Clinical manifestations and expression of CD18 to guide the diagnosis of leukocyte adhesion deficiency type 1: Mexico experience.

BACKGROUND: Leukocyte adhesion deficiency type 1 (LAD-1) is an inborn error of immunity characterized by a defect in leukocyte trafficking. METHODS: Patients with clinical suspicion of LAD-1 were referred to our institution. Complete blood count and flow cytometric analysis, to identify the expression of CD18, CD11b, and the lymphocyte population phenotyping, were performed, and statistical analysis was completed. RESULTS: We report clinical manifestations and immunological findings of six Mexican patients diagnosed with LAD-1. The diagnosis was based on typical clinical presentation, combined with laboratory demonstration of leukocytosis, and significant reduction or near absence of CD18 and its associated molecules CD11a, CD11b, and CD11c on leukocytes. We found atypical manifestations, not described in other countries, such as early-onset autoimmunity or infections caused by certain microorganisms. CONCLUSIONS: Patients with LAD-1 may present with atypical manifestations, making flow cytometry an indispensable tool to confirm the diagnosis. We present the first report of LAD-1 patients in a Latin American country.

Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia: The Randomized RAIN-FLOW Study.

Background ST-segment-elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow-mediated hyperemia in patients with ST-segment-elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN-FLOW (Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia) study, 67 patients with ST-segment-elevation myocardial infarction and no reflow were randomized to receive either pharmacologic-mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow-mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P=0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P=0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% (P=0.899). Flow-mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.

Clinical manifestations and expression of CD18 to guide the diagnosis of leukocyte adhesion deficiency type 1

Background: Leukocyte adhesion deficiency type 1 (LAD-1) is an inborn error of immunity characterized by a defect in leukocyte trafficking. Methods: Patients with clinical suspicion of LAD-1 were referred to our institution. Complete blood count and flow cytometric analysis, to identify the expression of CD18, CD11b, and the lymphocyte population phenotyping, were performed, and statistical analysis was completed. Results: We report clinical manifestations and immunological findings of six Mexican patients diagnosed with LAD-1. The diagnosis was based on typical clinical presentation, combined with laboratory demonstration of leukocytosis, and significant reduction or near absence of CD18 and its associated molecules CD11a, CD11b, and CD11c on leukocytes. We found atypical manifestations, not described in other countries, such as early-onset autoimmunity or infections caused by certain microorganisms. Conclusions: Patients with LAD-1 may present with atypical manifestations, making flow cytometry an indispensable tool to confirm the diagnosis. We present the first report of LAD-1 patients in a Latin American country (AU)

Antiplatelet efficacy of ticagrelor versus clopidogrel in Mediterranean patients with diabetes mellitus and chronic coronary syndromes: A crossover pharmacodynamic investigation.

Introduction: Patients with diabetes mellitus (DM) have augmented platelet reactivity and diminished responsiveness to clopidogrel. Ticagrelor, a more potent P2Y12 inhibitor, is clinically superior to clopidogrel in acute coronary syndromes, although its role in chronic coronary syndromes (CCS) is still the subject of debate. The aim of this investigation was to compare the pharmacodynamic effectiveness of ticagrelor and clopidogrel in Mediterranean DM patients with CCS. Materials and methods: In this prospective, randomized, crossover study, patients (n = 20) were randomized (1:1) to receive, on top of aspirin therapy, either ticagrelor 180 mg loading dose (LD)/90 mg maintenance dose (MD) b.i.d. or clopidogrel 600 mg LD/75 mg MD o.d. for 1 week in a crossover fashion with a 2-4 week washout period between regimens. Platelet function measurements were performed at 4 timepoints in each period (baseline, 2 h and 24 h after LD, and 1 week), including light transmission aggregometry (LTA, primary endpoint), VASP assay, Multiplate and VerifyNow P2Y12. Results: The ticagrelor LD achieved greater platelet inhibitory effect than clopidogrel LD, assessed with LTA (20 µM ADP as agonist), at 2 h (34.9 ± 3.9% vs. 63.6 ± 3.9%; p < 0.001) and 24 h (39.4 ± 3.5% vs. 52.3 ± 3.8%; p = 0.014). After 1 week of therapy, platelet reactivity was again significantly inferior with ticagrelor compared to clopidogrel (30.7 ± 3.0% vs. 54.3 ± 3.0%; p < 0.001). The results were consistent with the other platelet function assays employed. Conclusion: In Mediterranean patients with DM and CCS, ticagrelor provides a more potent antiplatelet effect than clopidogrel after the LD and during the maintenance phase of therapy. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02457130].

