Evaluation of Antithymocyte Globulin Efficacy in Reversing Refractory Graft Rejection Using Retrospective Event-Based Sequential Graft Biopsy Analysis in Living Related Donor Renal Transplant.

OBJECTIVES: The main risk factor for poor graft outcomes is refractory acute rejection and its consequences. In this study, we compared the efficacy of antithymocyte globulins versus other antirejection strategies in reversing refractory acute graft rejection after living donor renal transplant. MATERIALS AND METHODS: We retrospectively reviewed the records of 745 patients who received living-donor kidney transplants and experienced acute rejection episodes at Mansoura Urology and Nephrology Center in Egypt over the past 20 years. Based on the type of antirejection medication that they received, we divided patients into 2 groups, with 80 patients in the antithymocyte globulin group and 665 patients who had other antirejection strategies. By using event-based sequential graft biopsy histopathology analysis, we compared the efficacy of antithymocyte globulins in reversing refractory rejection in terms of graft and patient complications and survival. RESULTS: Patient survival was comparable in both groups; however, graft survival was better in the antithymocyte globulin group than in the other group; in addition, event-based sequential graft biopsies revealed a lower incidence of acute and chronic rejection episodes after treatment of severe acute rejection in the antithymocyte globulin group compared with the other group. Incidence of posttreatment complications, particularly infection and malignancy, was comparable in both groups. CONCLUSIONS: Our retrospective analysis of event-based sequential graft biopsy allowed us to track graft rejection resolution or worsening. Antithymocyte globulins are highly effective in reversing acute graft rejection when compared with other approaches, with no increased risk of infection or malignancy.

A hybrid CNN and ensemble model for COVID-19 lung infection detection on chest CT scans.

COVID-19 is highly infectious and causes acute respiratory disease. Machine learning (ML) and deep learning (DL) models are vital in detecting disease from computerized chest tomography (CT) scans. The DL models outperformed the ML models. For COVID-19 detection from CT scan images, DL models are used as end-to-end models. Thus, the performance of the model is evaluated for the quality of the extracted feature and classification accuracy. There are four contributions included in this work. First, this research is motivated by studying the quality of the extracted feature from the DL by feeding these extracted to an ML model. In other words, we proposed comparing the end-to-end DL model performance against the approach of using DL for feature extraction and ML for the classification of COVID-19 CT scan images. Second, we proposed studying the effect of fusing extracted features from image descriptors, e.g., Scale-Invariant Feature Transform (SIFT), with extracted features from DL models. Third, we proposed a new Convolutional Neural Network (CNN) to be trained from scratch and then compared to the deep transfer learning on the same classification problem. Finally, we studied the performance gap between classic ML models against ensemble learning models. The proposed framework is evaluated using a CT dataset, where the obtained results are evaluated using five different metrics The obtained results revealed that using the proposed CNN model is better than using the well-known DL model for the purpose of feature extraction. Moreover, using a DL model for feature extraction and an ML model for the classification task achieved better results in comparison to using an end-to-end DL model for detecting COVID-19 CT scan images. Of note, the accuracy rate of the former method improved by using ensemble learning models instead of the classic ML models. The proposed method achieved the best accuracy rate of 99.39%.

Peripheral magnetic theta burst stimulation to muscles can effectively reduce spasticity: a randomized controlled trial.

BACKGROUND: Spasticity is a common complication of many neurological diseases and despite contributing much disability; the available therapeutic options are limited. Peripheral magnetic stimulation is one promising option. In this study, we investigated whether peripheral intermittent theta burst stimulation (piTBS) will reduce spasticity when applied directly on spastic muscles. METHODS: In this sham-controlled study, eight successive sessions of piTBS were applied directly to spastic muscles with supra threshold intensity. Assessment was done by modified Ashworth scale (mAS) and estimated Botulinum toxin dose (eBTD) at baseline and after the 8th session in both active and sham groups. RESULTS: A total of 120 spastic muscles of 36 patients were included in the analysis. Significant reduction of mAS and eBTD was found in the active compared to sham group (p < 0.001). The difference in mAS was also significant when tested in upper limb and lower limb subgroups. The degree of reduction in mAS was positively correlated with the baseline scores in the active group. CONCLUSION: piTBS could be a promising method to reduce spasticity and eBTD. It consumes less time than standard high frequency protocols without compromising treatment efficacy. TRIAL REGISTRATION: Clinical trial registry number: PACTR202009622405087. Retrospectively Registered 14th September, 2020.

