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Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy and in those with a kidney transplant. Since the publication of the original Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2008, major advances in HCV management, particularly with the advent of direct-acting antiviral therapies, have now made the cure of HCV possible in CKD patients. In addition, diagnostic techniques have evolved to enable the noninvasive diagnosis of liver fibrosis. Therefore, the Work Group undertook a comprehensive review and update of the KDIGO HCV in CKD Guideline. This Executive Summary highlights key aspects of the guideline recommendations.

La diversidad e inclusión son conceptos que están tomando un enorme protagonismo en la gestión empresarial, y se está haciendo, principalmente, con el soporte ofrecido por la responsabilidad social empresarial. Así pues, las empresas, aunque no todas, están adoptando medidas favorecedoras de la diversidad en sus plantillas, lo que tiene como antesala la inclusión de los colectivos desfavorecidos en el mercado de trabajo. De ellos, en este estudio se centra la atención en las personas LGTBI, cuya discriminación laboral, de conformidad con los datos, es elevada y, en consecuencia, preocupante, sobre todo para las personas trans. Partiendo de la realidad de este colectivo y de la configuración jurídica de la causa o de las causas de esta discriminación, se analizan los informes y documentos empresariales —de grandes empresas y de multinacionales al ser las que están poniendo en práctica estas estrategias— que van a permitir conocer si, en efecto, se está favoreciendo la lucha contra la discriminación, la inclusión laboral y el respeto y el fomento de la diversidad de las plantillas como instrumentos, primero, de desarrollo personal y, segundo, profesional de las personas LGTBI. De dicho análisis se han extraído las oportunas conclusiones, que no son particularmente esperanzadoras, ya que esta pretendida diversidad e inclusión, al menos para los/as trabajadores/as LGTBI, es más formal que real, al responder, con más frecuencia de la deseada, a objetivos empresariales —económicos y de imagen corporativa— más que de normalización laboral de este colectivo.

The management of facial paralysis following skull base surgery is complex and requires multidisciplinary intervention. This review shows the experience of a facial nerve (FN) unit in a tertiary university referral center. A multidisciplinary approach has led to the breaking of some old treatment paradigms. An overview of five FN scenarios is presented. For each setting a contemporary approach is proposed in contrast to the established approach. 1) For patients with an anatomically preserved FN with no electrical response at the end of surgery for vestibular schwannoma, watchful waiting is usually advocated. In these cases, reinforcement with an interposed nerve graft is recommended. 2) In cases of epineural FN repair, with or without grafting, and a poor expected prognosis, an additional masseter-to-facial transfer is recommended. 3) FN transfer, mainly hypoglossal-to-facial and masseter-to facial, are usually chosen based on the surgeons' preference. The choice should be based on clinical factors. A combination of techniques improves the outcome in selected patients. 4) FN reconstruction following malignant tumors requires a combination of parotid and temporal bone surgery, involving different specialists. This collaboration is not always consistent. Exposure of the mastoid FN is recommended for lesions involving the stylomastoid foramen, as well as intraoperative FN reconstruction. 5) In patients with incomplete facial paralysis and a skull base tumor requiring additional surgery, consider an alternative reinnervation procedure, "take the FN out of the equation" before tumor resection. In summary, to achieve the best results in complex cases of facial paralysis, a multidisciplinary approach is recommended.

Resumen La paralisis de Bell es la forma mas comun de paresia o paralisis facial. Sin embargo, no todos los pacientes con paralisis facial tienen una paralisis de Bell. Otras causas frecuentes incluyen las secuelas del tratamiento del neurinoma del viii par, el cancer de cabeza y cuello, la iatrogenia, el zoster otico y los traumatismos. El abordaje de cada una de estas situaciones es totalmente diferente. El objetivo de esta guia es servir de consejo para el tratamiento y el seguimiento de los pacientes con paralisis facial. Nuestra idea es que la guia sea practica, haciendo hincapie en recomendaciones efectivas y utiles en el manejo diario de los pacientes. Esta guia ha sido promovida por la Sociedad Espanola de ORL y escrita por medicos con experiencia en la enfermedad del nervio facial, incluyendo al menos un especialista de cada comunidad autonoma. Redactada en un formato de preguntas y respuestas, incluye 56 cuestiones relevantes relacionadas con el nervio facial.