Anaphylaxis in Cold Induced Urticaria: A Case Report and Review of The Literature.

Cold-induced urticaria is considered as a subtype of physical urticaria and also the second most common type of chronic inducible urticaria. Contact with cold surfaces or the environment may cause systemic reactions, especially during aquatic activities. A 22-year-old female patient with a history of sulfa drug allergy began her condition 2 years before the presence of generalized pruritic erythema with hives as well as 2 episodes that had been characterized by facial angioedema and syncope 3-5 minutes after being in contact with cold air or surfaces.  On both events, she had just been outdoors on a cold, winter day. She was suspected to have cold-induced urticaria; thereby she had a positive reaction to the ice cube test. Due to the previous episodes of anaphylaxis, the patient was trained to administer intramuscular epinephrine. After 4 weeks of starting the treatment with antihistamines, no new events or injuries had occurred. Cold-induced urticaria may cause life-threatening reactions. The rate of anaphylaxis in these patients is low however, this case is presented to inform the importance of identifying this type of systemic reaction and preventing strategies.

Clinical Determinants and Prognosis of Left Ventricular Reverse Remodelling in Non-Ischemic Dilated Cardiomyopathy.

AIMS: Non-ischaemic dilated cardiomyopathy (NIDCM) is characterized by left ventricular (LV) chamber enlargement and systolic dysfunction in the absence of coronary artery disease. Left ventricular reverse remodelling (LVRR) is the ability of a dilated ventricle to restore its normal size, shape and function. We sought to determine the frequency, clinical predictors and prognostic implications of LVRR, in a cohort of heart failure (HF) patients with NIDCM. METHODS: We conducted a multicentre observational, retrospective cohort study of patients with NIDCM, with prospective serial echocardiography evaluations. LVRR was defined as an increase of ≥15% in left ventricular ejection fraction (LVEF) or as a LVEF increase ≥ 10% plus reduction of LV end-systolic diameter index ≥ 20%. We used multivariable logistic regression analyses to identify the baseline clinical predictors of LVRR and evaluate the prognostic impact of LVRR. RESULTS: LVRR was achieved in 42.5% of 527 patients with NIDCM during the first year of follow-up (median LVEF 49%, median change +22%), Alcoholic aetiology, HF duration, baseline LVEF and the absence of LBBB (plus NT-proBNP levels when in the model), were the strongest predictors of LVRR. During a median follow-up of 47 months, 134 patients died (25.4%) and 7 patients (1.3%) received a heart transplant. Patients with LVRR presented better outcomes, regardless of other clinical conditions. CONCLUSIONS: In patients with NIDCM, LVRR was frequent and was associated with improved prognosis. Major clinical predictors of LVRR were alcoholic cardiomyopathy, absence of LBBB, shorter HF duration, and lower baseline LVEF and NT-proBNP levels. Our study advocates for clinical phenotyping of non-ischaemic dilated cardiomyopathy and intense gold-standard treatment optimization of patients according to current guidelines and recommendations in specialized HF units.

Impact of Diabetes Mellitus on Vascular Healing Process After Everolimus-Eluting Stent Implantation: An Optical Coherence Tomography Study.

