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Abstract Dichroic techniques are highly relevant in the field of topological materials, layered systems, and spin-polarized electronic states. Dichroism in angle-resolved photoemission is per se a matrix element effect, which depends on the initial and final states as well as on the perturbation by the light field. Although matrix element effects in ARPES such as dichroism are important for addressing properties of the initial state wave functions, the results can strongly depend on experimental geometry or final state effects. Combining experimental data on bulk WSe2 taken at soft x-ray photon energies with state-of-the-art photoemission calculations, we demonstrate that a dichroic observable called time-reversal dichroism remains unaffected against variation of photon energy, light polarization, and the angle of incidence. We demonstrate a direct link of TRDAD obtained with both linearly and circularly polarized photons to the initial state properties indicating its broad applicability. The robustness of this matrix element effect indicates a considerable benefit over other dichroic techniques and encourages further experimental and theoretical investigations.

Weyl semimetals exhibit Berry flux monopoles in momentum-space, but direct experimental evidence has remained elusive. Here, the authors reveal topologically non-trivial winding of the orbital-angular-momentum at the Weyl nodes and a chirality-dependent spin-angular-momentum of the Weyl bands, as a direct signature of the Berry flux monopoles in TaAs.

Allograft infiltration has been described in up to 20% of all patients with posttransplant lymphoproliferative disorder (PTLD), most representing EBV-positive B-cell lymphomas. Plasma cells are often observed in humoral rejection biopsies, but graft infiltration by plasmacytoma-like PTLD is rare. We report the case of a 54-year-old simultaneous pancreas-kidney transplant recipient (immunosuppression: OKT3, methylprednisolone, cyclosporine, and azathioprine), diagnosed with an IgG-kappa monoclonal gammopathy of undetermined significance eighteen years after transplant. Nine months later, pancreas allograft biopsy performed due to new-onset hyperglycemia (HgA1C 8.6%, C-peptide 6.15ng/mL and anti-GAD 0.9UI/mL) revealed a monotypic plasma cell infiltrate, CD19, CD79a, CD138 positive, with IgG-kappa light chain restriction, and EBV negative. PET-scan FDG uptake was limited to pancreas allograft. Tumor origin could not be established (using DNA microsatellite analysis). Despite treatment with bortezomib and dexamethasone, patient eventually died one month later. This is the first report of a late onset extramedullary plasmacytoma involving a pancreas allograft.

Infections are among the most common complications transplant physicians face when dealing with solid organ transplant recipients. We present a case of pyomyositis caused by Staphylococcus aureus in a patient with IgA nephropathy and a kidney transplant, under treatment with mTOR inhibitors and prednisone. This entity is a rare intramuscular infection, given the resistance of healthy muscle to colonization. We review the most frequent agents, the diagnostic algorithm, and therapeutic alternatives. We also comment on the role of mTOR inhibitors in this case as possible predisposing factor for the infection.

Introduction: There is no reliable microbiological marker to guide responses to antiviral treatment in kidney transplant recipients (KTR) with COVID-19. We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) RT-PCR before and after receiving treatment with remdesivir compared with genomic RNA (gRNA) RT-PCR and its use as a surrogate marker of viral replication., Methods: We analyzed gRNA and sgRNA at baseline and after remdesivir treatment in KTR who received remdesivir for SARS-CoV-2 infection from November 2021 to February 2022., Results: Thirty-four KTR received remdesivir for SARS-CoV-2 infection. The median time since transplantation was 80 months (IQR 3-321) and 75% of patients had previously received 3 doses of a mRNA SARS-CoV-2 vaccine. Three patients (8%) were classified with mild, 25 (73%) with moderate, and 6 (17%) with severe SARS-CoV-2 infection. Thirty-two (94%) patients received 5 doses of remdesivir and two patients received 2 doses. The median time between symptom onset to remdesivir treatment was 5 days (IQR 3-8.5). The median days of hospitalization were 6 (IQR 2-112). gRNA was positive in all patients at baseline and after remdesivir. Five (15%) patients had negative sgRNA at baseline and 20 (59%) after receiving remdesivir. Patients presenting with negative sgRNA at baseline were discharged from hospital in ≤ 6 days without complications. Moreover, those with negative sgRNA after remdesivir therapy did not require ICU admission and had favorable outcomes. Nevertheless, patients with positive sgRNA after antiviral treatment presented worse outcomes, with 47% requiring ICU admission and the three (9%) recorded deaths in the study were in this group., Conclusions: Based on these data, we hypothesize that sgRNA may have clinical utility to help monitor virologic response more accurately than gRNA in KTR who receive remdesivir. Moreover, patients with negative sgRNA at baseline may not require antiviral treatment and others presenting positive sgRNA at day 5 could benefit from prolonged or combined therapies., (© 2024. The Author(s).)

Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area., Competing Interests: CB received speaker fees from Mallinckrodt Pharmaceuticals and honoraria for an advisory role from Zambon Pharma. FD received a research grant and speaker fees from Mallinckrodt Pharmaceuticals. AZ received speaker fees from Mallinckrodt Pharmaceuticals, Chiesi and Paragonix and honoraria for an advisory role from Novartis. J-FA received a research grant and speaker fees from Mallinckrodt Pharmaceuticals. The authors declare that this study received funding from Mallinckrodt Pharmaceuticals. The funder(s) had the following involvement in the study: study design, data collection and preparation of the manuscript., (Copyright © 2024 Augusto, Benden, Diekmann and Zuckermann.)

Background: Anemia is highly prevalent in end-stage chronic kidney disease patients, increasing their risk of receiving blood transfusions during and on the days after a kidney transplant (KTx) surgery. However, there is currently a lack of data that thoroughly describes this phenomenon in this population, the associated risk factors, and how they could benefit from the application of Patient Blood Management (PBM) guidelines., Materials and Methods: Observational study. All adult patients who received a KTx between January 1 st , 2020, and December 31 st , 2021, were included and followed up to six months after transplantation. Those who received a multiorgan transplant, whose data was missing in the electronic health records, and who had primary non-function were excluded. We recorded donor and recipient characteristics, cold ischemia time, preoperative hemoglobin concentration, iron status deficiency biomarkers, incidence of delayed graft function and biopsy-proven graft rejections, and graft function at discharge and 6 months after transplantation., Results: We found that a high amount (39%) of KTx recipients required at least one blood transfusion during the perioperative period. And that 1) most of these patients had anemia at the time of transplantation (85.4%), 2) iron status upon admission was associated with the transfusion of more blood units (3.9 vs 2.7, p=0.019), 3) surgical reintervention (OR 7.28, 2.35-22.54) and deceased donor donation (OR 1.99, 1.24-3.21) were associated with an increased risk of transfusion, and finally, 4) there was an association between a higher number of blood units transfused and impaired kidney graft function six months after hospital discharge (1.6 vs 1.9, p=0.02)., Conclusions: In conclusion, PBM guidelines should be applied to patients on the KTx deceased donor waiting list and especially those scheduled to receive a transplant from a living donor. This could potentially increase the utilization efficiency of blood products and avoid transfusion-related severe adverse effects.

Tacrolimus is pivotal in pancreas transplants but poses challenges in maintaining optimal levels due to recipient differences. This study aimed to explore the utility of time spent below the therapeutic range and intrapatient variability in predicting rejection and de novo donor-specific antibody (dnDSA) development in pancreas graft recipients. This retrospective unicentric study included adult pancreas transplant recipients between January 2006 and July 2020. Recorded variables included demographics, immunosuppression details, HLA matching, biopsy results, dnDSA development, and clinical parameters. Statistical analysis included ROC curves, sensitivity, specificity, and predictive values. A total of 131 patients were included. Those with biopsy-proven acute rejection (BPAR, 12.2%) had more time (39.9% ± 24% vs. 25.72% ± 21.57%, p = 0.016) and tests (41.95% ± 13.57% vs. 29.96% ± 17.33%, p = 0.009) below therapeutic range. Specific cutoffs of 31.5% for time and 34% for tests below the therapeutic range showed a high negative predictive value for BPAR (93.98% and 93.1%, respectively). Similarly, patients with more than 34% of tests below the therapeutic range were associated with dnDSA appearance (38.9% vs. 9.4%, p = 0.012; OR 6.135, 1.346-27.78). In pancreas transplantation, maintaining optimal tacrolimus levels is crucial. Suboptimal test percentages below the therapeutic range prove valuable in identifying acute graft rejection risk., Competing Interests: D-RE has received expenditures on travel, hospitality and conferences by Chiesi. PV-A has received expenditures on travel, hospitality and conferences by Chiesi and Astellas. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodríguez-Espinosa, Broseta, Montagud-Marrahí, Arana, Ferrer, Cuatrecasas, Garcia-Criado, Amor, Diekmann and Ventura-Aguiar.)

