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Introduction Central venous catheters (CVC) are associated with risks and complications. Complications like vessel perforation, thrombosis, infection with significant morbidity and mortality, knotting, and ventricular perforation have been described. Another less-frequent complication is retained CVC fragments. We present a case of a very late but fatal complication after a CVC placement. This report is written in line with the consensus-based surgical case report guidelines (SCARE). Case A 46-year-old male presented to the emergency department in a critical (septic) shock. The patients' medical history featured a long-intensive care admission 28 years ago. The cause of this sepsis was not evident until a computed tomography scan was performed to exclude a pulmonary embolism, revealing a remnant of a central catheter in both pulmonary arteries. Despite extensive resuscitation, the patient died within 24 hours after admission. An autopsy was performed confirming that the catheter remnant was the only possible cause of the fatal sepsis. Discussion CVC's are associated with (fatal) complications; however, retainment of remnants are described unfrequently but do occur in almost 2% of the cases. Endovascular removal of these remnants has been performed successfully and should be the first treatment of choice if removal is considered. No evidence is available that suggests that routine removal has to be attempted but some longer term complications can be expected, so awareness of possible remnants after CVC removal should exist. Conclusion Retained fragments of CVC's are rare but are described after prolonged use. This case shows that these retained intravascular fragments can cause fatal complications on the long-term. Upon removal of CVC's, there should be awareness that retainment of fragments can occur.
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The impact of primary cytomegalovirus infection (pCMV) on renal allograft function and histology is controversial. We evaluated the influence on incidence of acute rejection, allograft loss, allograft function and interstitial fibrosis/tubular atrophy (IF/TA). Retrospective case-control study, recipients transplanted between 2000 and 2014. Risk of acute rejection and allograft loss for those who experienced pCMV infection compared with those who did not, within an exposure period of two months after transplantation. Besides, its influence on allograft function and histology at one to three years after transplantation. Of 113 recipients experienced pCMV infection, 306 remained CMV seronegative. pCMV infection in the exposure period could not be proven as increasing the risk for acute rejection [HR = 2.18 (95% CI 0.80-5.97) P = 0.13] or allograft loss [HR = 1.11 (95%CI 0.33-3.72) P = 0.87]. Combination of pCMV infection and acute rejection posed higher hazard for allograft loss than acute rejection alone [HR = 3.69 (95% CI 1.21-11.29) P = 0.02]. eGFR(MDRD) values did not significantly differ at years one [46 vs. 50], two [46 vs. 51] and three [46 vs. 52]. No association between pCMV infection and IF/TA could be demonstrated [OR = 2.15 (95%CI 0.73-6.29) P = 0.16]. pCMV infection was not proven to increase the risk for acute rejection or allograft loss. However, it increased the risk for rejection-associated allograft loss. In remaining functioning allografts, it was not significantly associated with decline in function nor with presence of IF/TA.
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Infecciones por Citomegalovirus , Trasplante de Riñón , Estudios de Casos y Controles , Infecciones por Citomegalovirus/epidemiología , Rechazo de Injerto/etiología , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Polyomavirus-associated nephropathy (PVAN) occurs in a significant percentage of renal transplant recipients, with BK virus reactivation as the main causative agent. PVAN leads to tubular damage and may result in allograft loss. In this study, we analyzed the antiviral immune response in PVAN. Transcription of the proinflammatory cytokine interleukin-18 (IL-18) was significantly higher in PVAN biopsies compared with T cell-mediated rejection (TCMR) (1.42 ± 0.20 and 0.69 ± 0.10, respectively; *P = 0.0021). Tubular expression of IL-18 was significantly increased in PVAN compared with TCMR (2.00 ± 0.24 and 1.333 ± 0.13, respectively; *P = 0.028). In contrast, in TCMR, IL-18 was expressed predominantly by CD163-positive macrophages. These data suggest that the antiviral immune response in PVAN is partly coordinated by the tubular epithelium, whereas in TCMR, this may be controlled by inflammatory cells.
