Amyloid brain-dedicated PET images can diagnose Alzheimer's pathology with Centiloid Scale.

PURPOSE: To evaluate whether the Centiloid Scale may be used to diagnose Alzheimer's Disease (AD) pathology effectively with the only use of amyloid PET imaging modality from a brain-dedicated PET scanner. METHODS: This study included 26 patients with amyloid PET images with 3 different radiotracers. All patients were acquired both on a PET/CT and a brain-dedicated PET scanner (CareMiBrain, CMB), from which 4 different reconstructions were implemented. A new pipeline was proposed and used for the PET image analysis based on the original Centiloid Scale processing pipeline, but with only PET images. The Youden's Index was employed to calculate the optimal cutoffs for diagnosis and evaluated by the AUC, accuracy, precision, and recall metrics. RESULTS: The Centiloid Scale (CL) processing pipeline was validated with and without the use of MR images. The CL cutoffs for AD pathology diagnosis on the PET/CT and the 4 CMB reconstructions were 34.4 ±â€¯2.2, 43.5 ±â€¯3.5, 51.9 ±â€¯12.5, 57.5 ±â€¯6.8 and 41.8 ±â€¯1.2 respectively. Overall, for these cutoffs all metrics obtained the maximum score. CONCLUSION: The Centiloid scale applied to PET images allows for AD pathology diagnosis. The CMB scanner can be used with the Centiloid scale to automatically assist in the diagnosis of AD pathology, relieving the large burden of neurodegenerative diseases on a traditional PET/CT.

Relationship between neuroimaging and emotion recognition in mild cognitive impairment patients.

OBJECTIVE: Dementia is a major public health problem with high needs for early detection, efficient treatment, and prognosis evaluation. Social cognition impairment could be an early dementia indicator and can be assessed with emotion recognition evaluation tests. The purpose of this study is to investigate the link between different brain imaging modalities and cognitive status in Mild Cognitive Impairment (MCI) patients, with the goal of uncovering potential physiopathological mechanisms based on social cognition performance. METHODS: The relationship between the Reading the Mind in the Eyes Test (RMET) and some clinical and biochemical variables ([18 F]FDG PET-CT and anatomical MR parameters, neuropsychological evaluation, and CSF biomarkers) was studied in 166 patients with MCI by using a correlational approach. RESULTS: The RMET correlated with neuropsychological variables, as well as with structural and functional brain parameters obtained from the MR and FDG-PET imaging evaluation. However, significant correlations between the RMET and CSF biomarkers were not found. DISCUSSION: Different neuroimaging parameters were found to be related to an emotion recognition task in MCI. This analysis identified potential minimally-invasive biomarkers providing some knowledge about the physiopathological mechanisms in MCI.

Impact of a Cardiogenic Shock Program on Mortality in a Non-Transplant Hospital.

INTRODUCTION: Cardiogenic shock is associated with high in-hospital morbidity and mortality. Improvements in this care process could lead to better outcomes. METHODS: This retrospective study of patients with cardiogenic shock compared two periods: no specific program to address cardiogenic shock and implementation of a cardiogenic shock program. This program included the establishment of a multidisciplinary team (shock team), early alert to the transplant hospital, initiation of a ventricular assist extracorporeal membrane oxygenation (ECMO) program, and extension of continuous care by acute cardiovascular care specialists. The primary objective was to analyse whether there were differences between in-hospital mortality and mortality during follow-up. Predictors of in-hospital mortality were examined as a secondary objective. RESULTS: A total of 139 patients were enrolled: 69 of them in the previous period and 70 in the cardiogenic shock program period. There was a significant reduction in in-hospital mortality (55.1% vs 37.1%; p=0.03) and mortality during follow-up (62.7% vs 44.6%; p=0.03) in the second period. Diabetes mellitus, ejection fraction, out-of-hospital cardiac arrest, and implementation of the cardiogenic shock program were independent predictors of in-hospital mortality. CONCLUSIONS: The implementation of a comprehensive cardiogenic shock program in a non-transplanting hospital improved in-hospital and follow-up mortality of patients in cardiogenic shock.

Objective Image Quality Comparison Between Brain-Dedicated PET and PET/CT Scanners.