BACKGROUND/PURPOSE: To study the impact of diabetes mellitus (DM) on vascular healing process after implantation of everolimus-eluting stent (EES). METHODS/MATERIALS: Data from 3 prospective studies (HEAL-EES, REVER, and RESERVOIR), including patients with EES implantation and OCT follow-up, were merged. Differences in vascular healing process assessed by OCT were compared between DM and non-DM using generalized estimating equations. Neointimal proliferation, neointimal signal pattern (high, low, and layered), and uncovered/malapposed struts were evaluated. RESULTS: A total of 96 lesions (61 DM lesions and 35 non-DM lesions) were included. Mean OCT follow-up time was 8.9 ± 1.5 months and comparable between groups. DM were older, high frequently female and acute coronary syndrome, and received smaller stent than non-DM. No differences were observed in quantitative vascular healing process between groups. However, DM exhibited higher low and layered signal pattern neointima compared to non-DM at lesion level (p = 0.030) and cross-section level (p < 0.001). Uncovered/malapposed struts were comparable between groups. CONCLUSIONS: Quantitative vascular healing process was comparable between groups. However, DM was significantly associated with low signal pattern, which is characteristic of focal inflammation, after EES implantation. Further study might be required to study relationship between neointimal signal pattern and clinical events.

Coronary Endothelium-Dependent Vasomotor Function After Drug-Eluting Stent and Bioresorbable Scaffold Implantation.

Background Early generation drug-eluting stents (DESs) showed a high grade of coronary endothelial dysfunction that was attributed to lack of stent reendothelialization. Endothelium-dependent vasomotor response of current DESs and bioresorbable scaffolds (BRSs) remains unknown. This study sought to assess the device-related endothelial function of current devices and to correlate neointima healing with endothelial function. Methods and Results A total of 206 patients from 4 randomized trials treated with the durable-polymer everolimus-eluting Xience (n=44), bioresorbable-polymer sirolimus-eluting Orsiro (n=35), polymer-free biolimus-eluting Biofreedom (n=24), bioactive endothelial-progenitor cell-capturing sirolimus-eluting Combo DES (n=25), polymer-based everolimus-eluting Absorb (n=44), and Mg-based sirolimus-eluting Magmaris BRS (n=34) underwent endothelium-dependent vasomotor tests and optical coherence tomography imaging, as per protocol, at follow-up. Crude vasomotor responses of distal segments to low-dose acetylcholine (10-6 mol/L) were different between groups: bioresorbablepolymer DEShad the worst (-8.4%±12.6%) and durable-polymer DES had the most physiologic (-0.4%±11.8%; P=0.014). High-dose acetylcholine (10-4 mol/L) showed similar responses between groups (ranging from -10.8%±11.6% to -18.1%±15.4%; P=0.229). Device healing was different between devices. Uncovered struts ranged from 6.3%±7.1% (bioresorbable-polymer DES) to 2.5%±4.5% (bioactive DES; P=0.056). In multivariate models, endothelium-dependent vasomotor response was associated with age, bioresorbable-polymer DES, and angiographic lumen loss, but not with strut coverage nor plaque type. Endothelial dysfunction (defined as ≥4% vasoconstriction) was observed in 46.6% of patients with low-dose and 68.9% with high-dose acetylcholine, without differences between groups. Conclusions At follow-up, endothelial dysfunction was frequently observed in distal segments treated with current stents without remarkable differences between devices. Although neointima healing was different between devices, poor healing was not associated with endothelial dysfunction.

Knowledge of healthcare providers in the management of anaphylaxis.