Bell's palsy is the most common diagnosis associated with facial nerve weakness or paralysis. However, not all patients with facial paresis/paralysis have Bell's palsy. Other common causes include treatment of vestibular schwannoma, head and neck tumours, iatrogenic injuries, Herpes zoster, or trauma. The approach to each of these conditions varies widely. The purpose of this guideline is to provide clinicians with guidance on the treatment and monitoring of patients with different causes of facial paralysis. We intend to draft a practical guideline, focusing on operationalised recommendations deemed to be useful in the daily management of patients. This guideline was promoted by the Spanish Society of Otolaryngology and developed by a group of physicians with an interest in facial nerve disorders, including at least one physician from each Autonomous Community. In a question and answer format, it includes 56 relevant topics related to the facial nerve.

Resumen: La infección por el virus de la hepatitis C (VHC) es considerada un factor que reduce la supervivencia del paciente y del injerto en trasplante renal (TR). La disponibilidad de los nuevos antivirales de acción directa (AAD), muy eficaces y con un excelente perfil de seguridad, está permitiendo erradicar el VHC de los pacientes con enfermedad renal, y ello supone un revolucionario cambio radical en la evolución natural de esta infección, hasta ahora sin un tratamiento eficaz y seguro por la contraindicación del interferón en los trasplantados renales.La eficacia de algunos AAD para todos los genotipos, incluso en pacientes con insuficiencia renal, constituye una enorme contribución para erradicar el VHC en la población con TR al margen del genotipo, del grado de insuficiencia renal, de la progresión de la hepatopatía y de la existencia previa de tratamiento anti-VHC.Todo ello está planteando, aunque con controversias, la posibilidad de utilizar riñones de donantes infectados VHC+ para trasplante en receptores no infectados y poder tratarse y curarse tras el TR precoz, aumentando así el pool total de riñones para TR. Abstract: Hepatitis C virus (HCV) infection is a factor that reduces the survival of the patient and the graft in renal transplant (RT). The availability of directly acting antivirals agents (DAAs), very effective and with an excellent safety profile, it allows eradicate HCV from patients with kidney disease, and this is a revolutionary radical change in the natural evolution of this infection, until now without effective and safe treatment for the contraindication use of interferon in kidney transplant patients.The efficiency of some DAAs for all genotypes, even in patients with renal insufficiency constitutes a huge contribution to eradicate HCV in the RT population independently the genotype, severity of kidney failure, progression of liver disease and previous anti HCV therapy.All this is raising, although with controversies, the possibility of use kidneys from infected HCV+ donors for transplant in uninfected receptors and can be treated successfully in the early post-TR, thus increasing the total “pool” of kidneys for RT. Palabras clave: Trasplante renal, Hepatitis C, Antivirales de acción directa, Lista de espera, Donantes VHC positivo, Keywords: Renal transplant, Hepatitis C, Directly acting antiviral agents, Waiting list, HCV positive donors

Renal allograft thrombosis is the most frequent and devastating complication in the early postrenal transplantation period. Several risk factors to develop graft thrombosis depending on donors and recipients are well known. Antiphospholipid syndrome (APS) is well recognized as an important cause of kidney injury, with specific clinical and histological features that may lead to renal injury caused by thrombosis at any location within the renal vasculature. There are 3 forms of APS, primary (the most common form), associated to other systemic autoimmune diseases (SAD-APS), and catastrophic. Nevertheless, patients with SAD-APS and renal failure only represent 2% to 5% in hemodialysis or transplantation. The presence of pretransplant antiphospholipid antibodies increases risk of graft thrombosis. A new form of APS based on IgA anti-β-2-glycoprotein-I (B2GPI) antibodies, representing up to 30% of patients in end-stage renal disease and renal transplantation, is the main independent risk factor for graft thrombosis and early graft loss after renal transplantation. In addition, B2GP1 bound to IgA aB2GP1 immunocomplexes have been described as a marker to predict thrombosis after renal transplantation in patients with antiphospholipid antibodies. Anticoagulation remains the main treatment to prevent renal allograft thrombosis, although new preventive strategies are coming. Future studies may help to identify better therapeutic targets.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy and in those with a kidney transplant. Since the publication of the original Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2008, major advances in HCV management, particularly with the advent of direct-acting antiviral therapies, have now made the cure of HCV possible in CKD patients. In addition, diagnostic techniques have evolved to enable the noninvasive diagnosis of liver fibrosis. Therefore, the Work Group undertook a comprehensive review and update of the KDIGO HCV in CKD Guideline. This Executive Summary highlights key aspects of the guideline recommendations.

