patient survival with living donor grafts.


Assuntos
Hepatopatias , Transplante de Fígado , Criança , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Estudos Retrospectivos , Resultado do Tratamento
6.
Am J Transplant ; 21(5): 1705-1712, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33043624

RESUMO

Intestinal transplantation (ITx) is the treatment of choice for patients with intestinal failure who have developed life-threatening complications related to long-term parenteral nutrition. Patients may also undergo ITx as part of a combined liver-intestine or multivisceral transplant for a variety of indications, most commonly intestinal failure-associated liver disease or porto-mesenteric thrombosis. Endoscopy plays a critical role in the posttransplant management of these patients, most commonly in the diagnosis and management of rejection, which occurs in up to 30-40% of patients within the first-year posttransplant. With a lack of noninvasive biomarkers to identify the presence of rejection, endoscopy and biopsy remain the gold standard for its diagnosis. Endoscopic evaluation of the graft is also important in the identification of other complications post-ITx, including posttransplant lymphoproliferative disorder, graft-versus-host disease, and enteric infections. Each patient's posttransplant anatomy may be slightly different, making endoscopy sometimes technically challenging and necessitating clear and frequent communication with the surgical team in order to help identify the highest yield approach. Herein, we review the most common pathologies found endoscopically in the post-ITx patient and describe some of the unique challenges the endoscopist faces when evaluating these complex patients.


Assuntos
Enteropatias , Transplantados , Endoscopia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Enteropatias/etiologia , Intestino Delgado/diagnóstico por imagem , Intestinos
7.
Clin Transplant ; 35(6): e14291, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33740822

RESUMO

BACKGROUND: Trough-adjusted tacrolimus is commonly prescribed following intestinal transplantation to prevent allograft rejection. Despite established practice, there remains limited direct evidence linking tacrolimus levels with improved clinical outcomes. METHODS: This was a single-center review of all adult non-liver containing intestinal allograft recipients from 2011 to 2018. Patients received lymphocyte depleting induction and maintenance immunosuppression consisting of tacrolimus and a corticosteroid taper. Tacrolimus time-in-therapeutic range (TAC-TTR) was calculated for all patients from the date of transplant until 1-year post-transplant using Rosendaal's method. Cox-Proportional hazards modeling was utilized to assess freedom from acute rejection and graft failure stratified by TAC-TTR quartile. RESULTS: 47 patients were included in the review. Mean TAC-TTR for the cohort was 30.2% ± 11.4. Fifteen episodes of acute rejection were observed, 8 of which were severe. Patients in the highest TAC-TTR quartile >36% had a lower incidence of acute rejection and graft failure relative to patients with a TAC-TTR <20%. Cox-Proportional hazards modeling found a 10% decrease in TAC-TTR was associated with an increased hazard for acute rejection (2.03), severe acute rejection (2.19), and graft loss (3.33). CONCLUSION: The results of this study suggest that decreasing TAC-TTR is a risk factor for both acute rejection as well as intestinal allograft failure.


Assuntos
Transplante de Rim , Tacrolimo , Adulto , Liberdade , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico
8.
Am J Transplant ; 20(12): 3550-3557, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32431016

RESUMO

Recent data suggest that frequent endoscopy and biopsy without evidence of graft dysfunction does not appear to confer survival advantage after intestinal transplantation. After abandoning protocol surveillance, endoscopic examination was decreased significantly at our center. These observations led us to question the need for stoma creation in intestinal transplantation. Herein, we report clinical outcomes of intestinal transplantation without stoma, compared to conventional transplant with stoma. Data analysis was limited to adult intestinal transplantation without liver allograft between 2015 and 2018. We compared patient and graft survival, frequency of endoscopic evaluation, episodes of acute rejection, nutritional therapy, and renal function between "Control group (with stoma)," n = 18 grafts in 16 patients and "Study group (without stoma)," n = 16 grafts in 15 patients. Overall outcome was similar between the 2 groups with respect to graft and patient survival, episodes of acute rejection, and its response to treatment. Nutritional outcomes were similar in both groups. Fewer antidiarrheal medications were required in the study group, but this did not translate into demonstrable gains in preservation of renal function, despite an apparent trend to improvement. Intestinal transplantation without stoma appears to be an acceptable practice model without obvious adverse impact on outcome.