INTRODUCTION: Anaphylaxis is defined as a severe, life-threatening systemic hypersensitivity reaction. Early diagnosis and treatment of a severe allergic reaction requires recognition of the signs and symptoms, as well as classification of severity. It is a clinical emergency, and healthcare providers should have the knowledge for recognition and management. The aim of the study is to evaluate the level of knowledge in the management of anaphylaxis in healthcare providers. METHODS: It is an observational, descriptive, cross-sectional study conducted among healthcare providers over 18 years old via a Google Forms link and shared through different social media platforms. A 12-item questionnaire was applied which included the evaluation of the management of anaphylaxis, from June 2020 to May 2021. RESULTS: A total of 1023 surveys were evaluated; 1013 met inclusion criteria and were included in the statistical analysis. A passing grade was considered with 8 or more correct answers out of 12; the overall approval percentage was 28.7%. The group with the highest percentage of approval in the questionnaire was health-care providers with more than 30 years of work experience. There was a significant difference between the proportions of approval between all specialty groups, and in a post-hoc analysis, allergy and immunology specialists showed greater proportions of approval compared to general medicine practitioners (62.9% vs 25%; p=<0.001). CONCLUSIONS: It is important that healthcare providers know how to recognize, diagnose, and treat anaphylaxis, and later refer them to specialists in Allergy and Clinical Immunology in order to make a personalized diagnosis and treatment.

Coronary endothelial and microvascular function distal to polymer-free and endothelial cell-capturing drug-eluting stents. The randomized FUNCOMBO trial.

INTRODUCTION AND OBJECTIVES: The vasomotor function of new-generation drug-eluting stents designed to enhance stent healing and reendothelialization is unknown. This study aimed to compare the endothelial function of the infarct-related artery (IRA) treated with bioactive circulating endothelial progenitor cell-capturing sirolimus-eluting stents (COMBO) vs polymer-free biolimus-eluting stents (BioFreedom) in ST-segment elevation myocardial infarction patients at 6 months. Secondary objectives were to compare the microcirculatory function of the IRA and stent healing at 6 months. METHODS: Sixty patients were randomized to bioactive sirolimus-eluting stent vs polymer-free biolimus-eluting stents implantation. At 6 months, patients underwent coronary angiography with vasomotor, microcirculatory and optical coherence tomography examinations. Endothelial dysfunction of the distal coronary segment was defined as ≥ 4% vasoconstriction to intracoronary acetylcholine infusion. RESULTS: Endothelial dysfunction was similarly observed between groups (64.0% vs 62.5%, respectively; P=.913). Mean lumen diameter decreased by 16.0 ±20.2% vs 16.1 ±21.6% during acetylcholine infusion (P=.983). Microcirculatory function was similar in the 2 groups: coronary flow reserve was 3.23 ±1.77 vs 3.23±1.62 (P=.992) and the index of microcirculatory resistance was 24.8±16.8 vs 21.3±12.0 (P=.440). Optical coherence tomography findings were similar: uncovered struts (2.3% vs 3.2%; P=.466), malapposed struts (0.1% vs 0.3%; P=.519) and major evaginations (7.1% vs 5.6%; P=.708) were observed in few cases. CONCLUSIONS: Endothelial dysfunction of the IRA was frequent and was similarly observed with new-generation drug-eluting stents designed to enhance stent reendothelialization at 6 months. Endothelial dysfunction was observed despite almost preserved microcirculatory function and complete stent coverage. Larger and clinically powered studies are needed to assess the role of residual endothelial dysfunction in ST-segment elevation myocardial infarction patients. Registered in ClinicalTrials.gov: NCT04202172.

Association of fractalkine with functional severity of heart failure and impact on clopidogrel efficacy in patients with ischemic heart disease.

INTRODUCTION: Patients with heart failure (HF) display elevated levels of soluble fractalkine, a chemokine involved in inflammation processes, atherosclerosis and platelet activation. Further, fractalkine has been associated with reduced pharmacodynamic (PD) responsiveness to clopidogrel. The aim of this study was to investigate the association of fractalkine with the severity of HF and its impact on platelet activation and clopidogrel response in patients with coronary artery disease (CAD) with and without HF. MATERIALS AND METHODS: This prospective PD study included 116 stable CAD patients on DAPT with aspirin and clopidogrel. Subjects were classified in two groups: patients with HF and reduced (<40%) left ventricular ejection fraction (HFrEF group, n = 56) and patients without HF (no HF group, n = 60). Clinical severity of HF was graded according to NYHA classification. Platelet function assays included vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry and light transmittance aggregometry. Fractalkine and P-selectin concentrations were determined by ELISA. RESULTS: Fractalkine levels progressively increased with the severity of the disease in the HFrEF group (NYHA I: 471.2 ± 52.4 pg/ml, NYHA II: 500.5 ± 38.4 pg/ml, NYHA III: 638.9 ± 54.3 pg/ml, p for linear trend 0.023). Numerically higher concentrations of fractalkine were observed in the HFrEF group compared to the no HF group with borderline significance (p = 0.052). No significant differences in clopidogrel-induced platelet inhibition according to fractalkine values were observed in any of the groups. CONCLUSIONS: Fractalkine levels were increased in patients with HFrEF and positively associated with the functional severity of the disease. No evident impact of fractalkine on clopidogrel PD efficacy was found.

