The Global Burden of Disease (GBD) study measures the health of populations worldwide and by country on an annual basis and aims at helping guide public policy on health issues. The GBD estimates for ...Spain in 2016 and recent trends in mortality and morbidity from 2006 to 2016 were recently published. According to these estimates, chronic kidney disease was the 8th cause of death in Spain in 2016. Among the top ten causes of death, chronic kidney disease was the fastest growing from 2006 to 2016, after Alzheimer disease. At the current pace of growth, chronic kidney disease is set to become the second cause of death in Spain, after Alzheimer disease, by 2100. Additionally, among major causes of death, chronic kidney disease also ranked second only to Alzheimer as the fastest growing cause of Years Lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs). Public resources devoted to prevention, care and research on kidney disease should be in line with both its current and future burden.
El estudio Global Burden of Disease (GBD) mide la salud de las poblaciones en todo el mundo y en cada país de forma annual, y tiene como objetivo ayudar a orientar las políticas públicas sobre cuestiones de salud. Recientemente se publicaron las estimaciones GBD 2016 para España y las tendencias recientes en mortalidad y morbilidad de 2006 a 2016. Según estas estimaciones, la enfermedad renal crónica fue la octava causa de muerte en España en 2016. Entre las 10 principales causas de muerte, la enfermedad renal crónica fue la que más creció entre 2006 y 2016, después de la enfermedad de Alzheimer. Al ritmo actual de crecimiento, la enfermedad renal crónica se convertirá en la segunda causa de muerte en España, después del Alzheimer, hacia el 2100. Además, entre las principales causas de muerte, la enfermedad renal crónica también ocupa el segundo lugar después del Alzheimer como la que más creció en años vividos con discapacidad (AVD) y en años de vida ajustados por discapacidad (AVAD). Los recursos públicos dedicados a la prevención, atención e investigación de la enfermedad renal deberían estar en línea con su carga actual y futura.
ABSTRACT
Macrophages play a central role in tissue remodeling, repair, and resolution of inflammation. Macrophage polarization to Ml or M2 activation status may determine the progression or ...resolution of the inflammatory response. We have previously reported that cardiotrophin‐1 (CT‐1) displays both cytoprotective and metabolic activities. The role of CT‐1 in inflammation remains poorly understood. Here, we employed recombinant CT‐1 (rCT‐1) and used CT‐1–null mice and myeloid‐specif ic CT‐1 transgenic mice to investigate whether CT‐1 might play a role in the modulation of the inflammatory response. We observed that CT‐1 deficiency was associated with enhanced release of inflammatory mediators and with stronger activation of NF‐κB in response to LPS, whereas the inflammatory response was attenuated in CT‐1 transgenic mice or by administering rCT‐1 to wild‐type animals prior to LPS challenge. We found that CT‐1 promoted IL‐6 expression only by nonhematopoietic cells, whereas LPS up‐regulated IL‐6 expression in both hematopoietic and nonhematopoietic cells. Notably, rCT‐1 inhibited LPS‐mediated soluble IL‐6R induction. Using IL‐6−/− mice, we showed that rCT‐1 inhibited LPS‐induced TNF‐α and IFN‐γ response in an IL‐6–independent manner. Importantly, we demonstrated that CT‐1 primes macrophages for IL‐4–dependent M2 polarization by inducing IL‐4 receptor expression. Mechanistic analyses showed that the signal transducer and activator of transcription 3–suppressor of cytokine signaling 3 axis mediates this effect. Our findings support the notion that CT‐1 is a critical regulator of inflammation and suggest that rCT‐1 could be a molecule with potential therapeutic application in inflammatory conditions.—Carneros, D., Santamaría, E. M., Larequi, E., Vélez‐Ortiz, J. M., Reboredo, M., Mancheño, U., Perugorria, M. J., Navas, P., Romero‐Gómez, M., Prieto, J., Hervás‐Stubbs, S., Bustos, M. Cardiotrophin‐1 is an anti‐inflammatory cytokine and promotes IL‐4–induced M2 macrophage polarization. FASEB J. 33, 7578–7587 (2019). www.fasebj.org
Online patient registries are used to collect data on clinical conditions with rare occurrence or unclear diagnostic and management practices. The success of these registries depends on clear ...definition of goals, correct identification of patient population/inclusion criteria, availability of appropriate setup and maintenance tools, and the quality of dissemination. The Scientific and Standardization Committee (SSC) for Women's Health Issues in Thrombosis and Hemostasis, one of 20 committees of the International Society on Thrombosis and Haemostasis (ISTH) has developed 6 registries for women's bleeding and thrombotic conditions over the past 2 years and are currently in various stages of progress. Here, we provide information about these registries, including rationale, objectives, and methods for data collection. The aim is to enhance worldwide participation and thus promote the success of these registries. We used ISTH REDCap, a mature and secure Web application for building and managing online surveys and databases, and the ISTH advertising platform to maximize participation. Registries (links and project details available on ISTH and Women's SSC Web sites) include: (1) WiTEAM, project on thrombophilia and placenta‐mediated obstetric complications; (2) a registry for disseminated intravascular coagulation in pregnancy; (3) severe congenital protein C deficiency—an obstetric study; (4) obstetric and gynecologic outcomes of women with platelet function disorders; (5) thrombolysis and invasive treatments for massive pregnancy‐related pulmonary embolism; (6) pregnancy and exposure to direct oral anticoagulants. The ISTH promotes online registries on women's issues to enhance understanding of current practices, identify knowledge gaps, promote research, and ultimately improve patient safety and quality of life.