Assuntos
Rejeição de Enxerto , Transplante de Órgãos , Adulto , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Imunossupressores , Intestinos
9.
Curr Opin Organ Transplant ; 25(2): 196-200, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32142482

RESUMO

PURPOSE OF REVIEW: There has been a striking decline in the annual volumes of adult intestinal transplants performed in the United States from a peak in 2008, reaching its lowest volume in 2019. The current review examines the pattern and potential reasons for the decline. RECENT FINDINGS: We observe that while improvements in intestinal rehabilitation may be contributing to some of the decline, movements of key personnel and the paucity of experts in a rarefied field may also be contributing to declining volumes. SUMMARY: We suggest that the decline in volumes of adult intestinal transplants are likely to be multifactorial. At a time of improving transplant outcomes, the indications for intestinal transplant suggested by the Centers for Medicare and Medicaid Services, may be outdated and worthy of revision.


Assuntos
Enteropatias/terapia , Intestinos/transplante , Adulto , Humanos , Estados Unidos
10.
Clin Transplant ; 33(10): e13684, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31374126

RESUMO

The value of endoscopy and biopsy after intestinal transplantation in the absence of clinical concerns has never been investigated. We examined clinical yield of routine surveillance endoscopy and biopsy (control group, n = 28, Jan 2011 to Jun 2014). Most episodes of acute rejection were diagnosed when there were clinical symptoms or signs such as increased stoma output, fever, or bacteremia, but not by routine surveillance endoscopy and biopsy. The new protocol abandoned routine surveillance. Intestinal allografts were examined only when relevant clinical symptoms and/or signs raised concern for graft dysfunction. We compared outcomes between control and study groups (new protocol, n = 25, Jul 2014 to Dec 2016). Incidence of acute rejection (32% vs 32%), graft salvage rate after acute rejection treatment (78% vs 63%), patient survival (75% vs 88% 1 year, 71% vs 83% 3 years after intestinal transplantation), and graft survival (68% vs 80% 1 year, 61% vs 76% 3 years after intestinal transplantation) were similar between control and study groups. Protocol-driven, routine surveillance endoscopy, and biopsy do not appear to confer any survival advantage to patients or grafts. Endoscopy and biopsy "for cause" without routine surveillance seem to be effective and adequate to monitor intestinal allografts.


Assuntos
Endoscopia/métodos , Rejeição de Enxerto/diagnóstico , Intestinos/transplante , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Adulto , Biópsia , Estudos de Casos e Controles , Criança , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Vigilância da População , Complicações Pós-Operatórias/etiologia , Prognóstico , Fatores de Risco
11.
Clin Transplant ; 31(5)2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28295657

RESUMO

BACKGROUND: Severe acute cellular rejection (ACR) occurs frequently after intestinal transplantation (ITx). AIM: To evaluate the outcomes and the risk factors for graft failure and mortality in patients with severe ACR after ITx. METHODS: Retrospective study evaluating all ITx recipients who developed severe ACR between 01/2000 and 07/2014. Demographic and histologic data were reviewed. RESULTS: 20/126 (15.9%) ITx recipients developed severe ACR. Of these 20 episodes, 13 were in adults (median age: 47.1). The median (IQR) time from ITx to severe ACR was 206.5 (849) days. All patients received intravenous methylprednisolone and increased doses of tacrolimus. Sixteen (80%) patients did not respond to initial treatment and required thymoglobulin administration. Moreover, 11 (55%) patients required additional immunosuppressive medications. Six (30%) patients required graft enterectomy. Complications related to ACR treatment were the following: 10 (50%) patients developed bacterial infections, four (20%) patients developed cytomegalovirus infection and four (20%) patients developed post-transplant lymphoproliferative disease. At the end of follow-up, only 3/20 (15%) were alive with a functional allograft. The median patient survival time after diagnosis of severe ACR was 400 days (95% CI: 234.0-2613.0). CONCLUSIONS: Severe ACR episodes are associated with high rates of graft loss and complications related to treatment.