Use of intravenous iron in patients with iron deficiency and chronic heart failure: Real-world evidence.

INTRODUCTION AND OBJECTIVES: Treatment with intravenous iron in patients with heart failure (HF) and iron deficiency (ID) improves symptoms, however its impact on survival and safety is unknown. We aimed to evaluate the management of ID and anemia with intravenous iron in patients with HF and long-term safety of intravenous iron. METHODS: We evaluated anemia and ID in patients with chronic HF at 3 university hospitals. Anemia was defined using the World Health Organization definition and ID was defined as ferritin <100 ug/L or a Transferrin Saturation <20% if ferritin between 100 and 299 ug/L. We assessed treatment with intravenous iron during follow-up and its association with mortality and HF hospitalizations using multivariate cox regression analysis. RESULTS: We included 2,114 patients, median age 72 years and 57% had reduced left ventricular ejection fraction. ID was present in 55% and ID and anemia in 29%. Treatment with intravenous iron was used in 24% of patients with ID and 34% of patients with ID and anemia. In patients with ID, after multivariate adjustment, treatment with intravenous iron was associated with lower all-cause mortality: HR = 0.38 (0.28-0.56), lower cardiovascular mortality: HR = 0.34 (0.20-0.57) and no differences in HF hospitalizations: HR = 1.15 (0.88-1.50). Similar outcomes were found for patients with anemia and ID. CONCLUSIONS: In a real-world cohort of patients with HF, treatment with intravenous iron was used in one third of patients with ID and anemia and appears safe in mid-term follow-up.

Correlation between NT-proBNP levels and the maximun vasoactive-inotropic score in the first 24 hours post-intervention of cardiac surgery.

Introduction: The clinical utility of brain natriuretic peptide (NT-proBNP) as a prognostic marker in pediatric patients with heart failure is controversial. The maximum vasoactive inotropic score at 24 h after cardiac surgery in pediatric patients is an important predictor of morbidity and postoperative mortality. Objective: To determine if there is a correlation between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours after cardiac surgery in pediatric patients seen in the Intensive Care Unit. Material and methods: An analytical cross-sectional study. A Spearman correlation analysis (rs) was performed between the serum level of NT-proBNP and the maximum inotropic score both taken at 24 hours postoperatively. A value of p < 0.05 was considered statistically significant. Results: 40 patients were included, 52.5% to the male sex, 72.5% were older than 1 year of age at the time of surgery. A low correlation (rs = 0.26) was found between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours, this correlation was not statistically significant (p = 0.09). Conclusions: To our understanding, the present study is the first to investigate whether there is a correlation between these markers, so our results could set an important precedent that marks the beginning of multiple investigations in our critically ill patients in order to establish new diagnostic, prognostic and therapeutic approaches.