Renal ischemia-reperfusion injury (IRI) leads to endoplasmic reticulum (ER) stress, thereby initiating the unfolded protein response (UPR). When sustained, this response may trigger the inflammation and tubular cell death that acts to aggravate the damage. Here, we show that knockdown of the BET epigenetic reader BRD4 reduces the expression of ATF4 and XBP1 transcription factors under ER stress activation. BRD4 is recruited to the promoter of these highly acetylated genes, initiating gene transcription. Administration of the BET protein inhibitor, JQ1, one hour after renal damage induced by bilateral IRI, reveals reduced expression of ATF4 and XBP1 genes, low KIM-1 and NGAL levels and recovery of the serum creatinine and blood urea nitrogen levels. To determine the molecular pathways regulated by ATF4 and XBP1, we performed stable knockout of both transcription factors using CRISPR-Cas9 and RNA sequencing. The pathways triggered under ER stress were mainly XBP1-dependent, associated with an adaptive UPR, and partially regulated by JQ1. Meanwhile, treatment with JQ1 downmodulated most of the pathways regulated by ATF4 and related to the pathological processes during exacerbated UPR activation. Thus, BRD4 inhibition could be useful for curbing the maladaptive UPR activation mechanisms, thereby ameliorating the progression of renal disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The transplant community is focused on prolonging the ex vivo preservation time of kidney grafts to allow for long-distance kidney graft transportation, assess the viability of marginal grafts, and optimize a platform for the translation of innovative therapeutics to clinical practice, especially those focused on cell and vector delivery to organ conditioning and reprogramming. We describe the first case of feasible preservation of a kidney from a donor after uncontrolled circulatory death over a 73-h period using normothermic perfusion and analyze hemodynamic, biochemical, histological, and transcriptomic parameters for inflammation and kidney injury. The mean pressure and flow values were 71.24 ± 9.62 mmHg and 99.65 ± 18.54 mL/min, respectively. The temperature range was 36.7°C-37.2°C. The renal resistance index was 0.75 ± 0.15 mmHg/mL/min. The mean pH was 7.29 ± 0.15. The lactate concentration peak increased until 213 mg/dL at 6 h, reaching normal values after 34 h of perfusion (8.92 mg/dL). The total urine output at the end of perfusion was 1.185 mL. Histological analysis revealed no significant increase in acute tubular necrosis (ATN) severity as perfusion progressed. The expression of KIM-1, VEGF, and TGFβ decreased after 6-18 h of perfusion until 60 h in which the expression of these genes increased again together with the expression of β -catenin, Ki67, and TIMP1. We show that normothermic perfusion can maintain a kidney graft viable ex vivo for 3 days, thus allowing a rapid translation of pre-clinical therapeutics to clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Montagud-Marrahi, Luque, Ros, Ajami, Cuadrado-Payan, Estrella, Arancibia, Sánchez-Etayo, Bohils, Marrero, Fundora, Ramírez-Bajo, Banon-Maneus, Rovira, Larque, Campistol, Diekmann and Musquera.)

Introduction: An increased midnight cortisol (MC) has been described in end-stage kidney disease (ESKD) and type 1 diabetes (T1D). Lower circulating levels of the cytokine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) have been found in T1D and ESKD and associated with cardiovascular (CV) events in the latter. We aimed to study MC and sTWEAK in simultaneous pancreas-kidney transplant (SPKT) recipients, and the association of these markers with CV risk factors and transplant outcomes., Methods: This was a retrospective cohort study including subjects with T1D who received a first SPKT between 2008 and 2020. MC and sTWEAK at baseline were correlated with CV risk factors and evolution 1 year after SPKT., Results: We included 29 subjects (58.6% women, mean age 43.5 ± 7.5 years, diabetes duration 31.9 ± 9.4 years). Systolic blood pressure (SBP) increased directly with MC quartiles, despite similar hypertension prevalence (p < 0.05). At 1 year, antihypertensive treatment was deintensified in those in lower MC quartiles (p < 0.05). Diabetic neuropathy prevalence decreased progressively in higher cortisol quartiles (p for trend = 0.005). Low MC was associated with delayed kidney graft function (p for trend = 0.044), and high sTWEAK with kidney graft rejection (p for trend = 0.018). In multivariate analyses, MC (standardized-β 0.505, p = 0.004) and age (standardized-β - 0.460, p = 0.040) were independently correlated with SBP, and MC was independently associated with the presence of diabetic neuropathy (OR 0.633, 95% CI 0.425-0.944, p = 0.025), adjusted for confounders., Conclusions: In this exploratory study, lower MC was associated with a lower baseline SBP, an improvement of antihypertensive treatment 1 year after transplant, and a higher diabetic neuropathy prevalence in SPKT recipients., (© 2023. The Author(s).)

