Células madre como alternativa al marcapaso transvenoso / Stem cells as an alternative to the transvenous pacemaker

Resumen Objetivo: describir el estado del arte del marcapasos biológico y las perspectivas para crear tejido cardíaco de marcapasos utilizando modernas tecnologías genéticas y de ingeniería de tejidos. Métodos: revisión sistemática de la literatura. Resultados: los marcapasos se han convertido en el tratamiento primordial para cierto tipo de arritmias o bloqueos avanzados sintomáticos. Somos testigos de mejoras continuas en la tecnología del dispositivo, con avances en el diseño del cable, el tamaño del generador, la longevidad de la batería y los algoritmos de software que se han traducido en dispositivos más pequeños con funcionalidad mejorada. En la actualidad existen muchos sistemas implantables de cardioestimulación capaces de reemplazar la función de los marcapasos fisiológicos (seno y nódulos aurículo-ventriculares) que incluyen los recientemente desarrollados marcapasos secuenciales y autoprogramables. En la última década la investigación ha confirmado que el marcapasos biológico se puede crear mediante la terapia génica y la terapia celular. Hoy existen dos enfoques para construir marcapasos biológicos: uno es para introducir genes de marcapasos en células madre mesenquimales, y el otro es para inducir células madre pluripotentes en las células del nódulo sinoauricular. Conclusiones: los marcapasos biológicos, actualmente en la etapa preclínica, podrían ser una alternativa a los dispositivos electrónicos para pacientes seleccionados en el futuro.

Abstract Objective: To describe the state of the art of biological pacemakers and the perspectives for creating cardiac pacing tissue using modern genetic and tissue engineering technologies. Methods: A systematic review of the literature. Results: Pacemakers have become the first line treatment for certain types of arrhythmias and advanced symptomatic blocks. We are witnessing continuous improvements in the technology of the device, with advances in the design of the cable, the size of the generator, the longevity of the battery, as well as the software algorithms that have led to smaller devices with improved functions. There are currently many cardiac stimulation implantable systems capable of replacing the function of physiological pacemakers systems (sinus and atrial-ventricular nodes) that include the recently developed sequential and self-programmable pacemakers. In the last ten years or so, studies have confirmed that biological pacemakers can be created using gene therapy and cell therapy. There are currently to main efforts to construct biological pacemakers. One is to introduce pacemaker genes in mesenchymal stem cells, and the other is to introduce pluripotent stem cells in cells of the sinoatrial node. Conclusions: Biological pacemakers, currently in the pre-clinical stage, could be an alternative to the electronic devices for selected patients in the future.

Gonadotrophin-releasing hormone agonist-induced pituitary adenoma apoplexy and casual finding of a parathyroid carcinoma: A case report and review of literature.

BACKGROUND: Pituitary apoplexy represents one of the most serious, life threatening endocrine emergencies that requires immediate management. Gonadotropin-releasing hormone agonist (GnRHa) can induce pituitary apoplexy in those patients who have insidious pituitary adenoma coincidentally. CASE SUMMARY: A 46-year-old woman, with a history of hypertension and menorrhagia was transferred to our hospital from a secondary care hospital after complaints of headache and vomiting, with loss of consciousness 5 min after an injection of GnRHa. The drug was prescribed by her gynecologist due to the presence of uterine myomas. The clinical neurological examination revealed right cranial nerve III palsy, ptosis and movement limitation of the right eye. Our first clinical consideration was a pituitary apoplexy. Blood hormonal analysis revealed mild hyperprolactinemia and high follicle stimulating hormone level; PTH and calcium was high with glomerular filtration rate mildly to moderately decrease. A computed tomography scan, revealed an enlarged pituitary gland (3.5 cm) impinging upon the optic chiasm with bone involvement of the sella. Following contrast media administration, the lesion showed homogeneous enhancement with high-density focus that suggests hemorrhagic infarction of the tumor. Transsphenoidal endoscopic surgery was perfomed and adenomatous tissue was removed. Immunohistochemistry was positive for luteinizing hormone (LH) and follicular-stimulating hormone (FSH). A solid hypoechoic nodule (14 mm x 13 mm x 16 mm) was found in the caudal portion of the right thyroid lobe after a parathyroid ultrasound. A genetic test of Multiple Endocrine Neoplasia type 1 (MEN1) was negative. A right lower parathyroidectomy was performed and the pathologic study showed the presence of an encapsulated parathyroid carcinoma of 1.5 cm. A MEN type 4 genetic test was performed result was negative. CONCLUSION: This case demonstrates an uncommon complication of GnRH agonist therapy in the setting of a pituitary macroadenoma and the casual finding of parathyroid carcinoma. It also highlights the importance of suspecting the presence of a multiple endocrine neoplasia syndrome and to carry out relevant genetic studies.

AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients.

INTRODUCTION: One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR. METHODS: Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR. RESULTS: We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients. CONCLUSION: We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.

Polymorphisms in genes related to the complement system and antibody-mediated cardiac allograft rejection.

BACKGROUND: Heart transplantation (HT) is a life-saving treatment for patients with end-stage heart failure. One of the main problems after HT is the humoral response termed antibody-mediated rejection (AMR). Complement activation plays a key role in AMR contributing to graft damage. The aim of this study was to analyze genetic variants in genes related to the complement pathways that could be associated with the development of AMR. METHODS: Analysis of 51 genes related to the complement pathway was performed by next-generation sequencing in 46 HT recipients, 23 with and 23 without AMR. Statistical analysis was performed with SNPstats and R. RESULTS: We identified 2 single nucleotide polymorphisms, 1 in the mannose-binding lectin 2 gene (p.Gly54Asp-MBL2) and 1 in the complement factor properdin gene (p.Asn428(p=)-CFP), that showed significant association with the absence and development of AMR, respectively. Moreover, the presence of the rare allele in p.Gly54Asp-MBL2 control patients correlated with an immunodeficiency of mannose-binding lectin (6.24 ng/ml vs 207.50 ng/ml, p < 0.01), whereas the presence of the rare allele p.Asn428(p=)-CFP in patients with AMR correlated with higher levels of properdin protein (14.65 µg/ml vs 10.77 µg/ml, p < 0.05). CONCLUSIONS: AMR is a complex phenotype affected by many recipient factors. Variants in p.Gly54Asp-MBL2 and p.Asn428(p=)-CFP genes, encoding mannose-binding lectin 2 and properdin, may influence the risk of AMR.

Enfermedad pulmonar intersticial difusa como primera manifestación de macroglobulinemia de Waldenström: descripción de un caso y revisión de la literatura / Diffuse Interstitial Lung Disease as a First Manifestation of Waldenström’s Macroglobulinemia: Case Report and Review of the Literature

La macroglobulinemia de Waldenström (MW) es una neoplasia linfoide caracterizada por una infiltración principalmente de la médula ósea y del ganglio linfático por linfocitos pequeños maduros o con diferenciación plasmocitoide, con banda monoclonal IgM asociada, y en general un bajo grado de agresividad. Presentamos el primer caso publicado en la literatura española de enfermedad pulmonar intersticial difusa como forma de presentación de una MW y realizamos una revisión de la literatura

Waldenström's macroglobulinemia (WM) is a lymphoid malignancy characterized by infiltration, mainly of the bone marrow and lymph nodes, by small mature lymphocytes showing plasmacytoid differentiation, associated with an IgM monoclonal band, and in general, a low degree of aggressiveness. We present the first case reported in the Spanish literature of interstitial lung disease presenting as MW and we review the literature

Diffuse interstitial lung disease as a first manifestation of Waldenström's macroglobulinemia: case report and review of the literature.

Waldenström's macroglobulinemia (WM) is a lymphoid malignancy characterized by infiltration, mainly of the bone marrow and lymph nodes, by small mature lymphocytes showing plasmacytoid differentiation, associated with an IgM monoclonal band, and, in general, a low degree of aggressiveness. We present the first case reported in the Spanish literature of interstitial lung disease presenting as MW and we review the literature.