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Background: Intraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum., Methods: Intraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry., Results: Our results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin-15 (IL-15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL-15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL-15 receptor was not increased either on Intraepithelial lymphocytes from CD patients., Conclusions: IL-15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Breath tests with glucose, lactulose or lactitol are useful for diagnosis of small intestinal bacterial overgrowth (SIBO). Nevertheless, they have suboptimal sensitivity and specificity and, indeed, are positive in a considerable number of patients with irritable bowel syndrome (IBS). The complexity in the management of patients with functional intestinal disorders and the availability of these tests are leading to frequent diagnoses of SIBO. Intestinal Fatty-Acid Binding protein (I-FABP) is a protein present in the cytosol of intestinal epithelial cells. Its plasmatic levels have been related to different enteropathies and, therefore, could be a marker of early intestinal damage with unconfirmed clinical utility. Hence, we have studied the plasmatic I-FABP level of patients who are requested a lactitol test to confirm SIBO and related it to clinical and laboratory characteristics and SIBO test results.

Background: Guidelines recommend pharmacological treatment for systolic blood pressure (SBP) of 130 to 139 mm Hg in secondary prevention. However, uncertainty persists in primary prevention in low cardiovascular risk patients (CVR)., Methods: Cohort study representative of the general population of Albacete/Southeast Spain. We examined 1029 participants with untreated blood pressure and free of cardiovascular disease, followed-up during 1992 to 2019. Cox regression modeled the association of SBP with cardiovascular morbidity and mortality (outcome-1) and cardiovascular morbidity and all-cause mortality (outcome-2)., Results: Participants' mean age was 44.8 years (53.8%, women; 77.1% at low-CVR); 20.3% had SBP 120 to 129; 13.0% 130 to 139 at low-CVR and 3.4% at high-CVR; and 27.4% ≥140 mm Hg. After a 25.7-year median follow-up, 218 outcome-1 and 302 outcome-2 cases occurred. Unadjusted hazard ratios of outcome-1 for these increasing SBP categories (versus <120) were 2.72, 2.27, 11.54, and 7.52, respectively; and 2.69, 2.32, 10.55, and 7.34 for outcome-2 (all P <0.01). After adjustment for other risk factors, hazard ratio (95% CI) of outcome-1 were 1.49 (0.91-2.44), 1.65 (0.94-2.91, P =0.08), 1.36 (0.72-2.57), and 1.82 (1.15-2.88), respectively, and 1.39 (0.91-2.11), 1.69 (1.05-2.73), 1.09 (0.63-1.88), and 1.64 (1.11-2.41) for outcome-2. Compared with 130 to 139 at low-CVR, hazard ratio for 130 to 139 at high-CVR was 4.85 for outcome-1 ( P <0.001) and 4.43 for outcome-2 ( P <0.001)., Conclusions: In this primary prevention population of relatively young average age, untreated SBP of 130 to 139 mm Hg at low-CVR had long-term prognostic value and might benefit from stricter SBP targets. High-CVR patients had nonsignificant higher risk (limited sample size) but 4-fold greater risk when compared with low-CVR. Overall, results indicate the importance of risk stratification, supporting risk-based decision-making., Competing Interests: Disclosures None.

Background and objectives : Arterial hypertension (HTN) is the leading preventable cause of atherosclerotic cardiovascular diseases (ASCVD) and death from all causes. This study aimed to determine the prevalence rates of HTN diagnosed according to the threshold diagnostic criteria 130/80 mmHg and 140/90 mmHg, to compare blood pressure (BP) control, and to evaluate their associations with cardiovascular diseases and cardiometabolic and renal risk factors. Materials and Methods : This was a cross-sectional observational study conducted in primary care with a population-based random sample: 6588 people aged 18.0-102.8 years. Crude and adjusted prevalence rates of HTN were calculated. BP control was compared in HTN patients with and without ASCVD or chronic kidney disease (CKD). Their associations with cardiovascular diseases and cardiometabolic and renal factors were assessed using bivariate and multivariate analysis. Results : Adjusted prevalence rates of HTN diagnosed according to 140/90 and 130/90 criteria were 30.9% (32.9% male; 29.7% female) and 54.9% (63.2% male; 49.3% female), respectively. BP < 130/80 mmHg was achieved in 60.5% of HTN patients without ASCVD or CKD according to 140/90 criterion, and 65.5% according to 130/80 criterion. This BP-control was achieved in 70% of HTN patients with ASCVD and 71% with CKD, according to both criteria. Coronary heart disease (CHD), heart failure, atrial fibrillation, stroke, diabetes, prediabetes, low glomerular filtration rate (eGFR), hyperuricemia, hypercholesterolemia, obesity, overweight, and increased waist-to-height ratio were independently associated with HTN according to both criteria. Conclusions : Almost a third of the adult population has HTN according to the 140/90 criterion, and more than half according to the 130/90 criterion, with a higher prevalence in men. The main clinical conditions associated with HTN were heart failure, diabetes, CHD, low eGFR, and obesity.

