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Enhanced oxidative stress and damage in glycated erythrocytes
Get PDFDiabetes is associated with a dramatic mortality rate due to its vascular complications. Chronic hyperglycemia in diabetes leads to enhanced glycation of erythrocytes and oxidative stress. Even though erythrocytes play a determining role in vascular complications, very little is known about how erythrocyte structure and functionality can be affected by glycation. Our objective was to decipher the impact of glycation on erythrocyte structure, oxidative stress parameters and capacity to interact with cultured human endothelial cells. In vitro glycated erythrocytes were prepared following incubation in the presence of different concentrations of glucose. To get insight into the in vivo relevance of our results, we compared these data to those obtained using red blood cells purified from diabetics or non-diabetics. We measured erythrocyte deformability, susceptibility to hemolysis, reactive oxygen species production and oxidative damage accumulation. Altered structures, redox status and oxidative modifications were increased in glycated erythrocytes. These modifications were associated with reduced antioxidant defence mediated by enzymatic activity. Enhanced erythrocyte phagocytosis by endothelial cells was observed when cultured with glycated erythrocytes, which was associated with increased levels of phosphatidylserine-likely as a result of an eryptosis phenomenon triggered by the hyperglycemic treatment. Most types of oxidative damage identified in in vitro glycated erythrocytes were also observed in red blood cells isolated from diabetics. These results bring new insights into the impact of glycation on erythrocyte structure, oxidative damage and their capacity to interact with endothelial cells, with a possible relevance to diabetes
COVID-19 and Sick Leave: An Analysis of the Ibermutua Cohort of Over 1,651,305 Spanish Workers in the First Trimester of 2020
Get PDFObjectives: The worldwide SARS-COV2 pandemic has impacted the health of workers and companies. The aim is to quantify it according to sick leave. Methods: Using ICD-9 codes, we analyzed Ibermutua records of all sick leaves during the first trimester of 2020, compared to during the same months of 2017, 2018, and 2019. We stratified the analysis by causes, patient sex, activity sectors, and regional data. All sick leaves were adjusted by the number of Ibermutua-affiliated persons in each period. Results: In March 2020, there was an unprecedented (116%) increase in total sick leaves, mainly due to infectious and respiratory diseases. Men and women were equally affected. All activity sectors were impacted, with the highest increase (457%) observed among health-related workers, especially due to contagious disease. The incidences of sick leaves were heterogeneous among different regions. Cost-analysis of sick leaves during the first trimester of 2020 compared with in previous years showed 40.3% increment (mean 2,813 vs. 2,005 euro per 100 affiliated workers). Conclusions: The SARS-COV2 pandemic is having a huge impact on workers' health, as shown by data regarding sick leaves in March 2020. This is associated with greater economic burden for companies, both due to the cost associated with sick leaves and the losses in productivity due to confinement
Clinical impact of strain histogram EUS elastography and contrast-enhanced EUS for the differential diagnosis of focal pancreatic masses: A prospective multicentric study
No full textBackground: Recent advances in EUS techniques (real-time EUS elastography and contrast-enhanced EUS) have allowed a better characterization of focal pancreatic masses. Mean strain histograms (SHs) are considered a good parameter for the semi-quantitative evaluation of focal pancreatic masses, alongside complementary contrast-enhanced EUS parameters which can be quantified during both the early arterial and late venous phase. Materials and Methods: The study design was prospective, blinded, and multicentric, assessing real-time EUS elastography and contrast-enhanced EUS results for the characterization of focal pancreatic masses using parametric measurements, in comparison with pathology which is the gold standard. SHs were performed based on the embedded software of the ultrasound system, with the values being reversed as opposed to our initially published data on hue histograms. Consequently, a cutoff of 80 was derived from previous multicentric trials. Contrast-enhanced EUS also allowed the focal masses to be classified as hyper-, iso-, or hypoenhanced in comparison with the normal pancreatic parenchyma. EUS-FNA was then performed for all patients, with a positive cytological diagnosis taken as a final proof of malignancy for the pancreatic masses. The diagnoses obtained by EUS-FNA were verified further either by surgery or during a clinical follow-up of at least 6 months. Results: A total number of 97 consecutive patients with focal pancreatic masses were included in the study. Based on previously defined cutoffs of 80, the values of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the mean SHs for the diagnosis of pancreatic cancer were 100%, 29.63%, 78.65%, 100%, and 80.41%, respectively. Corresponding values for contrast-enhanced EUS (taking into consideration hypoenhencement as a predictive factor of malignancy) were 98.57%, 77.78%, 92%, 95.45%, and 92.78%, respectively. Combining contrast enhancement-EUS (hypoenhencement) and semi-quantitative EUS elastography (SH cutoffs <80), the resulting values corresponding for sensitivity, specificity, and accuracy were 98.57%, 81.48%, and 93.81%, respectively. Conclusion: The current study using objective parametric tools for both EUS elastography and contrast-enhanced EUS confirmed the results of previous studies and meta-analyses that indicated a complementary role for the differential diagnosis of focal pancreatic masses. Moreover, the best values for the receiver operating curves were obtained using a sequential clinical algorithm based on the initial use of elastography, followed by contrast enhancement
