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Advanced Maternal Age as an Obstetric Risk Factor: Current Experience in a Hospital from Northwestern Spain.
No full textStudies updating the evidence in advanced maternal age as an independent factor of obstetric risk are needed. The aim of this study was to determine the prevalence of ≥ 35-years-old pregnant women who give birth in a Spanish hospital in Northwestern Spain, and to describe the incidence of maternal and perinatal morbidity and mortality. Retrospective follow-up observational study including women ≥ 20 years-old who gave birth over one year (n = 1378). Data were collected from medical records, including socio-demographic characteristics, comorbidities, gestational conditions, variables related with the delivery and perinatal outcomes. Multivariable logistic regression analysis was performed to determine the association of advanced maternal age with obstetric and perinatal outcomes. Forty-two percent of pregnant women were ≥ 35 years old. In the multivariable analysis, advanced maternal age was associated with the likelihood of gestational diabetes (OR = 1.84; 95% CI = 1.10 - 3.07), hypothyroidism (OR = 2.11; 95% CI = 1.17 - 3.80), lower probability of an eutocic delivery (OR = 0.74; 95% CI = 0.56 - 0.98), and a hospital admission > four days (OR = 2.91; 95% CI = 1.95 - 4.35). An association with the rate of C-sections was not found (OR = 1.24; 95% CI = 0.89 - 1.72). A high prevalence of pregnant women of advanced maternal age was confirmed. There was a higher rate of comorbidities and longer hospital admissions in older women but not a higher rate of higher C-sections and other complications
Antiplatelet therapy at discharge and long-term prognosis in Takotsubo syndrome: Insights from the Spanish National Registry (RETAKO).
No full textEndothelial dysfunction and platelet activation have been highlighted as possible mediators in Takotsubo syndrome (TTS). Nevertheless, to date, evidence on the usefulness of antiplatelet therapy in TTS remains controversial. The aim of our study is to evaluate long-term prognosis in TTS patients treated with antiplatelet therapy (APT) at hospitalization discharge. An ambispective cohort study from the Spanish National Takotsubo Registry database was performed (June 2002 to March 2017). Patients were divided into two groups: those who received APT at hospital discharge (APT cohort) and those who did not (non-APT cohort). Primary endpoint was all-cause death. Secondary endpoints included the composite of recurrence or readmission and a composite of death, recurrence or readmission. From a total of 741 patients, 728 patients were alive at discharge. Follow-up was performed in 544 patients, who were included in the final analysis: 321 patients (59.0%) in the APT cohort and 223 patients (41.0%) in the non-APT cohort. The APT cohort had a better clinical presentation and received more heart failure and acute coronary syndrome-like therapies (angiotensin converting enzyme inhibitors/angiotensin receptor blockers: 75.1% vs. 51.1%; p Patients with TTS receiving APT at discharge presented better prognosis up to two-years of follow-up compared with their counterparts not receiving APT
Robust In Vitro and In Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9-mediated Apoptotic Mesenchymal Stromal/Stem Cell
No full textMesenchymal stromal stem/cells (MSC) therapies are clinically used in a wide range of disorders based on their robust HLA-independent immunosuppressive and anti-inflammatory properties. However, the mechanisms underlying MSC therapeutic activity remain elusive as demonstrated by the unpredictable therapeutic efficacy of MSC infusions reported in multiple clinical trials. A seminal recent study showed that infused MSCs are actively induced to undergo apoptosis by recipient cytotoxic T cells, a mechanism that triggers in vivo recipient-induced immunomodulation by such apoptotic MSCs, and the need for such recipient cytotoxic cell activity could be replaced by the administration of ex vivo-generated apoptotic MSCs. Moreover, the use of MSC-derived extracellular vesicles (MSC-EVs) is being actively explored as a cell-free therapeutic alternative over the parental MSCs. We hypothesized that the introduction of a "suicide gene" switch into MSCs may offer on-demand in vivo apoptosis of transplanted MSCs. Here, we prompted to investigate the utility of the iCasp9/AP1903 suicide gene system in inducing apoptosis of MSCs. iCasp9/AP1903-induced apoptotic MSCs (MSCiCasp9+) were tested in vitro and in in vivo models of acute colitis. Our data show a very similar and robust immunosuppressive and anti-inflammatory properties of both "parental" alive MSCGFP+ cells and apoptotic MSCiCasp9+ cells in vitro and in vivo regardless of whether apoptosis was induced in vivo or in vitro before administering MSCiCasp9+ lysates. This development of an efficient iCasp9 switch may potentiate the safety of MSC-based therapies in the case of an adverse event and, will also circumvent current logistic technical limitations and biological uncertainties associated to MSC-EVs
Diagnosis of Levator Ani Muscle Avulsion in Instrumented Delivery: Meta-analysis
No full textObjective: The objective of this meta-analysis was to establish the rates of levator ani muscle (LAM) avulsion in patients after forceps delivery (FD) and vacuum delivery (VD) as assessed by 3D/4D transperineal ultrasound. Methods: A systematic search was performed in the MEDLINE, PubMed, Google Scholar, and Embase databases up to December 31, 2021. Studies that studied primiparous women diagnosed with LAM avulsion by 3D/4D transperineal ultrasound in VD or FD were included. To do the meta-analysis, the jamovi project program version 2.2 (2021) was used. Results: The search yielded 1225 studies that met the MeSH criteria, of which 26 were included in the review. The estimated joint OR for VD vs. normal vaginal delivery (NVD) was 1.93 (95% CI: 1.31-2.86), for FD vs. NVD was 5.33 (95% CI: 3.78-8.11), and for FD vs. VD was 2.36 (95% CI: 1.46-3.84). Conclusions: Instrumented delivery with forceps or vacuum favors LAM avulsion. It is not possible to establish whether this injury is attributable to the specific instrument or to the type of delivery involved in the instrumentation itself