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Virus BK , Interleucina-18/genética , Enfermedades Renales/inmunología , Túbulos Renales/inmunología , Infecciones por Polyomavirus/inmunología , Infecciones Tumorales por Virus/inmunología , Adulto , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Femenino , Rechazo de Injerto , Humanos , Interleucina-18/análisis , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Receptores de Superficie Celular/análisis , Transcripción GenéticaRESUMEN
Although both polyomavirus infection and T cell-mediated rejection (TCMR) are characterized by tubulointerstitial inflammation in the renal allograft, these conditions are treated with opposing therapeutic regimens. To gain more insight into the differences between antiviral and alloimmune responses, we performed a case-control study, in which we immunophenotyped the inflammatory infiltrates in renal biopsy specimens with BK polyomavirus-associated nephropathy (BKPyVAN) and specimens with TCMR. Compared with TCMR, BKPyVAN was diagnosed later after transplantation; therefore, BKPyVAN specimens showed more chronic damage than TCMR specimens showed. However, TCMR and BKPyVAN specimens had comparable levels of tubulointerstitial inflammation. Adjustment for confounders in various multivariable models revealed more blood dendritic cell antigen-1(+) (BDCA-1(+)) myeloid dendritic cells (mDCs) present during BKPyVAN (odds ratio, 2.31; 95% confidence interval, 1.03 to 5.16; P=0.04) than during TCMR. Double immunostaining for SV40 and BDCA-1 showed that, during BKPyVAN, BDCA-1(+) mDCs localized in proximity to the polyomavirus-infected tubular epithelial cells. We ensured that time of biopsy after transplantation was not a confounding factor by including additional specimens with late TCMR and protocol biopsy specimens matched for biopsy time. These additional specimens showed amounts of BDCA-1(+) mDCs comparable with amounts in the early TCMR specimens. These results suggest that BDCA-1(+) mDCs, known to be involved in the antiviral immune response during various viral infections, might have a pivotal role during BKPyVAN infection in the grafted kidney.
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Virus BK , Células Dendríticas/inmunología , Rechazo de Injerto/inmunología , Rechazo de Injerto/virología , Enfermedades Renales/inmunología , Enfermedades Renales/virología , Trasplante de Riñón , Células Mieloides/inmunología , Infecciones por Polyomavirus/inmunología , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/virología , Linfocitos T/inmunología , Infecciones Tumorales por Virus/inmunología , Adulto , Antígenos CD1 , Estudios de Casos y Controles , Femenino , Glicoproteínas , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Transplant glomerulitis, observed in T cell-mediated and antibody-mediated rejection, is histologically characterized by intracapillary mononuclear cell infiltration. However, the prognostic value of counting various glomerular inflammatory cells during rejection has not been elucidated, which is a key step for the introduction of novel biomarkers in the clinics. We immunophenotyped glomerulitis during episodes of acute rejection in order to investigate their predictive value for transplant outcomes. To do so, we included 57 transplant biopsies of 57 renal transplant recipients with biopsy-proven acute rejection with a median follow-up of 4.2 years. We determined average glomerular cell counts for T cells, B cells, Tregs, IL-17(+) cells, neutrophils and macrophages. Logistic and Cox regression models were used to investigate the association of glomerular inflammatory cells with response to therapy and graft failure on a population level. We used novel time-dependent ROC curve analyses to investigate the value of glomerular inflammatory cell infiltrates for the prediction of transplant outcomes, applicable to the individual patient. We identified three cell types that were responsible for glomerulitis during rejection: macrophages, T cells and neutrophils. By quantification of glomerular macrophages, an emerging cell type associated with antibody-mediated rejection, we were able to predict the progression towards death-censored graft failure within the first 500 days after the initial episode of rejection. With the use of novel time-dependent ROC analyses, we propose dynamic sensitivities, specificities, and positive and negative predictive values with their corresponding cut-off values for the average amount of glomerular macrophages, depending on what time after rejection death-censored graft failure needs prediction.