Background: Carriers of the human leucocyte antigen variant HLADQA1*05 (rs2097432) are at risk of developing antibodies against infliximab and adalimumab with reduced tumor necrosis factor (TNF) antagonist persistence. The impact of proactive therapeutic drug monitoring (PTDM) on this association has been barely assessed., Methods: We conducted a retrospective single-center cohort study including patients with inflammatory bowel disease starting anti-TNF therapy between January 2017 and March 2021. Proactive therapeutic drug monitoring was defined as periodic drug level measurement (≥2 determinations during the first year of treatment and ≥1/annual determination during the following years), regardless of clinical condition, followed by dose optimization. Variables associated with treatment persistence were assessed with multivariable Cox regression analysis., Results: A total of 112 patients were included, 52 (46.4%) HLA-DQA1*05 carriers, with a median follow-up of 73.9 (interquartile range, 35.4-133.1) weeks. Combination therapy with thiopurines was more frequent among HLA-DQA1*05 noncarriers (28 [46.7%] vs 12 [23.1%]; P = .01). Clinical remission rates at week 14 (77.9% vs 73.9%; P = .69) and 56 (73.2% vs 68.4%; P = .64) were similar between HLA-DQA1*05 noncarriers and carriers. Drug persistence was higher among HLA-DQA1*05 carriers (hazard ratio [HR], 0.32; 95% confidence interval, 0.14-0.71; P = .01). Multivariable Cox regression analysis identified systemic steroids at anti-TNF initiation (HR, 4; 95% confidence interval, 1.7-9.7) as a risk factor and HLA-DQA1*05 carriers (HR, 0.31; 95% confidence interval, 0.12-0.81) as a protective factor of treatment cessation., Conclusion: In adult patients with PTDM, a positive HLA-DQA1*05 genotype does not associate a higher risk of treatment cessation nor worse clinical outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

General practitioners see in their consultation a a significant number of patients at high vascular risk (VR). The European Guidelines for Cardiovascular Disease Prevention (2021) recommend a new risk classification and intervention strategies on on vascular risk factors (RF), with the aim of providing a shared decision-making recommendations between professionals and patients. In this document we present a critical analysis of these guidelines, offering possible solutions that can be implemented in Primary Care. It should be noted that there are positive aspects (lights) such as that the SCORE2 (from forty to sixty-nine years) and SCORE2-OP models (from seventy to eighty-nine years) are based on more current cohorts and measure cardiovascular risk in a more accurately manner. In addition, it is proposed to differentiate different risk thresholds according to age-groups. For sake of practicality, cardiovascular risk can be estimated using different websites with the new computer models. However, among the negative aspects (shadows), it seems to be add complexity implementing nine subgroups of subjects according to their age or level of risk, with a defined thresholds that could cause a substantial increase in the potential number of subjects susceptible to treatment without a clear evidence that supports it. In addition, two-step RF interventions could delay achievement of therapeutic goals, especially in very high-risk patients, diabetics, or patients with cardiovascular disease. Given these limitations, in this document we propose practical recommendations in order to simplify and facilitate the implementation of the guideline in primary care.