GDP-mannose-pyrophosphorylase-B (GMPPB) facilitates the generation of GDP-mannose, a sugar donor required for glycosylation. GMPPB defects cause muscle disease due to hypoglycosylation of α-dystroglycan (α-DG). Alpha-DG is part of a protein complex, which links the extracellular matrix with the cytoskeleton, thus stabilizing myofibers. Mutations of the catalytically inactive homolog GMPPA cause alacrima, achalasia, and mental retardation syndrome (AAMR syndrome), which also involves muscle weakness. Here, we showed that Gmppa-KO mice recapitulated cognitive and motor deficits. As structural correlates, we found cortical layering defects, progressive neuron loss, and myopathic alterations. Increased GDP-mannose levels in skeletal muscle and in vitro assays identified GMPPA as an allosteric feedback inhibitor of GMPPB. Thus, its disruption enhanced mannose incorporation into glycoproteins, including α-DG in mice and humans. This increased α-DG turnover and thereby lowered α-DG abundance. In mice, dietary mannose restriction beginning after weaning corrected α-DG hyperglycosylation and abundance, normalized skeletal muscle morphology, and prevented neuron degeneration and the development of motor deficits. Cortical layering and cognitive performance, however, were not improved. We thus identified GMPPA defects as the first congenital disorder of glycosylation characterized by α-DG hyperglycosylation, to our knowledge, and we have unraveled underlying disease mechanisms and identified potential dietary treatment options.

Las Humanidades Digitales definen un marco donde la tecnología es un elemento indispensable para la investigación en Humanidades y Ciencias Sociales, y donde las bibliotecas académicas pueden desempeñar un papel esencial. Este trabajo se propone detectar y analizar cómo se está desarrollando ese papel de colaboración en España en este momento cuando en otros países ya es algo habitual. Partiendo de una revisión bibliográfica que contextualiza la cuestión, se muestran los resultados de una encuesta realizada a bibliotecas académicas en universidades donde existen proyectos de Humanidades Digitales, y que ha sido la herramienta metodológica de este análisis. Los resultados arrojan que mayoritariamente esa colaboración existe, pero queda diluida entre otros servicios de apoyo a la investigación de las bibliotecas. Contar con bibliotecarios integrados (embedded librarians) (Shumaker y Talley, 2009), de amplias capacidades para la gestión y análisis de datos, entre otras propuestas posibles, puede enriquecer este tipo de proyectos.

Summary:. Bilateral facial paralysis is a challenging situation requiring complex management. Surgical treatment can include nerve transfers, mainly masseter-to-facial, or muscle transfers, gracilis free flap, or temporalis transposition. Deciding on the surgical option depends on the duration of the paralysis and the feasibility of facial muscles. We present the case of a 10-year-old child with permanent bilateral facial paralysis after brainstem tumor surgery. The patient was treated with bilateral simultaneous hypoglossal-to-facial transfer followed by bilateral simultaneous masseter-to-facial 12 months later. After 23 months of follow-up and specific physical therapy, she has good and symmetric resting tone, complete eye closure, moderate bilateral smile excursion, mild lip pucker movement, and good oral competence. The combination of these two nerve transfers, when possible, gives the opportunity of restoring movement taking the best of each technique, with acceptable results and no significant clinical deficits in the donor sites.

