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• Plasticity can occur in areas of residual vision, at borders of lesions. • Study aimed to test the effect of rTMS at perilesional areas. • 16 sessions high frequency rTMS led to improvement of visual field. [ABSTRACT FROM AUTHOR]

Regulatory T cells are enriched within CD25highCD4+ leukocytes, however their role in renal transplant recipients with stable function vs. recipients with biopsy-proven chronic allograft dysfunction remains unclear. We therefore studied the number, phenotype, and function of CD25highCD4+ cells in the peripheral blood of 30 renal transplant recipients of living-related grafts, comprising 15 rejection-free recipients with stable graft function (Group A) and 15 with biopsy-proven chronic graft dysfunction (Group B). A higher absolute number of CD25highCD4+ cells were present in the peripheral blood of rejection-free recipients (Group A) vs. those recipients with chronic graft dysfunction (Group B) ( P = 0.019); but there was no significant difference with healthy volunteers ( P = 0.084). In carboxyfluorescein diacetate succinimidyl ester-mixed leukocyte culture assays, depletion of CD25highCD4+ revealed active regulation in 11 (74%) of 15 rejection-free recipient samples (Group A) in response to donor- but not third party-leukocytes, whereas no regulatory activity was observed in any samples from recipients with chronic graft dysfunction (Group B). In conclusion, these data provide evidence for the presence of an increased number of CD25highCD4+ T cells with donor-specific regulatory activity in the peripheral blood of renal transplant recipients with stable graft function compared with recipients with chronic graft dysfunction. [ABSTRACT FROM AUTHOR]

Aim T o quantify and characterize HLA-specific B cells subsets identified by single antigen HLA-coated multiplexed beads (SAB) in kidney transplant recipients. Methods PBMC from kidney transplant recipients ( n = 8) and healthy volunteers ( n = 10) were incubated with SAB (One lambda) for HLA class I and II. HLA Bead-B-cell Rosette (BBR) frequency & specificity were analyzed by flow cytometry. HLA-specific B cells specificities and polyreactivity was defined by the percentage of total SAB forming BBR. Transplant recipients serum was tested for circulating HLA antibodies using SAB & MFI were estimated. Results Significantly higher frequency of HLA-specific B cells were identified in transplant recipients with circulating anti-HLA antibodies compared to healthy volunteers. Circulating HLA-specific B cells (donor specific and non-specific) were in higher frequency (1.15% of B cells vs 0.17% of B cells; p < 0.05), wide breadth of polyreactivity (HLA class I 76.97 ± 28.3; HLA class II 91.9 ± 10.5) vs (HLA class I 13.1 ± 3.15; HLA class II 13.69 ± 10.3); p < 0.05 among recipients with poor graft outcome compared with those with good graft outcome. Not all HLA-specific B cells were associated with IgG HLA antibodies detected above the cutoff values. Conclusions The frequency & breadth of HLA-specific B cells reactivity may be a determinant of an aggressive clinical course after transplantation. This novel approach has the advantage of the wide array of available HLA antigens in a single test which will help in defining HLA B cell receptor poly & cross-reactivity. In addition to enable phenotyping, functional and gene expression analysis of HLA specific B cells. [ABSTRACT FROM AUTHOR]

Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suffering from a severe form of secondary hyperparathyroidism. Herein, we report a patient with chronic kidney allograft failure returned back to hemodialysis who experienced manifestations of cauda equina compression secondary to a lumbar brown tumor. Also, we had another patient on hemodialysis with a demineralized lesion affecting the cervical vertebrae. Although brown tumor is a rare complication, these two cases highlighted the importance of neurological symptoms in uremic patients. Spinal decompression surgery, in order to alleviate pressure on neurological structures, together with subtotal parathyroidectomy, were highly indicated. [ABSTRACT FROM AUTHOR]

