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Several organ allocation protocols give priority to wait-listed simultaneous kidney-pancreas (SPK) transplant recipients to mitigate the higher cardiovascular risk of patients with diabetes mellitus on dialysis. The available information regarding the impact of preemptive simultaneous kidney-pancreas transplantation on recipient and graft outcomes is nonetheless controversial. To help resolve this, we explored the influence of preemptive simultaneous kidney-pancreas transplants on patient and graft survival through a retrospective analysis of the OPTN/UNOS database, encompassing 9690 simultaneous transplant recipients between 2000 and 2017. Statistical analysis was performed applying a propensity score analysis to minimize bias. Of these patients, 1796 (19%) were transplanted preemptively. At ten years, recipient survival was significantly superior in the preemptive group when compared to the non-preemptive group (78.9% vs 71.8%). Dialysis at simultaneous kidney-pancreas transplantation was an independent significant risk for patient survival (hazard ratio 1.66 [95% confidence interval 1.32-2.09]), especially if the dialysis duration was 12 months or longer. Preemptive transplantation was also associated with significant superior kidney graft survival compared to those on dialysis (death-censored: 84.3% vs 75.4%, respectively; estimated half-life of 38.57 [38.33 -38.81] vs 22.35 [22.17 - 22.53] years, respectively). No differences were observed between both groups neither for pancreas graft survival nor for post-transplant surgical complications. Thus, our results sustain the relevance of early referral for pancreas transplantation and the importance of pancreas allocation priority in reducing patient mortality after simultaneous kidney-pancreas transplantation.

Given the increased COVID-19 observed in kidney transplant recipients (KTRs) and haemodialysis patients, several studies have tried to establish the efficacy of mRNA vaccines in these populations by evaluating their humoral and cellular responses. However, there is currently no information on clinical protection (deaths and hospitalizations), a gap that this study aims to fill.Observational prospective study involving 1,336 KTRs and haemodialysis patients from three dialysis units affiliated to Hospital Clínic of Barcelona, Spain, vaccinated with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 mRNA vaccines. The outcomes measured were SARS-CoV-2 infection diagnosed by a positive RT-PCR fourteen days after the second vaccine dose, hospital admissions derived from infection, and a severe COVID-19 composite outcome, defined as either ICU admission, invasive and non-invasive mechanical ventilation, or death.Six per cent (18/302) of patients on haemodialysis were infected, of whom four required hospital admission (1.3%), only one (0.3%) had severe COVID-19, and none of them died. In contrast, 4.3% (44/1034) of KTRs were infected, and presented more hospital admissions (26 patients, 2.5%), severe COVID-19 (11 patients, 1.1%) or death (4 patients, 0.4%). KTRs had a significantly higher risk of hospital admission than HD patients, and this risk increased with age and male sex (HR 3.37 and 4.74, respectively).The study highlights the need for booster doses in KTRs. In contrast, the haemodialysis population appears to have an adequate clinical response to vaccination, at least up to four months from its administration.

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy based on the infusion of autologous cellular products exposed to ultraviolet light (UV) in the presence of a photosensitizer. The study evaluates the ECP efficacy as induction therapy in a full-mismatch kidney transplant rat model. Dark Agouti to Lewis (DA-L) kidney transplant model has been established. ECP product was obtained from Lewis rat recipients after DA kidney graft transplantation (LewDA). Leukocytes of those LewDA rats were exposed to 8-methoxy psoralen, and illuminated with UV-A. The ECP doses assessed were 10 × 106 and 100 × 106 cells/time point. Lewis recipients received seven ECP infusions. DA-L model was characterized by the appearance of donor-specific antibodies (DSA) and kidney function deterioration from day three after kidney transplant. The dysfunction progressed rapidly until graft loss (6.1 ± 0.5 days). Tacrolimus at 0.25 mg/kg prolonged rat survival until 11.4 ± 0.7 days (p = 0.0004). In this context, the application of leukocytes from LewDA sensitized rats accelerated the rejection (8.7 ± 0.45, p = 0.0012), whereas ECP product at high dose extended kidney graft survival until 26.3 ± 7.3 days, reducing class I and II DSA in surviving rats. ECP treatment increases kidney graft survival in full-mismatch rat model of acute rejection and is a suitable immunomodulatory therapy to be explored in kidney transplantation.

Monoclonal immunoglobulin deposition disease (MIDD) usually leads to kidney failure. Treatment of patients with a bortezomib-based regimen followed by autologous stem cell transplantation (SCT) has been increasingly used, with improvements in the response rates and allograft outcomes in kidney transplant recipients. The objective of this report was to analyze the outcomes of 6 patients who underwent kidney transplantation in our institution after treatment of MIDD between 2010 and 2019. Monoclonal immunoglobulin deposition disease was initially treated with bortezomib-based therapy followed by high-dose melphalan and autologous SCT with complete hematologic response, although all patients remained on dialysis. During a median follow-up of 20.5 months from kidney transplant (54 months from SCT), 1 patient experienced hematologic relapse and 2 had hematologic progression (one of them with MIDD relapse in the allograft) requiring treatment. The patient with organ relapse received daratumumab monotherapy, achieving complete hematologic response but with graft failure. The other 5 patients had functional grafts with median serum creatinine 1.68 mg/dL. These results support that, in patients with MIDD and sustained complete hematologic response, a kidney transplant can be considered. The optimal approach to treatment of hematologic relapse or recurrence of MIDD after kidney transplant remains to be determined.