Background: Antiphospholipid syndrome is characterized by recurrent thrombosis and gestational morbidity in patients with antiphospholipid autoantibodies (aPLs). Predictive value of the presence of aPLs is low, and new markers are necessary to identify aPL carriers at higher risk and take preventive measures on them. The presence of circulating immune complexes of IgA bound to β 2 -glycoprotein I (B2A-CIC) has been associated with occurrence of acute thrombotic events. In this work we study its possible predictive value for the appearance of acute thrombotic events in patients who are going to undergo transplant surgery, a well-known trigger of acute thrombotic events in aPL carriers. Methods: We performed a follow-up study based on the Magnum 12+12 Cohort of patients who received a kidney transplant (n=1339). Three groups were established: group 1 patients who were positive for IgA anti-β 2 -glycoprotein I (aB2GP1) and B2A-CIC (n=125); group 2 patients who were positive only for IgA aB2GP1 (n=240); and control group, patients who were negative for IgA aB2GP1 (n=974). Levels of autoantibodies and B2A-CIC were quantified immediately before the transplant surgery and patients were followed up for 6 months. Results: In group 1, 46.4% of patients experienced any type of thrombosis versus 10.4% in group 2 ( P P P P Conclusions: The presence of B2A-CIC is a predictor of acute thrombotic events. Patients who were positive for IgA aB2GP1 only are at risk of experiencing thrombosis if they are B2A-CIC positive. If they are B2A-CIC–negative patients, they have the same risk as the control group. Treatments to prevent acute thrombotic events should focus on B2A-CIC–positive patients.

Background Immunoglobulin (Ig)A anti–β 2 –glycoprotein I (aB2GP1) antibodies are associated with thrombotic events, cardiovascular morbidity, and death in dialysis patients. About 30% of patients with chronic renal disease are positive for IgA aB2GP1; however, the origin of these antibodies is unknown. It has been speculated that dialysis membranes, age, or etiology of renal base disease are possible precipitating factors, although these factors do not appear to be the source of antibodies. B2GP1 is a protein of 326 amino acids grouped into five domains. Eight polymorphisms have been described; the most important are Val/Leu 247 , which appears to predispose aB2GP1 antibody production in patients with anti-phospholipid syndrome, and Trp/Ser 316 , which appears to have protective antibody production of aB2GP1. Methods DNA samples from 92 patients with renal failure on hemodialysis were randomly collected with a 1:1 ratio for the positivity for IgA aB2GP1. Forty-six samples were positive for IgA aB2GP1 (group 1) and 46 negative for IgA aB2GP1 (group 2). All samples were anonymized to study polymorphism Val/Leu 247 and polymorphism Trp/Ser 316 . Results No significant differences were observed between those who were positive or negative for IgA aB2GP1 in patients with renal failure treated with hemodialysis and the polymorphism located in codons 247 and 316. Conclusions The two groups of patients have the same prevalence in polymorphisms 247 and 316, and therefore there appears not to be a genetic predisposition in our population. New trigger factors must be studied.

BACKGROUND: The postharvest application of pectic‐oligosaccharides (POS) as an elicitor to improve the postharvest shelf‐life and nutritional quality by stimulating natural defense mechanisms in strawberries was studied. Strawberries (cv. Festival) were treated with POS (at 0, 2, 5, and 9 g L⁻¹) and evaluated for firmness, weight loss, color, soluble solids, titratable acidity (TA), total phenolic and anthocyanin content, antioxidant capacity, decay, and some defense‐related enzyme activity during storage at 2 ± 0.5 °C for 14 days. RESULTS: Treatment with POS significantly delayed (P