COVID-19 Booster Vaccine Hesitancy among Hemodialysis Patients in Saudi Arabia Using the Health Belief Model: A Multi-Centre Experience.

OBJECTIVE: Vaccination hesitance for the COVID-19 booster dosage among hemodialysis patients is an important barrier in reducing morbidity and mortality linked to COVID-19 infection. Hence, this study aimed to explore the predictors of the third (booster) dose of COVID-19 vaccine intention among CKD patients on hemodialysis from the Kingdom of Saudi Arabia (KSA). METHODS: This study was a multi-center cross-sectional study conducted at four dialysis centers in KSA from 13 February 2022 to 21 June 2022. The data was collected by the nephrologist in charge of the unit using a structured study questionnaire, which consisted of four parts; socio-demographic and clinical variables, questions about COVID-19 infection and subjective assessment of health state, COVID-19 booster dose vaccination intention and confidence in vaccines and preferences, and a health belief model. The study population consisted of 179 hemodialysis patients. RESULTS: Participants in the study had conflicting health beliefs about their vulnerability to COVID-19 infection and the severity of the COVID-19 infection. Study participants expressed positive health beliefs about the advantages of the COVID-19 booster dose, and reported less perceived obstacles in receiving the vaccine. The influence of cues on action among the study population was high. A total of 140 (78.2%) hemodialysis patients expressed their intention to receive the COVID-19 booster dose. Patients who reported poor health in the self-rating of their health status had a substantially higher definite intention to take the COVID-19 booster dose, according to the chi-square test (11.16, df = 3, p = 0.01). There was a significant association between the constructs in the HBM model and COVID-19 vaccine (booster) intention. Marital status (OR = 1.67, CI 1.07-2.58) was found to be the strongest predictors of a definite intention to receive a COVID-19 booster dose. Confidence in the locally manufactured vaccine (OR = 0.33, CI 0.17-0.60), education (OR = 0.62, CI 0.41-0.93), and rating of health status (OR = 0.43 CI 0.25-0.74) were the strongest significant correlates of having no definite intention to take the COVID-19 vaccination. CONCLUSIONS: HBM constructs were found to be significantly associated with vaccination intention, which can be considered while planning policies to promote COVID-19 booster vaccination among hemodialysis patients. The study results could be utilized in drafting policies to improve COVID-19 booster dose vaccination uptake among hemodialysis population.

Microbial Repercussion on Hemodialysis Catheter-Related Bloodstream Infection Outcome: A 2-Year Retrospective Study.

BACKGROUND: Albeit growing technical advances in the design of hemodialysis catheters, intravascular catheter-related bloodstream infection (CRBSI) still represents an utmost clinical challenge to the health-care workers (HCWs). Data regarding the influence of the culprit organism on the scenario of CRBSI in the literature are extremely lacking. Thereby, this research was carried out. METHODS: We undertook a retrospective cohort study over an interval of 2 years, involving patients who underwent regular hemodialysis via catheters in the Renal Dialysis Unit (RDU) of Dr. Soliman Fakeeh Hospital (DSFH), Jeddah, Kingdom of Saudi Arabia (KSA). The study enrolled 139 patients (56.8% females and 43.2% males), with mean age of 60.79 ± 11.45 years. RESULTS: The aggregate rate of CRBSI was 5.1/1000 catheter days. Amongst the 139 study candidates confirmed of having CRBSI, while 69.8% of CRBSIs were ascribed to Gram-positive cocci, about one-third of the infectious episodes were secondary to Gram-negative bacilli. Interestingly, fever was the most common presentation of S. aureus CRBSI compared to CoNS and Gram-negative bacilli CRBSIs (20.9% versus 12.9% versus 6.5%, p= 0.0001), whereas CRBSIs due to CoNS were presented mainly with rigors (19.4%). Of note, CRBSIs caused by Gram-negative bacilli had a tendency to manifest with unusual symptoms such as vomiting or hypotension. Besides, they were more prone to involve hospitalization or ICU admission. In this study, no mortality was attributed to CRBSIs. CONCLUSION: Our study disclosed that the illicit organism has a repercussion on the clinical presentation as well as the fate of CRBSI among hemodialysis patients. This highlights the worth of identifying the infected cases in a periodic manner, to avoid the occurrence of devastating complications. A large body of work from various hemodialysis centers should take place in the near future so as to provide more insight in this perspective.