BackgroundThe age of patients referred for kidney transplantation has increased progressively. However, the precise influence of age on transplant outcomes is controversial.MethodsEtrospective study in which graft and recipient survival were assessed in a cohort of ≥75 years old kidney recipients and compared with a contemporary younger one aged 60-65 years through a propensity score analysis.ResultsWe included 106 recipients between 60-65 and 57 patients of ≥75 years old with a median follow-up of 31 [13-54] months. Unadjusted one- and five-year recipient survival did not significantly differ between the older (91% and 74%) and the younger group (95% and 82%, P=0.06). In the IPTW weighted Cox regression analysis, recipient age was not associated with an increased risk of death (HR 1.88 95%CI [0.81-4.37], P=0.14). Unadjusted one- and five-year death-censored graft survival did not significantly differ between both groups (96% and 83% for the older and 99% and 89% for the younger group, respectively, P=0.08). After IPTW weighted Cox Regression analysis, recipient age ≥75 years was no associated with an increased risk of graft loss (HR 1.95, 95%CI [0.65-5.82], P=0.23).ConclusionsThese results suggest that recipient age should not be considered itself as an absolute contraindication for kidney transplant

In an overwhelming demand scenario, such as the SARS-CoV-2 pandemic, pressure over health systems may outburst their predicted capacity to deal with such extreme situations. Therefore, in order to successfully face a health emergency, scientific evidence and validated models are needed to provide real-time information that could be applied by any health center, especially for high-risk populations, such as transplant recipients. We have developed a hybrid prediction model whose accuracy relative to several alternative configurations has been validated through a battery of clustering techniques. Using hospital admission data from a cohort of hospitalized transplant patients, our hybrid Data Envelopment Analysis (DEA)—Artificial Neural Network (ANN) model extrapolates the progression towards severe COVID-19 disease with an accuracy of 96.3%, outperforming any competing model, such as logistic regression (65.5%) and random forest (44.8%). In this regard, DEA-ANN allows us to categorize the evolution of patients through the values of the analyses performed at hospital admission. Our prediction model may help guiding COVID-19 management through the identification of key predictors that permit a sustainable management of resources in a patient-centered model. Supplementary Information The online version contains supplementary material available at 10.1007/s10462-021-10008-0.

In kidney transplant recipients, there is discordance between the development of cellular and humoral response after vaccination against SARS-CoV-2. We sought to determine the interplay between the 2 arms of adaptive immunity in a 3-dose course of mRNA-1273 100 μg vaccine.Humoral (IgG/IgM) and cellular (N- and S-ELISpot) responses were studied in 117 kidney and 12 kidney-pancreas transplant recipients at the following time points: before the first dose, 14 d after the second dose' and before and after the third dose, with a median of 203 and 232 d after the start of the vaccination cycle, respectively.After the second dose, 26.7% of naive cases experienced seroconversion. Before the third dose and in the absence of COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion occurred in 80.0% of patients. Naive patients who had at any time point a detectable positivity for S-ELISpot were 75.2% of the population, whereas patients who maintained S-ELISpot positivity throughout the study were 34.3%. S-ELISpot positivity at 42 d was associated with final seroconversion (odds ratio' 3.14; 95% confidence interval' 1.10-8.96;A substantial proportion of kidney transplant recipients developed late seroconversion after 2 doses. Cellular immunity was associated with the development of a stronger humoral response.

The main applications of Data Envelopment Analysis (DEA) to medicine focus on evaluating the efficiency of different health structures, hospitals and departments within them. The evolution of patients after undergoing a medical procedure or their response to a given treatment are not generally studied through this programming technique. In addition to the difficulty inherent to the collection of this type of data, the use of a technique that is mainly applied to evaluate the efficiency of decision making units representing industrial and production structures to analyze the evolution of human patients may seem inappropriate. In the current paper, we illustrate how this is not actually the case and implement a decision engineering approach to model kidney transplantation patients as decision making units. As such, patients undergo three different phases, each composed by specific as well as interrelated variables, determining the potential success of the transplantation process. DEA is applied to a set of 12 input and 6 output variables - retrieved over a 10-year period - describing the evolution of 485 patients undergoing kidney transplantation from living donors. The resulting analysis allows us to classify the set of patients in terms of the efficiency of the transplantation process and identify the specific characteristics across which potential improvements could be defined on a per patient basis.