Background and Objective: The prevalence of type 2 diabetes (T2D) is high, it is increasing and its degree of control seems to be improvable with important social and health consequences. The objective of this study is to determine the regional differences in the degree of glycaemic control of T2D in Spain and its associated factors., Material and Methods: Cross-sectional, multicentre, observational study in patients with T2D between 18 and 85 years of age selected by consecutive sampling between 2014 and 2018. The population was divided into four regions: north, centre, Mediterranean and south-east. The main variable was the value of glycated haemoglobin (HbA1c). Sociodemographic and clinical variables, presence or absence of other risk factors and treatment were recorded., Results: A total of 1587 patients with T2D were analysed, with a mean age of 65.93 years (standard deviation [SD] 10.14); 54.5% were men; the mean duration of T2D was 8.63 years (SD 6.64) and the mean HbA1c value was 7.05%. Of the total, 59.8% had an HbA1c value ≤ 7% (north 59.5%, centre 59.5%, Mediterranean 60.6% and south-east 59.8%; P=.99). The factors for poor control were: in the north, duration of T2D and being sedentary; in the centre, duration of T2D and having a low income; in the Mediterranean, duration of T2D; and in the south-east, duration of T2D and having a low level of education or income. Overall, 76.2% of the subjects had hypertension, 75.1% dyslipidaemia, and 51.7% obesity, with significant differences between regions only being observed in the case of dyslipidaemia (P<.001)., Conclusions: No differences were observed in the degree of diabetes control in the different regions, with the percentage of patients needing intensification in their control being high in all of them. The factors associated with poor control were the duration of the disease, a low level of education or income, and a sedentary lifestyle., (Copyright © 2022 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Ambulatory blood pressure (BP) is associated with mortality, but it is also interesting to expand its association with cardiovascular morbidity. This study sought to evaluate association with cardiovascular morbidity and cardiovascular mortality. Patients without cardiovascular disease who had a first 24-hour ambulatory BP monitoring were followed-up until the onset of the first event (a combined variable of cardiovascular mortality, coronary heart disease, cerebrovascular disease, peripheral arteriopathy, or hospital admission for heart failure). Changes in antihypertensive treatment couldn't be collected. Cox regression analysis was adjusted for risk factors and office BP. We included 3907 patients (mean age, 58.0, SD 13.8 years), of whom 85.5% were hypertensive. The follow up period was 6.6 (95% CI 5.0-8.5) years. A total of 496 (12.7%) events were recorded. The incidence rate was 19.3 (95% CI 17.7-21.1) cases per 1000 person-years. The patients with an event compared to the rest of patients were mostly men, older, with higher office and ambulatory systolic BP, higher prevalence of diabetes, chronic kidney disease, dyslipidemia, and non-dipper or riser circadian profile. In the fully adjusted model, office BP loses its significant association with the main variable. Ambulatory BP association remained significant with cardiovascular morbidity and mortality, HR 1.494 (1.326-1.685) and 0.767 (0.654-0.899) for 24-hour systolic and diastolic BP, respectively. Nighttime systolic BP also maintained this significant association, 1.270 (1.016-1.587). We conclude that nighttime systolic BP and 24-hour BP are significantly associated with cardiovascular events and cardiovascular mortality in patients without cardiovascular disease attended under conditions of routine clinical practice., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The method typically used to diagnose and monitor hypertensive patients has been to measure blood pressure in the physician's surgery; however, it is a well-known fact that this approach poses certain drawbacks, such as observer bias, failure to detect an alert reaction in the clinic, etc., difficulties that affect its accuracy as a diagnostic method. In recent years, the varying international scientific societies have persistently recommended the use of blood pressure measurements outside the clinic (at home or in the outpatient setting), using validated automatic devices. Data from some studies suggest that if we rely solely on in-office measurements, approximately 15-20% of the time we may be wrong when making decisions, both in terms of diagnosis and patient follow-up. Home blood pressure measurements are a simple and very affordable method that has a similar reproducibility and prognostic value as ambulatory blood pressure monitoring, the availability of which is currently very limited. Moreover, ambulatory self-measurements have the significant benefit of being able to improve control of hypertensive individuals. Healthcare professionals and patients should be aware of the methodology of home blood pressure measurement, its usefulness and limitations., (Copyright © 2022 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

