Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction ...in the efficacy of antiarrhythmic treatments.
The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies.
A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations.
Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of INa and ICaL (P <.01), with no significant differences in the remaining currents. ICaL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 ± 2.01cm2) and presented an increased efficacy in models with a depressed INa (P <.01).
Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of ICaL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.
Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding ...and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures.
We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment.
The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio OR, 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively).
In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.
Social functioning is severely affected in psychotic disorders. Negative symptoms and social cognition seem to play an important role in social functioning, although the preponderance and ...relationship between these three domains is not clear. In this study, we sought to assess the interrelation between social cognition, social functioning, and the expressiveness and experiential factors of negative symptoms in first-episode psychosis (FEP).
216 patients, participants in a multicentre study (AGES-CM), comprised our study sample. The WHO Disability Assessment Schedule (WHODAS 2.0) was used to assess functioning, whereas the Positive and Negative Schizophrenia Syndrome Scale (PANSS) was used to measure the severity of negative symptoms, and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) was applied to assess the emotional processing component of social cognition. Network analyses were conducted with the aim of analysing the patterns of relationships between social cognition, social functioning, and the expressiveness and experiential factors of negative symptoms.
Our findings suggest that there is a direct relationship between social cognition and social functioning (weight = -.077), but also an indirect connection between them, mediated by the experiential (but not the expressiveness) factor of negative symptoms (weight = 0.300).
The importance of the affectation of subdomains of social cognition, as well as the role of negative symptoms, specifically the experiential factor, in the functioning of patients with FEP seems to be relevant. The inclusion of these factors in prevention and treatment programs would thus allow us to reduce their impact on the social functioning of these patients.
To detect modifiable factors and target populations associated with uncontrolled type 2 diabetes in primary care.
Retrospective cross-sectional descriptive study.
Health center of Barranco Grande, ...Tenerife.
Random selection of patients with DM2 attended by 12 family doctors and 12 nurses.
In addition to the control of DM2, sociodemographic, clinical data, lifestyle and follow-up of preventive and therapeutic measures were obtained. After bivariate analysis, a multilevel multivariate model was adjusted by taking the quota of patients assisted by each physician as a second-level mixed-effect variable and the rest as first-level variables.
587 patients were recruited (46.5% female), treated with 1.9-1.1 antidiabetic drugs, with 4.1% therapeutic non-compliance, and suffering 13.8% therapeutic inertia. 23.7% showed poor DM2 control, being significantly worse (p<0.05) in male sex, age <65 years, evolution DM2 -5 years, work-active, upper-middle studies, inadequate diet, metabolic syndrome, ratio TG/HDL-3, complications of DM2, Charlson index<5, nursing visits <3/year, without ECG in the last year, and more drugs prescribed for DM2. The doctor-nurse quota was associated with poor control with an intraclass coefficient of 0.01.
Men under 65 years of age with DM2 evolution longer than 5 years are a target population to intensify interventions. Therapeutic non-compliance, inadequate diet, lack of adherence protocols and ratio TG/HDL>3 are the main modifiable factors on which to intervene. The association of the doctor-nurse quota with the control of DM2 is weak, probably due to adequate follow-up of preventive programs.
The consumption of processed meats (PMs) and red meats are linked to the likelihood of developing colorectal cancer. Various theories have been proposed to explain this connection, focusing on ...nitrosyl-heme and heme iron intake. We hypothesized that differences in nitrosyl-heme and heme iron intakes will be associated with various sociodemographic and lifestyle factors.
The study included 38,471 healthy volunteers (62% females) from five Spanish regions within the EPIC-Spain cohort. High-Performance Liquid Chromatography (HPLC) determined nitrosyl-heme and heme iron levels in the 39 most consumed PMs. Food intake was assessed using validated questionnaires in interviews. Nitrosyl-heme and heme iron intakes, adjusted for sex, age, body mass index (BMI), center, and energy intake, were expressed as geometric means due to their skewed distribution. Variance analysis identified foods explaining the variability of nitrosyl-heme and heme iron intakes.