As part of a clinical validation of a new brain-dedicated PET system (CMB), image quality of this scanner has been compared to that of a whole-body PET/CT scanner. To that goal, Hoffman phantom and patient data were obtined with both devices. Since CMB does not use a CT for attenuation correction (AC) which is crucial for PET images quality, this study includes the evaluation of CMB PET images using emission-based or CT-based attenuation maps. PET images were compared using 34 image quality metrics. Moreover, a neural network was used to evaluate the degree of agreement between both devices on the patients diagnosis prediction. Overall, results showed that CMB images have higher contrast and recovery coefficient but higher noise than PET/CT images. Although SUVr values presented statistically significant differences in many brain regions, relative differences were low. An asymmetry between left and right hemispheres, however, was identified. Even so, the variations between the two devices were minor. Finally, there is a greater similarity between PET/CT and CMB CT-based AC PET images than between PET/CT and the CMB emission-based AC PET images.

Chelation Therapy Associated with Antioxidant Supplementation Can Decrease Oxidative Stress and Inflammation in Multiple Sclerosis: Preliminary Results.

An imbalance of oxy-inflammation status has been involved in axonal damage and demyelination in multiple sclerosis (MS). The aim of this study was to investigate the efficacy of an antioxidant treatment (calcium disodium ethylenediaminetetracetic acid-EDTA) chelation therapy associated with a micronutrient complex in MS patients. A total of 20 MS patients and 20 healthy subjects, enrolled as a control group (CTR), were recruited. We measured the plasma ROS production and total antioxidant capacity (TAC) by a direct assessment using Electron Paramagnetic Resonance; activities of the antioxidant system (thiols' redox status and enzymes); and the urinary presence of biomarkers of oxidative stress by immunoenzymatic assays. We also evaluated the levels of inflammation by plasmatic cytokines (TNFα, IL-1ß, and IL-6) and assessed the sICAM levels, as well as the nitric oxide (NO) catabolism and transthyretin (TTR) concentration. Comparing CTR and MS, in the latter ROS production, oxidative damage, inflammatory biomarkers, and NO metabolite concentrations results were significantly higher, while TAC was significantly lower. Treatment in MS induced significant (p < 0.05) down-regulating of pro-inflammatory sICAM1, TNF-α, IL6, as well as biomarkers of lipid peroxidation and DNA damage production. The protective effect exhibited may occur by decreasing ROS production and increasing antioxidant capacity, turning into a more reduced thiols' status.

Implant-supported full-arch rehabilitation with immediate loading using two different digital impression techniques: a case report with 2-year follow-up.

Immediate full-arch loading is a highly complex and technique-sensitive procedure. Digital impression techniques aim to replace conventional analog systems to carry out dental treatments in a more predictive, safer, and less time-consuming way. This case report describes a patient with a guarded periodontal prognosis, who was rehabilitated with implant-supported fixed prostheses after full-mouth extractions. Immediate full-arch loading was performed by means of two digital impression systems: photogrammetric technology with PIC dental in the maxillary arch, and MedicalFit in the mandible. Immediate provisional prostheses in acrylic resin (polymethyl methacrylate) were milled and placed within 12 hours after implant placement surgeries. Both provisional structures fitted properly providing adequate esthetics and function. After the implant osseointegration period, final digital impressions were registered, and definitive zirconia full-arch implant-supported prostheses were delivered. The 24-month follow-up did not show biologic or mechanical complications.

Targeting of low ALK antigen density neuroblastoma using AND logic-gate engineered CAR-T cells.

BACKGROUND AIMS: The targeting of solid cancers with chimeric antigen receptor (CAR) T cells faces many technological hurdles, including selection of optimal target antigens. Promising pre-clinical and clinical data of CAR T-cell activity have emerged from targeting surface antigens such as GD2 and B7H3 in childhood cancer neuroblastoma. Anaplastic lymphoma kinase (ALK) is expressed in a majority of neuroblastomas at low antigen density but is largely absent from healthy tissues. METHODS: To explore an alternate target antigen for neuroblastoma CAR T-cell therapy, the authors generated and screened a single-chain variable fragment library targeting ALK extracellular domain to make a panel of new anti-ALK CAR T-cell constructs. RESULTS: A lead novel CAR T-cell construct was capable of specific cytotoxicity against neuroblastoma cells expressing low levels of ALK, but with only weak cytokine and proliferative T-cell responses. To explore strategies for amplifying ALK CAR T cells, the authors generated a co-CAR approach in which T cells received signal 1 from a first-generation ALK construct and signal 2 from anti-B7H3 or GD2 chimeric co-stimulatory receptors. The co-CAR approach successfully demonstrated the ability to avoid targeting single-antigen-positive targets as a strategy for mitigating on-target off-tumor toxicity. CONCLUSIONS: These data provide further proof of concept for ALK as a neuroblastoma CAR T-cell target.