At least one in three adults has multiple chronic conditions. The assistance of patients with chronic conditions is mandatory. This is one of the main tasks of the primary care physicians. The approach in these patients is challenging, as there are many barriers at different levels (sanitary system, healthcare professionals and patients). In addition, COVID-19 pandemic has worsened this situation even more. Therefore, it is necessary to take actions that try to improve this state. For this purpose, with the aim to find solutions/recommendations that may be helpful to attain a better diagnosis, treatment and follow-up of patients with chronic diseases, a group of experts of SEMERGEN have tried to identify the problems in the attention to these patients, searching for potential solutions and areas of improvement. The present document has specifically focused on four prevalent chronic conditions in primary care: dyslipidemia, arterial hypertension, chronic venous disease and depression., (Copyright © 2022 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Dendritic cells and macrophages are the main antigen-presenting cells (APC). In the gut, they control the mechanisms of tolerance toward commensals and nutrients, at the time that they maintain their capacity to trigger immune responses against invading pathogens. Nevertheless, this balance is not perfect as it can get disrupted like in inflammatory bowel disease (where they drive an abnormal immune response against the microbiota) or in coeliac disease (where they trigger an immune response against dietary gluten). Therefore, the study of human intestinal APC subsets is crucial not just to get a deeper insight in the mechanisms of human intestinal homeostasis, but also to understand the pathogenesis of inflammatory bowel disease and coeliac disease. Nevertheless, their study is quite complicated as despite their relevance, their numbers are scare in the intestinal mucosa. Therefore, we hereby describe different approaches to study human intestinal dendritic cell and macrophage subsets in the human intestinal mucosa., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The efficacy and safety of acetylsalicylic acid (ASA) prophylaxis for the primary prevention of atherosclerotic cardiovascular disease (ACVD) remain controversial in people with diabetes (DM) without ACVD, because the possible increased risk of major bleeding could outweigh the potential reduction in the risk of mortality and of major adverse cardiovascular events (MACE) considered individually or together., Objective: To evaluate the overall risk-benefit of ASA prophylaxis in primary prevention in people with DM and to compare the recommendations of the guidelines with the results of the meta-analyses (MA) and systematic reviews (SR)., Material and Methods: We searched Medline, Google Scholar, Embase, and the Cochrane Library for SR and MA published from 2009 to 2020 which compared the effects of ASA prophylaxis versus placebo or control followed up for at least one year in people with DM without ACVD. Heterogeneity among the randomized clinical trials (RCT) included in the SR and MA was assessed. Cardiovascular outcomes of efficacy (all-cause mortality [ACM], cardiovascular mortality [CVM], myocardial infarction [MI], stroke and MACE) and of safety (major bleeding events [MBE], major gastrointestinal bleeding events [MGIBE], and intracranial and extracranial bleeding) were shown., Results: The recommendations of 12 guidelines were evaluated. The results of 25 SR and MA that included a total of 20 RCT were assessed. None of the MA or SR showed that ASA prophylaxis decreased the risk of ACM, CVM or MI. Only two of the 19 SR and MA that evaluated ischemic stroke showed a decrease in the stroke risk (mean 20.0% [SD±5.7]), bordering on statistical significance. Almost half of the MA and SR showed, bordering on statistical significance, a risk reduction for the MACE composite endpoint (mean 10.5% [SD±3.3]). The significant increases in MGIBE risk ranged from 35% to 55%. The significant increases in the risk of MBE and extracraneal bleeding were 33.4% (SD±14.9) and 54.5% (SD±0.7) respectively., Conclusion: The overall risk-benefit assessment of ASA prophylaxis in primary prevention suggests that it should not be applied in people with DM., (Copyright © 2022 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers., (© 2021 Wiley-VCH GmbH.)

The pandemic caused by coronavirus SARS-CoV-2 (COVID-19) has forced, in many cases, to replace face-to-face consultation with the telematic consultation, in order to reduce the risk of contagion associated with the presence of patients in health centres. This change may represent an opportunity for a different and more effective communication between professionals and patients, allowing better accessibility to medical care and more systematic and comprehensive approach to patients with hypertension and cardiovascular risk. However, organisational tools are needed to facilitate communication between patients and professionals, specifically with the exchange of clinical data by remote monitoring of variables associated with hypertension and cardiovascular risk (blood pressure, weight, height, blood tests…), and allow monitoring of adherence to treatments, lifestyles and risk factors. It would be desirable for this to be carried out by multidisciplinary teams, both from primary care, hospital and community pharmacy, with an adequate coordination of care. This document of the Spanish Society of Hypertension (SEH-LELHA) tries to give the keys to improve the quality of care of telematic consultations of patients with hypertension and cardiovascular risk, provide basic criteria of telematic or face to face attention and systematise their content. Likewise, the follow-up criteria are proposed by the different professionals., (Copyright © 2021 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Smoking is the leading cause of morbidity and mortality worldwide and is clearly involved as a cardiovascular risk factor. Smoking has different effects on the cardiovascular system, such as a decrease in nitric oxide, increased inflammatory response, increased adhesion of pro-atherogenic molecules, lipid disturbances, generation of oxidative stress and endothelial dysfunction as can be shown in different biomarkers modifications. Despite the aids currently available for smoking cessation, many smokers are unwilling or unable to achieve this. So alternative tools with potential harm reduction, such as non-combustion tobacco products, could be an option due to the better results they had shown on cardiovascular risk factors. This has led these devices to be taken into account as a risk-modifying tobacco product according to the FDA., (Copyright © 2021 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Dendritic cells (DC) and macrophages (Mϕ) constitute the most abundant antigen presenting cells in the human intestinal mucosa. In resting conditions, they are essential to maintain the mechanisms of immune tolerance toward food antigens and commensals, at the time that they keep the capacity to initiate and maintain antigen-specific pro-inflammatory immune responses toward invading pathogens. Nevertheless, this delicate equilibrium between immunity and tolerance is not perfect, like in coeliac disease (CD), where DC and Mϕ drive the development of antigen-specific immune responses toward dietary gluten peptides. In this review, we provide therefore a comprehensive discussion about CD pathogenesis, the human intestinal immune system and the biology of intestinal DC and Mϕ both in resting conditions and in CD. Last, but not least, we discuss about all the remaining issues pending to be studied regarding DC and Mϕ contribution toward CD pathogenesis. This may allow the identification of unique and specific factors which may be useful in the clinical practice, as well as identify new therapeutic targets in order to reestablish the loss intestinal homeostasis in CD., (© 2021 Elsevier Inc. All rights reserved.)