Background: Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with presence of anti-phospholipid antibodies (aPL). The APS classification criteria only consider the aPL of IgG/IgM isotype, however testing of aPL of IgA isotype is recommended when APS is suspected and consensus aPL are negative. IgA anti-βeta-2 glycoprotein-I (B2GP1) has been clearly related with occurrence of thrombotic events. Antibodies anti-B2GP1 of IgG/M isotypes recognize an epitope in Domain 1 (R39-G43), the epitopes that recognize IgA anti-B2GP1 antibodies are not well-identified. Aim: To determine the zones of B2GP1 recognized by antibodies of IgA isotype from patients with APS symptomatology and positive for IgA anti-B2GP1. Methods: IgA antibodies to Domain-1(D1) and Domain-4/5(D4/5) of B2GP1 (ELISA) and epitope mapping on oligopeptide arrays of B2GP1 were evaluated in sera from a group of 93 patients with at least one thrombotic and with isolated positivity for IgA anti-B2GP1 antibodies (negative for other aPL). Results: A total of 47 patients (50.5%) were positive for anti-D4/5 and 23(25%) were positive for anti-D1. When peptide arrays were analyzed, three zones of B2GP1 reactivity were identified for more than 50% of patients. The center of these zones corresponds to amino acids 140(D3), 204(D4), and 264(D5). The peptides recognized on D3 and D4 contain amino acid sequences sharing high homology with proteins of microorganism that were previously related with a possible APS infectious etiology. In the three-dimensional structure of B2GP1, the three peptides, as the R39-G43 epitope, are located on the right side of the molecule (L-shape). The left side (J-shape) does not bind the antibodies. Conclusions: Patients with thrombotic APS clinical-criteria, and isolated IgA anti-B2GP1 positivity appear to preferentially bind, not to the D1 or D4/5 domains of B2GP1, but rather to three sites in D3, D4, and D5. The sites on D3 and D4 were previously described as the target identified by human monoclonal antibodies derived from patients that were capable of inducing APS in animal models. The localization of these epitopes opens a new route to explore to increase understanding of the patholophysiology of the APS and to propose new alternatives and therapeutic targets.

Mexico is a country with a vast and extraordinary cultural heritage, which is the result of a rich history of cultural exchange, syncretism and transculturation. This rich culture has been materialized through the consolidation of a long and prestigious museum tradition, which at the same time is sadly characterized by an endemic lack of technological resources rather than professional skills. As a result, we have found that Mexican museums produce very heterogeneous forms of documentation, which are often not even managed using information technologies. Furthermore, most museums deploy ad hoc solutions that directly limit the usefulness and value of the documentation process itself. In response, the recently founded Mexican Ministry of Culture is undertaking the development of the Mexican cultural heritage data model (Modelo de Datos México), which is aimed at contributing to the cultural heritage domain of our country through the correct characterization and documentation of its cultural objects. It is the first documented experience in Mexico of a large-scale data model inspired by CIDOC-CRM, which is complemented by a set of terminological tools that attempt to capture the singularities and idiosyncrasies of the Mexican cultural sector. In the present paper, we will describe the motivations and decisions made so far to optimize the data model to the Mexican reality and the development of the project that will define a set of local terminologies built on the expertise of linguists, information architects, developers and especially, museum professionals., This research was funded by the Secretaría de Cultura of Mexico.

Se analizan los sitios web de las 35 bibliotecas nacionales (BN) del continente americano, considerando tanto las principales características del propio sitio como los servicios en línea que se ofertan. Los servicios se han agrupado en categorías para facilitar el tratamiento estadístico de los datos. Los resultados resaltan la relevancia alcanzada por la web como plataforma desde donde las BN pueden dar a conocer sus colecciones y acercarse a sus usuarios a través de los servicios en línea, pero también muestran las grandes diferencias que existen entre ellas en cuanto a las soluciones tecnológicas adoptadas y al abanico de servicios ofertados. Abstract: In this paper a brief analysis of the 35 National Libraries’ websites of the Americas is presented, considering both the main website features and the online services provided. These services have been categorised to ease the statistical data processing. The results highlight the relevance of the Web as a platform from which National Libraries can make public their collections and get closer to their users through online services, but they show as well a great gap between them regarding the technological solutions adopted and the range of services provided.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement.The Kidney Disease: Improving Global Outcomes (KDIGO) 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is an extensive update of KDIGO's 2008 guideline on HCV infection in CKD. This update reflects the major advances since the introduction of direct-acting antivirals (DAAs) in the management of HCV infection in the CKD population.The KDIGO work group tasked with developing the HCV and CKD guideline defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence previously summarized by the evidence review team. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to appraise the quality of evidence and rate the strength of the recommendations. Searches of the English-language literature were conducted through May 2017 and were supplemented with targeted searches for studies of DAA treatment and with abstracts from nephrology, hepatology, and transplantation conferences. A review process involving many stakeholders, subject matter experts, and industry and national organizations informed the guideline's final modification.The updated guideline comprises 66 recommendations. This synopsis focuses on 32 key recommendations pertinent to the prevention, diagnosis, treatment, and management of HCV infection in adult CKD populations.