Calcimimetics decrease parathyroid hormone (PTH) secretion in patients with secondary hyperparathyroidism. The decrease in PTH should cause a reduction in bone turnover; however, the direct effect of ...calcimimetics on bone cells, which express the calcium-sensing receptor (CaSR), has not been defined. In this study, we evaluated the direct bone effects of CaSR activation by a calcimimetic (AMG 641) in vitro and in vivo. To create a PTH “clamp,” total parathyroidectomy was performed in rats with and without uremia induced by 5/6 nephrectomy, followed by a continuous subcutaneous infusion of PTH. Animals were then treated with either the calcimimetic or vehicle. Calcimimetic administration increased osteoblast number and osteoid volume in normal rats under a PTH clamp. In uremic rats, the elevated PTH concentration led to reduced bone volume and increased bone turnover, and calcimimetic administration decreased plasma PTH. In uremic rats exposed to PTH at 6-fold the usual replacement dose, calcimimetic administration increased osteoblast number, osteoid surface, and bone formation. A 9-fold higher dose of PTH caused an increase in bone turnover that was not altered by the administration of calcimimetic. In an osteosarcoma cell line, the calcimimetic induced Erk1/2 phosphorylation and the expression of osteoblast genes. The addition of a calcilytic resulted in the opposite effect. Moreover, the calcimimetic promoted the osteogenic differentiation and mineralization of human bone marrow mesenchymal stem cells in vitro. Thus, calcimimetic administration has a direct anabolic effect on bone that counteracts the decrease in PTH levels.
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Global brain health initiatives call for improving methods for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic ...procedures in upper-middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers.
This cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants 904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs) collected in 11 clinical centres across five LAC (ReDLat cohort).
A fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex.
Results demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region.
This work was supported by the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by NIA/NIH (R01AG057234), Alzheimer's Association (SG-20-725707-ReDLat), Rainwater Foundation, Takeda (CW2680521), Global Brain Health Institute; as well as CONICET; FONCYT-PICT (2017-1818, 2017-1820); PIIECC, Facultad de Humanidades, Usach; Sistema General de Regalías de Colombia (BPIN2018000100059), Universidad del Valle (CI 5316); ANID/FONDECYT Regular (1210195, 1210176, 1210176); ANID/FONDAP (15150012); ANID/PIA/ANILLOSACT210096; and Alzheimer's Association GBHI ALZ UK-22-865742.
Genome-wide association studies (GWASs) have identified a number of genetic risk loci associated with systemic sclerosis (SSc) and Crohn's disease (CD), some of which confer susceptibility to both ...diseases. In order to identify new risk loci shared between these two immune-mediated disorders, we performed a cross-disease meta-analysis including GWAS data from 5,734 SSc patients, 4,588 CD patients and 14,568 controls of European origin. We identified 4 new loci shared between SSc and CD, IL12RB2, IRF1/SLC22A5, STAT3 and an intergenic locus at 6p21.31. Pleiotropic variants within these loci showed opposite allelic effects in the two analysed diseases and all of them showed a significant effect on gene expression. In addition, an enrichment in the IL-12 family and type I interferon signaling pathways was observed among the set of SSc-CD common genetic risk loci. In conclusion, through the first cross-disease meta-analysis of SSc and CD, we identified genetic variants with pleiotropic effects on two clinically distinct immune-mediated disorders. The fact that all these pleiotropic SNPs have opposite allelic effects in SSc and CD reveals the complexity of the molecular mechanisms by which polymorphisms affect diseases.