Background: Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN., Methods: We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. 'Tubulo-interstitial inflammation' (TII) was defined when 't' or 'i' were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL)., Results: A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9 months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3 years 18.0% vs 45.3%, log-rank 7.588, P  = .006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119-4.910, P  = .024) independently of other histologic and clinical variables., Conclusions: In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent histological examination. Early and sensitive biomarkers of graft damage and alloimmunity are needed to identify graft injury and eventually limit the need for a kidney biopsy. Moreover, other scenarios such as delayed graft function or interstitial fibrosis and tubular atrophy face the same problem. In recent years, interest has grown around extracellular vesicles, specifically exosomes actively secreted by immune cells, which are intercellular communicators and have shown biological significance. This review presents their potential as biomarkers in kidney transplantation and alloimmunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cuadrado-Payán, Ramírez-Bajo, Bañón-Maneus, Rovira, Diekmann, Revuelta and Cucchiari.)

Background: Bilateral lung transplantation (LuTx) remains the only established treatment for children with end-stage pulmonary arterial hypertension (PAH). Although PAH is the second most common indication for LuTx, little is known about optimal perioperative management and midterm clinical outcomes., Methods: Prospective observational study on consecutive children with PAH who underwent LuTx with scheduled postoperative VA-ECMO support at Hannover Medical School from December 2013 to June 2020., Results: Twelve patients with PAH underwent LuTx (mean age 11.9 years; age range 1.9-17.8). Underlying diagnoses included idiopathic ( n  = 4) or heritable PAH ( n  = 4), PAH associated with congenital heart disease ( n  = 2), pulmonary veno-occlusive disease ( n  = 1), and pulmonary capillary hemangiomatosis ( n  = 1). The mean waiting time was 58.5 days (range 1-220d). Three patients were bridged to LuTx on VA-ECMO. Intraoperative VA-ECMO/cardiopulmonary bypass was applied and VA-ECMO was continued postoperatively in all patients (mean ECMO-duration 185 h; range 73-363 h; early extubation). The median postoperative ventilation time was 28 h (range 17-145 h). Echocardiographic conventional and strain analysis showed that 12 months after LuTx, all patients had normal biventricular systolic function. All PAH patients are alive 2 years after LuTx (median follow-up 53 months, range 26-104 months)., Conclusion: LuTx in children with end-stage PAH resulted in excellent midterm outcomes (100% survival 2 years post-LuTx). Postoperative VA-ECMO facilitates early extubation with rapid gain of allograft function and sustained biventricular reverse-remodeling and systolic function after RV pressure unloading and LV volume loading., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor SM declared a shared committee working group lung transplantation with the author FI at the time of review., (© 2023 Jack, Carlens, Diekmann, Hasan, Chouvarine, Schwerk, Müller, Wieland, Tudorache, Warnecke, Avsar, Horke, Ius, Bobylev and Hansmann.)