Introducción: La utilidad clínica del péptido natriurético cerebral (NT-proBNP) como marcador pronóstico en pacientes pediátricos con falla cardíaca es controversial. El puntaje inotrópico vasoactivo 24 horas después de la operación cardíaca en pacientes pediátricos es un importante predictor de morbilidad y mortalidad posoperatoria. Objetivo: Determinar si existe correlación entre los valores séricos de NT-proBNP y el puntaje inotrópico vasoactivo a las 24 horas posteriores a la intervención cardíaca en pacientes pediátricos atendidos en una unidad de terapia intensiva. Material y métodos: Estudio transversal analítico. Se realizó un análisis de correlación de Spearman (rs) entre la cifra sérica de NT-proBNP y el puntaje inotrópico máximo tomados ambos a las 24 horas del postoperatorio. Se consideró estadísticamente significativo un valor de p < 0.05. Resultados: Se incluyó a 40 pacientes, 52.5% del sexo masculino, 72.5% era mayor de un año de edad al momento de la operación. Se encontró una baja correlación (rs = 0.26) entre las concentraciones séricos de NT-proBNP y el puntaje inotrópico vasoactivo máximo a las 24 horas; dicha correlación no fue estadísticamente significativa (p = 0.09). Conclusiones: Este estudio es el primero en investigar la correlación entre estos marcadores y los resultados podrían sentar un antecedente que marque el inicio de múltiples investigaciones, con la finalidad de establecer nuevas herramientas diagnósticas, pronósticas y terapéuticas.

Correlación entre los valores séricos de NT-proBNP y el puntaje inotrópico vasoactivo máximo en las primeras 24 horas después de una intervención de cirugía cardíaca / Correlation between NT-proBNP levels and the maximun vasoactive-inotropic score in the first 24 hours post-intervention of cardiac surgery

Resumen Introducción: La utilidad clínica del péptido natriurético cerebral (NT-proBNP) como marcador pronóstico en pacientes pediátricos con falla cardíaca es controversial. El puntaje inotrópico vasoactivo 24 horas después de la operación cardíaca en pacientes pediátricos es un importante predictor de morbilidad y mortalidad posoperatoria. Objetivo: Determinar si existe correlación entre los valores séricos de NT-proBNP y el puntaje inotrópico vasoactivo a las 24 horas posteriores a la intervención cardíaca en pacientes pediátricos atendidos en una unidad de terapia intensiva. Material y métodos: Estudio transversal analítico. Se realizó un análisis de correlación de Spearman (rs) entre la cifra sérica de NT-proBNP y el puntaje inotrópico máximo tomados ambos a las 24 horas del postoperatorio. Se consideró estadísticamente significativo un valor de p menor que 0.05. Resultados: Se incluyó a 40 pacientes, 52.5% del sexo masculino, 72.5% era mayor de un año de edad al momento de la operación. Se encontró una baja correlación (rs = 0.26) entre las concentraciones séricos de NT-proBNP y el puntaje inotrópico vasoactivo máximo a las 24 horas; dicha correlación no fue estadísticamente significativa (p = 0.09). Conclusiones: Este estudio es el primero en investigar la correlación entre estos marcadores y los resultados podrían sentar un antecedente que marque el inicio de múltiples investigaciones, con la finalidad de establecer nuevas herramientas diagnósticas, pronósticas y terapéuticas.

Abstract Introduction: The clinical utility of brain natriuretic peptide (NT-proBNP) as a prognostic marker in pediatric patients with heart failure is controversial. The maximum vasoactive inotropic score at 24 h after cardiac surgery in pediatric patients is an important predictor of morbidity and postoperative mortality. Objective: To determine if there is a correlation between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours after cardiac surgery in pediatric patients seen in the Intensive Care Unit. Material and methods: An analytical cross-sectional study. A Spearman correlation analysis (rs) was performed between the serum level of NT-proBNP and the maximum inotropic score both taken at 24 hours postoperatively. A value of p less 0.05 was considered statistically significant. Results: 40 patients were included, 52.5% to the male sex, 72.5% were older than 1 year of age at the time of surgery. A low correlation (rs = 0.26) was found between the serum levels of NT-proBNP and the maximum vasoactive inotropic score at 24 hours, this correlation was not statistically significant (p = 0.09). Conclusions: To our understanding, the present study is the first to investigate whether there is a correlation between these markers, so our results could set an important precedent that marks the beginning of multiple investigations in our critically ill patients in order to establish new diagnostic, prognostic and therapeutic approaches.