Neuron Protection by EDTA May Explain the Successful Outcomes of Toxic Metal Chelation Therapy in Neurodegenerative Diseases.

Many mechanisms have been related to the etiopathogenesis of neurodegenerative diseases (NDs) such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. In this context, the detrimental role of environmental agents has also been highlighted. Studies focused on the role of toxic metals in the pathogenesis of ND demonstrate the efficacy of treatment with the chelating agent calcium disodium ethylenediaminetetraacetic acid (EDTA) in eliminating toxic metal burden in all ND patients, improving their symptoms. Lead, cadmium, aluminum, nickel, and mercury were the most important toxic metals detected in these patients. Here, I provide an updated review on the damage to neurons promoted by toxic metals and on the impact of EDTA chelation therapy in ND patients, along with the clinical description of a representative case.

A novel anti-B7-H3 chimeric antigen receptor from a single-chain antibody library for immunotherapy of solid cancers.

B7-H3 (CD276) has emerged as a target for cancer immunotherapy by virtue of consistent expression in many malignancies, relative absence from healthy tissues, and an emerging role as a driver of tumor immune inhibition. Recent studies have reported B7-H3 to be a suitable target for chimeric antigen receptor-modified T cell (CAR-T) therapy using CARs constructed from established anti-B7-H3 antibodies converted into single-chain Fv format (scFv). We constructed and screened binders in an scFv library to generate a new anti-B7-H3 CAR-T with favorable properties. This allowed access to numerous specificities ready formatted for CAR evaluation. Selected anti-human B7-H3 scFvs were readily cloned into CAR-T and evaluated for anti-tumor reactivity in cytotoxicity, cytokine, and proliferation assays. Two binders with divergent complementarity determining regions were found to show optimal antigen-specific cytotoxicity and cytokine secretion. One binder in second-generation CD28-CD3ζ CAR format induced sustained in vitro proliferation on repeat antigen challenge. The lead candidate CAR-T also demonstrated in vivo activity in a resistant neuroblastoma model. An empirical approach to B7-H3 CAR-T discovery through screening of novel scFv sequences in CAR-T format has led to the identification of a new construct with sustained proliferative capacity warranting further evaluation.

Live donor kidney transplantation. Situation analysis and roadmap.

Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spainhave adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.

Interacciones vinculares mamá-bebé: impacto de las creencias maternas / Mother and baby interactions: Impact of maternal beliefs / Interações entre a mãe e o bebê: impacto das crenças maternas

Resumen (analítico) Las ideas parentales sobre el desarrollo infantil pueden guiarse por falsas creencias e influir en las interacciones tempranas. En este trabajo se estudian las ideas e interacciones en la relación mamá adolescente-bebé. La maternidad adolescente implica riesgos vinculares, llegando incluso hasta el maltrato. Se clasificó a las madres en modernas (activas) o tradicionales (pasivas), según la estimulación y acompañamiento del niño/a. Se evaluaron 145 díadas en los primeros dos años de vida. Los resultados indican peores interacciones en las madres tradicionales, siendo significativos en los contactos cara a cara, las interacciones táctiles y la función de sostén materna. El patrón de apego también se presenta más inseguro. Estos resultados permiten organizar programas de capacitación parental apuntando a la deconstrucción de ideas erróneas sobre el desarrollo y orientando interacciones saludables.

Abstract (analytical) Parental ideas about child development can be guided by false beliefs and influence early interactions. Adolescent mother and baby bonding ideas and interactions are related in this study. Adolescent motherhood implies additional risks, which even include abuse. Mothers are classified as modern -active- or traditional -passive-, based on the stimulation and accompaniment they provide to their child. 145 dyads are evaluated in the first two years of life. The results indicate worse interactions among traditional mothers, based on face-to-face contact, tactile interactions and the maternal support function. The attachment pattern is also more insecure. These results make it possible to organize parental training programs aimed at the deconstruction of erroneous ideas about development and guiding healthy interactions.