Objectives: To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy., Methods: Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity. After lopinavir/ritonavir treatment completion, immunosuppressive treatment was restarted with reduced doses of prednisone-tacrolimus (target minimum blood concentration -C 0 - approximately 5 ng/mL). Patients were observed for 3 months to confirm the absence of rejection., Results: The median time from discontinuation of tacrolimus to initiation of lopinavir/ritonavir was 14 hours (interquartile range [IQR], 12-15) and from discontinuation of lopinavir/ritonavir to resumption of tacrolimus 58 hours (IQR, 47-81). The duration of lopinavir/ritonavir treatment was 7 days (IQR, 5-7). Nine of the 21 (42.8%) patients on tacrolimus treatment had C 0 above the cutoff point after lopinavir/ritonavir initiation, despite having been substituted with prednisone before lopinavir/ritonavir initiation. Three patients had very high concentrations (>40 ng/mL) and developed toxicity. No episodes of acute rejection were diagnosed., Discussion: We did not observe toxicity in patients for whom tacrolimus was discontinued 24 hours before starting lopinavir/ritonavir and reintroduced at half dose 48 to 72 hours after lopinavir/ritonavir discontinuation. Prednisone monotherapy during lopinavir/ritonavir therapy was safe with no episodes of acute rejection. Experience with lopinavir/ritonavir may be applicable to the use of nirmatrelvir/ritonavir, but larger multicentre studies are needed to confirm these findings., (Copyright © 2023. Published by Elsevier Ltd.)

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 (Lew DA ). Leukocytes of those Lew DA rats were exposed to 8-methoxy psoralen, and illuminated with UV-A. The ECP doses assessed were 10 × 10 6 and 100 × 10 6 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Piñeiro, Lazo-Rodriguez, Ventura-Aguiar, Ramirez-Bajo, Banon-Maneus, Lozano, Cid, Hierro-Garcia, Cucchiari, Revuelta, Montagud-Marrahi, Palou, Bayés-Genís, Campistol, Diekmann and Rovira.)

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., (Copyright © 2022. Published by Elsevier España, S.L.U.)

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 (<3 months). During this period immune subsets presented a good discriminative ability (CD4+ AUC 0.79; CD8+ AUC 0.80; B cells AUC 0.86; 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 (<3 months) had a significant increase in T-cell frequencies pre-transplant, both CD4+ T cells and CD8+ T cells ( 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rovira, Ramirez-Bajo, Bañón-Maneus, Hierro-Garcia, Lazo-Rodriguez, Piñeiro, Montagud-Marrahi, Cucchiari, Revuelta, Cuatrecasas, Campistol, Ricart, Diekmann, Garcia-Criado and Ventura-Aguiar.)

Background and Objectives: Emerging evidence suggests that increased degradation of von Willebrand factor and decrease in high molecular weight multimers occurs in patients with pulmonary hypertension (PH). However, the link between acquired von Willebrand Syndrome (AVWS) type 2 and PH remains poorly understood., Material and Methods: We retrospectively evaluated the charts of 20 children with PH who underwent bilateral lung transplantation (LuTx) between 2013 and 2022. Von Willebrand variables were determined in 14 of these patients; 11 patients had complete diagnostics including multimer analysis., Results: We confirmed AVWS in 82% of the children studied (9 of 11 patients by multimer analysis). The two remaining patients had suspected AVWS type 2 because of a VWF:Ac/VWF:Ag ratio of <0.7. Platelet dysfunction or suspicion of VWD type 1 were found in two separate patients. All but one of the 14 children with severe PH had a coagulation disorder. Most patients (9 proven, 2 suspected) had AVWS type 2. Notably, 3 of 5 patients (60%) with normal VWF:Ac/VWF:Ag ratio >0.7 had abnormal VWF multimers, indicating AVWS type 2. Hemostatic complications were observed in 4 of 12 (33%) patients with VWS and 3 of 6 (50%) patients without diagnostics and therapy., Conclusion: For children with moderate to severe PH, we recommend systematic analysis of von Willebrand variables, including multimer analysis, PFA-100 and platelet function testing. Awareness of the diagnosis "AVWS" and adequate therapy may help to prevent these patients from bleeding complications in case of surgical interventions or trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Wieland, Diekmann, Carlens, Hinze, Lambeck, Jack and Hansmann.)

Background: The age of patients referred for kidney transplantation has increased progressively. However, the precise influence of age on transplant outcomes is controversial., Methods: Etrospective 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., Results: We 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)., Conclusions: These results suggest that recipient age should not be considered itself as an absolute contraindication for kidney transplant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cuadrado-Payán, Montagud-Marrahi, Casals-Urquiza, del Risco-Zevallos, Rodríguez-Espinosa, Cacho, Arana, Cucchiari, Ventura-Aguiar, Revuelta, Piñeiro, Esforzado, Cofan, Bañon-Maneus, Campistol, Oppenheimer, Torregrosa and Diekmann.)