Assuntos
Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Intestinos/transplante , Transplante de Órgãos/mortalidade , Complicações Pós-Operatórias/mortalidade , Índice de Gravidade de Doença , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
12.
Clin Transplant ; 31(5)2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28241392

RESUMO

INTRODUCTION: Using data from the Scientific Registry of Transplant Recipients (SRTR), cumulative incidence, risk factors for, and impact on survival of severe chronic kidney disease (CKD) in intestinal transplantation (ITx) recipients were assessed. METHODS: First-time adult ITx recipients transplanted in the United States between January 1, 1990 and December 31, 2012 were included. Severe CKD after ITx was defined as: glomerular filtration rate (GFR) <30 mL/min/1.73 m2 , chronic hemodialysis initiation, or kidney transplantation (KTx). Survival analysis and extended Cox model were conducted. RESULTS: The cumulative incidence of severe CKD 1, 5, and 10 years after ITx was 3.2%, 25.1%, and 54.1%, respectively. The following characteristics were significantly associated with severe CKD: female gender (HR 1.34), older age (HR 1.38/10 year increment), catheter-related sepsis (HR 1.58), steroid maintenance immunosuppression (HR 1.50), graft failure (HR 1.76), ACR (HR 1.64), prolonged requirement for IV fluids (HR 2.12) or TPN (HR 1.94), and diabetes (HR 1.54). Individuals with higher GFR at the time of ITx (HR 0.92 for each 10 mL/min/1.73 m2 increment), and those receiving induction therapies (HR 0.47) or tacrolimus (HR 0.52) showed lower hazards of severe CKD. In adjusted analysis, severe CKD was associated with a significantly higher hazard of death (HR 6.20). CONCLUSIONS: The incidence of CKD after ITx is extremely high and its development drastically limits post-transplant survival.


Assuntos
Sobrevivência de Enxerto , Intestinos/transplante , Transplante de Órgãos/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/mortalidade , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Incidência , Testes de Função Renal , Masculino , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Prognóstico , Insuficiência Renal Crônica/etiologia , Fatores de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologia
13.
Clin Transplant ; 31(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28801969

RESUMO

BACKGROUND: Intestinal transplantation (ITx) is the definitive therapy for patients suffering from intestinal failure. Previously published reports suggest that these cases should be managed perioperatively with the same intensive monitors and techniques as in liver transplantation. METHODS: We retrospectively reviewed the anesthetic management of 67 isolated intestinal, intestinal-pancreas, and intestinal-kidney transplants over the previous decade (2005-2015) in our tertiary care institution. RESULTS: Patients were typically managed with a single arterial line, a single central venous catheter, and rarely intensive modalities such as a pulmonary artery catheter, a transesophageal echocardiography, a second arterial catheter or central venous catheter, a rapid infusion system, a cell salvage device, or viscoelastic testing. Significant hemodynamic derangements were rare, and the rate of postreperfusion syndrome was 8.96%. Our fluid administration type and volume and transfusion type and volume were similar to previous reports in which more intensive anesthetic management was employed. CONCLUSION: We demonstrate that ITx can safely occur without utilizing the intensive resources requisite for a liver transplant.


Assuntos
Anestésicos/administração & dosagem , Intestinos/transplante , Transplante de Rim/mortalidade , Transplante de Fígado/mortalidade , Complicações Pós-Operatórias/mortalidade , Adulto , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
14.
Histopathology ; 69(4): 600-6, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27061581

RESUMO

AIMS: To compare the diagnosis of acute cellular rejection (ACR) based on biopsies (Bx) performed simultaneously in the small bowel (SB) and colonic grafts (paired Bx) after intestinal transplantation (ITx). METHODS AND RESULTS: Retrospective study including all ITx with colon at Mount Sinai Hospital between 2009 and 2014. Paired Bx were reviewed blindly by two experienced gastrointestinal (GI) pathologists and were graded based on the VIII International Small Bowel Transplant Symposium Consensus criteria, with minor modifications for evaluation of colon biopsies. Each Bx was classified as negative or positive for ACR. Cohen's kappa statistic was used to quantify the interpathologist agreement and the agreement between SB and colonic Bx for the diagnosis of ACR. Fifteen patients underwent 51 paired Bx. The strength of agreement for the grade of ACR in the SB biopsies (kappa = 0.62) and the colonic biopsies (kappa = 0.65) was good. The inter-rater agreement was better for Bx negative for ACR and for higher grades of ACR. Overall, 74.5% of paired Bx were concordant for the presence or absence of ACR. The strength of agreement for the presence or absence of ACR between the SB and colonic Bx (kappa = 0.44) was moderate. Two cases of severe ACR were restricted to the SB allograft. CONCLUSIONS: Paired Bx in the SB and the colon are usually in agreement regarding the presence or the absence of ACR. However, colonic Bx alone may not suffice to exclude ACR following ITx. With minor modifications, the histopathological criteria of the SB may be adaptable to the colonic allograft.


