The paradigmatic relationship between aging and atherosclerotic cardiovascular events does not apply to all patient populations. Though trisomy 21 (T21) and its phenotypic expression, Down syndrome ...(DS), are conditions that involve premature aging, the cardiovascular system of adults with DS appears to be particularly spared from this early senescence. Despite a higher prevalence of some classic cardiovascular risk factors in adults with DS than in the general population, such as dyslipidemia, obesity, or sedentarism, these individuals do not develop hypertension or suffer major cardiovascular events as they age. The protective factors that prevent the development of hypertension in T21 are not well established. Genes like RCAN1 and DYRK1A, both on chromosome 21 and over‐expressed in adults with DS, appear to play a major role in cardiovascular prevention. Their regulation of the renin‐angiotensin‐aldosterone system (RAAS) and neprilysin synthesis could underlie the constitutive protection against arterial hypertension in adults with DS and explain the absence of increased arterial stiffness in this population. A better understanding of these molecular pathways could have enormous implications for the clinical management of adults with DS and might foster the development of novel therapeutic targets in cardiovascular prevention for the general population.
The increase and persistence of inflammation in community-acquired pneumonia (CAP) patients can lead to higher mortality. Biomarkers capable of measuring this inadequate inflammatory response are ...likely candidates to be related with a bad outcome. We investigated the association between concentrations of several inflammatory markers and mortality of CAP patients.
This was a prospective study of hospitalised CAP patients in a Spanish university hospital. Blood tests upon admittance and in the early-stage evolution (72-120 hours) were carried out, where C-reactive protein, procalcitonin, proadrenomedullin, copeptin, white blood cell, Lymphocyte Count Percentage (LCP), Neutrophil Count Percentage (NCP) and Neutrophil/Lymphocyte Ratio (NLR) were measured. The outcome variable was mortality at 30 and 90 days. Statistical analysis included logistic regression, ROC analysis and area-under-curve test.
154 hospitalised CAP patients were included. Patients who died during follow-up had higher levels of procalcitonin, copeptin, proadrenomedullin, lower levels of LCP, and higher of NCP and NLR. Remarkably, multivariate analysis showed a relationship between NCP and mortality, regardless of age, severity of CAP and comorbidities. AUC analysis showed that NLR and NCP at admittance and during early-stage evolution achieved a good diagnostic power. ROC test for NCP and NLR were similar to those of the novel serum biomarkers analysed.
NLR and NCP, are promising candidate predictors of mortality for hospitalised CAP patients, and both are cheaper, easier to perform, and at least as reliable as the new serum biomarkers. Future implementation of new biomarkers would require comparison not only with classic inflammatory parameters like White Blood Cell count but also with NLR and NCP.
Patients with community-acquired pneumonia (CAP) undergo a dysregulated host response that is related to mortality. MicroRNAs (miRNAs) participate in this response, but their expression pattern and ...their role as biomarkers in CAP have not been fully characterized.
A prospective observational study was performed in a cohort of 153 consecutive patients admitted to hospital with CAP. Clinical and analytical variables were collected, and the main outcome variable was 30-day mortality. Small RNA was purified from plasma of these patients obtained on the first day of admission, and miRNA expression was analyzed by RT-PCR. Univariate and multivariate analyses were carried out through the construction of a logistic regression model. The proposed model was compared with established prognostic clinical scales using ROC curve analysis.
The mean age of the patients included was 74.7 years SD 15.9. Their mean PSI was 100.9 SD 34.6 and the mean modified Charlson index was 2.9 SD 3.0. Both miR-146a and miR-16-5p showed statistically significant association with 30-day mortality after admission due to CAP (1.10 vs. 0.23 and 51.74 vs. 35.23, respectively), and this association remained for miR-16-5p in the multivariate analysis adjusted for age, gender and history of bronchoaspiration (OR 0.95, p = 0.021). The area-under-the-curve (AUC) of our adjusted multivariate model (AUC = 0.954 95%CI 0.91-0.99), was better than those of prognostic scales such as PSI (AUC = 0.799 0.69-0.91) and CURB-65 (AUC = 0.722 0.58-0.86).
High levels of miR-146a-5p and miR-16-5p upon admission due to CAP are associated with lower mortality at 30 days of follow-up. Both miRNAs could be used as biomarkers of good prognosis in subjects hospitalized with CAP.