Resumo (analítico) As ideias dos pais sobre o desenvolvimento infantil podem ser guiadas por falsas crenças e influenciar as interações iniciais. As idéias e interações do vínculo mãe-bebê adolescente estão relacionados aqui. A maternidade na adolescência implica riscos relacionados, chegando mesmo ao abuso. As mães são classificadas em modernas -ativas- ou tradicionais -passivas-, de acordo com o estímulo e o acompanhamento do filho. 145 díades são avaliadas nos primeiros dois anos de vida. Os resultados indicam piores interações nas mães tradicionais, sendo significativos nos contatos face a face, nas interações táteis e na função de apoio materno. O padrão de apego também é mais inseguro. Esses resultados possibilitam a organização de programas de treinamento parental com o objetivo de desconstruir ideias errôneas sobre o desenvolvimento e orientar interações saudáveis.

Association of obesity with 3-month mortality in kidney failure patients with COVID-19.

Background: In the general population with coronavirus disease 2019 (COVID-19), obesity is associated with an increased risk of mortality. Given the typically observed obesity paradox among patients on kidney function replacement therapy (KFRT), especially dialysis patients, we examined the association of obesity with mortality among dialysis patients or living with a kidney transplant with COVID-19. Methods: Data from the European Renal Association COVID-19 Database (ERACODA) were used. KFRT patients diagnosed with COVID-19 between 1 February 2020 and 31 January 2021 were included. The association of Quetelet's body mass index (BMI) (kg/m2), divided into: <18.5 (lean), 18.5-24.9 (normal weight), 25-29.9 (overweight), 30-34.9 (obese I) and ≥35 (obese II/III), with 3-month mortality was investigated using Cox proportional-hazards regression analyses. Results: In 3160 patients on KFRT (mean age: 65 years, male: 61%), 99 patients were lean, 1151 normal weight (reference), 1160 overweight, 525 obese I and 225 obese II/III. During follow-up of 3 months, 28, 20, 21, 23 and 27% of patients died in these categories, respectively. In the fully adjusted model, the hazard ratios (HRs) for 3-month mortality were 1.65 [95% confidence interval (CI): 1.10, 2.47], 1 (ref.), 1.07 (95% CI: 0.89, 1.28), 1.17 (95% CI: 0.93, 1.46) and 1.71 (95% CI: 1.27, 2.30), respectively. Results were similar among dialysis patients (N = 2343) and among those living with a kidney transplant (N = 817) (Pinteraction = 0.99), but differed by sex (Pinteraction = 0.019). In males, the HRs for the association of aforementioned BMI categories with 3-month mortality were 2.07 (95% CI: 1.22, 3.52), 1 (ref.), 0.97 (95% CI: 0.78. 1.21), 0.99 (95% CI: 0.74, 1.33) and 1.22 (95% CI: 0.78, 1.91), respectively, and in females corresponding HRs were 1.34 (95% CI: 0.70, 2.57), 1 (ref.), 1.31 (95% CI: 0.94, 1.85), 1.54 (95% CI: 1.05, 2.26) and 2.49 (95% CI: 1.62, 3.84), respectively. Conclusion: In KFRT patients with COVID-19, on dialysis or a kidney transplant, obesity is associated with an increased risk of mortality at 3 months. This is in contrast to the obesity paradox generally observed in dialysis patients. Additional studies are required to corroborate the sex difference in the association of obesity with mortality.

Artificial Intelligence on FDG PET Images Identifies Mild Cognitive Impairment Patients with Neurodegenerative Disease.

The purpose of this project is to develop and validate a Deep Learning (DL) FDG PET imaging algorithm able to identify patients with any neurodegenerative diseases (Alzheimer's Disease (AD), Frontotemporal Degeneration (FTD) or Dementia with Lewy Bodies (DLB)) among patients with Mild Cognitive Impairment (MCI). A 3D Convolutional neural network was trained using images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The ADNI dataset used for the model training and testing consisted of 822 subjects (472 AD and 350 MCI). The validation was performed on an independent dataset from La Fe University and Polytechnic Hospital. This dataset contained 90 subjects with MCI, 71 of them developed a neurodegenerative disease (64 AD, 4 FTD and 3 DLB) while 19 did not associate any neurodegenerative disease. The model had 79% accuracy, 88% sensitivity and 71% specificity in the identification of patients with neurodegenerative diseases tested on the 10% ADNI dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.90. On the external validation, the model preserved 80% balanced accuracy, 75% sensitivity, 84% specificity and 0.86 AUC. This binary classifier model based on FDG PET images allows the early prediction of neurodegenerative diseases in MCI patients in standard clinical settings with an overall 80% classification balanced accuracy.