BACKGROUND: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. OBJECTIVE: We sought to investigate the incidence of gene mosaicism in patients with PIDs. METHODS: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. RESULTS: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. CONCLUSION: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:143 issue:1 pages:359-368 ispartof: location:United States status: published

Summary Introduction In recent years, we have been witnessing increased clinical interest in the determination of IgA anti-beta 2-glycoprotein I (aB2GPI) antibodies as well as increased demand for this test. Some ELISA-based diagnostic systems for IgA aB2GPI antibodies detection are suboptimal to detect it. The aim of our study was to determine whether the diagnostic yield of modern detection systems based on automatic platforms to measure IgA aB2GPI is equivalent to that of the well-optimized ELISA-based assays. Methods In total, 130 patients were analyzed for IgA aB2GPI by three fully automated immunoassays using an ELISA-based assay as reference. The three systems were also analyzed for IgG aB2GPI with 58 patients. Results System 1 was able to detect IgA aB2GPI with good sensitivity and kappa index (99% and 0.72, respectively). The other two systems had also poor sensitivity (20% and 15%) and kappa index (0.10 and 0.07), respectively. On the other hand, kappa index for IgG aB2GPI was >0.89 in the three systems. Conclusion Some analytical methods to detect IgA aB2GPI are suboptimal as well as some ELISA-based diagnostic systems. It is important that the scientific community work to standardize analytical methods to determine IgA aB2GPI antibodies.

BACKGROUND Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT). METHODS We compared species distribution and antimicrobial susceptibility patterns in 1052 isolates from urine cultures obtained in 2 different cohorts of kidney transplant recipients in a single center (Cohort A: 189 patients undergoing KT between January 2002 and December 2004 [336 isolates]; Cohort B: 115 patients undergoing KT between January 2011 and December 2013 [716 isolates]). RESULTS Asymptomatic bacteriuria accounted for most of the isolates (86.9% in Cohort A and 92.3% in Cohort B). Klebsiella pneumoniae (9.5% vs. 15.6%), Pseudomonas aeruginosa (1.8% vs. 7.9%), and Enterobacter cloacae (0.6% vs. 3.1%) were significantly more common in Cohort B. The isolation of K. pneumoniae in Cohort B was associated with the occurrence of acute pyelonephritis (9.8% of all K. pneumoniae isolates vs. 2.8% of the remaining uropathogens; P = 0.001). Non-susceptibility rates among Enterobacteriaceae in Cohort B were higher for every class of antibiotics (P ≤ 0.003) with the exception of fosfomycin. Compared to Cohort A, significant increases were seen in isolates from Cohort B for multidrug-resistant (MDR) (43.9% vs. 67.8%, respectively; P = 0.001), extended-spectrum beta-lactamase (ESBL)-producing (6.6% vs. 26.1%; P = 0.001), and carbapenemase-producing Enterobacteriaceae strains (0.0% vs. 5.0%; P = 0.001). Such differences were mostly attributable to K. pneumoniae (as 54.5% and 13.4% of isolates in Cohort B were ESBL-producing and carbapenemase-producing, respectively). MDR isolates were responsible for 69.1% of episodes of symptomatic urinary tract infection in Cohort B. CONCLUSION The increase in resistance rates among Enterobacteriaceae uropathogens is significant and may have an effect on KT programs.

