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BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. METHODS: The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. RESULTS: The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01). CONCLUSIONS: D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.
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Infecções por Vírus Epstein-Barr , Transtornos Linfoproliferativos , Transplante de Órgãos , Complicações Pós-Operatórias , Humanos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/virologia , Infecções por Vírus Epstein-Barr/epidemiologia , Masculino , Estudos Prospectivos , Criança , Feminino , Estados Unidos/epidemiologia , Pré-Escolar , Adolescente , Lactente , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/virologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Herpesvirus Humano 4 , Adulto JovemRESUMO
In testing the prognostic value of the occurrence of an intervening event (clinical event that occurs posttransplant), 3 proper statistical methodologies for testing its prognostic value exist (time-dependent covariate, landmark, and semi-Markov modeling methods). However, time-dependent bias has appeared in many clinical reports, whereby the intervening event is statistically treated as a baseline variable (as if it occurred at transplant). Using a single-center cohort of 445 intestinal transplant cases to test the prognostic value of first acute cellular rejection (ACR) and severe (grade of) ACR on the hazard rate of developing graft loss, we demonstrate how the inclusion of such time-dependent bias can lead to severe underestimation of the true hazard ratio (HR). The (statistically more powerful) time-dependent covariate method in Cox's multivariable model yielded significantly unfavorable effects of first ACR (P < .0001; HR = 2.492) and severe ACR (P < .0001; HR = 4.531). In contrast, when using the time-dependent biased approach, multivariable analysis yielded an incorrect conclusion for the prognostic value of first ACR (P = .31, HR = 0.877, 35.2% of 2.492) and a much smaller estimated effect of severe ACR (P = .0008; HR = 1.589; 35.1% of 4.531). In conclusion, this study demonstrates the importance of avoiding time-dependent bias when testing the prognostic value of an intervening event.
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Intestinos , Transplante de Rim , Humanos , Prognóstico , Intestinos/transplante , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologiaRESUMO
Epstein-Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) results in significant morbidity and mortality in pediatric transplant recipients. Identifying individuals at an increased risk of EBV-positive PTLD could influence clinical management of immunosuppression and other therapies, improving posttransplant outcomes. A 7-center prospective, observational clinical trial of 872 pediatric transplant recipients evaluated the presence of mutations at positions 212 and 366 of EBV latent membrane protein 1 (LMP1) as an indicator of risk of EBV-positive PTLD (clinical trials: NCT02182986). DNA was isolated from peripheral blood of EBV-positive PTLD case patients and matched controls (1:2 nested case:control), and the cytoplasmic tail of LMP1 was sequenced. Thirty-four participants reached the primary endpoint of biopsy-proven EBV-positive PTLD. DNA was sequenced from 32 PTLD case patients and 62 matched controls. Both LMP1 mutations were present in 31 of 32 PTLD cases (96.9%) and in 45 of 62 matched controls (72.6%) (P = .005; OR = 11.7; 95% confidence interval, 1.5, 92.6). The presence of both G212S and S366T carries a nearly 12-fold increased risk of development of EBV-positive PTLD. Conversely, transplant recipients without both LMP1 mutations carry a very low risk of PTLD. Analysis of mutations at positions 212 and 366 of LMP1 can be informative in stratifying patients for risk of EBV-positive PTLD.
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Infecções por Vírus Epstein-Barr , Transtornos Linfoproliferativos , Humanos , Criança , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Estudos Prospectivos , Transtornos Linfoproliferativos/etiologia , Mutação , Proteínas de MembranaRESUMO
OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.
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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.