Background:
The COVID-19 pandemic has led to an increase in the behavior of self-medication (SM). Given the massive release of misleading information during the pandemic, some pharmacies recommend ...drugs such as ivermectin, azithromycin, and hydroxychloroquine that are not useful for preventing or treating COVID-19 and could expose patients to unnecessary adverse drug reactions (ADRs), drug-drug interactions (DDIs), disease masking, and antibiotic resistance.
Rationale:
SM with drugs advertised for COVID-19 can have consequences, and people should be aware of approved uses, potential contraindications, and ADRs. Thus, the aim of this study was to know the drug therapies including natural products and homeopathic drugs offered by Colombian pharmaceutical establishments for the prevention and treatment of COVID-19, as well as the information provided on the safe use of the product.
Methods:
An observational, cross-sectional mystery shopping study was carried out to determine the pharmaceutical alternatives for the management of COVID-19 offered by pharmaceutical establishments (drugstores, pharmacies, homeopathic pharmacies, and nutritional supplements stores) in Colombia, and information related to the safe use of the product. The study included 482 pharmaceutical establishments from 16 Colombian departments. Data collection was done through telephone calls to each of the establishments following an interview protocol pretending to be a patient who presents symptoms related to COVID-19.
Results:
About 57.3% (276) of the establishments recommended a product for the treatment of COVID-19 infection, 66.6% (321) asked whether the caller had COVID-19 symptoms and what they are, and 44.2% (213) suggested taking a COVID-19 test. Of 59 drugs suggested by pharmacies, the most recommended were azithromycin, ivermectin, acetaminophen, ibuprofen, and ASA (aspirin). From the establishments that recommended a product, dosage was indicated in 85.5% (236) of the pharmaceutical establishments and 14.5% (40) of the establishments reported the most common adverse effects of this substance. About 9.4% (26) of the establishments reported possible interactions of the recommended drugs and substances with food, beverages, or supplements.Conclusion: Pharmaceutical establishments in Colombia seem to have significantly contributed to self-medication for COVID-19 in Colombia during the pandemic. This behavior is inappropriate, since the mild forms of the disease do not have a specific treatment.
Plain Language Summary
Self-medication induced by pharmaceutical establishments in Colombia during the COVID-19 pandemic
Background: The COVID-19 pandemic has led to an increase in the behavior of self-medication (SM). Given the massive release of misleading information during the pandemic, some pharmacies recommend drugs such as ivermectin, azithromycin, hydroxychloroquine among others, which are not useful for preventing or treating COVID-19 and could expose patients to unnecessary side effects and interactions with other medications. People should be aware of the approved and non-approved uses, and potential side effects of these drugs. Rationale: The aim of this study was to know the drugs, including natural products and homeopathic drugs, offered by Colombian pharmaceutical establishments for the prevention and treatment of COVID-19, as well as the information provided on the safe use of the product. Methods: The study was done using the mystery shopping method, collecting data through telephone calls to each of the establishments by a trained individual pretending to be a patient with COVID-19 symptoms. The study included 482 pharmaceutical establishments from 16 Colombian departments. Results: Of 59 drugs suggested by pharmacies, the most recommended were azithromycin, ivermectin, acetaminophen, ibuprofen, and aspirin. The recommended dose was indicated in 85.5% (236) of the pharmaceutical establishments, and 14.5% (40) of them reported the most common adverse effects of the recommended product. About 9.4% (26) of the establishments reported possible interactions of the recommended drugs and substances with food, beverages, or supplements. Conclusion: The majority of the pharmaceutical establishments included in the study promoted inadequate self-medication for COVID-19 in Colombia during the pandemic.
