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Desensitization allows the performance of human leukocyte antigen (HLA)-incompatible transplants. However, the incidence of acute rejection (AR) is high. This study aims to analyze the incidence of AR after transplantation with HLA-incompatible living donors in patients who underwent desensitization. Patients were immunosuppressed with tacrolimus, mycophenolic acid derivatives, and steroids after being desensitized with rituximab, plasma exchange, and/or immunoadsorption with specific cytomegalovirus immunoglobulins. A negative complement-dependent cytotoxicity or flow cytometry crossmatch and a donor-specific antibody titer < 1000 mean fluorescence intensity (MFI) were used to determine desensitization efficacy. A total of 36 patients underwent desensitization, and 27 (75%) were transplanted. After a follow-up of 58 ± 58 months (Min−Max: 0.13−169.5), five episodes of AR occurred: two antibody-mediated and three T-cell-mediated. No differences were found in baseline calculated panel-reactive antibodies (cPRA), class I or II MFI, number of antibodies, or Relative Intensity Scale (RIS) between AR and non-AR patients. Patients with antibody-mediated AR had higher cPRA (NS), MFI class I (p = 0.07) and class II (p = 0.006), and RIS (p = 0.01). The two patients with antibody-mediated AR and one patient with T-cell-mediated AR lost their grafts. In conclusion, the incidence of acute antibody-mediated rejection after desensitization was 7.4%, which occurred early post-transplantation in patients with high MFI and was associated with early graft loss.

The chemokine receptor CCR5 has been implicated in COVID-19. CCR5 and its ligands are overexpressed in patients. The pharmacological targeting of CCR5 would improve the COVID-19 severity. We sought to investigate the role of the CCR5-Δ32 variant (rs333) in COVID-19. The CCR5-Δ32 was genotyped in 801 patients (353 in the intensive care unit, ICU) and 660 healthy controls, and the deletion was significantly less frequent in hospitalysed COVID-19 than in healthy controls (p = 0.01, OR = 0.66, 95%CI = 0.49-0.88). Of note, we did not find homozygotes among the patients, compared to 1% of the controls. The CCR5 transcript was measured in leukocytes from 85 patients and 40 controls. We found a significantly higher expression of the CCR5 transcript among the patients, with significant difference when comparing the non-deletion carriers (controls = 35; patients = 81; p = 0.01). ICU-patients showed non-significantly higher expression than no-ICU cases. Our study points to CCR5 as a genetic marker for COVID-19. The pharmacological targeting of CCR5 should be a promising treatment for COVID-19., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Preservation of the peritoneal membrane is an essential determinant of the long-term outcome of peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) plays a central role in the pathogenesis of PD-related peritoneal membrane injury. We hypothesized that mitochondria may be implicated in the mechanisms that initiate and sustain peritoneal membrane damage in this setting. Hence, we carried out ex vivo studies of effluent-derived human mesothelial cells, which disclosed a significant increase in mitochondrial reactive oxygen species (mtROS) production and a loss of mitochondrial membrane potential in mesothelial cells with a fibroblast phenotype, compared to those preserving an epithelial morphology. In addition, in vitro studies of omentum-derived mesothelial cells identified mtROS as mediators of the EMT process as mitoTEMPO, a selective mtROS scavenger, reduced fibronectin protein expression induced by TGF-ß1. Moreover, we quantified mitochondrial DNA (mtDNA) levels in the supernatant of effluent PD solutions, disclosing a direct correlation with small solute transport characteristics (as estimated from the ratio dialysate/plasma of creatinine at 240 min), and an inverse correlation with peritoneal ultrafiltration. These results suggest that mitochondria are involved in the EMT that human peritoneal mesothelial cells suffer in the course of PD therapy. The level of mtDNA in the effluent dialysate of PD patients could perform as a biomarker of PD-induced damage to the peritoneal membrane.