Profiling of circulating immune cells provides valuable insight to the pathophysiology of acute rejection in organ transplantation. Herein we characterized the peripheral blood mononuclear cells in simultaneous kidney-pancreas transplant recipients. We conducted a retrospective analysis in a biopsy-matched cohort (n = 67) and compared patients with biopsy proven acute rejection (BPAR; 41%) to those without rejection (No-AR). We observed that CD3+ T cells, both CD8+ and CD4+, as well as CD19+ B cells were increased in patients with BPAR, particularly in biopsies performed in the early post-transplant period (p < 0.05) and outperformed lipase (AUC 0.62; p = 0.12) for the diagnosis of acute rejection. We further evaluated whether this could be explained by differences in frequencies prior to transplantation. Patients presenting with early post-transplant rejection (p < 0.01), which were associated with a significant inferior rejection-free graft survival. T cell frequencies in peripheral blood correlated with pancreas acute rejection episodes, and variations prior to transplantation were associated with pancreas early acute rejection.

BACKGROUND AND AIMS The evidence regarding the benefits of performing preemptive SPK (pSPK) is controversial. The aim of the present study was to evaluate the impact of pSPK on long-term patient and grafts outcomes when compared with npSPK and pKTA through a national registry study with recipients reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) registry, and to analyse the potential benefits associated with pSPK not only in patients with T1D but also in patients with T2D. METHOD To explore the survival advantage of performing a pSPK, we compared the outcomes in pSPK with nonpreemptive SPK (npSPK) recipients between 2000 and 2017 from the OPTN/UNOS registry. To account for the potential benefit provided solely by the kidney transplant, we further compared to recipients of preemptive Kidney Transplantation Alone (pKTA) with diabetes. A propensity score analysis was applied. RESULTS A total of 1522 patients received a pSPK, 7894 an npSPK and 3343 a pKTA. Overall recipient survival was superior for the pSPK group when compared with the pKTA (97.7%, and 80.9% versus 97.7% and 72.9% at 1 and 10 years, respectively, P CONCLUSION In conclusion, the observed survival benefit of performing an SPK preemptively reinforces the need for early referral for transplantation in patients with insulin-dependent diabetes and advanced chronic kidney disease.

BACKGROUND AND AIMS Seroconversion after a two-dose course of mRNA COVID-19 vaccination in kidney transplant recipients ranges between 30% and 50% in different series. We previously demonstrated that a substantial proportion of patients (35%) without a humoral response, develop a cellular response after the second dose assessed by the ELISpot technique. We aim to study the evolution of both humoral and cellular responses in the same cohort before and 1 month after the administration of the third dose of 100 mcg of mRNA-1273 COVID-19 vaccine. METHOD Final population included 129 KTRs studied at four time-points: at baseline before the first dose, after the second dose (median 42 days) and before (203 days) and after (232 days) the third dose. At all the time-points, IgG and IgM were assessed as well as N- and S-protein specific ELISpot. The main outcome was seroconversion after the third dose. RESULTS After the second dose, 26.7% of naïve cases experienced seroconversion. Before the third dose and in the absence of clinically evident COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion was observed in 80.0% of patients. S-ELISpot positivity after the second dose was significantly associated with final seroconversion [OR (95% CI) 3.14 (1.10–8.96); P = .032], while transplantation CONCLUSION A substantial proportion of KTRs vaccinated with mRNA-1273 develops a late seroconversion after two doses and only a fifth remained seronegative after a third. Cellular immunity seems to play a major role in the development of a final strong humoral response.

Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically amylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management.Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples. dd-cfDNA was measured using the Prospera test (Natera, Inc.) and reported both as a fraction of the total cfDNA (fraction; %) and as concentration in the recipient's plasma (quantity; copies/mL).In the absence of P-BPAR, dd-cfDNA was significantly higher in samples collected within the first 45 d after SPKTx compared with those measured afterward (median, 1.00% versus 0.30%; median, 128.2 versus 35.3 cp/mL, respectively with both; P = 0.001). In samples obtained beyond day 45, P-BPAR samples presented a significantly higher dd-cfDNA fraction (0.83 versus 0.30%; P = 0.006) and quantity (81.3 versus 35.3 cp/mL; P = 0.001) than stable samples. Incorporating dd-cfDNA quantity along with dd-cfDNA fraction outperformed dd-cfDNA fraction alone to detect active rejection. Notably, when using a quantity cutoff of 70 cp/mL, dd-cfDNA detected P-BPAR with a sensitivity of 85.7% and a specificity of 93.7%, which was more accurate than current biomarkers (area under curve of 0.89 for dd-cfDNA (cp/ml) compared with 0.74 of lipase and 0.46 for amylase).dd-cfDNA measurement through a simple noninvasive blood test could be incorporated into clinical practice to help inform graft management in SPKTx patients.