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Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Fígado , Transplante Homólogo , Intestinos/transplante , Rejeição de Enxerto/prevenção & controle , Sobrevivência de EnxertoRESUMO
BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common posttransplantation infections and has been associated with increased rejection and mortality. Data in intestinal transplants recipients are limited. METHODS: This is a single-center, retrospective cohort study of all intestinal transplants performed between January 1, 2009, and August 31, 2020. We included recipients of all ages who were at risk of CMV infection. To identify the risk factors, we conducted at first univariate and multivariate analysis. For the multivariate analysis, we developed a logistic regression model based on the result of univariate analysis. RESULTS: Ninety five patients with a median age of 32 (interquartile range [IQR] 4, 50) were included. CMV donor seropositive/recipient seronegative were 17 (17.9%). Overall, 22.1% of the recipients developed CMV infection at a median time of 155 (IQR 28-254) days from transplant, including 4 CMV syndrome and 6 CMV end-organ disease. Overall, 90.4%, (19/21) developed DNAemia while on prophylaxis. Median peak viral load and time to negativity was 16â¯000 (IQR 1034-43â¯892) IU/mL and 56 (IQR 49-109) days, respectively. (Val)ganciclovir and foscarnet were utilized in 17 (80.9%) and 1 (4.76%) recipients, respectively. Recurrences of CMV DNAemia and graft rejection were observed in three and six recipients, respectively. Younger age was identified as a risk factor (p = .032, odds ratio 0.97, 95% confidence interval 0.95-0.99) to develop CMV DNAemia. CONCLUSION: A significant proportion of intestinal transplant recipients developed CMV infection while on prophylaxis. Better methods such as CMV cell mediated immunity guided prophylaxis should be used to prevent infections in this population.
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Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3-5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17-121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT.Clinical trial registration www.clinicaltrials.gov ; NCT01147380; registration date: June 17, 2010.
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Carcinoma Hepatocelular/terapia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Neoplasias Hepáticas/terapia , Transplante de Fígado , Fígado/imunologia , Transferência Adotiva , Adulto , Idoso , Biomarcadores , Terapia Combinada , Estudos de Viabilidade , Feminino , Sobrevivência de Enxerto , Humanos , Imuno-Histoquímica , Células Matadoras Naturais/metabolismo , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Complexity of combined heart-liver transplantation has resulted in low adoption rates. We report a case series of adult patients receiving en-bloc heart-liver transplantation (HLTx), describe technical aspects, and discuss benefits of the technique. METHODS: Retrospective review of patients receiving en-bloc HLTx over 18 months, with clinical follow up to 1 year. Primary outcomes included postoperative mortality and major complications. Secondary outcomes included 1-year survival, cardiac or hepatic allograft rejection, and infection. RESULTS: Five patients received en-bloc HLTx. Mean recipient age was 43 years (26-63), and 3 patients were male. Total operative time was 430 minutes (393-480), cold and warm ischemic times of 85 (32-136) and 37.5 (31-47) minutes. Hospital survival was 80%. One patient died on postoperative day 55 due to fungal sepsis. Major postoperative complications included prolonged mechanical ventilation in 2 of 5 patients (40%), and renal insufficiency requiring hemodialysis in 2 of 5 patients (40%). Among patients discharged from hospital 1-year survival was 100%, with no evidence of rejection or infectious complications. CONCLUSION: En-bloc HLTx technique is a safe and effective strategy, decreasing operative times, and allograft ischemic times, whereas offering protection of implanted allografts during early stages of reperfusion while patient is hemodynamically supported on cardiopulmonary bypass.
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Insuficiência Cardíaca/cirurgia , Transplante de Coração , Falência Hepática/cirurgia , Transplante de Fígado , Adulto , Feminino , Insuficiência Cardíaca/complicações , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Humanos , Falência Hepática/complicações , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The Coronavirus disease 2019(COVID-19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS-CoV-2 infection. A full understanding of this scenario is required, as transplantation is a life-saving procedure and COVID-19 remains an ongoing threat. METHODS: Abdominal organ transplant recipients diagnosed with COVID-19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post-transplant. RESULTS: We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS-CoV-2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow-up was 79 (22-190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow-up, only one patient developed rejection; thirteen patients had favorable graft outcomes. CONCLUSIONS: We were able to perform abdominal transplantation for patients with COVID-19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS-CoV-2 infection.