From Elemental Sulfur to Hydrogen Sulfide in Agricultural Soils and Plants.

Sulfur is an essential element in determining the productivity and quality of agricultural products. It is also an element associated with tolerance to biotic and abiotic stress in plants. In agricultural practice, sulfur has broad use in the form of sulfate fertilizers and, to a lesser extent, as sulfite biostimulants. When used in the form of bulk elemental sulfur, or micro- or nano-sulfur, applied both to the soil and to the canopy, the element undergoes a series of changes in its oxidation state, produced by various intermediaries that apparently act as biostimulants and promoters of stress tolerance. The final result is sulfate S+6, which is the source of sulfur that all soil organisms assimilate and that plants absorb by their root cells. The changes in the oxidation states of sulfur S0 to S+6 depend on the action of specific groups of edaphic bacteria. In plant cells, S+6 sulfate is reduced to S-2 and incorporated into biological molecules. S-2 is also absorbed by stomata from H2S, COS, and other atmospheric sources. S-2 is the precursor of inorganic polysulfides, organic polysulfanes, and H2S, the action of which has been described in cell signaling and biostimulation in plants. S-2 is also the basis of essential biological molecules in signaling, metabolism, and stress tolerance, such as reactive sulfur species (RSS), SAM, glutathione, and phytochelatins. The present review describes the dynamics of sulfur in soil and plants, considering elemental sulfur as the starting point, and, as a final point, the sulfur accumulated as S-2 in biological structures. The factors that modify the behavior of the different components of the sulfur cycle in the soil-plant-atmosphere system, and how these influences the productivity, quality, and stress tolerance of crops, are described. The internal and external factors that influence the cellular production of S-2 and polysulfides vs. other S species are also described. The impact of elemental sulfur is compared with that of sulfates, in the context of proper soil management. The conclusion is that the use of elemental sulfur is recommended over that of sulfates, since it is beneficial for the soil microbiome, for productivity and nutritional quality of crops, and also allows the increased tolerance of plants to environmental stresses.

Massive open online courses (MOOCs) for long-distance education in geriatric medicine across Europe : A pilot project launched by the consortium of the project "Screening for Chronic Kidney Disease among Older People": SCOPE project.

PURPOSE: To cover the increasing need for professional knowledge, skills and competences in the care of older people, new learning techniques have been developed. Using the Internet to provide educational material has come into focus of many academic institutions as the learning content can easily be transferred to a larger audience. Since the first launch of a "massive open online course" (MOOC) in 2008, this educational format has raised increasing interest among education experts. The current publication provides insight into the new format of MOOCs in general and specifically describes a MOOC developed by a Pan-European Consortium "Screening for Chronic Kidney Disease (CKD) among Older People across Europe" (SCOPE), a project funded by the European Commission under the umbrella of the Horizon 2020 program. METHODS: Technical background, learning theories and content of the MOOC of the SCOPE project are presented in this overview. RESULTS: The MOOC of the SCOPE project is provided on the MOOC ICT platform iMoox. The courses are built up of video clips, textual descriptions, graphics, animations and audio designed with a clear structure and learning goals. The concise video clips with a maximum length of 15-20 min are equipped with additional learning material such as documents, links and asynchronous communication opportunities. CONCLUSION: MOOCs are recognized as a contemporary approach to transfer required knowledge and skills not only in general but also in geriatric medicine, as the health and social care environment is ever-changing and becoming more complex.

Importance of iron deficiency in patients with chronic heart failure as a predictor of mortality and hospitalizations: insights from an observational cohort study.