Aim: Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis and/or gestational morbidity in patients with antiphospholipid autoantibodies (aPL). Over recent years, IgA anti-beta2-glycoprotein I (B2GPI) antibodies (IgA aB2GPI) have reached similar clinical relevance as IgG or IgM isotypes. We recently described the presence of immune complexes of IgA bounded to B2GPI (B2A-CIC) in the blood of patients with antecedents of APS symptomalology. However, B2A-CIC's clinical associations with thrombotic events (TEV) have not been described yet. Methods: A total of 145 individuals who were isolate positive for IgA aB2GPI were studied: 50 controls without any APS antecedent, 22 patients with recent TEV (Group-1), and 73 patients with antecedents of old TEV (Group-2). Results: Mean B2A-CIC levels and prevalence in Group-1 were 29.6 ± 4.1 AU and 81.8%, respectively, and were significantly higher than those of Group-2 and controls (p < 0.001). In a multivariable analysis, positivity of B2A-CIC was an independent variable for acute thrombosis with a 22.7 odd ratio (confidence interval 5.1 –101.6, 95%, p < 0.001). Levels of B2A-CIC dropped significantly two months after the TEV. B2A-CIC positive patients had lower platelet levels than B2A-CIC-negative patients (p < 0.001) and more prevalence of thrombocytopenia (p < 0.019). Group-1 had no significant differences in C3 and C4 levels compared with other groups. Conclusion: B2A-CIC is strongly associated with acute TEV. Patients who did not develop thrombosis and were B2A-CIC positive had lower platelet levels, which suggest a hypercoagulable state. This mechanism is unrelated to complement-fixing aPL. B2A-CIC could potentially select IgA aB2GPI-positive patients at risk of developing a thrombotic event.

Hepatitis C virus (HCV) infection is a factor that reduces the survival of the patient and the graft in renal transplant (RT). The availability of directly acting antivirals agents (DAAs), very effective and with an excellent safety profile, it allows eradicate HCV from patients with kidney disease, and this is a revolutionary radical change in the natural evolution of this infection, until now without effective and safe treatment for the contraindication use of interferon in kidney transplant patients.The efficiency of some DAAs for all genotypes, even in patients with renal insufficiency constitutes a huge contribution to eradicate HCV in the RT population independently the genotype, severity of kidney failure, progression of liver disease and previous anti HCV therapy.All this is raising, although with controversies, the possibility of use kidneys from infected HCV+ donors for transplant in uninfected receptors and can be treated successfully in the early post-TR, thus increasing the total “pool” of kidneys for RT. Resumen: La infección por el virus de la hepatitis C (VHC) es considerada un factor que reduce la supervivencia del paciente y del injerto en trasplante renal (TR). La disponibilidad de los nuevos antivirales de acción directa (AAD), muy eficaces y con un excelente perfil de seguridad, está permitiendo erradicar el VHC de los pacientes con enfermedad renal, y ello supone un revolucionario cambio radical en la evolución natural de esta infección, hasta ahora sin un tratamiento eficaz y seguro por la contraindicación del interferón en los trasplantados renales.La eficacia de algunos AAD para todos los genotipos, incluso en pacientes con insuficiencia renal, constituye una enorme contribución para erradicar el VHC en la población con TR al margen del genotipo, del grado de insuficiencia renal, de la progresión de la hepatopatía y de la existencia previa de tratamiento anti-VHC.Todo ello está planteando, aunque con controversias, la posibilidad de utilizar riñones de donantes infectados VHC+ para trasplante en receptores no infectados y poder tratarse y curarse tras el TR precoz, aumentando así el pool total de riñones para TR. Keywords: Renal transplant, Hepatitis C, Directly acting antiviral agents, Waiting list, HCV positive donors, Palabras clave: Trasplante renal, Hepatitis C, Antivirales de acción directa, Lista de espera, Donantes VHC positivo

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti–β2-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.

Background The antiphospholipid syndrome (APS) is defined by simultaneous presence of vascular clinical events and antiphospholipid antibodies (aPL). The aPL considered as diagnostics are lupus anticoagulant and antibodies anticardiolipin (aCL) and anti-s2 glycoprotein-I (aB2GP1). During recent years, IgA aB2GP1 antibodies have been associated with thrombotic events both in patients positive, and mainly negative for other aPL, however its value as a pro-thrombotic risk-factor in asymptomatic patients has not been well defined. Objective To test the role of IgA anti B2GP1 as a risk factor for the development of APS-events (thrombosis or pregnancy morbidity) in asymptomatic population with a 5-year follow-up. Methods 244 patients isolated positive for anti-beta2-glycoprotein I IgA (Group-1 study) and 221 negative patients (Group-2 control) were studied. All the patients were negative for IgG and IgM aCL. Results During the follow-up, 45 patients (9.7%) had APS-events, 38 positive for IgA-aB2GP1 and 7 negative (15.6% vs 3.2%, p