This study is part of a doctoral research that analyzes the relationship between socioemotional competencies (SEC) and the teaching beliefs of secondary school teachers. In this sense, it is necessary to have a valid, reliable instrument adapted to the sociocultural reality of public school teachers in Metropolitan Lima in coherence with international theoretical frameworks and existing empirical research. Thus, an ad hoc test was designed under the Classical Test Theory, taking into account a classification of teaching beliefs, and the respective psychometric analysis was carried out. A total of 393 teachers from the seven Local Educational Management Units (UGEL) of Metropolitan Lima participated. The methodology included the determination of content and construct validity, as well as the analysis of reliability by internal consistency. This research provides an instrument of 30 items on a Likert scale with optimal validity and reliability indicators for the Peruvian reality with the possibility of being extrapolated to other South American contexts for the diagnosis, research and evaluation of the effectiveness of ICT training programs within the framework of the paradigm of teacher thinking. Este estudio forma parte de una investigación doctoral que analiza la relación entre las competencias socioemocionales (CSE) y las creencias docentes del profesor de secundaria. En este sentido es necesario contar con un instrumento válido, confiable y adaptado a la realidad sociocultural de los maestros de escuelas públicas de Lima Metropolitana en coherencia con los marcos teóricos internacionales y la investigación empírica existente. Así, se diseñó una prueba ad hoc bajo la Teoría Clásica de los Test, teniendo en cuenta una clasificación de las creencias docentes y se realizó el análisis psicométrico respectivo. En total participaron 393 docentes pertenecientes a las siete Unidades de Gestión Educativa Local (UGEL) de Lima Metropolitana. La metodología abarcó la determinación de la validez de contenido y constructo; así como el análisis de confiabilidad por consistencia interna. Con esta investigación se provee un instrumento de 30 ítems en una escala Likert con indicadores de validez y confiabilidad óptimos para la realidad peruana con posibilidad de ser extrapolado a otros contextos sudamericanos para el diagnóstico, investigación y evaluación de la efectividad de programas de capacitación en TIC en el marco del paradigma del pensamiento docente.

Background: Despite recent advances in immunosuppression treatment, antibody-mediated rejection (ABMR) remains the leading cause of kidney graft loss. Information about prognostic markers and the efficacy of treatment is scarce.Methods: Retrospective study with kidney recipients diagnosed an active ABMR from January 1, 2004 to December 31, 2019 to explore the influence of persistent inflammation in follow-up biopsies on graft survival after ABMR treatment.Results: About 116 patients were included. Active ABMR were treated with a combination of plasma exchange (PE), intravenous immunoglobulin (IVIg), rituximab, and steroids. At 6 months of treatment, 63 (54.3%) patients presented a stabilization or improvement in kidney-graft function. The effectiveness varied depending on the timepoint of the presentation between transplantation and rejection, which is lower for those with late ABMR (63 vs. 21% for early vs. late ABMR, respectively). Ninety patients (77%) underwent a control biopsy after ABMR treatment, from which 46 (51%) responded to the treatment. Microvascular inflammation (MVI) persisted in 64 (71%) biopsies, whereas tubulitis persisted in 17 (19%) biopsies. Death-censored graft survival at 1 year was significantly lower in patients with persistent MVI (86% vs. 95% without persistent MVI, P = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, P = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35–14.96), P = 0.01] and tubulitis [HR 2.88 95%CI (1.24–6.69), P = 0.01) in follow-up biopsies significantly increased the risk of graft failure.Conclusion: Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria.Study Registration: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Living donor kidney transplantation (LDKT) is the best treatment for end-stage renal disease. In this setting, a significant percentage of transplants are not undertaken because of medical and nonmedical reasons of both donors and recipients. However, the impact of these discards in a transplant program has not been identified thoroughly so far. Our objective was to clarify key reasons for exclusion of LDKTs and the consequences for the discarded transplant candidates in the following 5 years.Analysis of donors' and recipients' characteristics of 781 couples evaluated in our hospital from January 2005 to December 2013. The consequences of discards in transplant candidates were analyzed in the cohort 2012 to 2013 (n = 106) and followed up until October 2018.In our study group, 402 (51.5%) LDKT couples were successfully donated, and 379 (48.5%) were excluded. Donor and transplant recipient candidates discarded were older at the evaluation (55.07 ± 12.14 years vs 51.73 ± 10.93 years, P .001; 48.81 ± 14.05 years vs 44.62 ± 13.91 years, P .001, respectively). The most frequent reason for kidney discard was medical contraindication found in the potential donor (47.5%; low eGFR, diabetes mellitus, impaired glucose tolerance, high blood pressure, cardiovascular pathology casually found during evaluation, and proteinuria). Of the discarded candidates from 2012 to 2013, 36.8% received a deceased donor kidney transplant, 17% a LDKT with another donor, 7.5% stayed on the waiting list, 18.9% died, 3.8% were excluded from the waiting list, and 14.2% were lost to follow-up.In most cases, transplantation was not undertaken because of donor pathology. Fifty-three percent of the discarded patients were eventually transplanted, with a 31.4% probability to receive an organ from another living donor.

This paper is part of a doctoral research that analyses the relationship between socioemotional competences (SEC) and pedagogical beliefs in secondary school teachers. Specifically, we sought to study the relationship between the SEC of 115 teachers and 228 secondary school students in two UGELs (Local Education Management Units) in Peru in the context of the "Learning at home" experience as a way of responding to the challenges arising from Covid-19. The problem was approached from the quantitative paradigm with a correlational design. Two questionnaires were applied to measure the study variables based on the CASEL proposal. The results indicate that the levels of SEC are acceptable and do not differ significantly in both groups, while there is a low and very low correlation between the variables and sub-variables of the study. Results are discussed and conclusions are drawn.