Treatment Outcomes of Proliferative vs. Non-proliferative Adult Lupus Nephritis: A 10-Year Follow-Up.

Introduction Systemic lupus erythematosus (SLE) is a systemic disease with clinically heterogeneous outcomes. Lupus nephritis (LN) is a common complication of SLE. LN impacts clinical SLE outcomes both directly, in the form of target organ damage, and indirectly, through the adverse effects of immunosuppressive therapy. Patients & methods The study included 402 SLE cases with biopsy-proven lupus nephritis who were under follow-up for the past 13 years at Mansoura Urology and Nephrology Center, Egypt. We studied the differences in outcome among various LN classes and between 275 proliferative cases and 102 non-proliferative cases. Results Class IV was the main LN class in our series with renal survival of 60% at 10 years. The major induction regimen after the first biopsy was cyclophosphamide. Mycophenolate mofetil was the main induction and adjunctive regimen after the second biopsy. The mean follow-up period was 6.7 + 5.2 years. Higher serum creatinine, proteinuria, activity, and chronicity indices were noted in proliferative LN. Patients suffering from proliferative lesions received higher immunosuppression and demonstrated higher morbidity than those with non-proliferative lesions. Remission was higher among the non-proliferative compared to the proliferative group. Conclusions Serum creatinine, proteinuria, and LN class were the most relevant prognostic factors for renal survival among Egyptian LN patients.

Barriers to Kidney Transplantation among Adults on Maintenance Dialysis in Western Region Saudi Arabia: A Cross-Sectional Study.

Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease. However, in Saudi Arabia, KT accounts for only 4.5% of the total existing renal replacement therapies in 2016. This cross-sectional study was conducted from September 2017 to January 2018. The aim was to assess the main barriers to the low KT rate in the Saudi community. Data were obtained by direct interviewing using a specifically pre-coded and pre-tested online questionnaire. A total of 321 adult hemodialysis and peritoneal dialysis (PD) (hemodialysis and PD, respectively) patients eligible for KT were selected from several dialysis units in Jeddah, accounting for 11% of the total dialysis population in Jeddah. The mean age was 49.9 ± 14.9 years, and 62.1% were male. Twenty-six percent were employed, and 88.2% were Saudis. Of those interviewed, 90.7% had been counseled for KT mostly by the nephrologist (86.5%) and 178 (55.5%) were referred for pre-transplant evaluation and 92 (28.6 %) were on the active transplant list. The most common barriers were lack of donor availability for 107 patients (40.5%), 58 patients (22%) worried about long-term complications, and 24 (9.1%) worried about surgical complications. Only 17 patients (6.4 %) reported financial constraints as the main reason for not having a KT, especially in non-Saudi patients. Additional initiatives to promote and improve the education and knowledge about kidney donation and the current outcome of KT is needed to improve the transplant rate in the country.

Navigated perilesional transcranial magnetic stimulation can improve post-stroke visual field defect: A double-blind sham-controlled study.

BACKGROUND: Visual field defects (VFD) usually do not show improvement beyond 12 weeks from their onset. It has been shown that repetitive presentation of a stimulus to areas of residual vision in cases of visual field defect can improve vision. The counterpart of these areas in the brain are the partially damaged brain regions at the perilesional areas where plasticity can be enhanced. OBJECTIVE: We aimed to study the effect of navigated repetitive transcranial magnetic stimulation (rTMS) applied to perilesional areas on the recovery of patients with cortical VFD. METHODS: Thirty-two patients with cortical VFD secondary to stroke of more than 3 months duration received 16 sessions of either active or sham high frequency navigated perilesional rTMS. Automated perimetry and visual functioning questionnaire (VFQ-25) were performed at baseline and after completion of the sessions. RESULTS: The active group showed significant improvement after intervention, compared to the sham group, in both mean deviation (MD), visual field index (VFI) and in the VFQ-25 scores. CONCLUSIONS: Navigated rTMS is a new treatment option for post-stroke VFD as it can selectively stimulate areas of residual vision around the infarcted tissue, improving the threshold of visual stimulus detection which could be used alone or in combination with existing therapies.