Despite new strategies, such as evaluating deep intronic variants and new genes in whole-genome-sequencing studies, the diagnostic yield of genetic testing in hypertrophic cardiomyopathy (HCM) is still around 50%. FHOD3 has emerged as a novel disease-causing gene for this phenotype, but the relevance and clinical implication of copy-number variations (CNVs) have not been determined. In this study, CNVs were evaluated using a comparative depth-of-coverage strategy by next-generation sequencing (NGS) in 5493 HCM probands and 2973 disease-controls. We detected three symmetrical deletions in FHOD3 that involved exons 15 and 16 in three HCM families (no CNVs were detected in the control group). These exons are part of the diaphanous inhibitory domain of FHOD3 protein, considered a cluster of mutations for HCM. The clinical characteristics of the affected carriers were consistent with those reported in FHOD3 in previous studies. This study highlights the importance of performing CNV analysis systematically in NGS genetic testing panels for HCM, and reinforces the relevance of the FHOD3 gene in the disease., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients with coronary heart disease (CHD) can be particularly susceptible to the adverse effects of excessive blood pressure (BP) lowering by antihypertensive treatment. The identification of hypotension is thus especially important. This study estimated the prevalence of hypotension among CHD-treated hypertensive patients undergoing ambulatory blood pressure monitoring (ABPM) in routine clinical practice. We performed a cross-sectional study with 2892 CHD-treated hypertensive patients from the Spanish ABPM Registry. Based on previous studies, hypotension was defined as systolic/diastolic BP < 120 and/or 70 mmHg according to office measurements, <115 and/or 65 mmHg according to daytime ABPM, <100 and/or 50 mmHg according to nighttime ABPM, and <110 and/or 60 mmHg according to 24 h ABPM. The participants' mean age was 67.1 years (69.8% men). A total of 19.6% of the patients had office hypotension, 26.5% had daytime hypotension, 9.0% had nighttime hypotension, and 16.1% had 24-hr ABPM hypotension. Low diastolic BP values were responsible for most cases of hypotension. Fifty-eight percent of the cases of hypotension detected by daytime ABPM did not correspond to hypotension according to office BP. The variables independently associated with daytime ambulatory systolic/diastolic hypotension and diastolic hypotension (the latter being the most frequent type of ambulatory hypotension) were age, female sex, and the number of antihypertensive medications. In conclusion, in a large ABPM registry, one out of every four CHD-treated hypertensive patients was potentially at risk because of hypotension according to daytime ABPM, and more than half of them were not identified if office BP was relied on alone. We suggest that ABPM should be performed in these patients.