The estimated intakes were 528.6 µg/day for nitrosyl-heme and 1676.2 µg/day for heme iron. Significant differences in nitrosyl-heme intake were found by sex, center, energy, and education level. Heme iron intake varied significantly by sex, center, energy, and smoking status. "
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the highest intake values, while "
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This is the first study to estimate levels of nitrosyl-heme intake directly in PMs for a large sample, revealing variations based on sex, BMI, smoking, and activity. Its data aids future exposure estimations in diverse populations.
Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. ...Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.
•IgG4 responder index correlates with response to treatment in IgG4-related disease.•Glucocorticoids and rituximab are the only treatments with a minimum of evidence supporting their ...use.•Anti-rheumatic disease modifying drugs combined with glucocorticoids could be useful in cases of a relapsing disease.
IgG4-related disease (IgG4-RD) is an autoimmune disease triggering an inflammatory cascade that leads to fibrosis. Outcome measures are limited and treatment options remain underexplored.
To assess the variation of the IgG4 responder index (IgG4-RI) in a cohort of IgG4-RD patients and to explore their treatments and outcomes.
We studied the clinical phenotype, severity of the disease and response to treatment in an ambispective multicenter cohort study including 14 different hospitals in Spain. All patients met the 2012 international consensus on pathology criteria for diagnosis.
Sixty-eight patients were included, with a mean age of 53.4 years and predominance of male sex. The most commonly involved tissues were: retroperitoneum (33%), orbital pseudotumor (28%) and maxillary and paranasal sinuses (24%). IgG4-RI values were higher in patients with multiorgan disease and before treatment. After being treated, IgG4-RI values were lower, in accordance with the high rates of treatment response. Most patients received: glucocorticoids (GC), surgery, azathioprine (AZA), mofetil mycophenolate or rituximab. GC alone, GC plus surgery and GC plus AZA were given in the most of the IgG4-RD disease activity episodes. All treatments had high response rates but relapses and flares were common.
IgG4-RI is a promising outcome measure in IgG4-RD, but still in development. Treatment algorithms are ill defined. GC and rituximab are the drugs with more evidence available. Disease modifying anti-rheumatic drugs may have a role in IgG4-RD and warrant more prospective studies.
IgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and ...there is a lack of large series of patients.To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients.A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis.Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses.Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent.This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD.
Personalized nutrition (PN) has been proposed as a strategy to increase the effectiveness of dietary recommendations and ultimately improve health status.
We aimed to assess whether including ...omics-based PN in an e-commerce tool improves dietary behavior and metabolic profile in general population.
A 21-wk parallel, single-blinded, randomized intervention involved 193 adults assigned to a control group following Mediterranean diet recommendations (n = 57, completers = 36), PN (n = 70, completers = 45), or personalized plan (PP, n = 68, completers = 53) integrating a behavioral change program with PN recommendations. The intervention used metabolomics, proteomics, and genetic data to assist participants in creating personalized shopping lists in a simulated e-commerce retailer portal. The primary outcome was the Mediterranean diet adherence screener (MEDAS) score; secondary outcomes included biometric and metabolic markers and dietary habits.
Volunteers were categorized with a scoring system based on biomarkers of lipid, carbohydrate metabolism, inflammation, oxidative stress, and microbiota, and dietary recommendations delivered accordingly in the PN and PP groups. The intervention significantly increased MEDAS scores in all volunteers (control—3 points; 95% confidence interval CI: 2.2, 3.8; PN—2.7 points; 95% CI: 2.0, 3.3; and PP—2.8 points; 95% CI: 2.1, 3.4; q < 0.001). No significant differences were observed in dietary habits or health parameters between PN and control groups after adjustment for multiple comparisons. Nevertheless, personalized recommendations significantly (false discovery rate < 0.05) and selectively enhanced the scores calculated with biomarkers of carbohydrate metabolism (β: −0.37; 95% CI: −0.56, −0.18), oxidative stress (β: −0.37; 95% CI: −0.60, −0.15), microbiota (β: −0.38; 95% CI: −0.63, −0.15), and inflammation (β: −0.78; 95% CI: −1.24, −0.31) compared with control diet.
Integration of personalized strategies within an e-commerce–like tool did not enhance adherence to Mediterranean diet or improved health markers compared with general recommendations. The metabotyping approach showed promising results and more research is guaranteed to further promote its application in PN.
This trial was registered at clinicaltrials.gov as NCT04641559 (https://clinicaltrials.gov/study/NCT04641559?cond=NCT04641559&rank=1).
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