Dengue Virus Infection Presenting as Membranoproliferative Glomerulonephritis Type 1.

The renal complications of dengue virus infection cover a wide spectrum of manifestations from acute kidney injury to glomerular injury with nephritic/nephrotic syndrome. Majority of cases remain symptom free and show full recovery. We present a 61-year-old previously healthy male who developed a pyrexial illness with haemolytic anaemia that was diagnosed on the basis of a positive serological test as a case of dengue fever. He received supportive treatment and showed general recovery except for his renal dysfunction that showed persistent proteinuria at 14 gm/24 hours. A kidney biopsy revealed membranoproliferative glomerulonephritis type 1 (MPGN-l). Complete remission was achieved by steroids and mycophenolate mofetil therapy. We provide convincing biopsy evidence that dengue virus is yet another viral cause of MPGN-l and also document its successful management with mycophenolate mofetil and steroids therapy.

Pregnancy-associated hemolytic uremic syndrome.

Pregnancy-associated hemolytic uremic syndrome (P-aHUS) is not an uncommon condition. It is considered a medical emergency that is associated with a high risk of mortality and serious morbidity. End-stage renal disease as a consequence of P-aHUS occurs in >50% of the patients if left untreated; the majority of identified cases (79%) are during the postpartum period. Its mechanism of action is related mainly to the disturbance in the activation of the complement alternative pathway, leading to damage of the microvascular endothelium. The clinical picture of P-aHUS mimics several conditions occurring during post-partum thrombotic microangiopathy, for example, severe pre-eclampsia, hemolysis, elevated liver enzymes, and low platelet count, thrombotic-thrombocytopenic purpura, and acute fatty liver of pregnancy. Genetic analysis of known genetic mutations together with the analysis of anti-CFH antibodies might confirm the diagnosis of aHUS in the post-partum period. The absence of causative genetic mutations does not always exclude a diagnosis of aHUS, since 40% of patients show no known genetic abnormalities. The mainstay of management is supportive care and immediate initiation of plasmapheresis. Eculizumab has been proved to be both safe and effective in inducing and maintaining remission in P-aHUS and it is recommended to be started as soon as the diagnosis is established.

Living-Donor Kidney Transplant-Associated Thrombotic Microangiopathy Successfully Treated With Thymoglobulin: A Case Report.

Transplantation is the ultimate therapy for end-stage kidney disease. Early graft dysfunction is a devastating event to patients and carries risk of graft loss. Medical causes of early graft loss include graft rejection, drug toxicity, and thrombotic microangiopathy. Here, we report a case of posttransplant thrombotic microangiopathy associated with cellular vascular rejection. Thymoglobulin successfully reversed vascular rejection and thrombotic microangiopathy associated with half dosing of calcineurin inhibitors.

Three months interval therapy of Eculizumab in a patient with atypical hemolytic uremic syndrome with hybrid CFHR1/CFH gene.

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.

Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature.

Transplant is the optimal therapy for patients with end-stage renal disease. Acute cellular rejection refractory to treatment remains a major risk factor for graft loss and poor outcomes. In this study, we describe a 39-year-old man who received a living-related kidney transplant. Two days after transplant, the patient displayed acute deterioration of graft function. Conventional anti-rejection therapy was initiated, but graft function did not improve. Biopsy revealed acute cellular rejection (grade IIA), and C4d and HLA antibodies were negative. Immunohistochemistry phenotyping revealed clusters of CD20-positive lymphocytes, with 80% being CD3 positive. Rituximab was prescribed, and graft function improved dramatically. After 1 week, a second graft biopsy was done due to lagging of graft function, shown by serum creatinine of 2.1 mg/dL. Biopsy revealed regenerating acute tubular necrosis with disappearance of the CD20-positive lymphocyte cluster infiltrates. Two year, after transplant, the patient's graft function maintained stable. Phenotyping of the cellular infiltrate is important as it may lead to a proper selection of immunosuppression and consequent improvement of graft outcome.