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COVID-19 , Transplante de Rim , Hospitalização , Humanos , SARS-CoV-2 , TransplantadosRESUMO
PURPOSE OF REVIEW: Intestinal transplantation has evolved to be a viable treatment option for patients with intestinal failure. This review shows the most current tendencies and practices of intestinal transplant centers and an overall comparison to intestinal rehabilitation. RECENT FINDINGS: This review outlines that timing for referral and advances in preoperative and postoperative care of intestinal and multivisceral transplant candidates are crucial to achieve results comparable to intestinal rehabilitation. SUMMARY: Current practices have shown that intestinal transplantation continues to improve overall results and could be considered in patients with permanent home parenteral nutrition. Timing for referral and preoperative and postoperative management are crucial to optimize long-term results.
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Enteropatias , Transplante de Fígado , Nutrição Parenteral no Domicílio , Humanos , Enteropatias/cirurgia , IntestinosRESUMO
Clostridium difficile infection (CDI) is the most common health care-associated infection in the United States. Thirty-nine percent of intestinal transplant recipients may develop CDI. Induction of rejection has been reported as a rare event. To our knowledge, this will be the second report of an association between CDI and rejection in the literature. We describe our experience with four pediatric MVT recipients, three of whom on treatment of their CDI alone had resolution of biopsy findings of intestinal ACR. Our patients were males aged 2-5 years old who had their first CDI post-MVT occurring from 2 months to 15 months post-transplant. All first episodes of CDI were treated with a 10-14 day course of metronidazole with one additionally receiving vancomycin. All four recipients had recurrent CDI, and two recipients had septic shock as a manifestation of their CDI. Three recipients had biopsies showing mild rejection during episodes of CDI, and treatment of the CDI resulted in resolution of biopsy findings of rejection. Our case series suggests CDI may mimic ACR on intestinal biopsy. Treatment of rejection during active CDI carries the risk of over-suppression and worsening of CDI. Our experience has taught us that surveillance endoscopy for rejection may be deceiving during an active CDI, and if mild acute rejection is noted during active CDI, treatment of rejection can be safely delayed and potentially avoided.
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Clostridioides difficile , Infecções por Clostridium/diagnóstico , Rejeição de Enxerto/diagnóstico , Intestinos/transplante , Complicações Pós-Operatórias/diagnóstico , Biópsia , Criança , Pré-Escolar , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/etiologia , Diagnóstico Diferencial , Humanos , Intestinos/microbiologia , Intestinos/patologia , Transplante de Fígado , Masculino , Transplante de Pâncreas , Recidiva , Estômago/transplanteRESUMO
The combination of pediatric multivisceral and kidney transplantation leads to additional recipient risks due to the number of anastomoses and to the small sizes of donor structures. The inclusion of donor kidneys, ureters, and a bladder patch en bloc with multivisceral organs decreases the number and complexity of anastomoses and has not yet been reported. Four patients were transplanted in this fashion; three underwent multivisceral-kidney and one underwent liver-kidney transplantation. The first patient was a 3-year-old male with polycystic kidney disease and congenital hepatic fibrosis. The second was a 7-year-old female with complications from necrotizing enterocolitis. The third was a 12-month-old male with megacystis microcolon intestinal hypoperistalsis syndrome and secondary hydronephrosis, and the fourth was a 3-year-old male with multiple intestinal resections secondary to incarcerated hernia. The third patient developed a right ureteral stenosis with an intact bladder patch. The fourth child expired from maintained abdominal sepsis. The first 3 patients maintained normal graft function. There were no cases of thrombosis, arterial stenosis, or urinary leakages. These reported cases demonstrate that small pediatric en bloc transplantation of the multivisceral organs and dual kidneys with a bladder patch anastomosis is a feasible and less complex alternative to the standard procedure.
