Hospital Universitario La Paz

About: Hospital Universitario La Paz is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Medicine. The organization has 8960 authors who have published 11499 publications receiving 191509 citations.

Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease in Patients With a History of Heart Failure or Left Ventricular Dysfunction: Insights From the ISCHEMIA Trial.

Abstract: Background: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or...

First case of homozygous C1 inhibitor deficiency.

Abstract: Background C1 Inhibitor (C1-Inh) deficiency causes angioedema and can be hereditary (HAE), caused by mutations in the C1-Inh gene (C1NH), or acquired (AAE). Patients with HAE show a complement profile different from that of patients with AAE with normal levels of C1 (C1q, C1r, and C1s). Objective We sought to characterize the complement profile of a patient with HAE and a mutation in homozygosis in the C1NH gene (c.1576T>G, Ile462Ser) and study his family. Methods Biochemical diagnosis of HAE was confirmed by analyzing the C1NH gene. Further studies on the levels and activation states of the C1q, C1r, C1s, and C1-Inh components of the classical pathway of complement activation were also performed. Results Another 7 members of the family were given diagnoses of HAE: 1 was homozygous and 6 were heterozygous for the C1NH mutation c.1576T>G. The homozygous patients showed undetectable C1q levels, reduced C1s levels, the circulating active form of C1r, and a C1-Inh mostly in its cleaved inactive form in plasma. Conclusion This is the first report of patients homozygous for a mutation affecting the coding region of C1NH. These patients showed a unique activation and consumption profile of the classical complement activation pathway different from that commonly observed in patients with HAE but similar to that of patients with AAE. Clinical implications The most common HAE treatment is attenuated androgens, which increase the C1NH gene transcription levels. Because the homozygous patients lack a wild-type allele, long-term prophylactic treatment with attenuated androgens might not be advisable.

Constitutively altered frequencies of circulating follicullar helper T cell counterparts and their subsets in rheumatoid arthritis

Abstract: Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of follicular helper T cells (Tfh). There are three subpopulations of circulating Tfh (cTfh): CXCR5 + CXCR3 + CCR6- (Tfh-Th1), CXCR5 + CXCR3-CCR6- (Tfh-Th2) and CXCR5 + CXCR3-CCR6+ (Tfh-Th17). Our objective was to study the B cell helping capacity of cTfh subsets, and examine their frequency in Rheumatoid Arthritis (RA) patients, together with the frequency of circulating plasmablasts (CD19 + CD20-CD38high). Peripheral blood was drawn from RA patients with active disease (RA-a, DAS28 >2.6) (n = 17), RA in remission (RA-r, DAS28 <2.6) (n = 17) and healthy controls (HC) (n = 34). cTfh and plasmablast frequencies were determined by flow cytometry. Cocultures of sorted CD4 + CXCR5+ T cell subpopulations were established with autologous CD19 + CD27- naive B cells of HC, and concentrations of IgG, A and M were measured in supernatants. Isolated Tfh-Th2 and Tfh-Th17 but not Tfh-Th1 cells, induced naive B cells to secrete IgG and IgA. The frequency of CXCR5+ cells gated for CD4+ T cells was not different among HC, RA-a and RA-r. In contrast, both RA-a and RA-r patients demonstrated an increased frequency of CD4 + CXCR5 + ICOS+ T cells and augmented (%Tfh-Th2 + %Tfh-Th17)/%Tfh-Th1 ratio as compared with HC. In addition, RA-a but not RA-r patients, showed an increased frequency of circulating plasmablasts. Both RA-a and RA-r patients demonstrate an increased frequency of cTfh and overrepresentation of cTfh subsets bearing a B cell helper phenotype, suggesting that altered germinal center dynamics play a role in RA pathogenesis. In contrast, only RA-a patients show an increased proportion of circulating plasmablasts.

Practical aspects of extended half-life products for the treatment of haemophilia

Abstract: Haemophilia A and haemophilia B are congenital X-linked bleeding disorders caused by deficiency of coagulation factor VIII (FVIII) and IX (FIX), respectively. The preferred treatment option for patients with haemophilia is replacement therapy. For patients with severe disease, prophylactic replacement of coagulation factor is the treatment of choice; this has been shown to reduce arthropathy significantly, reduce the frequency of bleeds and improve patients' quality of life. Prophylaxis with standard recombinant factor requires regular intravenous infusion at least two (FIX) to three (FVIII) times a week. Recombinant FVIII and FIX products with an extended half-life are in development, or have been recently licensed. With reported mean half-life extensions of 1.5-1.8 times that of standard products for FVIII and 3-5 times that of standard products for FIX, these products have the potential to address many of the unmet needs of patients currently treated with standard factor concentrates. For example, they may encourage patients to switch from on-demand treatment to prophylaxis and improve the quality of life of patients receiving prophylaxis. Indeed, extended half-life products have the potential to reduce the burden of frequent intravenous injections, reducing the need for central venous lines in children, promote adherence, improve outcomes, potentially allow for more active lifestyles and, depending on the dosing regimen, increase factor trough levels. Members of the Zurich Haemophilia Forum convened for their 19th meeting to discuss the practicalities of incorporating new treatments into the management of people with haemophilia. This review of extended half-life products considers their introduction in haemophilia treatment, including the appropriate dose and schedule of infusions, laboratory monitoring, patient selection, safety considerations, and the economic aspects of care.

Comparison between xenogeneic and allogeneic adipose mesenchymal stem cells in the treatment of acute cerebral infarct: proof of concept in rats

Abstract: Background Rat adipose tissue-derived-mesenchymal stem cells (rAD-MSCs) have proven to be safe in experimental animal models of stroke. However, in order to use human AD-MSCs (hAD-MSCs) as a treatment for stroke patients, a proof of concept is needed. We analyzed whether the xenogeneic hAD-MSCs were as safe and effective as allogeneic rAD-MSCs in permanent Middle Cerebral Artery Occlusion (pMCAO) in rats.