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Aloinjertos/inmunología , Rechazo de Injerto/diagnóstico , Glomérulos Renales/inmunología , Trasplante de Riñón , Leucocitos/inmunología , Enfermedad Aguda , Adulto , Movimiento Celular , Femenino , Rechazo de Injerto/etiología , Humanos , Interleucina-17/metabolismo , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , PronósticoRESUMEN
In the consortium "ALLOVIR" we aim to characterize the effect of CMV and BKV infections on the innate immune responses to viral and alloantigens. Furthermore, we want to characterize the interplay between adaptive immune responses to viral and alloantigens with emphasis on the role of heterologous immunity. Thirdly, we will characterize the manifestations of these immune responses in the allograft, as reflected in tissue and urine, and their correlation with graft function. Finally, we will assess how immunosuppressive drugs interfere with these cross-reactive immune responses.
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Reacciones Cruzadas/inmunología , Infecciones por Citomegalovirus/inmunología , Isoantígenos/inmunología , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/inmunología , Antivirales/uso terapéutico , Virus BK/inmunología , Citomegalovirus/inmunología , Rechazo de Injerto/inmunología , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Riñón/virología , Países Bajos , Trasplante HomólogoRESUMEN
Interleukin-17 (IL-17) plays an important role in the regulation of cellular and humoral immune responses. Recent studies suggest a role for IL-17 in transplantation. Our study investigated whether quantifying IL-17(+) cells in renal transplant biopsies during acute rejection could have additional prognostic value for better stratifying patients at risk for nonresponsiveness to anti-rejection therapy and future graft dysfunction. Forty-nine renal biopsies with acute rejection were double immunostained and quantitatively analyzed for IL-17 and CD3 (IL-17(+) T-lymphocytes), tryptase (IL-17(+) mast cells) or CD15 (IL-17(+) neutrophils). Total IL-17(+) cell count correlated with total percentage of inflamed biopsy and estimated GFR during rejection. Most IL-17(+) cells were mast cells and neutrophils. We could hardly find any IL-17(+) T-lymphocytes. IL-17(+) mast cells correlated with interstitial fibrosis/tubular atrophy (IF/TA). None of the IL-17(+) cell counts had an additional prognostic value for response to anti-rejection treatment. Multivariate analysis correcting for C4d positivity and time from transplantation to biopsy showed that total IL-17(+) cell count independently predicts graft dysfunction at the last follow-up, which was validated in an independent cohort of 48 renal biopsies with acute rejection. We conclude that intragraft IL-17(+) cell count during acute allograft rejection could have an additional value for predicting late graft dysfunction.
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Interleucina-17/biosíntesis , Trasplante de Riñón/métodos , Mastocitos/citología , Insuficiencia Renal/terapia , Adolescente , Adulto , Anciano , Biopsia , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto , Humanos , Inmunohistoquímica/métodos , Masculino , Mastocitos/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Neutrófilos/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: Forkhead box (FOXP3) is considered to be a specific marker for regulatory T cells. The aim of this study was to correlate intragraft FOXP3 at mRNA and cellular levels during renal allograft rejection to response to therapy and late clinical outcome. METHODS: Immunostainings and quantitative reverse-transcriptase polymerase chain reaction for FOXP3, CD3, and transforming growth factor (TGF)-beta were performed and results were related to histopathologic and clinical outcome. RESULTS: A good correlation between immunohistochemical analysis and mRNA levels for both CD3 and FOXP3 was observed. Intragraft FOXP3 was significantly related to tubulitis and interstitial fibrosis. A strong correlation was found between FOXP3 and CD3 mRNA and between FOXP3 and TGF-beta mRNA. No correlation was found between FOXP3 and response to therapy. DISCUSSION: In conclusion, intragraft FOXP3 at both cellular and molecular levels parallels T-cell infiltration during acute rejection. FOXP3 does not predict response to antirejection therapy. FOXP3 correlates with renal fibrosis, TGF-beta, and poor late renal outcome.