Assuntos
Colo/transplante , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Intestino Delgado/transplante , Adulto , Idoso , Biópsia , Pré-Escolar , Feminino , Humanos , Incidência , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos
15.
J Immunol ; 188(1): 163-9, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22131333

RESUMO

SHIP is an SH2-containing inositol-5-phosphatase expressed in hematopoietic cells. It hydrolyzes the PI3K product PI(3,4,5)P(3) and blunts the PI3K-initiated signaling pathway. Although the PI3K/Akt pathway has been shown to be important for osteoclastogenesis, the molecular events involved in osteoclast differentiation have not been revealed. We demonstrate that Akt induces osteoclast differentiation through regulating the GSK3ß/NFATc1 signaling cascade. Inhibition of the PI3K by LY294002 reduces formation of osteoclasts and attenuates the expression of NFATc1, but not that of c-Fos. Conversely, overexpression of Akt in bone marrow-derived macrophages (BMMs) strongly induced NFATc1 expression without affecting c-Fos expression, suggesting that PI3K/Akt-mediated NFATc1 induction is independent of c-Fos during RANKL-induced osteoclastogenesis. In addition, we found that overexpression of Akt enhances formation of an inactive form of GSK3ß (phospho-GSK3ß) and nuclear localization of NFATc1, and that overexpression of a constitutively active form of GSK3ß attenuates osteoclast formation through downregulation of NFATc1. Furthermore, BMMs from SHIP knockout mice show the increased expression levels of phospho-Akt and phospho-GSK3ß, as well as the enhanced osteoclastogenesis, compared with wild type. However, overexpression of a constitutively active form of GSK3ß attenuates RANKL-induced osteoclast differentiation from SHIP-deficient BMMs. Our data suggest that the PI3K/Akt/GSK3ß/NFATc1 signaling axis plays an important role in RANKL-induced osteoclastogenesis.


Assuntos
Diferenciação Celular/imunologia , Quinase 3 da Glicogênio Sintase/imunologia , Fatores de Transcrição NFATC/imunologia , Osteoclastos/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia , Transdução de Sinais/imunologia , Transporte Ativo do Núcleo Celular , Animais , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Diferenciação Celular/genética , Núcleo Celular/genética , Núcleo Celular/imunologia , Núcleo Celular/metabolismo , Ativação Enzimática/genética , Ativação Enzimática/imunologia , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Inositol Polifosfato 5-Fosfatases , Camundongos , Camundongos Knockout , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/imunologia , Fosfatidilinositol 3-Quinases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/imunologia , Monoéster Fosfórico Hidrolases/metabolismo , Fosforilação/genética , Fosforilação/imunologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/genética , Ligante RANK/imunologia , Ligante RANK/metabolismo , Transdução de Sinais/genética
16.
Pediatr Transplant ; 18(6): E193-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24923672

RESUMO

Gastric variceal bleeding is associated with high morbidity and mortality. Balloon-occluded retrograde transvenous obliteration is a relatively new treatment used to control bleeding gastric varices that involves transvenous sclerosis of gastric varices through a spontaneous gastrorenal shunt. Here, we report on a 14-yr-old patient that underwent balloon-occluded retrograde transvenous obliteration for refractory bleeding fundal varices in the setting of esophageal varices and cirrhosis, which did not respond to medical management or endoscopic injection. This case report serves as a reminder that balloon-occluded retrograde transvenous obliteration can successfully control fundal variceal bleeding in pediatric patients and may serve as a bridge to liver transplantation.


Assuntos
Oclusão com Balão/métodos , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Cirrose Hepática/complicações , Transplante de Fígado , Adolescente , Diagnóstico Diferencial , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Recidiva , Soluções Esclerosantes/uso terapêutico
17.
Transplant Direct ; 10(6): e1605, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38715978

RESUMO

Background: Organ shortage remains a major challenge for the field of transplantation. Maximizing utilization and minimizing discard of available organs is crucial to reduce waitlist times. Our aim was to investigate the landscape of liver recovery, discard over the past decade in the United States, and identify areas to reduce organ discard. Methods: This study used the Scientific Registry of Transplant Recipients United Network for Organ Sharing database to analyze the rates and associated reasons of discarded organs from 2010 to 2021. All deceased donors were evaluated, and data were analyzed by organ type, year, and region. Organ disposition was analyzed by year and region. Donor demographics and liver biopsy data were also analyzed. Results: The volume of liver transplantation increased steadily, with a 44% increase from 2010 to 2021. Donation after circulatory death transplantation increased by 239%, comprising 10.6% of transplants in 2021, yet discard rates remained high at 30% for this donor subset. For all donor types, the liver discard rate has remained stable around 10% despite a 74% increase in available donors. Seventy percent of liver discards were attributed to organ factors, with biopsy findings accounting for 40% of all discards. Of livers that were biopsied, 70% had macrosteatosis of <30%. Conclusions: Analysis of trends in transplantation and discard allow for identifying areas of underutilization. Donation after circulatory death livers have expanded the pool of transplanted livers but remain discarded at high rates. Significant differences remain in discard rates between geographic regions. We identify several areas to lower the discard rates. The expanding role of machine perfusion may allow for utilization of previously discarded organs.