The transperitoneal laparoscopic approach is considered the gold standard technique for living kidney donation. Other accepted laparoscopic techniques include the retroperitoneal approach, natural orifice transluminal endoscopic surgery (NOTES)-assisted, laparo-endoscopic single-site surgery (LESS), with excellent results in the donor and graft. Many studies have compared these techniques with open ones. Our objective is to describe our experience and results in minimally invasive living-donor nephrectomies (MILDN): laparoscopic, NOTES-assisted, and LESS since their introduction in March 2002.We conducted a retrospective observational study of donors undergoing MILDN between March 2002 and March 2020.A total of 714 MILDNs were performed at our centre. All were completed, except for one, because of recipient death. The conventional laparoscopic approach was used in 541 cases (75.88%), NOTES in 116 (16.9%), LESS in 55 (7.7%), and one mini open (0.14%). Two-thirds of the donors were females (478 cases). The mean donor age was 52.87 years (SD 10.93). Six donors (0.8%) were diagnosed beforehand with a small renal mass, which was removed before transplantation in bench surgery. The right kidney was removed in 17.8% of cases. Warm ischaemia time was higher in the NOTES and LESS groups. We had eight conversions. The global intraoperative and postoperative complication rates were 6.8% and 4.9%, respectively. None of the donors developed renal disease during follow-up (mean 3.68 years). Five-year recipient and graft survival rates were 98.8% and 96.8%, respectively.MILDN techniques are safe for donors and grafts, with low complication.

Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL2 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity., Graphical abstract

Background and Aims Monoclonal immunoglobulin deposition disease (MIDD) is a systemic rare condition that usually leads to end stage renal disease. Treatment of patients with a bortezomib-based regimen followed by autologous stem cell transplantation (ASCT) has been increasingly used, with improvements in the response rates and the renal graft outcomes in kidney transplant recipients Method Retrospective study of 6 patients diagnosed of MIDD with complete response but not renal response after hematologic treatment that underwent kidney transplant in our institution between 2010 and 2019. Results A total of 6 patients (5 women) were analyzed, with mean age at diagnosis of 47 years (range 40-53). At presentation their mean eGFR was 18 mL/minute (range 9-25) and mean proteinuria of 5.5 g (range 0.290-12.5). The deposit was kappa type except in 1 case (heavy and light lambda type chains). In all of them there was an absence of monoclonal component in blood and urine but positive immunofixation in 5 cases (2 only in urine). 3 started chronic hemodialysis during admission and the others at 3, 5 and 44 months after diagnosis. As hematological treatment, all received bortezomib followed by ASCT, being under complete hematological response at the time of kidney transplant. It was performed at 28 months on average from ASCT (range 11-42), with mean kappa/lambda ratio of 2.6 (range 1.33-3.75). 3 patients received induction with thymoglobulin and 3 with basiliximab, followed by triple therapy with tacrolimus + prednisone + mTOR inhibitor (4 patients) or mycophenolate (2 patients). During a median follow-up of 20,5 months from kidney transplant and 54 months from ASCT, 1 patient experienced hematologic relapse and 2 had hematologic progression (one of them with MIDD relapse in the allograft) requiring treatment. The patient with organ relapse received Daratumumab monotherapy achieving complete hematologic response but graft failure. The other 5 patients had functional graft with median serum creatinine 1.68 mg/dl. Conclusion In patients with MIDD and sustained complete hematologic response, a kidney transplant can be considered. The optimal approach to treatment of hematologic relapse or recurrence of MIDD after kidney transplant remains to be determined

The aim objective of this study was to analyze the incorporation procedure for the Portal 2 video game in the subject Mathematical Knowledge in Early Childhood Education. Two specific objectives were proposed: (a) to consider whether the inclusion of a video game is a motivating educational resource, and (b) to determine the degree of knowledge related to visuospatial perception acquired through interaction with the video game. A total of 170 students from the Faculty of Education Sciences of the University of Cádiz participated in this study. Three variables were analyzed: the use of the video game as a resource, the degree of motivation towards mathematics-related learning, and the acquisition of visuospatial skills. The results show that the students affirmed the video game's suitability as a learning resource, although as a supplementary resource to the dynamics of the subject, highlighting the strong motivational factor and the set of knowledge acquired.