The current study aimed to assess the efficacy of duloxetine in reducing pain and improving the quality of life of individuals with chronic low back pain (CLBP). An extensive literature search was conducted to identify relevant studies that examined the efficacy of duloxetine in CLBP management. The primary objective of the present study was to assess the role of duloxetine use on pain levels, as well as improvements in quality of life, using validated instruments. The results were synthesized using a random-effects model. A total of 8 studies were included in the analysis. Duloxetine demonstrated clear benefits in pain reduction, evidenced by improvements across multiple scales including the visual analogue scale, brief pain inventory-interference (BPI), BPI-severity, weekly worst pain over 24 hours and Roland-Morris Disability Questionnaire scores. Quality of life improved with duloxetine treatment, as indicated by the 36-item short form survey (SF-36). However, there was no significant impact on the physical function component of SF-36. The present study provides evidence to affirm the efficacy of duloxetine in treating CLBP. Further research is required to validate these findings and to establish whether combining duloxetine with other CLBP treatments yields superior outcomes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Bafail et al.)

Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare condition. It is characterized by very high maternal mortality and morbidity. Most cases of P-aHUS (79%) manifest in the postpartum period; this is probably due to the complement's involvement in aHUS pathogenesis. Eculizumab is approved for aHUS treatment, but its use is limited due to cost, unknown duration of treatment, and vague dose intervals to keep patients in remission. In this case report, we present a 26-year-old female with P-aHUS with hybrid CFHR1/CFH gene. Eculizumab was initiated after 5 weeks of being on hemodialysis and plasmapheresis sessions. Full remission successfully achieved after 6th dose of Eculizumab, within 13 weeks of onset of aHUS. Due to financial issues and inability to financially cover the cost, Eculizumab was set in hold. Within 6 months, she suffered recurrence of the disease and Eculizumab was re-instated. After re-inducing full remission, the patient was switched to Eculizumab every 3 months instead of the recommended manufacture dose interval of every 2 weeks. We followed this patient for 3 years and she continued to be in remission based on clinical and laboratory data. In conclusion, achievement of successful and maintenance of remission of P-aHUS in this patient who had limited access to Eculizumab raise the attention of the efficacy of Eculizumab at longer time intervals. However, it is time to consider conducting a long-term study to learn about the safety and efficacy of this approach, which may have a major financial advantage for patients.

Objectives: To investigate the frequency and risk factors affecting the incidence of post-transplantation glomerulonephritis (GN) and the impact of GN on the survival of the graft and the patient., Patients and Methods: Patients were classified based on histological findings into three groups. Graft survival was ascertained using the Kaplan-Meier method and significance calculated using log-rank tests. For multivariate analysis the Cox model was used., Results: Transplant glomerulopathy was the most prevalent glomerular disease in our series followed by recurrent GN and lastly de novo GN. In all, 50% of the de novo GN group had diabetes. The worst graft outcomes were in the recurrent GN group (P = 0.044). Multivariate analysis revealed ageing of the graft and mammalian target of rapamycin (mTOR) immunosuppression as risk factors for development of GN. While, the age of the recipient and donor, anti-lymphocyte globulin induction therapy, and acute rejection were risk factors for poor graft outcomes., Conclusions: GN is an important issue after transplantation. Tracking the incidence and progression of histological findings in the graft may help to guide proper management and improve graft outcome.

Selectin-selectin ligand interactions mediate the initial steps in leukocyte migration, an integral part of immune responses. Fucosyltransferase-VII (FucT-VII), encoded by Fut7, is essential for biosynthesis of selectin ligands. In an established model of cardiac allograft vasculopathy and chronic rejection, Fut7(-/-) recipients exhibited long-term graft survival with minimal vasculopathy compared with WT controls. Graft survival was associated with CD4 T-cell exhaustion in the periphery, characterized by impaired effector cytokine production, defective proliferation, increased expression of inhibitory receptors programmed death-1 (PD-1) and T cell Ig- and mucin-domain-containing molecule-3 (Tim-3), low levels of IL-7Rα on CD4 T cells, and reduced migration of polyfunctional CD4 memory T cells to the allograft. Blocking PD-1 triggered rejection only in Fut7(-/-) recipients, whereas depleting regulatory T cells had no effect in either Fut7(-/-) or WT recipients. Adoptive transfer experiments confirmed that this CD4 T cell-exhausted phenotype is seen primarily in Fut7(-/-) CD4 T cells. These data suggest that impaired leukocyte recruitment is a novel mechanism leading to CD4 T-cell exhaustion. Our experimental system serves as an excellent model to study CD4 T-cell exhaustion as a dominant mechanism of transplant tolerance. Further, targeting FucT-VII may serve as a promising strategy to prevent chronic allograft rejection and promote tolerance.