Scope: Circulating dendritic cell (DC) and monocyte subsets contribute to the pool of intestinal DC and macrophages in celiac disease (CeD), an autoimmune gut disorder triggered by dietary gluten. Here, this study aims to characterize these circulating subsets in CeD and assess the effect of different gliadin-derived peptides on conventional DC (cDC)., Methods and Results: Flow cytometry profiling of peripheral blood mononuclear cells reveals a slight decrease in the proportion of plasmacytoid and type 1 cDC in gluten-free diet (GFD)-treated CeD patients. In comparison to healthy donors, DC and monocyte subsets from active and GFD-treated CeD patients display an increased gut-homing profile. Type 2 cDC (cDC2) are sorted and stimulated with the gliadin-derived peptides 8-mer, 19-mer, and 33-mer. All peptides induce cDC2 maturation, although the profile is different. While peptide 8-mer induces a Th1/Th17 pro-inflammatory cytokine profile in active CeD patients, cDC2 primed with peptide 33-mer displays a higher capacity to promote gut-homing CCR9 + expression onto autologous T-cells., Conclusion: Distinct gliadin-derived peptides elicit different effects on cDC2 phenotype and function. This effect is compatible with a model where diverse gliadin peptides may cooperate to promote full cDC2 activation and the subsequent T-cell response in genetically predisposed individuals., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To determine the prevalence of hypotension and associated factors in hypertensive patients treated in the Primary Care setting., Materials and Methods: A cross-sectional, descriptive, and multicentre study was conducted with a total of 2635 general practitioners consecutively including 12,961 hypertensive patients treated in a Primary Care setting in Spain. An analysis was performed on the variables of age, gender, weight, height, body mass index, waist circumference, cardiovascular risk factors (diabetes, dyslipidaemia, smoking, obesity, sedentary lifestyle), fasting plasma glucose, complete lipid profile, as well as the presence of target organ damage (left ventricular hypertrophy, microalbuminuria, carotid atherosclerosis) and associated clinical conditions. Hypotension was defined as a systolic blood pressure less than 110mmHg or a diastolic blood pressure less than 70mmHg. A multivariate analysis was performed to determine the variables associated with the presence of hypotension., Results: The mean age was 66.2 years, and 51.7% of patients were women. The mean time of onset of hypertension was 9.1 years. A total of 13.1% of patients (95% confidence interval 12.4-13.6%) had hypotension, 95% of whom had low diastolic blood pressure. The prevalence of hypotension was higher in elderly patients (25.7%) and in those individuals with coronary heart disease (22.6%). The variables associated with the presence of hypotension included a history of cardiovascular disease, being treated with at least 3 antihypertensive drugs, diabetes, and age., Conclusions: One out of 4-5 elderly patients, or those with cardiovascular disease, had hypotension. General practitioners should identify these patients in order to determine the causes and adjust treatment to avoid complications., (Copyright © 2019 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Conventional blood pressure (BP) measurement in clinical practice is the most used procedure for the diagnosis and treatment of hypertension (HT), but is subject to considerable inaccuracies due to, on the one hand, the inherent variability of the BP itself and, on the other hand biases arising from the measurement technique and conditions, Some studies have demonstrated the prognosis superiority in the development of cardiovascular disease using ambulatory blood pressure monitoring (ABPM). It can also detect "white coat" hypertension, avoiding over-diagnosis and over-treatment in many cases, as well detecting of masked hypertension, avoiding under-detection and under-treatment. ABPM is recognised in the diagnosis and management of HT in most of international guidelines on hypertension. The present document, taking the recommendations of the European Society of Hypertension as a reference, aims to review the more recent evidence on ABPM, and to serve as guidelines for health professionals in their clinical practice and to encourage ABPM use in the diagnosis and follow-up of hypertensive subjects. Requirements, procedure, and clinical indications for using ABPM are provided. An analysis is also made of the main contributions of ABPM in the diagnosis of "white coat" and masked HT phenotypes, short term BP variability patterns, its use in high risk and resistant hypertension, as well as its the role in special population groups like children, pregnancy and elderly. Finally, some aspects about the current situation of the Spanish ABPM Registry and future perspectives in research and potential ABPM generalisation in clinical practice are also discussed., (Copyright © 2019 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Treatment for coeliac disease is a lifelong strict gluten-free diet. Although guidelines recommend regular follow-up with dietary interviews and coeliac serology, these methods may be inaccurate., Aim: To evaluate the usefulness of faecal gluten immunogenic peptides to support the diagnosis and to determine the adherence to the gluten-free diet in coeliac children., Methods: Multicentre prospective observational study including 64 coeliac children. Faecal gluten peptides, and tissue transglutaminase and deamidated gliadin peptide antibodies were analyzed at diagnosis, and 6, 12 and 24 months thereafter. Gluten consumption was estimated from gluten peptide levels., Results: Most children (97%) had detectable gluten peptides at diagnosis. On a gluten-free diet, the rate of gluten peptides increased from 13% at 6 months to 25% at 24 months. Mean estimated gluten exposure dropped from 5543 mg/d at diagnosis to 144 mg/d at 6 months, then increased to 606 mg/d by 24 months. In contrast, deamidated gliadin peptide antibodies normalised and only 20% had elevated tissue transglutaminase antibody by 24 months. The elevation of tissue transglutaminase antibody was more prolonged in patients with detectable gluten peptides (P < 0.05). Nevertheless, absolute levels of tissue transglutaminase antibody had low sensitivity to identify patients with detectable gluten peptides (P > 0.1). Dietitian assessment was only moderately correlated with gluten peptide detection (κ = 0.5)., Conclusions: Faecal gluten peptides testing may guide treatment of coeliac disease prior to diagnosis and during the assessment diet adherence. Further studies could determine if early identification of gluten exposure reduces the need for expensive/invasive investigations for non-responsive coeliac disease. ClinicalTrials.gov Number: NCT02711397., (© 2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.)