BACKGROUND Low adherence to chronic immunosuppression is associated with suboptimal transplantation outcomes. Mobile-health technology is a promising tool to monitor medication adherence, but data on patient engagement to these tools are lacking. METHODS Prospective, observational, multicenter, 2-phase trial in kidney and liver transplant recipients, investigating the degree of engagement to TrackYourMed® (TYM), a novel m-Health technology with a QR code-scan app to track immunosuppression adherence and its association with drug monitoring. RESULTS Out of 204 consecutive transplant patients, 90 patients were eligible to participate. 61 (68%) used TYM regularly, 21 (23%) never or barely used it, 5 (5.5%) were irregular users, and 3 (3.3%) were lost to follow-up. 6-month total correct intakes (CIN) ranged between 69%-76%, 12%-19% intakes were out-of-time (OUT), and 9%-12% were missed (MIS). Notably, a rate of intakes out of the scheduled time higher than 20% in the 6 days prior to blood immunosuppressant trough levels was associated with a higher intra-patient variability (17 IQR 13-21% vs. 29 IQR 23%-36%, p = .001), and with a higher dose-adjustment (p

Outcomes of kidney transplantation (KT) after controlled circulatory death (cDCD) with highly expanded criteria donors (ECD) and recipients have not been thoroughly evaluated. We analyzed in a multicenter cohort of 1161 consecutive KT, granular baseline donor and recipient factors predicting transplant outcomes, selected by bootstrapping and Cox proportional hazards, and were validated in a contemporaneous European KT cohort (n = 1585). 74.3% were DBD and 25.7% cDCD-KT. ECD-KT showed the poorest graft survival rates, irrespective of cDCD or DBD (log-rank

Altres ajuts: The project leading to these results has also received funding from "la Caixa" Foundation (ID 100010434), under agreement CI19-00048. This activity has received funding from the European Institute of Innovation and Technology (EIT). This body of the European Union receives support from the European Union's Horizon 2020 research and innovation program. LCP is sponsored by the Spanish Government FPU grant ("Formación de Personal Universitario", FPU17/01444). MF is supported by ISCIII (MS19/00018), co-funded by ERDF/ESF, "Investing in your future". FEB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Direcció General de Recerca i Innovació, Dept. Salut, Generalitat de Catalunya). In kidney transplantation, fibrosis represents the final and irreversible consequence of the pathogenic mechanisms that lead to graft failure, and in the late stages it irremediably precedes the loss of renal function. The invasiveness of kidney biopsy prevents this condition from being frequently monitored, while clinical data are rather unspecific. The objective of this study was to find noninvasive biomarkers of kidney rejection. We carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF). Shotgun mass spectrometry of uEV-proteins identified differential expression of several proteins among these different groups. Up to 23 of these proteins were re-evaluated using targeted proteomics in a new independent cohort of patients (n = 41) classified in the same diagnostic groups. Among other results, we found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA). Urinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion. The online version of this article (10.1007/s40620-020-00886-y) contains supplementary material, which is available to authorized users.

Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs).Methods: BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles. We analyzed stored serum samples from positive crossmatch LDKT recipients before and after desensitization at first post-transplant biopsy and at 12-month protocol biopsy (n = 11). Control groups were formed by hypersensitized patients who were not submitted to desensitization (n = 10) and by low-risk recipients (n = 9). A prospective validation cohort of 11 patients also included the analysis of B cells subpopulations in recipients' blood and lymph nodes recovered upon graft implantation, along with BEVs analysis before and after desensitization.Results: We found out that CD19+ and HLA-II+BEVs dropped significantly after desensitization and relapse in patients who later developed ABMR was evident. We validated these findings in a proof-of-concept prospective cohort of 6 patients who received the same desensitization protocol and also in a control group of 5 LDKT recipients. In these patients, B cell subpopulations were also studied in recipients' blood and lymph nodes that were recovered before the graft implantation. We confirmed the significant drop in BEVs after desensitization and that this paralleled the reduction in CD19+cells in lymph nodes, while in peripheral blood B cells, this change was almost undetectable.Conclusions: BEVs reflected B cell residual activity after desensitization and this could be a valid surrogate of humoral alloreactivity in this setting.

Background It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. Methods To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). Results Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). Conclusions This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.

Endothelial–to–mesenchymal transition (EndMT) is a cellular transdifferentiation program in which endothelial cells partially lose their endothelial identity and acquire mesenchymal-like features. Renal capillary endothelial cells can undergo EndMT in association with persistent damage of the renal parenchyma. The functional consequence(s) of EndMT in kidney fibrosis remains unexplored. Here, we studied the effect of Twist or Snail deficiency in endothelial cells on EndMT in kidney fibrosis. Conditional deletion of Twist1 (which encodes Twist) or Snai1 (which encodes Snail) in VE-cadherin(+) or Tie1(+) endothelial cells inhibited the emergence of EndMT and improved kidney fibrosis in two different kidney injury/fibrosis mouse models. Suppression of EndMT limited peritubular vascular leakage, reduced tissue hypoxia, and preserved tubular epithelial health and function. Hypoxia, which was exacerbated by EndMT, resulted in increased Myc abundance in tubular epithelial cells, enhanced glycolysis, and suppression of fatty acid oxidation. Pharmacological suppression or epithelial-specific genetic ablation of Myc in tubular epithelial cells ameliorated fibrosis and restored renal parenchymal function and metabolic homeostasis. Together, these findings demonstrate a functional role for EndMT in the response to kidney capillary endothelial injury and highlight the contribution of endothelial-epithelial crosstalk in the development of kidney fibrosis with a potential for therapeutic intervention.

