74 research outputs found
Stented ureterovesical anastomosis in renal transplantation: does it influence the rate of urinary tract infections?
<p>Abstract</p> <p>Objective</p> <p>Our objective was to evaluate the impact of routine use of double-J stents on the incidence of urinary tract infection after renal transplantation.</p> <p>Methods</p> <p>We conducted a retrospective-comparative single-centre study in 310 consecutive adult deceased donor kidney recipients transplanted from 2002 to 2006. Patients were divided in two groups, with or without urinary stent implantation. To evaluate the predictive factors for UTI, donor and recipients pre- and post-transplantation data were analysed. Early urological complications and renal function within 12 months of transplantation were included as well.</p> <p>Results</p> <p>A total of 157 patients were enrolled to a stent (ST) and 153 patients to a no-stent (NST) group. The rate of urinary tract infection at three months was similar between the two groups (43.3% ST vs. 40.1% NST, p = 0.65). Of the identified pathogens Enterococcus and Escherichia coli were the most common species. In multivariate analysis neither age nor immunosuppressive agents, BMI or diabetes seemed to have influence on the rate of UTI. When compared to males, females had a significantly higher risk for UTI (54.0% vs. 33.5%).</p> <p>Conclusion</p> <p>Prophylactic stenting of the ureterovesical anastomosis does not increase the risk of urinary tract infection in the early postoperative period.</p
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Mixed Chimerism, Lymphocyte Recovery, and Evidence for Early Donor-Specific Unresponsiveness in Patients Receiving Combined Kidney and Bone Marrow Transplantation to Induce Tolerance
Background
We have previously reported operational tolerance in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT). We now report on transient multilineage hematopoietic chimerism and lymphocyte recovery in five patients receiving a modified CKBMT protocol, and evidence for early donor-specific unresponsiveness in one of these patients.
Methods
Five patients with end-stage renal disease received CKBMT from HLA-mismatched, haploidentical living related donors following modified non-myeloablative conditioning. Polychromatic flow cytometry (FCM) was used to assess multilineage chimerism where evaluable and lymphocyte recovery post-transplant. Limiting dilution analysis was used to assess helper-T-lymphocyte reactivity to donor antigens.
Results
Transient multilineage mixed chimerism was observed in all patients but chimerism became undetectable by 2 weeks post-CKBMT. A marked decrease in T and B lymphocyte counts immediately following transplant was followed by gradual recovery. Initially recovering T cells were depleted of CD45RA+/CD45RO− “naïve-like” cells, which have shown strong recovery in two patients and CD4/CD8 ratios increased immediately following transplant but then declined markedly. NK cells were enriched in the peripheral blood of all patients following transplant.
For Subject 2, a pre-transplant limiting dilution assay revealed T helper cells recognizing both donor and third-party PBMCs. However, the anti-donor response was completely undetectable by Day 24, while third-party reactivity persisted.
Conclusion
These results characterize the transient multilineage mixed hematopoietic chimerism and recovery of lymphocyte subsets in patients receiving a modified CKBMT protocol. The observations are relevant to the mechanisms of donor-specific tolerance in this patient group
Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device
This study aimed to validate a wearable device’s walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson’s Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and − 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application.
Trial registration: ISRCTN – 12246987
2005 immunosuppressive strategies in kidney transplantation: which role for the calcineurin inhibitors?
The calcineurin inhibitors (CNIs) cyclosporine and tacrolimus have been the cornerstones of immunosuppressive strategies in clinical transplantation. Currently, regimens that are most widely used for induction and maintenance therapy include CNIs. However, many clinical trials aiming at reducing or eliminating CNIs have been performed in recent years. Here, we review and discuss current and future immunosuppressive strategies with a special emphasis on the role of CNIs, in the light of recent studies in the field of kidney transplantation. In the current era, CNIs still play an important role
Hepatitis C, acute humoral rejection, and renal allograft survival
The effect of recipient hepatitis C virus (HCV) infection on renal allograft loss and acute rejection in kidney transplantation remains controversial. We studied 354 renal allograft recipients transplanted during 1996 to 2001 who had HCV antibodies (Ab) measured before transplantation. The primary outcome was death-censored allograft loss and the secondary outcome was acute humoral rejection (AHR). Compared with HCV Ab-negative patients, those with positive HCV Ab had longer time on dialysis before transplantation, higher percentage of panel-reactive antibodies (PRA), were more likely to receive a cadaveric transplant, and were more likely to develop delayed graft function (DGF). In univariate analyses, predictors of renal allograft loss included HCV, cadaveric graft, PRA >20%, HLA mismatch > or =5, retransplantation, DGF, induction therapy, and AHR. When adjusted for PRA >20%, HLA mismatch > or =5, and multiple transplant status, HCV was not a statistically significant predictor of allograft loss. HCV was also associated with AHR but lost significance when adjusted for PRA >20%. HCV Ab-positive patients were more likely to have longer duration of dialysis before transplantation prior to kidney transplants, higher PRA, and to receive cadaveric transplants. These characteristics likely resulted in more DGF and AHR after transplantation. After adjusting for these confounding factors, the association between HCV Ab positivity and renal allograft loss was notably attenuated and no longer statistically significant
Hepatitis C virus infection in haemodialysis and kidney transplant patients.