Cell-to-cell communication is essential for proper embryonic development and its dysfunction may lead to disease. Recent research has drawn attention to a new group of molecules called connexins ...(Cxs) and pannexins (Panxs). Cxs have been described for more than forty years as pivotal regulators of embryogenesis; however, the exact mechanism by which they provide this regulation has not been clearly elucidated. Consequently, Cxs and Panxs have been linked to congenital neurodegenerative diseases such as Charcot-Marie-Tooth disease and, more recently, chronic hemichannel opening has been associated with adult neurodegenerative diseases (e.g., Alzheimer’s disease). Cell-to-cell communication via gap junctions formed by hexameric assemblies of Cxs, known as connexons, is believed to be a crucial component in developmental regulation. As for Panxs, despite being topologically similar to Cxs, they predominantly seem to form channels connecting the cytoplasm to the extracellular space and, despite recent research into Panx1 (Pannexin 1) expression in different regions of the brain during the embryonic phase, it has been studied to a lesser degree. When it comes to the nervous system, Cxs and Panxs play an important role in early stages of neuronal development with a wide span of action ranging from cellular migration during early stages to neuronal differentiation and system circuitry formation. In this review, we describe the most recent available evidence regarding the molecular and structural aspects of Cx and Panx channels, their role in neurodevelopment, congenital and adult neurological diseases, and finally propose how pharmacological modulation of these channels could modify the pathogenesis of some diseases.
Background: Since the end of 2023, an elevated incidence and severity of Mycoplasma pneumoniae infections among children in Asia has been noted. Subsequently, this trend was observed in several ...European countries although limited data are currently available. We conducted a national study to delineate the ongoing M. pneumoniae outbreak in our country. Methods: A multicenter retrospective observational study was conducted across 32 hospitals in Spain, encompassing patients under 18 years old hospitalized for M . pneumoniae infection from January 2023 to March 2024. Infection was confirmed by positive polymerase chain reaction and/or by 2 serological tests. Results: A total of 623 children were included, with 79% of cases diagnosed in the final 3 months of the study period. Pneumonia was the most common diagnosis (87%). Respiratory symptoms were present in 97% of cases, with 62% requiring oxygen supplementation and 14% requiring admission to the pediatric intensive care unit (PICU). Risk factors for PICU admission included the presence of neurological symptoms, hypoxemia and a history of prematurity. Children admitted to the PICU exhibited significantly higher neutrophil counts upon admission. Conclusions: We have observed a notable increase in hospital admissions, including PICU support by up to 14%, due to M. pneumoniae infection in our country since November 2023, indicative of a more severe clinical course associated with this pathogen.
To evaluate the influence of ABO and Rh blood groups on morbidity among SARS-CoV-2 infected pregnancies.
Prospective observational study.
78 centers of the Spanish Obstetric Emergency Group.
Pregnant ...women with SARS-CoV-2 tested with polymerase-chain-reaction between 26-February and 5-November 2020. A cohort of 1278 SARS-CoV-2(+) pregnant women was analyzed and a concurrent comparison group of 1453 SARS-COV-2(−) patients was established.
Data were collected from medical charts. SARS-COV-2(+) was compared with SARS-COV-2(−) for differences in distribution of blood groups. We performed multivariate analysis, controlling for maternal age and ethnicity, to evaluate association of ABO and Rh blood groups with maternal and perinatal outcomes in SARS-CoV-2(+) patients with adjusted odds ratios (aOR) and 95% confidence intervals (CI).
Medical morbidity: Symptomatic COVID-19 and medical complications. Obstetric outcomes: caesarean delivery, preterm deliveries, preterm premature rupture of membranes (PPROM), hemorrhagic events, pre-eclampsia, maternal and neonatal mortality, stillbirth.
Differences were noted between blood types and Rh for age and ethnicity comparing SARS-CoV-2(+) and SARS-CoV-2(−) groups (p < 0.05). Among the SARS-CoV-2(+) cohort, the odds of symptomatic COVID-19 and obstetric hemorrhagic event were higher in Rh+ vs Rh− mothers (aOR 1.48, 95% CI 1.02–2.14, p = 0.037, and aOR 8.72, 95% CI 1.20–63.57, p = 0.033, respectively), and PPROM were higher among blood type A vs non-A mothers (aOR 2.06, 95% CI 1.01–4.18, p = 0.046).
In SARS-CoV-2(+) pregnant women, Rh− status was associated with a lower risk of symptomatic COVID-19, while Rh+ and blood group A were associated with obstetric hemorrhage and PPROM, respectively.
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