In the recent years, more than 60% of available deceased donors are either older than 50 yr or have significant vascular comorbidities. This makes the acceptance and rejection criteria of renal allografts very rigorous, especially in cases of younger recipients, and at the same time encourages live donations. In our country, there is a lack of homogeneity in the percentages of use of expanded criteria donor (ECD) allografts between the different autonomous communities. Furthermore, the criteria vary greatly, and in some cases, great importance is given to the biopsy while in others very little. In this study, we present a unified and homogenous criteria agreed upon by consensus of a 10-member Panel representing major scientific societies related to renal transplantation in Spain. The criteria are to be used in accepting and/or rejecting kidneys from the so-called ECDs. The goal was to standardize the use of these organs, to optimize the results, and most importantly to provide for the maximum well being of our patients. Finally, we believe that after taking into account the Panel's thorough review of specific scientific literature, this document will be adaptable to other national renal transplant programmes.

Problem Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells). Method of study Observational study of RRF women with NK or NKT-like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation. Results By multivariant logistic regression analysis after adjusting for age, NK cells subsets and other therapies, IVIg significantly improved the live birth rate to 96.3% in women with recurrent miscarriage (RM) compared with 30.6% in case not receiving IVIg (P

The introduction of new immunosuppressive drugs in the last two decades has been associated with a significant decline in the prevalence of acute rejection and a huge improvement of graft survival. Monitoring blood levels of immunosuppressive drugs is the most common way to control drug doses in renal transplant patients. This approach is useful and widely used but doesn't give accurate information about the immune status of the patient. For this goal, there are many “in house” protocols which give more information, but cannot be standardized, limiting their applicability to compare results between different laboratories. In this study we compare three classical functional methods to evaluate the immune response: Mixed lymphocyte reaction (MLR), phytohemagglutinin stimulated peripheral blood lymphocytes (PBLs), and anti-CD3 monoclonal antibodies (mAbs) against PBL with the only FDA-labeled assay to measure the patient immune status: Cylex ImmuKnow® that measures the intracelullar ATP in CD4 + lymphocytes. We used n = 111 stable renal transplant patients, all the patients with more than one year functioning grafts. We referred the results to a control population of healthy blood donors (n = 125). Results: Measurement of intracellular ATP in CD4 + lymphocytes is able to differentiate immunosuppressed populations in renal transplant patients from health controls (242.30 ± 21.62 vs. 386.43 ± 25.12, p 0.0001). By contrary, there were no differences between controls and renal recipients when functional response was measured by MLR, PHA and anti-CD3 mAbs (2.48 ± 0.45 vs. 2.37 ± 0.41; 2.84 ± 0.76 vs. 2.37 ± 0.32; 2.32 ± 0.34 vs. 1.89 ± 0.38 respectively). In summary, our results show that the measurement of ATP in CD4 + lymphocytes gives more accurate information in comparison to the classical methods.

Seronegative antiphospholipid syndrome (SNAPS) is an autoimmune disease present in patients with clinical manifestations highly suggestive of Antiphospholipid Syndrome (APS) but with persistently negative consensus antiphospholipid antibodies (a-PL). IgA anti-β2 Glycoprotein I (aB2-GPI) antibodies are associated with APS. However, they are not currently considered to be laboratory criteria due to the heterogeneity of published works and the use of poor standardized diagnostic systems. We have aimed to assess aPL antibodies in a group of patients with clinical manifestations of APS (C-APS) to evaluate the importance of the presence of IgA aB2GPI antibodies in APS and its relation with other aPL antibodies. Only 14% of patients with C-APS were positive for any consensus antibody, whereas the presence of isolated IgA aB2GPI antibodies was found in 22% of C-APS patients. In patients with arterial thrombosis IgA aB2GPI, antibodies were the only aPL antibodies present. Serologic profile in primary APS (PAPS) is different from systemic autoimmune disorders associated APS (SAD-APS). IgA aB2GPI antibodies are more prevalent in PAPS and IgG aB2GPI antibodies are predominant in SAD-APS. The analysis of IgA aB2GPI antibodies in patients with clinical manifestations of PAPS might avoid underdiagnosed patients and provide a better diagnosis in patients with SAD-APS. Laboratory consensus criteria might consider including analysis of IgA aB2GPI for APS diagnosis.