The Scientific Societies of Primary Care, being the area in which there is a considerable prevalence of Arterial Hypertension (AHT), need to periodically evaluate the international guidelines for its management. This is particularly relevant when disparate guidelines make it difficult to make decisions in daily clinical practice. The present document has as its aim to analyse the changes and new developments proposed in the guidelines of the American College of Cardiology and the American Heart Association (ACC/AHA 2017), as well as in the guidelines of the European Society of Cardiology and European Society of Hypertension (ESC/ESH 2018). An analysis will be made of any differences, limitations, and their applicability to Primary Care in Spain. Finally, the most relevant available and appropriate information is extracted and integrated in order to homogenise the care of the hypertensive patient, from a critical, but also a reasoned, perspective. The discrepancies between the recommendations in such essential aspects as the management of the disease, require the compiling and critical analysis of the information that enables us as scientific society, interested in providing all PC physicians with the most relevant, and at the same time, sensible, recommendations of all the guidelines., (Copyright © 2019 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy., Objectives: This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy., Methods: FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes., Results: The authors identified 94 candidate variants in 132 probands. The variants' frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 [2.32%]) than in disease control subjects (18 of 2,777 [0.65%]; p < 0.001) or in the gnomAD database (1,049 of 138,606 [0.76%]; p < 0.001). FHOD3 mutations cosegregated with hypertrophic cardiomyopathy in 17 families, with a combined logarithm of the odds score of 7.92, indicative of very strong segregation. One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects (95% confidence interval: 1.3 to 37.9; p < 0.001) and 14.1 against gnomAD (95% confidence interval: 6.9 to 28.7; p < 0.001). Hypertrophic cardiomyopathy patients carrying (likely) pathogenic mutations in FHOD3 (n = 70) were diagnosed after age 30 years (mean 46.1 ± 18.7 years), and two-thirds (66%) were males. Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 ± 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up., Conclusions: FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Celiac disease (CD) is an immune-mediated enteropathy involving genetic and environmental factors, whose interaction influences disease risk. The intestinal microbiota, including viruses and bacteria, could play a role in the pathological process leading to gluten intolerance. In this study, we investigated the prevalence of pathogens in the intestinal microbiota of infants at familial risk of developing CD. We included 127 full-term newborns with at least one first-degree relative with CD. Infants were classified according to milk-feeding practice (breastfeeding or formula feeding) and HLA-DQ genotype (low, intermediate or high genetic risk). The prevalence of pathogenic bacteria and viruses was assessed in the faeces of the infants at 7 days, 1 month and 4 months of age. The prevalence of Clostridium perfringens was higher in formula-fed infants than in breast-fed over the study period, and that of C. difficile at 4 months. Among breastfed infants, a higher prevalence of enterotoxigenic E. coli (ETEC) was found in infants with the highest genetic risk compared either to those with a low or intermediate risk. Among formula-fed infants, a higher prevalence of ETEC was also found in infants with a high genetic risk compared to those of intermediate risk. Our results show that specific factors, such as formula feeding and the HLA-DQ2 genotype, previously linked to a higher risk of developing CD, influence the presence of pathogenic bacteria differently in the intestinal microbiota in early life. Further studies are warranted to establish whether these associations are related to CD onset later in life.

Background: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation., Methods: We developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL not caused by GJB2/GJB6, OTOF nor MT-RNR1 mutations., Results: The analytical sensitivity of the test to detect SNVs and indels on the DNA mixture from the cell lines was > 99.5%, with a specificity > 99.9%. The diagnostic yield on the SNHL patients was 42% (21/50): 47.6% (10/21) with autosomal recessive inheritance pattern (BSND, CDH23, MYO15A, STRC [n = 2], USH2A [n = 3], RDX, SLC26A4); 38.1% (8/21) autosomal dominant (ACTG1 [n = 3; 2 de novo], CHD7, GATA3 [de novo], MITF, P2RX2, SOX10), and 14.3% (3/21) X-linked (COL4A5 [de novo], POU3F4, PRPS1). 46.9% of causative variants (15/32) were not in the databases. 28.6% of genetically diagnosed cases (6/21) had previously undetected syndromes (Barakat, Usher type 2A [n = 3] and Waardenburg [n = 2]). 19% of genetic diagnoses (4/21) were attributable to large deletions/duplications (STRC deletion [n = 2]; partial CDH23 duplication; RDX exon 2 deletion)., Conclusions: In the era of precision medicine, obtaining an etiologic diagnosis of SNHL is imperative. Here, we contribute to show that, with the right methodology, NGS can be transferred to the clinical practice, boosting the yield of SNHL genetic diagnosis to 50-60% (including GJB2/GJB6 alterations), improving diagnostic/prognostic accuracy, refining genetic and reproductive counseling and revealing clinically relevant undiagnosed syndromes.

Coeliac disease (CD) is a chronic autoimmune enteropathy triggered by gluten and related prolamines in genetically predisposed individuals. Although CD is a polygenic disease, there is a strong association with genes of the human leukocyte antigen (HLA) region. Most patients present the HLA-DQ2 heterodimer, specifically the DQ2.5 isoform, which is present in around 90-96% of patients of European ancestry.