Caffeine, a Risk Factor for Osteoarthritis and Longitudinal Bone Growth Inhibition
Get PDFOsteoarthritis (OA), the most common chronic rheumatic disease, is mainly characterized by a progressive degradation of the hyaline articular cartilage, which is essential for correct joint function, lubrication, and resistance. Articular cartilage disturbances lead to joint failure, pain, and disability. Hyaline cartilage is also present in the growth plate and plays a key role in longitudinal bone growth. Alterations of this cartilage by diverse pathologies have been related to longitudinal bone growth inhibition (LBGI), which leads to growth retardation. Diet can play a crucial role in processes involved in the OA and LBGI's onset and evolution. Specifically, there is ample evidence pointing to the negative impacts of caffeine consumption on hyaline cartilage. However, its effects on these tissues have not been reviewed. Accordingly, in this review, we summarize all current knowledge in the PubMed database about caffeine catabolic effects on articular and growth plate cartilage. Specifically, we focus on the correlation between OA and LBGI with caffeine prenatal or direct exposure. Overall, there is ample evidence indicating that caffeine intake negatively affects the physiology of both articular and growth plate cartilage, increasing consumers predisposition to suffer OA and LBGI. As a result, caffeine consumption should be avoided for these pathologies
Does the problem begin at the beginning? Medical students' knowledge and beliefs regarding antibiotics and resistance: a systematic review
Get PDFBACKGROUND: Studies have detected that prescribers display gaps in knowledge and inappropriate attitudes regarding antibiotics and resistances, but it is not known whether these are generated during professional practice or derive from the undergraduate stage of their education. Accordingly, the aim of this study was to identify medical students' knowledge, beliefs and attitudes regarding antibiotic use and antibiotic resistance, and whether these change over the course of their time at medical school. METHODS: We conducted a search of the MEDLINE and EMBASE databases, and included studies that measured knowledge and/or beliefs and/or attitudes regarding antibiotic prescribing and/or resistance, among medical students. RESULTS: Of the 509 studies retrieved, 22 met the inclusion criteria. While medical students perceived resistance as posing a major public health problem, both worldwide and in their own countries, students in the last two course years were more aware of overprescription of antibiotics in general, and of broad-spectrum antibiotics, at their teaching hospital. There was a considerable lack of knowledge about the treatment of high-incidence infections, and upper respiratory tract infections in particular (41-69% of participants believed antibiotics to be useful for treating these), without any differences by course year. Students were conscious of their personal shortcomings and thus showed willing to improve their education. CONCLUSIONS: Future physicians display important gaps in knowledge, particularly in terms of treatment of high-incidence infections. This finding may be of use when it comes to designing more effective training in antibiotic stewardship for undergraduates
Impact of cardiovascular risk factors on the clinical presentation and survival of pulmonary embolism without identifiable risk factor
Get PDFBackground: The nature of pulmonary embolism (PE) without identifiable risk factor (IRF) remains unclear. The objective of this study is to investigate the potential relationship between cardiovascular risk factors (CVRFs) and PE without IRF (unprovoked) and assess their role as markers of disease severity and prognosis. Methods: A case-control study was performed of patients with PE admitted to our hospital [2010-2019]. Subjects with PE without IRF were included in the cohort of cases, whereas patients with PE with IRF were allocated to the control group. Variables of interest included age, active smoking, obesity, and diagnosis of arterial hypertension, dyslipidemia or diabetes mellitus. Results: A total of 1,166 patients were included in the study, of whom 64.2% had PE without IRF. The risk for PE without IRF increased with age [odds ratio (OR): 2.68; 95% confidence interval (CI): 1.95-3.68], arterial hypertension (OR: 1.63; 95% CI: 1.27-2.07), and dyslipidemia (OR: 1.63; 95% CI: 1.24-2.15). The risk for PE without IRF was higher as the number of CVRF increased, being 3.99 (95% CI: 2.02-7.90) for subjects with >/=3 CVRF. The percentage of high-risk unprovoked PE increased significantly as the number of CVRF rose [0.6% for no CVRF; 23.8% for a CRF, P/=3, P<0.001 (OR: 14.1; 95% CI: 4.06-49.4)]. No significant differences were observed in 1-month survival between cases and controls, whereas differences in 24-month survival reached significance. Conclusions: A relationship was observed between CVRF and PE without IRF, as the risk for unprovoked PE increased with the number of CVRF. In addition, the number of CVRF was associated with PE without IRF severity, but not with prognosis
A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry
Get PDFBACKGROUND: The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry. METHOD: TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain. RESULTS: Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p<0.0001). The 12-month cumulative incidence of venous rethrombosis was 7.1% (95% CI, 4.7-10.2) in stage IV vs 3.0% (95% CI, 0.9-7.1) in stages I-III. The 12-month cumulative incidence of major/clinically relevant bleeding was 9.6% (95% CI, 6.1-14.0) in the presence of risk factors. CONCLUSION: CAT continues to be a relevant problem in the era of immunotherapy and targeted therapies. The initial TESEO data highlight the evolution of CAT, with new agents and thrombotic risk factors
Exposure to Residential Radon and COPD?: A Systematic Review
Get PDFIntroduction: The aim of this study was to analyse the relationship between exposure to residential radon and chronic obstructive pulmonary disease (COPD) by means of a systematic review. Material and Methods: A search was conducted in PubMed and OVID for papers making reference to the radon-COPD relationship. No search filters were applied, whether by date of publication, study type or sample size. All studies not written in English or Spanish were discarded. Results: A total of 174 and 57 papers were found in PubMed and OVID, respectively: of these, 13 (11 on miners and 2 on the general population) fulfilled the inclusion criteria. Only four of the studies on cohorts of miners analysed COPD as a specific disease, and only one reported statistically significant results. In addition, many of these studies lacked information on tobacco use among miners. In contrast, studies conducted on the general public showed an association between mortality and hospital admissions, on the one hand, and residential radon on the other. Conclusion: There are not enough studies to provide a basis for confirming or ruling out an association between radon exposure and COPD. Nonetheless, the most recent general population studies point to evidence of a possible association. In view of the heterogeneity of available studies, it is impossible to say whether this gas may or may not affect COPD morbidity and mortality, until such a time as further studies are carried out
The FXII c.-4T > C Polymorphism as a Disease Modifier in Patients With Hereditary Angioedema Due to the FXII p.Thr328Lys Variant
Get PDFBackground: Hereditary angioedema due to the Thr328Lys variant in the coagulation factor XII (HAE-FXII) affects mainly women in whom the symptomatology is dependent on high estrogen levels. Clinical variability and incomplete penetrance are challenging features that hinder the diagnosis and management of HAE-FXII. The c.-4T>C Kozak polymorphism is the only common variation accounting for FXII plasma levels and was previously shown to modify the course of HAE due to C1-Inhibitor deficiency. Objectives: To assess the influence of the c.-4T>C polymorphism on disease expression in 39 Spanish HAE-FXII index patients. Methods: The c.-4T>C polymorphism was sequenced by the standard Sanger method, and HAE severity was calculated according to the score by Cumming et al. (2003) The activation of the contact system was quantified by the kallikrein-like activity of plasma in chromogenic assays upon activation with high-molecular-weight dextran sulfate. Results: The c.-4CC genotype was overrepresented in the studied cohort: 82% were CC-homozygous (expected frequency = 59%) and 18% were CT-heterozygous (expected frequency = 39%) (p = 0.001). Patients with a c.-4CC genotype exhibited higher kallikrein-like activity (0.9659 +/- 0.1136) than those with a c.-4TC genotype (0.7645 +/- 0.1235) (p = 0.024) or healthy donors. Moreover, the polymorphism influenced HAE-FXII severity score (c.-4CC = 4.43 +/- 2.28 vs c.-4TC = 2.0 +/- 1.15; p = 0.006) but not the degree of estrogen dependence or time until remission. Conclusion: The c.-4T>C polymorphism is overrepresented in a Spanish HAE-FXII cohort and significantly influences the degree of contact system activation and the clinical severity of the disease
Health Outcome Predictive Evaluation for COVID 19 international registry (HOPE COVID-19), rationale and design
Get PDFThe disease produced by the new coronavirus known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), named COVID-19 (Coronavirus Disease-2019) has recently been classified as a pandemic by the World Health Organization (WHO). However, scarce clinical data is available and generally limited to the Chinese population due to the first cases were identified in Wuhan (Hubei, China).This article describes the rationale and design of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID 19) registry (ClinicalTrials.gov Identifier: NCT04334291). With an ambispective cohort design, eligible patients are those discharged, deceased or alive, from any hospital center with a confirmed diagnosis or a COVID-19 high suspicion. With a current recruitment of more than 7000 cases, in 46 hospitals in 8 countries, since it is not possible to estimate the sample size based on literature reports, the investigators will try to get the maximum numbers of patients possible. The study primary objective is all cause mortality and aims to characterize the clinical profile of patients infected in order to develop a prognostic clinical score allowing, rapid logistic decision making. As secondary objectives, the analysis of other clinical events, the risk-adjusted influence of treatments and previous comorbidities of patients infected with the disease will be performed.The results of HOPE COVID-19 will contribute to a better understanding of this condition. We aim to describe the management of this condition as well as the outcomes in relation to the therapy chosen, in order to gain insight into improving patient care in the coming months. Clinical Trial registration: ClinicalTrials.gov. Unique identifier: NCT04334291