Clinical, Functional, and Mental Health Outcomes in Kidney Transplant Recipients 3 Months After a Diagnosis of COVID-19.

BACKGROUND: Kidney transplant patients are at high risk for coronavirus disease 2019 (COVID-19)-related mortality. However, limited data are available on longer-term clinical, functional, and mental health outcomes in patients who survive COVID-19. METHODS: We analyzed data from adult kidney transplant patients in the European Renal Association COVID-19 Database who presented with COVID-19 between February 1, 2020, and January 31, 2021. RESULTS: We included 912 patients with a mean age of 56.7 (±13.7) y. 26.4% were not hospitalized, 57.5% were hospitalized without need for intensive care unit (ICU) admission, and 16.1% were hospitalized and admitted to the ICU. At 3 mo follow-up survival was 82.3% overall, and 98.8%, 84.2%, and 49.0%, respectively, in each group. At 3 mo follow-up biopsy-proven acute rejection, need for renal replacement therapy, and graft failure occurred in the overall group in 0.8%, 2.6%, and 1.8% respectively, and in 2.1%, 10.6%, and 10.6% of ICU-admitted patients, respectively. Of the surviving patients, 83.3% and 94.4% reached their pre-COVID-19 physician-reported functional and mental health status, respectively, within 3 mo. Of patients who had not yet reached their prior functional and mental health status, their treating physicians expected that 79.6% and 80.0%, respectively, still would do so within the coming year. ICU admission was independently associated with a low likelihood to reach prior functional and mental health status. CONCLUSIONS: In kidney transplant recipients alive at 3-mo follow-up, clinical, physician-reported functional, and mental health recovery was good for both nonhospitalized and hospitalized patients. Recovery was, however, less favorable for patients who had been admitted to the ICU.

Performance of Coronary Angiography in the Detection of Coronary Artery Disease in Patients with Systolic Left Ventricular Dysfunction and No Prior Ischemic Heart Disease.

The diagnosis of ischemic cardiomyopathy is not well established. Our objective is to determine predictive variables of coronary disease in unselected patients with ventricular dysfunction. This study is a retrospective cohort study of consecutive patients with left ventricular dysfunction and no known history of ischemic heart disease. We analyse the demographic variables, clinical data, electrocardiogram, and echocardiogram that are associated with the presence of coronary stenosis on coronary angiography. A total of 536 patients with left ventricular dysfunction were studied, with 135 (25.2%) of them having significant coronary lesions. In the multivariate logistic regression analysis, age ≤ 50 years, female gender, and the presence of atrial fibrillation on the electrocardiogram (ECG) were predictors of the absence of coronary lesions. Diabetes, hypercholesterolemia, the existence of Q waves in the ECG, and segmental alterations in contractility in the echocardiogram were predictors of coronary heart disease (C-Statistics 0.771, 95% CI 0.727 to 0.814). The information obtained from the clinical history, the ECG, and the echocardiogram of patients with ventricular dysfunction allows us to select subjects in whom coronary angiography has shown poor performance in diagnosing coronary disease.

Late-onset methylmalonic acidemia and homocysteinemia / Acidemia metilmalónica y homocisteinemia de inicio tardío

Introduction: cobalamin C (Cbl C) deficiency is the most common defect in intracellular cobalamin metabolism, associated with methylmalonic acidemia and homocystinuria. Its late clinical presentation is heterogeneous and may lead to a diagnostic delay. Case report: we report the case of a 45-year-old man with a 20-year history of chronic kidney disease and recently diagnosed spastic paraparesis, both of unknown origin. Metabolic studies revealed elevated levels of homocysteine and methylmalonic acid in the blood and urine. A genetic study confirmed cobalamin C deficiency. Treatment with hydroxocobalamin, betaine, carnitine, and folic acid was started. The patient eventually received a kidney transplant. Discussion: early diagnosis and appropriate treatment improve the clinical evolution of patients with Cbl C deficiency. Determination of homocysteine, organic acids, and other amino acids should be included in the differential diagnosis of patients with nephrological-neurological symptoms without a clear etiology. (AU)