Impact of Donor Source on the Outcome of Live Donor Kidney Transplantation: A Single Center Experience.

BACKGROUND: Renal transplantation is the ideal method for management of end-stage renal disease. The use of living donors for renal transplantation was critical for early development in the field and preceded the use of cadaveric donors. Most donors are related genetically to the recipients, like a parent, a child, or a sibling of the recipient, but there are an increasing percentage of cases where donors are genetically unrelated like spouses, friends, or altruistic individuals. Donor shortages constitute the major barrier for kidney transplantation, and much effort has been made to increase the supply of living donors. The impact of donor source on the outcome of renal transplantation is not adequately studied in our country. OBJECTIVES: The aim of the study was to evaluate the impact of donor source on the outcome of live donor kidney transplantation. PATIENTS AND METHODS: From March 1976 to December 2013, the number of patients that underwent living renal transplantation sharing at least one HLA haplotype with their donors was 2,485. We divided these patients into two groups: (1) 2,075 kidney transplant recipients (1,554 or 74.9% male and 521 or 25.1% female) for whom the donors were living related, (2) 410 kidney transplant recipients (297 or 72.4% male and 113 or 27.6% female) for whom the donors were living unrelated. All patients received immunosuppressive therapy, consisting of a calcineurin inhibitor, mycophenolate mofetil, or azathioprine and prednisolone. We compared acute rejection and complication rates, as well as long-term graft and patient survival of both groups. Demographic characteristics were compared using the chi-square test. Graft survival and patient survival were calculated using the Kaplan-Meier method. RESULTS: The percentages of patients with acute vascular rejection were significantly higher in the unrelated group, while percentages of patients with no rejection were significantly higher in the related group, but there were no significant differences regarding patient and graft survivals between both groups. CONCLUSIONS: Kidney transplant recipients who received their grafts either from live related donors or live unrelated donors had comparable patient and graft survival outcomes.

Investigation of Sacral Needle Depth in Minimally Invasive Sacrocolpopexy.

PURPOSE: The aims of the study were to optimize surgical safety and to minimize vertebral disc puncture during sacral needle placement at the time of minimally invasive sacrocolpopexy. Cadaveric studies report that the anterior longitudinal ligament (ALL), which covers the vertebral disc and vertebrae, has a reported thickness of only 1.4 to 2.3 mm at L5-S1. Intervertebral disc puncture can accelerate disc degeneration, disc herniation, and loss of disc height, a risk that may be avoidable. MATERIALS AND METHODS: After institutional review board approval, research consent was obtained from women undergoing primary laparoscopic sacrocolpopexy. Intraoperatively, sacral sutures were placed in the ALL with a 1.5 cm diameter CV-2 needle using Gore-Tex suture. Depth measurements were collected using a laparoscopic ultrasound transducer positioned on the sacral promontory (SP) between the 2 ends of the needle visible through the ALL. Two still-frame US images of the single needle were taken using the BK Medical software. Needle depth was calculated by measuring the distance from the top of the ALL to the needle. RESULTS: Two satisfactory intraoperative images were obtained for all 9 participants. The mean needle depth at the SP was 3.96 mm. The interpatient needle depth varied from 2.07 to 9.04 mm. CONCLUSIONS: In most participants (78%), the sacral needle depth exceeded 2.3 mm, suggesting that there may be risk to sacral suture placement without depth guidance at the promontory. During minimally invasive sacrocolpopexy, the depth of the ALL and the placement of the needle at the SP may result in inadvertent disc penetration. Surgeons should be conscious of the minimal depth of the ALL and consider placing the suture below the promontory to avoid the disc.

Outcome of glomerulonephritis in live-donor renal transplant recipients: A single-centre experience.

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.

Impaired selectin-dependent leukocyte recruitment induces T-cell exhaustion and prevents chronic allograft vasculopathy and rejection.

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.