Chronic infection with hepatitis C virus (HCV) is an important global health problem. The prevalence of HCV is significantly higher in haemodialysis and kidney transplant patients, as compared to the general population. In spite of the relatively milder liver disease activity reported in HCV-infected haemodialysis patients, HCV infection adversely affects survival. Likewise, HCV has a detrimental effect on both patient and graft survival after kidney transplantation. However, patient survival is significantly better with kidney transplantation compared to remaining on dialysis; therefore, HCV infection alone should not be a contraindication to transplantation. Combination antiviral therapy with pegylated interferon-alpha and low-dose ribavirin is currently evolving in haemodialysis patients. Interferon-alpha (standard/pegylated) is relatively contraindicated after kidney transplantation because of an increased risk of allograft rejection. Therefore, antiviral treatment of transplant candidates while on dialysis remains the best option and may avoid the risk of HCV-associated liver and renal disease after transplantation. Large multi-centre clinical trials are required in HCV-infected haemodialysis and kidney transplant patients in order to define optimal therapeutic strategies before and after transplantation
Helicobacter pylori Accumulates Photoactive Porphyrins and Is Killed by Visible Light
Helicobacter pylori colonizes the mucus layer of the human stomach and duodenum, causes chronic gastritis, gastric ulcer, and is a risk factor for gastric adenocarcinoma. There is a 20% failure rate in antibiotic therapy, which is increasingly due to antibiotic resistance and necessitates the search for alternative antimicrobial methods. We have discovered that H. pylori when cultured in liquid medium, accumulates significant quantities of coproporphyrin and protoporphyrin IX, both in the cells and secreted into the medium. These photoactive porphyrins lead to cell death (up to 5 logs) by photodynamic action upon illumination with low doses of visible light, with blue/violet light being most efficient. The degree of killing increases with the age of the culture and is greater than that found with Propionibacterium acnes (another bacterium known to be photosensitive due to porphyrin accumulation). Both virulent and drug-resistant strains are killed. The data suggest that phototherapy might be used to treat H. pylori infection in the human stomach
Overlapping Pathways to Transplant Glomerulopathy: Chronic Humoral Rejection, Hepatitis C Infection and Thrombotic Microangiopathy
Background:Transplant glomerulopathy (TG) has received much attention in recent years as a manifestation of chronic humoral rejection (CHR). However, many cases lack C4d deposition and/or circulating donor-specifi c antibodies, and the contribution of other potential causes has not been fully addressed.Methods: Of 209 consecutive renal allograft indication biopsies performed for chronic allograft dysfunction, 25 that met pathologic criteria of TG (>10% duplication of the GBM without immune complex deposition) were examined for various etiologies, including hepatitis C infection (HCV), thrombotic microangiopathy (TMA), and CHR. 29 cases of biopsy-proven isolated chronic calcineurin inhibitor toxicity from the same time period were used as controls for comparing the prevalence of HCV.Results: Three partially overlapping categories accounted for 84% of the cases: C4d+TG (48%), HCV+TG (36%) and TMA+TG (32%). The majority of TMA+ cases were HCV+ (63%) and the majority of HCV+ cases had TMA (56%). Donor specifi c antibodies were associated with C4d+TG (7/8 vs. 1/4 C4d-TG; P<0.02), but not with HCV+TG. The prevalence of HCV was higher in the TG group than in 29 control patients without TG (36% vs. 7%, P<0.01). HCV+TG patients developed allograft failure earlier than HCV-TG patients (67.2 ± 60.2 mo versus 153.4 ± 126.2 mo, P=0.02). On a multivariate analysis, out of HCV, TG and C4d, only HCV was found to be a signifi cant risk factor for a more rapid allograft loss.Conclusion: We conclude that TG is not a specifi c diagnosis, but a pattern of pathologic injury with 3 major overlapping pathways involving CHR, HCV infection and TMA. It is important to distinguish these mechanisms, as they may have differentprognostic and therapeutic implications
Interferon-alpha therapy in liver transplant recipients: lack of association with increased production of anti-HLA antibodies
Interferon-alpha (IFN) is a useful treatment for active HCV infection. In kidney transplantation, IFN has been shown to trigger acute rejection with de novo anti-HLA antibodies. Interferon-alpha has not been reported to enhance the risk of acute rejection in HCV-positive liver transplant recipients (LTRs). Sera were collected from 44 LTRs greater than 6 months post-transplant. Sera were tested with ELISA for the presence and the specificity of anti-HLA antibodies. The prevalence of anti-HLA antibodies was 11% and was not significantly different in 13 HCV-positive recipients who received IFN, compared with 10 who did not receive IFN (8% vs. 20%), or with 21 HCV-negative recipients (10%). None of the patients had an acute rejection after starting IFN. In this study, LTRs receiving IFN did not have an increased frequency of anti-HLA antibodies. This may partially explain the safety of IFN previously reported in LTRs requiring antiviral therapy
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