Introducción: la deficiencia de cobalamina C (Cbl C) es el defecto más común en el metabolismo intracelular de la cobalamina, asociado a acidemia metilmalónica y homocistinuria. Su presentación clínica tardía es heterogénea y puede llevar a un retraso en el diagnóstico. Caso clínico: presentamos el caso de un varón de 45 años con 20 años de evolución de enfermedad renal crónica y paraparesia espástica de reciente diagnóstico, ambos de origen desconocido. Los estudios metabólicos revelaron niveles elevados de homocisteína y ácido metilmalónico en sangre y orina. El estudio genético confirmó el déficit de cobalamina C. Se inició tratamiento con hidroxocobalamina, betaína, carnitina y ácido fólico. El paciente pudo recibir un trasplante renal. Discusión: el establecimiento de un diagnóstico precoz y un tratamiento adecuado mejora la evolución clínica de los pacientes con déficit de Cbl C. La determinación de homocisteína, ácidos orgánicos y otros aminoácidos debe incluirse en el diagnóstico diferencial de los pacientes con síntomas nefrológico-neurológicos sin una etiología clara. (AU)

Live donor kidney transplantation. Situation analysis and roadmap. / Trasplante renal de donante vivo. Análisis de situación y hoja de ruta.

Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spain have adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.

COVID-19 in Solid Organ Transplant Recipients in Spain Throughout 2020: Catching the Wave?

BACKGROUND: Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) across different pandemic waves. METHODS: In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management, and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020. RESULTS: Of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second periods, respectively. Compared with the first wave, recipients in the second were younger (median: 63 y [interquartile range, IQR: 53-71] versus 59 y [IQR: 49-68]; P < 0.001) and less likely to receive anti-severe acute respiratory syndrome coronavirus 2 drugs (81.8% versus 8.1%; P < 0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; P = 0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; P < 0.001). Hospital admission (86.7% versus 58.1%; P < 0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; P < 0.001), and case-fatality rate (25.8% versus 16.7%; P < 0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% confidence interval [CI], 1.12-1.93; P = 0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI, 0.73-1.29; P = 0.873) or intensive care unit admission (OR: 0.65; 95% CI, 0.35-1.18; P = 0.157). CONCLUSIONS: We observed meaningful changes in demographics, therapeutic approaches, level of care, and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.

Late-onset methylmalonic acidemia and homocysteinemia.

INTRODUCTION: Introduction: cobalamin C (Cbl C) deficiency is the most common defect in intracellular cobalamin metabolism, associated with methylmalonic acidemia and homocystinuria. Its late clinical presentation is heterogeneous and may lead to a diagnostic delay. Case report: we report the case of a 45-year-old man with a 20-year history of chronic kidney disease and recently diagnosed spastic paraparesis, both of unknown origin. Metabolic studies revealed elevated levels of homocysteine and methylmalonic acid in the blood and urine. A genetic study confirmed cobalamin C deficiency. Treatment with hydroxocobalamin, betaine, carnitine, and folic acid was started. The patient eventually received a kidney transplant. Discussion: early diagnosis and appropriate treatment improve the clinical evolution of patients with Cbl C deficiency. Determination of homocysteine, organic acids, and other amino acids should be included in the differential diagnosis of patients with nephrological-neurological symptoms without a clear etiology.

INTRODUCCIÓN: Introducción: la deficiencia de cobalamina C (Cbl C) es el defecto más común en el metabolismo intracelular de la cobalamina, asociado a acidemia metilmalónica y homocistinuria. Su presentación clínica tardía es heterogénea y puede llevar a un retraso en el diagnóstico. Caso clínico: presentamos el caso de un varón de 45 años con 20 años de evolución de enfermedad renal crónica y paraparesia espástica de reciente diagnóstico, ambos de origen desconocido. Los estudios metabólicos revelaron niveles elevados de homocisteína y ácido metilmalónico en sangre y orina. El estudio genético confirmó el déficit de cobalamina C. Se inició tratamiento con hidroxocobalamina, betaína, carnitina y ácido fólico. El paciente pudo recibir un trasplante renal. Discusión: el establecimiento de un diagnóstico precoz y un tratamiento adecuado mejora la evolución clínica de los pacientes con déficit de Cbl C. La determinación de homocisteína, ácidos orgánicos y otros aminoácidos debe incluirse en el diagnóstico diferencial de los pacientes con síntomas nefrológico-neurológicos sin una etiología clara.