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., Methods: 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., Results: 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; P  = 0.032). Final IgG titer was significantly higher in patients with constant S-ELISpot positivity ( P  < 0.001)., Conclusions: 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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

The advances in transplant immunosuppression have reduced substantially the incidence of kidney graft rejection. In recent years, the focus has moved from preventing rejection to preventing the long-term consequences of long-standing immunosuppression, including nephrotoxicity induced by calcineurin inhibitors (CNI), as well as infectious and neoplastic complications. Since the appearance in the late 1990s of mTOR inhibitors (mTORi), these unmet needs in immunosuppression management could be addressed thanks to their benefits (reduced rate of viral infections and cancer). However, management of side effects can be troublesome and hands-on experience is needed. Here, we review all the available information about them. Thanks to all the basic, translational and clinical research achieved in the last twenty years, we now use mTORi as de novo immunosuppression in association with CNI. Another possibility is represented by the conversion of either CNI or mycophenolate (MPA) to an mTORi later on after transplantation in low-risk kidney transplant recipients.

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ventura-Aguiar, Bayés-Genís, Amor, Cuatrecasas, Diekmann, Esmatjes, Ferrer-Fàbrega, García-Criado, Musquera, Olivella, Palou, Paredes, Perea, Perez, Poch, Romano, Escarrabill.)

Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000-2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group ( n = 267), 10.8% of Celsior (CS) group ( n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group ( n = 7), and none for Institut Georges Lopez-1 (IGL-1) group ( n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 ( p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferrer-Fàbrega, Folch-Puy, Lozano, Ventura-Aguiar, Cárdenas, Paredes, García-Criado, Bombí, García-Pérez, López-Boado, Rull, Esmatjes, Ricart, Diekmann, Fondevila, Fernández-Cruz, Fuster and García-Valdecasas.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cucchiari, Tubita, Rovira, Ramirez-Bajo, Banon-Maneus, Lazo-Rodriguez, Hierro-Garcia, Borràs, Ventura-Aguiar, Piñeiro, Martorell, Peri, Musquera, Hertig, Oppenheimer, Campistol, Diekmann and Revuelta.)

Objectives: Interleukin-7 (IL-7) secures B cell maturation, regulatory T and natural killer (NK) cell survival, and homeostasis, all of which are important for beneficial immunomodulation in pulmonary arterial hypertension (PAH). However, the role and potential impact of IL-7, VEGF-C and the vascular injury markers ICAM-1, and VCAM-1 on the pathobiology and severity of PAH is unknown. Methods: EDTA blood was collected during cardiac catheterization from the superior vena cava (SVC), pulmonary artery (PA), and ascending aorta (AAO) in children with pulmonary hypertension (PH) [ n = 10; 9.1 (3.9-18.5) years] and non-PH controls [ n = 10; 10.5 (2.0-17.3) years]. Compartment-specific plasma concentrations of IL-7, VEGF-C, aldosterone, ICAM-1, and VCAM-1 were determined using Meso Scale Discovery's multi array technology and the LIAISON Aldosterone Assay. Results: Children with PH had approximately 50% lower IL-7 ( p < 0.01) and 59% lower VEGF-C plasma levels ( p < 0.001) in the SVC, PA, and AAO versus non-PH controls. IL-7 and VEGF-C concentrations negatively correlated with the pulmonary vascular resistance (PVR)/systemic vascular resistance (SVR) ratio (rho = -0.51 and r = -0.62, respectively). Central-venous IL-7 strongly positively correlated with VEGF-C ( r = 0.81). Most patients had a step down in ICAM-1 and VCAM-1 plasma concentrations across the pulmonary circulation and both ICAM-1 and VCAM-1 transpulmonary gradients negatively correlated with invasive hemodynamics. Conclusion: This manuscript is the first report on decreased circulating IL-7 and VEGF-C plasma concentrations in human PAH and their inverse correlations with invasive surrogates of PAH severity. Additional and larger studies are needed to explore the role of the immune-modulatory IL-7 and VEGF-C in pediatric and adult PAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Diekmann, Legchenko, Chouvarine, Lichtinghagen, Bertram, Happel and Hansmann.)

