Abstract
CERN’s North Area comprises several target and experimental systems and is a zone of interest for future development. Provision of beam to this area relies upon several beam-intercepting ...devices located in various branched transfer lines from the Super Proton Synchrotron. In several lines, these include a primary production target system of beryllium plates followed by a combined collimation, attenuation and dump device made from a set of aluminum, copper and iron blocks and known as a ‘TAX’ (Target Attenuator for eXperimental areas). These may operate in a range of configurations depending on experimental needs. Future operational regimes with higher beam intensities (increased from a current specification of 1.5× 10
13
to 4.0× 10
13
p
+
/pulse), shorter pulse times (4.8 s reduced to 1.2 s), greater repetition rates (14.4 s cycle time reduced to 7.2 s) and ten times the annual intensity place more stringent thermo-structural demands on these existing devices, beyond their original specification. This contribution outlines the engineering analysis, including beam-matter interaction studies and thermo-structural simulations, carried out to assess their robustness under such conditions.
•BK polyomavirus infection is not an uncommon complication after kidney transplant.•Male sex, older age, and retransplant are risk factors for BK polyomavirus infection.•Acute rejection is more ...frequent in patients with history of BK polyomavirus infection.•Stepwise minimization of immunosuppression is the first-line approach in patients with BK polyomavirus infection.•High-level BK viremia negatively impacts on kidney transplant survival.
BK polyomavirus infection (BKVi) is an important cause of kidney transplant (KT) loss, but there is scarce evidence on the impact of BK plasma viral load on graft function and long-term KT survival.
A retrospective cohort study including all KT recipients with BKVi (BK viremia identified in ≥3 consecutive samples by polymerase chain reaction) in our center from January 2010 to December 2020 was performed. A case-control study (1:2) was performed. We grouped the cases according to their highest peak viral load: low-level viremia (<10,000 copies/mL) and high-level viremia (≥10,000 copies/mL). To identify risk factors for BKVi, a logistic regression analysis was achieved, and a multivariable Cox regression was used to describe risk factors for graft loss.
A total of 849 KTs were performed, and 67 presented BKVi (low-level viremia, n = 35 and high-level viremia, n = 26). In logistic regression analysis male sex (odds ratio OR, 4.226; 95% CI, 1.660-10.758, P = .002), age (OR, 1.047; 95% CI, 1.008-1.088; P = .018), and retransplant (OR, 4.162; 95% CI, 1.018-17.015; P = .047) were predictors of BKVi. Acute rejection was more frequent in the BKVi group (18% vs 4.9%, P = .004), and graft survival was lower in patients with BKVi and high-level viremia (P = .027). In Cox regression analysis, BKVi (hazard ratio, 3.657; 95% CI, 1.146-11.670; P = .029) and specific BKV (BK polyomavirus) high-level viremia (hazard ratio, 1.988; 95% CI, 1.012-3.907; P = .046) were predictors of shorter graft survival.
BKV high-level viremia was associated with BKV nephropathy and poorer graft survival. Additionally, acute rejection is more frequent after BKVi. It is necessary to develop strategies safe and effective for these patients.
Acute kidney injury (AKI) is a manifestation of SARS-CoV-2 infection. The evidence in kidney transplant (KT) is limited, as there are scarce data about the histologic features in graft biopsies of ...these patients.
A retrospective cohort study of KTs with SARS-CoV-2 infection from August 28, 2020, to April 23, 2021. We collected the incidence of AKI and the presence of urinary and histopathological disorders. Both groups were compared (AKI vs no AKI). Immunohistochemical and reverse transcription-polymerase chain reaction studies were performed on the anatomopathological samples.
In our study, 72 KTs had SARS-CoV-2 infection and, among them, 27 patients (35.1%) developed AKI related to increased severity and a worse evolution of the infection, defined by a greater presence of pneumonia (P < .001), hospitalization (P < .001), admission to the intensive care unit (P < .001), the need for ventilation support (P < .001), and continuous renal replacement therapy (P < .001). In the multivariable analysis, pneumonia behaved as an independent predictor for AKI development (P = .046). No differences were observed between proteinuria a month before and after infection (P = .224). In addition, 5 patients showed microhematuria and 2 patients presented transient glycosuria without hyperglycemia. Of the 5 kidney biopsies performed, 1 biopsy (20%) showed positive reverse transcription polymerase chain reaction for SARS-CoV-2.
AKI is a frequent and potentially serious complication in KT patients. Occasionally it could be accompanied by abnormalities in the urinary sediment. Of 5 biopsied patients, 1 patient had positive reverse transcription polymerase chain reaction in renal tissue, which suggests the systemic spread of the virus and the tropism for the renal graft.
An integrative and innovative communication model to enhance the knowledge, comprehension and delectation of cultural and natural heritage through technology-based contemporary art is described. By ...relating these two traditionally dissociated fields (heritage and contemporary art), a particular form of dialogue between them occurs and it is transferred to society within an emotional and intellectual discourse away from those merely informative. The heritage sites Alhambra Lions Court in Granada (Spain), Santa Croce's second cloister in Florence (Italy) and Marzamemi underwater Wreck of Church (Italy) are under study in the framework of the European research and knowledge transfer project, WARMEST3. A strategy of communication based on pieces and actions of contemporary art will be proposed to set up a new frame in the diffusion of the cultural and natural legacy. That will encourage its preservation and, at the same time, will set up a new research line around site specific art work related to heritage sites communication.