To evaluate the role of power Doppler in the identification and differentiation between acute renal transplant rejection and acute tubular necrosis (ATN), we studied 67 live donor renal transplant recipients. All patients were examined by spectral and power Doppler sonography. Assessment of cortical perfusion (CP) by power Doppler was subjective, using our grading score system: P0 (normal CP); homogenous cortical blush extending to the capsule, P1 (reduced CP); cortical vascular cut-off at interlobular level, P2 (markedly reduced CP); scattered cortical color flow at the interlobar level. Renal biopsies were performed during acute graft dysfunction. Pathological diagnoses were based on Banff classification 1997. The Mann- Whitney test was used to test the difference between CP grades with respect to serum creatinine (SCr), and resistive index (RI). For 38 episodes of acute graft rejection grade I, power Doppler showed that CP was P1 and RI ranging from 0.78 to 0.89. For 21 episodes of acute graft rejection grade II, power Doppler showed that CP was P1, with RI ranging from 0.88 to >1. Only one case of grade III rejection had a CP of P2. Twelve biopsies of ATN had CP of P0 and RI ranging from 0.80 to 0.89 There was a statistically significant correlation between CP grading and SCr (P <0.01) as well as between CP grading and RI (P <0.05). CP grading had a higher sensitivity in the detection of early acute rejection compared with RI and cross-sectional area measurements. We conclude that power Doppler is a non-invasive sensitive technique that may help in the detection and differentiation between acute renal transplant rejection and ATN, particularly in the early post-transplantation period.

Objective: We aimed to analyse donor and recipient predictors of graft survival in children who received live-donor renal grafts., Patients and Methods: The study comprised 273 children who received live-donor renal transplants at our center between March 1976 and October 2010. The follow-up ranged from 6 months to 25 years. Donor variables included donor age, gender, donor/recipient body weight ratio (DR BWR), ABO blood groups, human leukocyte antigen, and DR mismatching. Donor-specific problems, e.g., ischemia time during surgery and number of renal arteries, were included. Recipient variables included recipient age, sex, original kidney disease, ischemia time, acute tubular necrosis (ATN) after transplantation, immunosuppression, number of acute rejection episodes, re-transplantation, and development of hypertension., Results: Independent variables with a sustained effect on the 5- and 10-year graft survival on multivariate analysis were: ATN after transplant, number of acute rejections, hypertension, and DR BWR. At the last follow-up, 185 patients (67.8%) had a functioning graft, while 82 (30.0%) had graft failure. Only six patients (0.02%) were lost to follow-up., Conclusion: Donor and recipient variables that affect short- and long-term graft survival in children with a live-donor renal allograft are DR BWR, number of acute rejections, ATN and hypertension after transplant. Considering these variables provides a better outcome.

Objectives: The goal of this project was to develop a nomogram that predicts the probability of graft survival at 5 years., Materials and Methods: From our dataset, 1,581 patients were used to construct a nomogram (modeling group), the remaining 319 patients (testing group) were used for its validation. Initially, the modeling group variables were correlated with graft survival by univariate analysis. Significant factors were subjected to a multivariate analysis using a Cox regression model. The results formed the basis of our nomogram construction. Internal validation was done first by discrimination using the concordance index. Second, the calibration was assessed graphically. And finally, for external validation, the nomogram was used to predict graft survival using the testing group. The predicted probability(s) was compared with the actual survival estimates., Results: Validation of the nomogram yielded a concordance index of 0.77, and the observed correspondence between predicted and actual outcomes suggested a high level of calibration. Nomogram predictions of the testing group revealed no differences in the means of predicted and observed graft survival at 5 years, with a high correlation coefficient and accepted predictive accuracy (concordance index, 0.72)., Conclusions: We developed a well-validated and reasonably precise nomogram for predicting 5-year graft survival.