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 < 0.001). Besides standard ECD classification, dialysis vintage, older age, and previous cardiovascular recipient events together with low class-II-HLA match, long cold ischemia time and combining a diabetic donor with a cDCD predicted graft loss (C-Index 0.715, 95% CI 0.675-0.755). External validation showed good prediction accuracy (C-Index 0.697, 95%CI 0.643-0.741). Recipient older age, male gender, dialysis vintage, previous cardiovascular events, and receiving a cDCD independently predicted patient death. Benefit/risk assessment of undergoing KT was compared with concurrent waitlisted candidates, and despite the fact that undergoing KT outperformed remaining waitlisted, remarkably high mortality rates were predicted if KT was undertaken under the worst risk-prediction model. Strategies to increase the donor pool, including cDCD transplants with highly expanded donor and recipient candidates, should be performed with caution., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Piñeiro, Montagud-Marrahi, Ríos, Ventura-Aguiar, Cucchiari, Revuelta, Lozano, Cid, Cofan, Esforzado, Palou, Oppenheimer, Campistol, Bayés-Genís, Rovira and Diekmann.)

Background: Calciphylaxis is not uniquely observed in uraemic patients, as some cases have also been reported in patients with normal renal function or moderate chronic kidney disease (CKD), in association with severe vasculopathy or systemic inflammation. A particular subset worthy of studying is represented by those patients who develop calciphylaxis after kidney transplantation (KT)., Methods: Analysis of the local series of calciphylaxis after KT ( n  = 14) along with all the other cases reported in the literature from 1969 to 2019 ( n  = 31), for a total population of 45 patients, is presented. Demographic data, CKD history, risk factors, immunosuppression, clinical presentation and management have been analysed both as a whole and according to the time period (before or after the year 2000)., Results: Calciphylaxis developed during the first year after KT in 43.2% of patients and median (interquartile range) creatinine at diagnosis was 2.4 (1.25-4.64) mg/dL. The most frequent presentation included distal purpura or ulcers in one-third of cases and 39.1% of patients were receiving vitamin K antagonists. PTH values were above 500 pg/mL and below 100 pg/mL in 50.0% and 25.0% of cases, respectively. Whole population mortality was 55.6%. As expected, clinical presentation, immunosuppression and management varied depending on the time period. Patients diagnosed after 2000 were older, with longer dialysis vintage, and treatment was usually multimodal; on the contrary, in patients diagnosed before 2000, parathyroidectomy was the treatment of choice in 61.9% of cases., Conclusions: Calciphylaxis can still occur after KT, in many cases during the first year and in patients with a good renal function. Risk factors and management varied according to the time period studied., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

We aimed to ascertain the interaction and effects of combined reactivations of BK virus and cytomegalovirus on kidney graft function. All consecutive kidney transplant recipients (KTR) between 2003 and 2016 were included. Of 1976 patients who received a kidney transplant, 23 (1.2%) presented BKV-associated nephropathy (BKVAN). Factors independently associated with BKVAN were diabetes mellitus (odds ratios (OR) 3.895%, confidence intervals (CI) (1.4-10.5)), acute allograft rejection (OR 2.8 95%, CI (1.1-7.6)) and nephrostomy requirement (OR 4.195%, CI (1.3-13)). Cytomegalovirus infection was diagnosed in 19% of KTR patients. Recipients with BKVAN presented more frequently with cytomegalovirus (CMV) infection compared to patients without BKVAN (39% vs. 19%, p = 0.02). Acute allograft rejection (OR 2.95%, CI (1.4-2.4)) and nephrostomy requirement (OR 2.95%, CI (1.2-3)) were independently associated with CMV infection. Sixteen patients (69%) with BKVAN had graft dysfunction at one-year post-transplant and eight of them (35%) lost their graft. Patients presenting with BKVAN and graft loss presented more frequently a cytomegalovirus infection (OR 2.295%, CI (1.3-4.3)). In conclusion, we found a relation between CMV infection and graft loss in patients presenting BKVAN, suggesting that patients with CMV reactivation should be actively screened for BKV.