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Anormalidades Múltiplas/cirurgia , Colo/anormalidades , Doenças Genéticas Inatas/cirurgia , Hidronefrose/cirurgia , Pseudo-Obstrução Intestinal/cirurgia , Transplante de Rim/métodos , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Doenças Renais Policísticas/cirurgia , Bexiga Urinária/anormalidades , Bexiga Urinária/transplante , Anastomose Cirúrgica/métodos , Criança , Pré-Escolar , Colo/cirurgia , Enterocolite Necrosante/complicações , Evolução Fatal , Feminino , Doenças Genéticas Inatas/complicações , Humanos , Hidronefrose/etiologia , Lactente , Pseudo-Obstrução Intestinal/complicações , Cirrose Hepática/complicações , Masculino , Doenças Renais Policísticas/complicações , Ureter/transplante , Bexiga Urinária/cirurgiaRESUMO
Multivisceral transplant (MVT) for cirrhosis, and portomesenteric vein thrombosis (PVT), is fraught with life-threatening thrombo-hemorrhagic complications. Embolization of native viscera has been attempted in a handful of cases with mixed results. We carried out a comparative analysis of angiographic, intra-operative, and pathological findings in three recipients of MVT who were deemed exceptionally high hemorrhagic risk and therefore underwent preoperative visceral embolization. All recipients were male with cirrhosis, PVT, and a surgical history indicative of diffuse visceral adhesions; status post-liver transplantation (n = 2) and proctocolectomy (n = 1). The first patient had two Amplatzer II embolization plugs placed 2 cm from the origins of celiac and superior mesenteric (SMA) arteries. Distal migration of the celiac plug into gastroduodenal artery (GDA) and ensuing ischemia reperfusion injury, presumably contributed to severe disseminated intravascular coagulation (DIC) and intra-operative mortality. In the other two recipients, distal Gelfoam embolization of the SMA, GDA, and splenic arteries was performed, and although remarkable hemorrhage and coagulopathy occurred, embolization, undoubtedly, facilitated exenteration and improved outcomes. Pathologic examination in these cases confirmed ischemic necrosis of eviscerated bowel. In conclusion, liver-sparing, preoperative distal embolization of native viscera with Gelfoam is beneficial, but entails several pitfalls. It should currently be reserved for MVT recipients who otherwise are at unacceptably high risk.
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Abdome/patologia , Embolização Terapêutica/métodos , Cirrose Hepática/terapia , Transplante de Órgãos/métodos , Trombose Venosa/terapia , Vísceras/irrigação sanguínea , Vísceras/transplante , Adulto , Angiografia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Prognóstico , Transplantados , Trombose Venosa/patologiaRESUMO
BACKGROUND: Data on bloodstream infection (BSI) due to enteric organisms are scarce. METHODS: This retrospective study (1/2009-5/2017) was aimed to evaluate the incidence of BSI episodes due to enteric organisms during the first 6 months after intestinal transplant (ITx). Differences between the first (2009-2012) and second period (2013-2017) were evaluated as they differed from each other in the perioperative fungal prophylaxis and immunosuppressive regimen. RESULTS: Fifty-five adult patients were analyzed. Twenty-eight (51%) patients developed a total of 51 episodes of BSI. Mean time from transplant to BSI was 85.5 ± 58.8 days. The most common organisms were Klebsiella pneumoniae (33%), Enterococcus spp (31%), and Candida spp (18%). Twenty-three (45%) were multidrug resistant. The most common sources were gut translocation (35%), central line infection (20%), and intra-abdominal abscess (14%). Biopsy-proven rejection was associated with 16 (31%) of the BSI episodes. Patients during the first period were more likely to develop BSI (79% vs 41%, P = 0.03). There were more episodes of rejection associated with BSI in the first period (45% vs 14%, P = 0.03). The rate of reoperation into the abdominal cavity within 2 weeks after ITx was higher and the transplant hospital stay was longer among those who developed BSI (P = 0.04 for both). CONCLUSIONS: Half of our patients developed BSI (typically during the first 3 months). Gut translocation was the most common source of BSI. Patients with rejection and/or enteritis should be monitored closely for BSI.