Background and Aims Getting a preemptive kidney transplant has many benefits but no studies have assessed the potential deleterious effect of uremia on peritransplant complications. Uremic toxins interact negatively with biologic functions and may contribute to infections and bleeding or thormbosis. Method we evaluated 255 living-donor kidney transplant recipients (117 preemptive and 138 non-preemptive) from January 2006 to December 2015. Patients iniciated immunosuppression treatment 3 days prior to transplant. Exclusion criteria included: history of solid organ transplant, chronic immunosuppression treatment at the time of transplant (including prednisone), peritransplant rituximab/eculizumab treatment and HIV infection. An analysis of baseline characteristics and the incidence of symptomatic infection, bleeding or thrombosis during first week was performed in both groups. To analyze bleeding, the need of transfusion, drop of hematocrit in 72h and need of bladder washout was assessed. Results baseline characteristics are descrived in table 1. Non preemptive patients were older (50 vs 46 years) and had a higher prevalence of Diabetes Mellitus and dialypemia (22 vs 11% and 43 vs 30% respectively), without differences in the immunosupression scheme. The median eGFR in preemptive group at transplant was 12 ml/min. A more anemic profile was detected in the preemptive group with median hemoglobin of 116 vs 127 g/L in the non-preemptive group with no-differences in albumin levels. There were a total of 38 symptomatic infections (22 in the preemptive and 16 in the non-preemptive group), without statistical differences in the incidence between the groups (OR 1,75 CI 0,879-3,5, P =0,107). Hematocrit drop was greater in the non-preemptive group (8 vs 6 points in the first 72h p = 0.004) but thrombosis was more common in the preemptive group (5 vs 1, OR 6,116 CI 0,704-53,1, p = 0.062). Conclusion Uremia in preemptive living kidney transplant recipients does not seem to have influence on the incidence of infections in the first week after transplantation. The bleeding profile in the non-preemptive group in contrast to the prothrombotic profile in preemptive recipients needs further investigation in future studies that assess parameters of platelet and coagulation function as well as endothelial activation.

This systematic literature review aimed to discover how the concept of digital teaching competence (DTC) has been developed, how its dimensions have been defined, and how educational development models and models that evaluate teachers’ digital teaching competence have been constructed. Concurrently, this review aimed to draw conclusions on the implementation processes of digital teaching competence in order to uncover its strengths and limitations, and to propose future lines of research to develop it further in initial teacher training programmes. A systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was proposed in order to achieve these aims. We chose the time frame of 2015 to the end of 2021 in an attempt to cover the appearance of the first scientific articles dealing with the subject, up until the present day. Thus, the inclusion criteria covered scientific research articles from the Web of Science (WoS) and Scopus databases, in English or Spanish, that focused on samples of teachers in primary education, secondary education, baccalaureates, and initial teacher training. The database searches, which will be detailed in depth later, initially provided a corpus of 127 articles, which was reduced to 26 articles after screening for duplicity and applying the inclusion criteria.

Somos conscientes de la dimensión temporal que existe desde el inicio de los estudios de los videojuegos desde diferentes prismas hasta el momento actual. Si nos detenemos en el punto de vista de la inclusión del videojuego en los procesos de enseñanza y aprendizaje, hemos podido comprobar a lo largo de estas décadas que se ha evolucionado desde el uso de videojuegos como recursos para cambiar patrones (desde el más puro estilo conductista) hasta la situación actual que transita por 3 líneas claramente diferenciadas: (a) el uso de videojuegos comerciales como recurso para afianzar un determinado contenido educativo, (b) el uso de los denominados «juegos serios» cuyo modelo integra el desarrollo de contenidos educativos que requieren ser utilizados en el juego como si de una simulación se tratase, esto conlleva la adquisición de nuevos aprendizajes y afianzar otros aprendizajes que adquiridos de otras formas, y; (c) los desarrollos y aplicaciones de la «deconstrucción» del juego que se denomina «gamificación», y que trata de «edulcorar» situaciones de aprendizaje a través del análisis del juego en su contexto general.

La consideración del juego como herramienta educativa es una constante en la cultura humana. Actualmente, la esencia del juego es la misma, pero han cambiado los formatos para llevarlo a cabo. En éste marco nacen los videojuegos, los cuáles han tenido una vertiginosa evolución considerándose en los últimos años como elementos educativos mediante el Digital Game Based Learning. También se han tenido en cuenta las emociones como elementos propios de los procesos de aprendizaje vinculados con una serie de atributos y habilidades identificados con la docencia. La investigación realizada a una muestra (n=31) de estudiantes versa sobre la identificación de aprendizajes de atributos y habilidades docentes y el tratamiento de las emociones a través del análisis de videojuegos con temáticas sociales. Los videojuegos son This War of Mine, Papers, please! Y Unmanned. Las técnicas de acopio de información han sido la observación y la entrevista. Mediante estas técnicas los videojugadores deben identificar qué emociones, atributos y habilidades son capaces de experimentar y/o desarrollar mientras están jugando. Los resultados obtenidos muestran que los sujetos investigados perciben esas emociones y les afecta para la consecución o desarrollo de los atributos y habilidades docentes. A modo de conclusión, se puede señalar que el análisis de los videojuegos fue efectivo y se hallaron respuestas emocionales ante acciones desarrolladas en el juego, así como aprendizajes destacados para el docente del siglo XXI presentes en los tres videojuegos. The consideration of play as an educational tool is a constant in human culture. Currently, the essence of the game is the same, but the formats have changed to make it happen. Within this framework, videogames are born, which have undergone a vertiginous evolution and have been considered in recent years as educational elements through the Digital Game Based Learning. Emotions have also been taken into account as elements of learning processes linked to a series of attributes and skills identified with teaching. The research carried out on a sample (n=31) deals with the identification of learning attributes and teaching skills and the treatment of emotions through the analysis of video games with social themes. Video games are This War of Mine, Papers, please! and Unmanned. The information gathering techniques have been observation and interview. Using these techniques, gamers must identify what emotions, attributes and skills they are able to experience and/or develop while playing. The results obtained show that the subjects investigated perceive these emotions and are affected for the achievement or development of the teaching attributes and skills. By way of conclusion, it can be pointed out that the analysis of the video games was effective and emotional responses were found to actions developed in the game, as well as outstanding learning for the 21st century teacher present in the three video games.