Pulmonary arterial hypertension (PAH) is a progressive condition with an unmet need for early diagnosis, better monitoring, and risk stratification. The receptor for advanced glycation end products (RAGE) is activated in response to hypoxia and vascular injury, and is associated with inflammation, cell proliferation and migration in PAH. For the adult cohort, we recruited 120 patients with PAH, 83 with idiopathic PAH (IPAH) and 37 with connective tissue disease-associated PAH (CTD-PAH), and 48 controls, and determined potential plasma biomarkers by enzyme-linked immunoassay. The established heart failure marker NTproBNP and IL-6 plasma levels were several-fold higher in both adult IPAH and CTD-PAH patients versus controls. Plasma soluble RAGE (sRAGE) was elevated in IPAH patients (3044 ± 215.2 pg/mL) and was even higher in CTD-PAH patients (3332 ± 321.6 pg/mL) versus controls (1766 ± 121.9 pg/mL; p < 0.01). All three markers were increased in WHO functional class II+III PAH versus controls ( p < 0.001). Receiver-operating characteristic analysis revealed that sRAGE has diagnostic accuracy comparable to prognostic NTproBNP, and even outperforms NTproBNP in the distinction of PAH FC I from controls. Lung tissue RAGE expression was increased in IPAH versus controls (mRNA) and was located predominantly in the PA intima, media, and inflammatory cells in the perivascular space (immunohistochemistry). In the pediatric cohort, plasma sRAGE concentrations were higher than in adults, but were similar in PH (n = 10) and non-PH controls (n = 10). Taken together, in the largest adult sRAGE PAH study to date, we identify plasma sRAGE as a sensitive and accurate PAH biomarker with better performance than NTproBNP in the distinction of mild PAH from controls.

According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. At baseline, 31 patients (20.9%) had either IgM/IgG or ELISpot positivity and were considered to be SARS-CoV-2-pre-immunized, while 117 (79.1%) patients had no signs of either cellular or humoral response and were considered SARS-CoV-2-naïve. After vaccination, naïve patients who developed either humoral or cellular response were finally 65.0%, of which 29.9% developed either IgG or IgM and 35.0% S-ELISpot positivity. Factors associated with vaccine unresponsiveness were diabetes and treatment with antithymocytes globulins during the last year. Side effects were consistent with that of the pivotal trial and no DSAs developed after vaccination. In conclusion, mRNA-1273 SARS-CoV-2 vaccine elicits either cellular or humoral response in almost two thirds of KTRs., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Since the early days of Dirac flux quantization, magnetic monopoles have been sought after as a potential corollary of quantized electric charge. As opposed to magnetic monopoles embedded into the theory of electromagnetism, Weyl semimetals (WSM) exhibit Berry flux monopoles in reciprocal parameter space. As a function of crystal momentum, such monopoles locate at the crossing point of spin-polarized bands forming the Weyl cone. Here, we report momentum-resolved spectroscopic signatures of Berry flux monopoles in TaAs as a paradigmatic WSM. We carried out angle-resolved photoelectron spectroscopy at bulk-sensitive soft X-ray energies (SX-ARPES) combined with photoelectron spin detection and circular dichroism. The experiments reveal large spin- and orbital-angular-momentum (SAM and OAM) polarizations of the Weyl-fermion states, resulting from the broken crystalline inversion symmetry in TaAs. Supported by first-principles calculations, our measurements image signatures of a topologically non-trivial winding of the OAM at the Weyl nodes and unveil a chirality-dependent SAM of the Weyl bands. Our results provide directly bulk-sensitive spectroscopic support for the non-trivial band topology in the WSM TaAs, promising to have profound implications for the study of quantum-geometric effects in solids.

In the context of the coronavirus disease 2019 (COVID-19) pandemic, we aimed to evaluate the impact of anti-cytokine therapies (AT) in kidney transplant recipients requiring hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is an observational retrospective study, which included patients from March to May 2020. An inverse probability of treatment weighting from a propensity score to receive AT was used in all statistical analyses, and we applied a bootstrap procedure in order to calculate an estimation of the 2.5th and 97.5th percentiles of odds ratio (OR). outcomes were measured using an ordinal scale determination (OSD). A total of 33 kidney recipients required hospitalization and 54% of them received at least one AT, mainly tocilizumab (42%), followed by anakinra (12%). There was no statistical effect in terms of intensive care unit (ICU) admission, respiratory secondary infections (35% vs. 7%) or mortality (16% vs. 13%) comparing patients that received AT with those who did not. Nevertheless, patients who received AT presented better outcomes during hospitalization in terms of OSD ≥5 ((OR 0.31; 2.5th, 97.5th percentiles (0.10; 0.72)). These analyses indicate, as a plausible hypothesis, that the use of AT in kidney transplant recipients presenting with COVID-19 could be beneficial, even though multicenter randomized control trials using these therapies in transplanted patients are needed.