Alterations of spliceosome components in leukocytes from patients with rheumatoid arthritis influence their autoimmune and inflammatory profile, and the development of cardiovascular disease
No full textBackground: A significant percentage of genetic and inflammatory diseases derive from splicing alterations. Therefore, the understanding of what modifications in spliceosome determine an alternative splicing and its association with the development of such pathologies is of critical importance. Objectives: To identify the alterations present in the spliceosome machinery of patients with rheumatoid arthritis (RA), its influence on the development and activity of the disease and their atherothrombotic profile. Methods: An array of selected components of the major- (n=12) and minor-spliceosome (n=4) and associated splicing factors (n=28) was developed, and their expression levels were evaluated using a Fluidigm methodology, in purified leukocytes from 14 RA patients and 14 healthy donors (HD). In parallel, an extensive clinical/serological evaluation was performed. Carotid intimate media thickness (CIMT) was used as atherosclerosis marker. Endothelial activity was monitored by laser-doppler flowmetry, and pro-inflammatory and oxidative stress markers were quantified. Association of these splicing components with clinical and analytical features were investigated.S
Development of secretome-based strategies to improve cell culture protocols in tissue engineering.
No full textAdvances in skin tissue engineering have promoted the development of artificial skin substitutes to treat large burns and other major skin loss conditions. However, one of the main drawbacks to bioengineered skin is the need to obtain a large amount of viable epithelial cells in short periods of time, making the skin biofabrication process challenging and slow. Enhancing skin epithelial cell cultures by using mesenchymal stem cells secretome can favor the scalability of manufacturing processes for bioengineered skin. The effects of three different types of secretome derived from human mesenchymal stem cells, e.g. hADSC-s (adipose cells), hDPSC-s (dental pulp) and hWJSC-s (umbilical cord), were evaluated on cultured skin epithelial cells during 24, 48, 72 and 120 h to determine the potential of this product to enhance cell proliferation and improve biofabrication strategies for tissue engineering. Then, secretomes were applied in vivo in preliminary analyses carried out on Wistar rats. Results showed that the use of secretomes derived from mesenchymal stem cells enhanced currently available cell culture protocols. Secretome was associated with increased viability, proliferation and migration of human skin epithelial cells, with hDPSC-s and hWJSC-s yielding greater inductive effects than hADSC-s. Animals treated with hWJSC-s and especially, hDPSC-s tended to show enhanced wound healing in vivo with no detectable side effects. Mesenchymal stem cells derived secretomes could be considered as a promising approach to cell-free therapy able to improve skin wound healing and regeneration.This study was supported by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I) of the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III), grants FIS PI18/0331, FIS PI21/0980, FIS PI18/0332, FIS PI20/0317, ICI19/00024 and ICI21/00010, and by grants PE-0395-2019 and PI-0442-2019 from the Consejería de Salud y Familias, Junta de Andalucía, Spain. Additional support was provided through grant B-CTS-450-UGR20 (proyectos de I + D + i en el marco del Programa Operativo FEDER Andalucía 2014–2020, University of Granada and Consejería de Transformación Económica, Industria, Conocimiento y Universidades), and cofinancing was provided from the European Regional Development Fund (ERDF) through the “Una manera de hacer Europa” program.S
Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis.
No full textMetabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient´s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients.S
SEOM-GEMCAD-TTD Clinical Guideline for the diagnosis and treatment of esophageal cancer (2021).
No full textEsophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.S
UVEITIS DUE TO IMMUNE-MEDIATED INFLAMMATORY DISEASES TREATED WITH CERTOLIZUMAB PEGOL. MULTICENTER STUDY OF 80 PATIENTS.
No full textGlia fuel neurons with locally synthesized ketone bodies to sustain memory under starvation.
No full textDuring starvation, mammalian brains can adapt their metabolism, switching from glucose to alternative peripheral fuel sources. In the Drosophila starved brain, memory formation is subject to adaptative plasticity, but whether this adaptive plasticity relies on metabolic adaptation remains unclear. Here we show that during starvation, neurons of the fly olfactory memory centre import and use ketone bodies (KBs) as an energy substrate to sustain aversive memory formation. We identify local providers within the brain, the cortex glia, that use their own lipid store to synthesize KBs before exporting them to neurons via monocarboxylate transporters. Finally, we show that the master energy sensor AMP-activated protein kinase regulates both lipid mobilization and KB export in cortex glia. Our data provide a general schema of the metabolic interactions within the brain to support memory when glucose is scarce.S