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Bacteriemia/etiologia , Candidíase/sangue , Intestino Delgado/microbiologia , Intestinos/transplante , Transplante de Órgãos/efeitos adversos , Adulto , Translocação Bacteriana , Candida/isolamento & purificação , Candidíase/etiologia , Farmacorresistência Bacteriana Múltipla , Enterococcus/isolamento & purificação , Feminino , Florida/epidemiologia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Infecções por Klebsiella/sangue , Infecções por Klebsiella/etiologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
HBL is the most common malignant liver neoplasm in children. The etiology of HBL is largely unknown but there are certain syndromes, such as Beckwith-Wiedemann syndrome, that have been clearly associated with an increased incidence of this malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly characterized by lax abdominal musculature, bilateral cryptorchidism requiring, in some cases, hemodialysis due to significant kidney and urinary tract dysfunctions. Despite an improvement on the survival rates of patients with advanced-stage HBL, the presence of concomitant end-stage renal disease that occurs in patients with EBS constitutes a therapeutic challenge for the clinician not only due to the use of nephrotoxic chemotherapy but also due to the potential need for multi-organ transplant. We report case of a 2-year-old male patient with EBS diagnosed with stage IV, metastatic HBL successfully treated with multi-agent chemotherapy while on dialysis whom then underwent a simultaneous liver-kidney transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved cancer remission with normalization of his renal function. Our report emphasizes that patients with HBL in the setting of EBS will not only require careful kidney function monitoring while receiving chemotherapy, but they might also need to undergo multi-organ transplantation in order to achieve adequate cancer control and also normalization of their kidney function. Awareness of this unusual association calls for further investigation to potentially establish a genetic association between these two disease processes.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hepatoblastoma/terapia , Falência Renal Crônica/terapia , Transplante de Rim , Neoplasias Hepáticas/terapia , Transplante de Fígado , Síndrome do Abdome em Ameixa Seca/complicações , Quimioterapia Adjuvante , Pré-Escolar , Hepatoblastoma/secundário , Humanos , Falência Renal Crônica/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Masculino , Terapia NeoadjuvanteRESUMO
BIs are ubiquitous among the pediatric intestinal transplant patient population. Personalizing postoperative prophylaxis antibiotic regimens may improve outcomes in this population. A retrospective analysis of all pediatric patients who underwent intestinal transplantation was evaluated to compare standardized and tailored regimens of antibiotics provided as prophylaxis postoperatively. Patients in the standard group have both shorter time to and higher rate of BIs, which was statistically significant (P < 0.001). Of the children who developed a BI, there was no statistical difference in average times to the development of a second BI (293 vs 119 days, P = 0.211). The tailored group had prolonged times until the development of a MDRO (52.6 vs 63.9 days, P = 0.677). Although not statistically significant, the tailored group had a propensity to present with gram-negative pathogens after transplant as compared to the standard regimen group, which presented with gram-positive pathogens (P = 0.103). Children with a history of an MDRO held a 7.3 (P < 0.01) times more likelihood of death within a year of transplant. A tailored prophylactic antibiotic regimen in the post-transplant period appears to prolong the time to the first BI. Although the data do not show differences in mortality, further study may prove the impact of a tailored antibiotic regimen on morbidity and mortality rates.
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Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Infecções Bacterianas/prevenção & controle , Intestinos/transplante , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Infecções Bacterianas/etiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
ADV is frequently seen in our pediatric SOT population. It presents in a variety of clinical presentation and can cause severe disease. In this population, there are very few studies to determine the safety of CDV as a potential therapeutic agent. We present the findings of our retrospective study evaluating the efficacy and safety of CDV as 2 separate dosing regimens. Regimen A uses the standard 5 mg/kg once a week (Regimen A), and the second uses the 1 mg/kg 3 times per week (Regimen B). Overall, the dosing regimen did not differ in nephrotoxicity, but Regimen B had a higher, although non-significant, rate of viral load clearance. This suggests that more frequent dosing at lower levels may be more efficacious without any significant side effects in our SOT population.