18.
Transplantation ; 108(4): 827-835, 2024 Apr 01.
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.


Assuntos
Rejeição de Enxerto , Enteropatias , Humanos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/patologia , Intestinos/transplante , Transplante Homólogo , Endoscopia Gastrointestinal/efeitos adversos , Endoscopia Gastrointestinal/métodos , Aloenxertos , Enteropatias/patologia
19.
Korean J Intern Med ; 39(2): 327-337, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38268194

RESUMO

BACKGROUND/AIMS: The prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in peripheral T-cell lymphomas (PTCLs) are controversial. We explored the prognostic impact of sequential 18F-FDG PET/CT during frontline chemotherapy of patients with PTCLs. METHODS: In total, 143 patients with newly diagnosed PTCLs were included. Sequential 18F-FDG PET/CTs were performed at the time of diagnosis, during chemotherapy, and at the end of chemotherapy. The baseline total metabolic tumor volume (TMTV) was calculated using the the standard uptake value with a threshold method of 2.5. RESULTS: A baseline TMTV of 457.0 cm3 was used to categorize patients into high and low TMTV groups. Patients with a requirehigh TMTV had shorter progression-free survival (PFS) and overall survival (OS) than those with a low TMTV (PFS, 9.8 vs. 26.5 mo, p = 0.043; OS, 18.9 vs. 71.2 mo, p = 0.004). The interim 18F-FDG PET/CT response score was recorded as 1, 2-3, and 4-5 according to the Deauville criteria. The PFS and OS showed significant differences according to the interim 18F-FDG PET/CT response score (PFS, 120.7 vs. 34.1 vs. 5.1 mo, p < 0.001; OS, not reached vs. 61.1 mo vs. 12.1 mo, p < 0.001). CONCLUSION: The interim PET/CT response based on visual assessment predicts disease progression and survival outcome in PTCLs. A high baseline TMTV is associated with a poor response to anthracycline-based chemotherapy in PTCLs. However, TMTV was not an independent predictor for PFS in the multivariate analysis.


Assuntos
Linfoma de Células T Periférico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Prognóstico , Fluordesoxiglucose F18 , Linfoma de Células T Periférico/diagnóstico por imagem , Linfoma de Células T Periférico/tratamento farmacológico , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons
20.
Nucl Med Mol Imaging ; 57(2): 103-109, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36998587

RESUMO

Purpose: Delayed images may not be acquired due to severe pain, drowsiness, or worsening vital signs while waiting after blood pool imaging in three-phase bone scintigraphy. If the hyperemia in the blood pool image contains information from which increased uptake on the delayed images can be inferred, the generative adversarial network (GAN) can generate the increased uptake from the hyperemia. We attempted to apply pix2pix, a type of conditional GAN, to transform hyperemia into increased bone uptake. Methods: We enrolled 1464 patients who underwent three-phase bone scintigraphy for inflammatory arthritis, osteomyelitis, complex regional pain syndrome (CRPS), cellulitis, and recent bone injury. Blood pool images were acquired 10 min after intravenous injection of Tc-99 m hydroxymethylene diphosphonate, and delayed bone images were obtained after 3 h. The model was based on the open-source code of the pix2pix model with perceptual loss. Increased uptake in the delayed images generated by the model was evaluated using lesion-based analysis by a nuclear radiologist in areas consistent with hyperemia in the blood pool images. Results: The model showed sensitivities of 77.8% and 87.5% for inflammatory arthritis and CRPS, respectively. In osteomyelitis and cellulitis, their sensitivities of about 44% were observed. However, in cases of recent bone injury, the sensitivity was only 6.3% in areas consistent with focal hyperemia. Conclusion: The model based on pix2pix generated increased uptake in delayed images matching the hyperemia in the blood pool image in inflammatory arthritis and CRPS.

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