Pancreas outcomes in pancreas after kidney transplantation (PAK) patients have been reported as being inferior to those of patients who receive simultaneous pancreas and kidney transplantation (SPK). The influence of the kidney donor (i.e. living versus deceased) has never been previously addressed.We retrospectively analysed all pancreas transplants performed in a single centre since 2007 and compared the outcomes between those patients who had previously received a living-donor kidney transplant (pancreas transplantation after living-donor kidney transplantation, PAldK; n = 18) or a deceased-donor kidney transplant (pancreas transplantation after deceased-donor kidney transplantation, PAddK; n = 28), using SPK (n = 139) recipients as a reference.Pancreas survival was similar between all groups, but inferior for PAldK when including only those with a functioning graft at day 90 post-transplantation (P = 0.004). Pancreas acute rejection was significantly increased in PAldK (67%; 1.8 ± 1.4 episodes/graft) when compared with PAddK (25%) and SPK (32%) (P 0.05) patients. In a multivariate Cox regression model including known risk factors for pancreas rejection, PAldK was the only predictor of acute rejection (hazard ratio 6.82, 95% confidence interval 1.51-30.70, P 0.05). No association was found between donor-recipient HLA mismatches and graft rejection. Repeated HLA mismatches between kidney and pancreas donors (0 versus 1-6) did not correlate with pancreas graft rejection or survival in either PAK transplantation group (P 0.05).Pancreas graft outcomes are worse for PAldK when compared with PAddK and SPK patients.

Video game use is widespread among all age groups, from young children to older adults. The wide variety of video game genres, which are adapted to all tastes and needs, is one of the factors that makes them so attractive. In many cases, video games function as an outlet for stress associated with everyday life by providing an escape from reality. We took advantage of this recreational aspect of video games when investigating whether there are similarities between the procedures used to pass a video game level and those used to solve a mathematical problem. Moreover, we also questioned whether the use of video games can reduce the negative emotions generated by mathematical problems and logical–mathematical knowledge in general. To verify this, we used the Portal 2 video game as a research method or tool. This video game features concepts from the spatial–geometric field that the students must identify and relate in order to carry out the procedures required to solve challenges in each level. The procedures were recorded in a questionnaire that was separated into two blocks of content in order to compare them with the procedures used to solve mathematical problems. The first block pertains to the procedures employed and the second block to the emotions that the students experienced when playing the video game and when solving a mathematical problem. The results reveal that the recreational aspect of video games is more important than the educational aspect. However, the students were not aware of using the problem-solving procedures they learned at school to solve different challenges in the video games. Furthermore, overcoming video game challenges stimulates positive emotions as opposed to the negative emotions generated when solving mathematical problems.

Aims Information on the impact of insulin therapy before pancreas donation on pancreas outcomes is scarce. We aim to explore the influence of insulin therapy before donation on recipient and pancreas graft survival. Methods Registry study including 12,841 pancreas recipients from the OPTN/UNOS registry performed between 2000 and 2017. Inverse probability of treatment weighting (IPTW) was used to account for covariate imbalance between recipients from a donor with and without insulin requirements. Results A total of 7765 (60%) patients received a pancreas from a donor with insulin before donation (IBD). Pancreas graft survival (death-censored) was similar between recipients from IBD and non-IBD donors at 1, 5 and 10 years (89% vs 89%, 78% vs 79 and 69% vs 70%, respectively, P = 0.35). Recipients from IBD donors presented a similar 90-days pancreas graft survival. After IPTW weighting, IBD donors were neither associated with any post-transplant surgical complication (HR 1.11 [95% CI 0.98–1.24], P = 0.06), nor with risk for recipient death (HR 0.94 [95% CI 0.85–1.04], P = 0.26), nor pancreas graft failure (HR 1.06 [95% CI 0.98–1.16], P = 0.15). Conclusions Insulin therapy before donation in accepted pancreas donors was not associated, per se, with an impaired pancreas graft and patient survival.