Prolonged‐release tacrolimus was developed to provide a more convenient once‐daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12‐month study ...to describe the efficacy, safety and patient preference of conversion from tacrolimus twice‐daily to once‐daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg: 1 mg basis (1 mg: 1.1 mg in patients with trough levels <6 ng/mL). The study included 1832 patients (mean age (±SD): 50.0 ± 13.4 years; 62.7% male). After conversion, a modest reduction in tacrolimus trough levels, necessitating an increase in daily dose, was observed (mean changes at 12 months of –9.1% and +1.24%, respectively; p < 0.0001). Mean glomerular filtration rate did not change significantly (56.5 ± 19.7 mL/min at conversion vs. 55.7 ± 20.6 mL/min at 12 months). Proteinuria, blood pressure, lipid, hepatic and glucose parameters remained stable. Eight patients (0.4%) had acute rejection and 34 patients (1.85%) discontinued treatment. Almost all patients (99.4%) preferred the once‐daily formulation, because of less frequent dosing (66%) and improved adherence (34%). In conclusion, at similar doses to twice‐daily tacrolimus, once‐daily formulation provided stable renal function, a low acute rejection rate, and good tolerability in stable kidney transplant recipients in the routine clinical practice setting.
This study of 1832 renal transplant patients reports that conversion from twice‐daily tacrolimus to the once‐daily prolonged‐release formulation in a routine clinical practice setting results in stable renal function and a low acute rejection rate with a good tolerability profile.
The increasing comorbidity of kidney transplant (KT) donors make it necessary to develop scores to correctly assess the quality of kidney grafts. This study analyzes the usefulness of the ...preimplantation biopsy and the Kidney Donor Profile Index (KDPI) as indicators of KT survival from expanded criteria donors (ECD). Retrospective study of KT in our center between January 2010 to June 2019 who received a kidney from an ECD and underwent a preimplantation biopsy. 266 KT were included. Graft survival was categorized by KDPI quartiles: Q1 = 86%, Q2 = 95%, Q3 = 99% and Q4 = 100%. KT from KDPI Q1 presented better survival (
p
= 0.003) and Q4 donors had worse renal function (
p
= 0.018) and poorer glomerular filtration rate (3rd month;
p
= 0.017, 1st year;
p
= 0.010). KT survival was analyzed according to KDPI quartile and preimplantation biopsy score simultaneously: Q1 donors with biopsy score ≤3 had the best survival, especially comparing against Q3 with a biopsy score >3 and Q4 donors (
p
= 0.014). In multivariable analysis, hyaline arteriopathy, glomerulosclerosis, and KDPI Q4 were predictors for graft survival. High KDPI and a greater histological injury in the preimplantation biopsy, especially glomerular and vascular lesions, were related to a higher rate of KT loss from ECD.
Surgical wound dehiscence (SWD) is a frequent complication after kidney transplantation (KT) but there is not enough evidence of its impact on graft survival.
A retrospective cohort study including ...all KT patients with SWD in our center from January 2015 to July 2020 was performed. A case–control study was performed and for each case of SWD, 2 controls were selected (2:1). To identify risk factors for SWD, a logistic regression analysis was carried out and a multivariable Cox regression was used to describe risk factors for graft survival.
In our center, 503 KT were performed, and 39 patients presented SWD. They were older (62.1 vs 57.1 years; P = .030), most had diabetes mellitus (59% vs 28.6%; P = .002) and their body mass index was higher (31 vs 26.9 kg/m2; P < .001). In multivariable logistic regression analysis, diabetes mellitus (P = .024) and a body mass index ≥30 kg/m2 at time of transplantation (P = .018) were predictors of SWD. A higher rate of delayed graft function was described in SWD (P = .013) and it was associated with a longer hospital stay (20.9 vs 15 days; P = .004). Graft survival was lower in patients with SWD (P = .036). In multivariable Cox regression analysis, time in renal replacement therapy (P = .020) and SWD (P = .028) were predictors of shorter graft survival.
SWD is a risk factor for graft survival. The presence of diabetes mellitus and a higher body mass index are predictors for the appearance of this complication.
Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its ...pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A‐I, named ApoA‐Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS‐unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA‐Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS‐unrelated proteinuria tested positive for ApoA‐Ib, and was not detected in familial patients. Urinary ApoA‐Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.
This study finds a modified form of apolipoprotein A‐I, named Apo A‐Ib, associated to focal segmental glomerulosclerosis (FSGS) relapses after transplantation; Apo A‐Ib is present in the urine of relapsing idiopathic FSGS patients, while absent in non‐relapsing FSGS, in familiar FSGS and in patients with FSGS‐unrelated proteinuria.
The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study ...112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six‐ and 12‐week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio HR: 2.29; p‐value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p‐value = 0.017) were independent predictors for 6‐week all‐cause mortality, whereas the initial use of a voriconazole‐based regimen showed a protective effect (HR: 0.34; p‐value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.
Invasive pulmonary aspergillosis presents a high mortality rate in kidney transplant recipients, with diagnosis within the first 6 months posttransplantation and bilateral lung involvement as independent risk factors for mortality.
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