The Angiotensin system is implicated in the pathogenesis of COVID-19. First, ACE2 is the cellular receptor for SARS-CoV-2, and expression of the ACE2 gene could regulate the individuaĺs susceptibility to infection. In addition, the balance between ACE1 and ACE2 activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID-19. Functional ACE1/ACE2 gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID-19. We studied 204 COVID-19 patients (137 non-severe and 67 severe-ICU cases) and 536 age-matched controls. The ACE1 insertion/deletion and ACE2 rs2285666 polymorphism were determined. Variables frequencies were compared between the groups by logistic regression. We also sequenced the ACE2 coding nucleotides in a group of patients. Severe COVID-19 was associated with hypertension male gender (p < 0.001), hypertension (p = 0.006), hypercholesterolaemia (p = 0.046), and the ACE1-DD genotype (p = 0.049). In the multiple logistic regression hypertension (p = 0.02, OR = 2.26, 95%CI = 1.12-4.63) and male gender (p = 0.002; OR = 3.15, 95%CI = 1.56-6.66) remained as independent significant predictors of severity. The ACE2 polymorphism was not associated with the disease outcome. The ACE2 sequencing showed no coding sequence variants that could explain an increased risk of developing COVID-19. In conclusion, an adverse outcome of COVID-19 was associated with male gender, hypertension, hypercholesterolemia and the ACE1 genotype. Our work suggested that the ACE1-I/D might influence COVID-19 severity, but the effect was dependent on the hypertensive status. This result requires further validation in other large cohorts., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: ABO-incompatible living-donor kidney transplantation was regarded as an absolute contraindication. However, it has been carried out for years with good outcomes., Objective: Our aim was to show the results obtained with this technique in our hospital., Methods: Forty-eight patients with a mean age of 50.9±10.9 years were included. Follow-up was 44.6±30.9 months. Conditioning: rituximab 375mg/m 2 , tacrolimus, mycophenolate mofetil or mycophenolate sodium, prednisone, plasmapheresis/immunoadsorption and intravenous immunoglobulin. Accepted IgG and IgM titres for transplantation:<1:8., Results: Pre-process IgG titre 1:124±1:140, IgM titre 1:77±1:55. After 6±3 sessions, IgG decreased to<1:8 in 47 patients and to<1:16 in one. IgM was<1:8 in all cases. Twenty-four patients (50%) had haematoma, 7 re-intervention (14.6%), 29 (60%) required transfusion. At 5 years, acute rejection had occurred in 5 cases (8.7%), CMV infection in 9 (19.7%), BK viraemia in 5 (12.4%), post-transplant diabetes in 10 (23.4%) and lymphocele in 3 (6.4%). Patient survival was 97.1% at 5 years and graft survival 95.7% at one year and 93% at 5 years. Causes of graft loss: thrombosis (n=1); mixed rejection (n=1); and death (n=2). Serum creatinine levels were 1.4±0.4mg/dl at one and 3 years and 1.3±0.3mg/dl at 5 years. Proteinuria was 0.2±0.2g/24h at one, 3 and 5 years., Conclusions: ABO-incompatible living-donor kidney transplantation after conditioning with rituximab, plasmapheresis/immunoadsorption and immunoglobulins is a valid option offering excellent outcomes. There is a low incidence of acute rejection and no increase in infectious complications. An increased tendency for postoperative bleeding was found., (Copyright © 2019 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To compare outcomes between transdiscal and conventional pedicle fixation for high-grade L5-S1 spondylolisthesis., Methods: This was a retrospective case-control study with patients prospectively followed. Twenty-five consecutive patients with mean age of 36.7 years underwent transdiscal fixation, and 31 other with mean age of 42.0 years to pedicle fixation were clinically and radiographically compared. Clinical assessments were performed using Oswestry Disability Index (ODI), Core Outcomes Measures Index (COMI), Short-Form 12 (SF-12), and pain visual analog scale (VAS). Radiographic spinopelvic parameters were also evaluated. The mean follow-up was 2.7 years (range 2.0-5.3)., Results: Preoperative data were comparable between groups. Surgery time, blood loss, and hospital stay were similar between groups. At last follow-up, clinical and radiographic outcomes were significantly improved in both groups. Postoperatively, both lumbar and leg pain VAS were similar between groups, but ODI (20.2 vs. 31.6, p = 0.010), COMI (1.6 vs. 2.8, p = 0.012), and SF-12 physical (84.3 vs. 61.5, p = 0.004) and mental (81.5 vs. 69.4, p = 0.021) scores were significantly better in the transdiscal group. The neurologic complication rate was similar in both groups. There were 4 pseudoarthroses in the pedicle group, and none in the transdiscal group., Conclusion: L5-S1 transdiscal screw fixation provided better functional and radiographic outcomes at medium-term than conventional pedicle fixation for high-grade spondylolisthesis, although transdiscal sacral screws are difficult to place in correct position.

Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis (HP) caused by inhaling microorganisms from hay or grain stored in conditions of high humidity in the agricultural workplace. It is probably underdiagnosed, especially in northern Spain, where climatic conditions favor the development of this disease. According to previous studies, the most common antigens are usually thermophilic actinomycetes and fungi. The epidemiology of the disease is not well known, and is based on studies conducted by Central European and Asian groups. The clinical presentation may vary, differentiating the chronic (exposure to lower concentrations of the antigen over a longer period time) and the acute forms (after exposure to high concentrations of the antigen). In patients with respiratory symptoms and agricultural occupational exposure, radiological, lung function and/or anatomical pathology findings must be compatible with FLD, bronchoalveolar lavage must show lymphocytosis, and tests must find sensitivity to the antigen. The main treatment is avoidance of the antigen, so it is essential to educate patients on preventive measures. To date, no controlled studies have assessed the role of immunosuppressive therapy in this disease. Corticosteroid treatment has only been shown to accelerate resolution of the acute forms, but there is no evidence that it is effective in preventing disease progression in the long-term or reducing mortality., (Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.)

Objective: To report two cases of prostate sarcoma and perform a review of the published literature., Methods / Results: The first case is a 21 year old patient who presented acute urine retention and lung metastases on diagnosis. He was diagnosed by TURP of rhabdomyosarcoma of the prostate dying 1 month after surgery. The second case was a 33 years old male who presented to the emergency room with anal pain, urinary symptoms, hematochezia and loss of 20 kg over the past 3 months. Abdominal CT scan showed an 11 x 10 x 9 cm mass in the lower pelvis that infiltrated the bladder and rectum, being unable to define its origin. CA 19.9, CEA and PSA were normal. The suspected diagnosis was a prostate sarcoma infiltrating rectum and bladder. A pelvic exenteration was performed with a wet colostomy. The pathologic diagnosis was a high grade sarcoma not clearly identified of the prostate. He was treated with adriamycin as adjuvant chemotherapy, having local recurrence, nodal involvement and multiple pulmonary metastases after 3 months of follow up, Conclusions: Prostate sarcomas are rare tumors. This makes difficult to know their natural history. Their rapid progression and systemic spread, despite multimodal treatment, gives a mean survival of 24 months. Main survival factors are grade, a complete resection of the tumor and a low local stage. There is a need to find new chemotherapy protocols to increase survival rates as it has been shown in extremities sarcomas.

Background: Diabetes mellitus, especially if complicated by poor glycemic control, portends an increased risk of infection. The significance of this association in the case of diabetic patients undergoing peritoneal dialysis (PD) has not been assessed., Methods: Using a retrospective observational design, we analyzed the association between glycemic control at the start of PD (estimated from glycosylated hemoglobin levels) and the risk of peritoneal and catheter tunnel and exit-site infections during follow-up in 183 incident patients on PD. We used the median value of glycosylated hemoglobin to classify patients into good (group A) or poor (group B) glycemic control groups. We applied multivariate strategies of analysis to control for other potential predictors of PD-related infection., Results: Groups A and B differed significantly in age, dialysis vintage, use of insulin, and rate of Staphylococcus aureus carriage. Neither the incidence (0.60 episodes in group A vs 0.56 episodes in group B per patient-year) nor the time to a first peritoneal infection (median: 42 months vs 38 months) differed significantly between the study groups. In contrast, group B had a significantly higher incidence of catheter tunnel and exit-site infections (0.23 episodes vs 0.12 episodes per patient-year) and shorter time to a first infection episode (64 months vs 76 months, p = 0.004). The difference persisted in multivariate analysis (adjusted hazard ratio: 2.65; 95% confidence interval: 1.13 to 6.05; p = 0.013). We observed no differences between the study groups in the spectrum of causative organisms or in the outcomes of PD-related infections., Conclusions: Poor glycemic control is a consistent predictor of subsequent risk of catheter tunnel and exit-site infection, but not of peritoneal infection, among diabetic patients starting PD therapy., (Copyright © 2014 International Society for Peritoneal Dialysis.)