Objective: Increased BP-variability predicts cardiovascular morbidity and mortality in hypertensives. This study aimed to examine short-term BP-variability according to renal function stage., Methods: We included 16 546 patients [10 270 (62.1%) without/6276 (38.9%) with CKD Stage 1-5] from the Spanish Ambulatory-Blood-Pressure Monitoring (ABPM) Registry. Stages of CKD were defined according to K/DIGO criteria, based on estimated glomerular filtration rate calculated with the CKD-EPI equation and albumin-to-creatine ratio. BP-variability was assessed with standard deviation (SD), weighted SD (wSD), coefficient of variation (CV), and average real variability (ARV)., Results: Compared with those without CKD, a lower proportion of CKD patients were dippers (51.9 versus 39.6%; P < 0.001). Across CKD stages, a progressive decrease in dipper (from 39.1 to 20.4%; P < 0.001) and increase in riser proportion (from 12.3 to 36.7%; P < 0.001) were noted. Patients with CKD had significantly higher SBP SD, wSD, CV and ARV and lower DBP SD compared with those without CKD (P < 0.001). Within CKD Stages, an increasing trend from Stage 1 towards Stage 5 was observed for SBP SD (from 13.8 ± 3.7 to 15.6 ± 5.4 mmHg), wSD (from 12.0 ± 3.2 to 13.9 ± 5.1 mmHg), CV (from 10.4 ± 2.7 to 11.5 ± 4.1%), ARV (from 9.9 ± 2.3 to 11.4 ± 3.2 mmHg); P < 0.001 for all comparisons. DBP SD (P < 0.001), wSD and ARV (P = 0.002) were slightly decreasing, whereas DBP CV increased from Stage 1 to Stage 4 (P < 0.001). In multivariate analysis, male gender, older age, abdominal obesity, diabetes, number of antihypertensive medications, and clinic SBP were independent factors for higher SBP 24-h ARV in CKD., Conclusion: An increase in short-term SBP-variability was present with advancing CKD stages in a large cohort. This increased SBP-variability may be involved in the sharp elevation of cardiovascular risk with worsening renal function.

Introduction: Non-HDL cholesterol (non-HDL-C) is becoming relevant both in its participation in cardiovascular risk assessment and as a therapeutic target. The objective of the present study was to assess the independent predictive capacity of both non-HDL-C and LDL-C (the main priority in dyslipidemias to reduce cardiovascular risk), in cardiovascular morbidity in a population-based sample., Methods: A prospective cohort study involving 1186 individuals in the non-HDL-C group and 1177 in the LDL-C group, followed for 10.7years (SD=2.2), who had not had any previous cardiovascular event. The predictor variables included in the adjustment were: gender, age, arterial hypertension, diabetes mellitus, smoker status and non-HDL-C in one group. In the other group, consisting of patients presenting TG levels of 400mg/dL, non-HDL-C was replaced by LDL-C. Survival curves (Kaplan-Meier) were calculated and two Cox regression models were applied, one for each group., Results: Non-HDL-C group presented 6.2% of non-fatal cardiovascular episodes during follow-up and the LDL-C group 6.0%. After adjustment, for each 30mg/dL increase in non-HDL-C, the incidence of new non-fatal cardiovascular events increased by 31% (HR=1.31, 95%CI: 1.06-1.61; P=.018) and in the LDL-C group by 27% (HR=1.27, 95%CI: 0.97-1.61, P=.068)., Conclusions: After a follow-up of 10.7years, non-HDL-C has been shown in our population as a prognostic factor of non-fatal cardiovascular disease, but not LDL-C, although its HR is close to statistical significance., (Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

The development of treatments that modulate corneal wound healing to avoid fibrosis during tissue repair is important for the restoration of corneal transparency after an injury. To date, few studies have studied the influence of growth factors (GFs) on human corneal fibroblast (HCF) expression of extracellular matrix (ECM) proteins such as collagen types I and III, proteoglycans such as perlecan, or proteins implicated in cellular migration such as α5β1-integrin and syndecan-4. Using in vitro HCFs, a mechanical wound model was developed to study the influence of the GFs basic fibroblast GF (bFGF), platelet-derived GF (PDGF-BB) and transforming GF-β1 (TGFβ1) on ECM protein production and cellular migration. Our results show that mechanical wounding provokes the autocrine release of bFGF and TGFβ1 at different time points during the wound closure. The HCF response to PDGF-BB was a rapid closure due to fast cellular migration associated with a high focal adhesion replacement and a high expression of collagen and proteoglycans, producing nonfibrotic healing. bFGF stimulated nonfibrotic ECM production and limited the migration process. Finally, TGFβ1 induced expression of the fibrotic markers collagen type III and α5β1 integrin, and it inhibited cellular migration due to the formation of focal adhesions with a low turnover rate. The novel in vitro HCF mechanical wound model can be used to understand the role played by GFs in human corneal repair. The model can also be used to test the effects of different treatments aimed at improving the healing process. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)