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PURPOSE: We sought to identify factors associated with increased resource utilization and in-hospital mortality for pediatric liver transplantation (LT). METHODS: Kids' Inpatient Database (1997-2009) was used to identify cases of LT in patients <20 years old. RESULTS: Overall, 2905 cases were identified, with an in-hospital survival of 91 %. LT was performed most frequently in < 5 year olds (61 %), females (51 %), and Caucasians (56 %). LT was performed at urban teaching hospitals (97 %) and facilities with children's units (51 %). Indications included pathologic conditions of the biliary tract (44 %) and inborn errors of metabolism (34 %), though unspecified end stage liver disease was the most common (75 %). Logistic regression found higher mortality in children undergoing LT for malignant conditions (odds ratio: 4.8) and acute hepatic failure (OR 3.4). Cases complicated by renal failure (OR 7.7) and complications of LT (OR 2.7) had higher mortality rates. Resource utilization increased for children with renal failure and those with hemorrhage as a complication of LT, p < 0.05. CONCLUSION: Hospital survival is predicted by indication and complications associated with LT. Resource utilization increased with renal failure and complications related to LT. Admission length was sensitive to payer status, hospital characteristics, and UNOS region, whereas total costs were unaffected by payer status or hospital type.
Assuntos
Hepatopatias/epidemiologia , Hepatopatias/cirurgia , Transplante de Fígado/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Recursos em Saúde/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Lactente , Hepatopatias/mortalidade , Transplante de Fígado/mortalidade , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
PURPOSE: To present our experience in abdominal transplantations to manage unresectable abdominal neoplasms in children and to describe the role of extensive surgeries in such cases. METHODS: This is a retrospective study of 22 abdominal transplantations in 21 patients for abdominal tumors over 16 years. Transplantation techniques included liver transplant (LT), multivisceral transplant (MVTx), and intestinal autotransplant (IA). Follow-up intervals ranged from 0.3 to 168 months (median 20 months). RESULTS: LT alone was performed in 15 patients for primary malignant (11) and benign (4) liver tumors. Pathological classification included HB hepatoblastoma (6), HCC hepatocellular cancer (3), hepatic epithelioid hemangioendothelioma HEH (1), angiosarcoma (1), benign vascular tumors (3), and adenoma (1). IA was performed in four patients for lesions involving the root of the mesentery; tumors of the head of pancreas (3) and mesenteric hemangioma (1). MVTx was performed in 2 patients for malignancies; pancreaticoblastoma (1), recurrent hepatoblastoma (1), and in one patient as a rescue procedure after IA failure. Four of the eleven patients who underwent LT for malignant liver tumor had metastatic disease at presentation. Six of them died of recurrent neoplasm (3), transplant-related complications (2), and underlying disease (1). All LT patients who had benign tumors are alive with functioning grafts. All IA patients survived and are on an oral diet, with one patient requiring TPN supplementation. One of the three patients who underwent MVTx died of metastatic disease. CONCLUSIONS: Allo/auto transplantation for abdominal tumors is a valuable modality when conventional treatments fail or are not feasible.
Assuntos
Neoplasias Abdominais/cirurgia , Neoplasias do Sistema Digestório/cirurgia , Intestinos/transplante , Transplante de Órgãos/métodos , Vísceras/transplante , Adolescente , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/terapia , Humanos , Imunossupressores/uso terapêutico , Lactente , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Masculino , Mesentério/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Peritoneais/cirurgia , Estudos Retrospectivos , Transplante Autólogo , Transplante HomólogoRESUMO
New antibiotic options are urgently needed for the treatment of carbapenem-resistant Enterobacteriaceae infections. We report a 64-year-old female with prolonged hospitalization following an intestinal transplant who developed refractory bacteremia due to a serine carbapenemase-producing pandrug-resistant isolate of Klebsiella pneumoniae. After failing multiple antimicrobial regimens, the patient was successfully treated.