To describe congenital and acquired heart diseases in a Spanish cohort of adults with Down syndrome (DS), which could inform potential health recommendations for this population. Cross-sectional, ...observational study of adults with DS evaluated consecutively at a tertiary care, outpatient center between January 1 and December 31, 2019. The study population comprised 937 patients (51.8% men; median IQR age, 42 18 years). An echocardiogram was available in the clinical chart of 420 patients (44.8%). The diagnosis of any form of heart disease was confirmed in 211 patients (22.5%): 101 (10.8%) had congenital heart defects, 80 (8.5%) simultaneous congenital and valvular heart diseases, and 30 (3.2%) isolated valvular heart disease. 111 patients (52.6% of those with congenital or valvular heart disease) had received corrective cardiac surgery. A total of 65 individuals were receiving medical management alone (30.8%), while 35 did not require any treatment because their cardiac disease was mild (16.6%). We found a high overall prevalence of heart disease in patients with DS, higher than previously reported for the pediatric population. Management of cardiovascular disease in adults with DS differs from that of the general population and should include universal echocardiography-based screening.
Gastroenterology is one of the medical specialties offered to residency training candidates each year. This project analyzes the data associated with the choice of a Gastroenterology residency ...program in recent years.
Data related to specialty selection were obtained from official reports with regard to the allocation of residency places by the Spanish Ministry of Health, Social Services and Equality. Information was collected from various teaching centers via their training guides, the Spanish National Catalogue of Hospitals and the National Transplant Organization.
The median consecutive number involved in the choice of Gastroenterology training has decreased year after year, and this specialty is now positioned among the five most commonly selected residency programs in 2015. The median number of hospitals with a higher number of beds, adult liver transplantation activities and dedicated GI bleeding units is significantly lower. This is also true when centers are analyzed according to the presence of specific Gastroenterology on-call shifts for residents or their association with medical schools. Data from the past five years highlight Madrid, Aragón and the Basque Country as the autonomous communities where Gastroenterology is the most popular. Centers selected by candidates with the lowest median consecutive numbers from 2011-2015 included the university hospitals Ramón y Cajal, Santiago de Compostela and Gregorio Marañón.
Gastroenterology has gradually escalated in the ranking of residency choices and is now one of the five most popular options. Potential residents prefer larger centers with complex-care patients and more research activity.
Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its ...underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a signature of 15 dysregulated miRNAs between COVID-19 and CAP patients. Additionally, multivariate analysis displayed a combination of 4 miRNAs (miR-106b-5p, miR-221-3p, miR-25-3p and miR-30a-5p) that significantly discriminated between both pathologies. Search for targets of these miRNAs, combined with plasma protein measurements, identified a differential cytokine signature between COVID-19 and CAP that included EGFR, CXCL12 and IL-10. Significant differences were also detected in plasma levels of CXCL12, IL-17, TIMP-2 and IL-21R between mild and severe COVID-19 patients. These findings provide new insights into the etiopathological mechanisms underlying COVID-19.
Long-COVID (LC) is characterised by persistent symptoms for at least 3 months after acute infection. A dysregulation of the immune system and a persistent hyperinflammatory state may cause LC. LC ...patients present differences in activation and exhaustion states of innate and adaptive compartments. Different T CD4+ cell subsets can be identified by differential expression of chemokine receptors (CCR). However, changes in T cells with expression of CCRs such as CCR6 and CXCR3 and their relationship with CD8+ T cells remains unexplored in LC. Here, we performed unsupervised analysis and found CCR6+ CD4+ subpopulations enriched in COVID-19 convalescent individuals upon activation with SARS-CoV-2 peptides. SARS-CoV-2 specific CCR6+ CD4+ are decreased in LC patients, whereas CXCR3+ CCR6- and CCR4+ CCR6- CD4+ T cells are increased. LC patients showed lower IFN-γ-secreting CD8+ T cells after stimulation with SARS-CoV-2 Spike protein. This work underscores the role of CCR6 in the pathophysiology of LC.
•Decreased SARS-CoV-2-specific CCR6+ CD4+ cells in patients with long-COVID•Increased SARS-CoV-2 specific CXCR3+ CCR6- and CCR4+ CCR6- CD4 cells in long-COVID•Patients with long-COVID have lower IFN-γ + CD8+ T cells
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