IgG4-Related Disease Affecting Testicle and Myelodysplastic Syndrome: Just a Coincidence?

Immunoglobulin G4-related disease (IgG4-RD) is progressive immune-mediated fibrotic condition characterised by a tendency to form tumefactive lesions in different organs and by elevated IgG4 serum concentrations. Urological manifestations are rare and normally occur together with other systemic affections. Myelodysplastic syndromes (MDS) are hematopoietic stem cell neoplasms, with different subtypes based on the type of blood cells involved. MDS can be associated with other pathologies or medical treatments. We present an uncommon case of testicular manifestation associated with myelodysplastic syndrome here

The Effects of Parenteral K1 Administration in Pseudoxanthoma Elasticum Patients Versus Controls. A Pilot Study

Introduction: Pseudoxanthoma elasticum (PXE) is a rare disease caused by mutations in the ABCC6 gene. Vitamin K1 is involved in the posttranslational carboxylation of some proteins related to inhibition of the calcification process. Our aim was to investigate, in patients affected by PXE, baseline levels of vitamin K1-dependent proteins and -metabolites and whether parenteral administration of phytomenadione was effective in modulating their levels. Methods: We included eight PXE patients with typical clinical symptoms (skin, retina, and vascular calcification) and two ABCC6 causative mutations; 13 clinically unaffected first-degree patients' relatives (9 carrying one ABCC6 mutation and 4 non-carriers). We assessed urinary vitamin K1 metabolites and serum Glu- and Gla-OC, Gas6 and undercaboxylated prothrombin (PIVKA-II), at baseline and after 1 and 6\u2009weeks after a single intramuscular injection of 10\u2009mg vitamin K1. Results: Comparison of PXE patients, heterozygous, and non-carriers revealed differences in baseline levels of serum MK-4 and of urinary vitamin K metabolites. The response to phytomenadione administration on vitamin K-dependent proteins was similar in all groups. Conclusion: The physiological axis between vitamin K1 and vitamin K-dependent proteins is preserved; however, differences in the concentration of vitamin K metabolites and of MK-4 suggest that vitamin K1 metabolism/catabolism could be altered in PXE patients

Cutaneous and Vascular Deposits of 18F-NaF by PET/CT in the Follow-Up of Patients with Pseudoxanthoma Elasticum

Active microcalcification of elastic fibers is a hallmark of pseudoxanthoma elasticum and it can be measured with the assessment of deposition of 18F-NaF using a PET/CT scan at the skin and vascular levels. It is not known whether this deposition changes over time in absence of specific therapy. We repeated in two years a PET/CT scan using 18F-NaF as a radiopharmaceutical in patients with the disease and compared the deposition at skin and vessel. Furthermore, calcium score values at the vessel wall were also assessed. Main results indicate in the vessel walls that calcification progressed in each patient; by contrast, the active microcalcification, measured and target-to-background ratio showed reduced active deposition. By contrast, at skin levels (neck and axillae) the uptake of the pharmaceutical remains unchanged. In conclusion, because calcification in the arterial wall is not specific for pseudoxanthoma elasticum condition, the measurement of the deposition of 18F-NaF in the neck might be potentially used as a surrogate marker in future trials for the disease.This research was funded by Grant number PI16/01579 from Fondo de Investigaciones Sanitarias (FIS), ISCIII, European Regional Development Fund (FEDER, “A Way to Make Europe”) and funds from the CTS-159 Group, PAIDI.Ye

Lansoprazole Increases Inorganic Pyrophosphate in Patients with Pseudoxanthoma Elasticum: A Double-Blind, Randomized, Placebo-Controlled Crossover Trial

Pseudoxanthoma elasticum (PXE) is characterized by low levels of inorganic pyrophosphate (PPi) and a high activity of tissue-nonspecific alkaline phosphatase (TNAP). Lansoprazole is a partial inhibitor of TNAP. The aim was to investigate whether lansoprazole increases plasma PPi levels in subjects with PXE. We conducted a 2 × 2 randomized, double-blind, placebo-controlled crossover trial in patients with PXE. Patients were allocated 30 mg/day of lansoprazole or a placebo in two sequences of 8 weeks. The primary outcome was the differences in plasma PPi levels between the placebo and lansoprazole phases. 29 patients were included in the study. There were eight drop-outs due to the pandemic lockdown after the first visit and one due to gastric intolerance, so twenty patients completed the trial. A generalized linear mixed model was used to evaluate the effect of lansoprazole. Overall, lansoprazole increased plasma PPi levels from 0.34 ± 0.10 µM to 0.41 ± 0.16 µM (p = 0.0302), with no statistically significant changes in TNAP activity. There were no important adverse events. 30 mg/day of lansoprazole was able to significantly increase plasma PPi in patients with PXE; despite this, the study should be replicated with a large number of participants in a multicenter trial, with a clinical end point as the primary outcome.Funding for open access charge: Universidad de Málag

Algunas evidencias de aplicación

Libro temático especializadoLa sustentabilidad también debe aplicarse al sistema de producción, buscando impulsar transformaciones graduales de los estilos y modelos productivos tradicionales a unas de mayor eficiencia. Y donde se incorpore la dimensión ambiental y geográfico-espacial, para crear estructuras productivas más progresivas y equitativas en las sociedades. Todo esto, como alternativa para revertir las tendencias de escasez y agotamiento de los recursos naturales, así como de los desequilibrios globales, cuyos costos permean todos los tejidos humanos. De esta manera, la “sustentabilidad productiva” se concibe como la generación de bienes y servicios con ciertos estándares de calidad, bajo un esquema de eficiencia, rendimiento y de organización inclusiva e integrada, con baja presión al ambiente y uso racional de los recursos, garantizando la estadía y permanencia de los insumos y materiales en el tiempo. Desde esta perspectiva, la producción sustentable y el crecimiento de largo plazo pueden ser explicados por la capacidad que tienen las economías para generar e incorporar conocimientos y tecnologías. De ahí que, la educación y las cualificaciones del capital humano, los cambios en la organización de la producción y la calidad institucional, sean elementos nodales para avanzar en la consolidación de este ambiente productivo

Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients

Caracterización en la dinámica temporal de los macrohábitats acuáticos en la región de La Mojana

Con el fin de consolidar el levantamiento y análisis de la información sobre ecología de hábitats acuáticos en La Mojana, este documento describe la biodiversidad asociada a las zonas de transición entre los principales macrohábitats naturales y agroecosistemas identificados en esta región, su relación con la variabilidad en cuatro periodos hídricos desde la estacionalidad seca a la más húmeda e identificando la ocupación en el territorio por los distintos grupos biológicos.Bogotá, ColombiaPrograma Gestión Territorial de la Biodiversida

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.Tis project was funded in part by CRIS CANCER FOUNDATION

Caracterización en la dinámica espacial de los macrohábitats acuáticos en la región de La Mojana

Con el fin de consolidar el levantamiento y análisis de la información sobre ecología en los humedales de La Mojana, este documento describe la biodiversidad asociada a las zonas de transición entre los principales macrohábitats acuáticos naturales identificados en esta región. Caracterizando por sectores desde la transición más húmeda hasta la más seca, identificando y caracterizando los micro-hábitats presentes dentro de cada uno de ellos e identificando la ocupación en el territorio por los distintos grupos biológicos.Bogotá, ColombiaPrograma Gestión Territorial de la Biodiversida