BACKGROUND: Iron deficiency (ID) in patients with chronic heart failure (CHF) is considered an adverse prognostic factor. We aimed to evaluate if ID in patients with CHF is associated with increased mortality and hospitalizations. METHODS: We evaluated ID in patients with CHF at 3 university hospitals. ID was defined as absolute (ferritin < 100 µg/L) or functional (transferrin Saturation index < 20% and ferritin between 100 and 299 µg/L). We excluded patients who received treatment with intravenous Iron or Erythropoietin during follow-up. We evaluated if ID was a predictor of death or hospitalization due to heart failure or any cause using univariate and multivariate cox regression analysis. RESULTS: We included 1684 patients, 65% males, 38% diabetics, median age of 72 years, 37% in functional class III-IV and 30% of patients with a left ventricular ejection fraction > 45%. Patients were well treated, with 87% and 88% of patients receiving renin-angiotensin inhibitors and beta-blockers, respectively. Median transferrin saturation index was 20%, median ferritin 155 ng/mL and median haemoglobin 13 g/dL. ID was present in 53% of patients; in 35% it was absolute and in 18% functional. Median follow-up was 20 months. ID was a predictor of death, hospitalization due to heart failure or to any cause in univariate analysis but not after multivariate analysis. No differences were found between absolute or functional ID regarding prognosis. CONCLUSION: In a real life population of patients with CHF and a high prevalence of heart failure with preserved ejection fraction, ID did not predict mortality or hospitalizations after adjustment for comorbidities, functional class and neurohormonal treatment.

Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study.

BACKGROUND: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016. METHODS/DESIGN: An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months- follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for 'basic' parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months. DISCUSSION: Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people. TRIAL REGISTRATION: This study was registered prospectively on the 25th February 2016 at clinicaltrials.gov ( NCT02691546 ).

Estimated glomerular filtration rate and functional status among older people: A systematic review.

BACKGROUND: The association between chronic kidney disease (CKD) and functional status may change as a function of the equation used to estimate glomerular filtration rate (eGFR). We reviewed the predictive value of different eGFR equations in regard to frailty and disability outcomes. METHODS: We searched Pubmed from inception to March 2018 for studies investigating the association between eGFR and self-reported and/or objective measures of frailty or disability. Cross-sectional and longitudinal studies were separately analysed. RESULTS: We included 16 studies, one of which reporting both cross-sectional and longitudinal data. Three out of 7 cross-sectional studies compared different eGFR equations in regard to their association with functional status: two studies showed that cystatin C-based, but not creatinine-based eGFR may be associated with hand-grip strength or frailty; another study showed that two different creatinine-based eGFR equations may be similarly associated with disability. Four out of 10 longitudinal studies provided comparative data: two studies reported similar association with disability for different creatinine-based eGFR equations; one study showed that creatinine-based eGFR was not associated with frailty, but a not significant trend for association was observed with cystatin C-based eGFR; one study showed that cystatin C-based but not creatinine-based eGFR may predict incident mobility disability, while both methods may predict gait speed decline. High heterogeneity was observed in regard to confounders included in reviewed studies. None of them included the most recently published equations. CONCLUSION: Available data do not support the superiority of one of the eGFR equations in terms of measuring or predicting functional decline.

One-year optical coherence tomography findings in patients with late and very-late stent thrombosis treated with intravascular imaging guided percutaneous coronary intervention.

Patients with late/very-late stent thrombosis (ST) are at high risk of recurrent-ST. The mechanisms of recurrent-ST are largely unknown. The objective is to describe the 1-year optical coherence tomography (OCT) findings of patients suffering from late/very-late ST treated with intravascular imaging guided percutaneous coronary intervention (PCI). All consecutive patients with late/very-late ST undergoing intravascular imaging guided PCI were screened to undergo coronary angiography and OCT examination at 1 year. Patients were classified according to the observation of stent malapposition as most contributing cause of the ST. Thirty-four patients were included. Stent malapposition was observed in 17 (50%) and the remaining 17 cases were classified as: neoatherosclerosis (n = 9), underexpansion (n = 3) and unknown mechanism (n = 5). Patients with malapposition had a remarkable reduction of the malapposition volume (from 6.4 to 1.3 mm3; p = 0.02) during the ST procedure, but this was not fully corrected in 13 (76.5%). At 12 months, two patients of the malapposition group presented with uneventful target vessel re-occlusion. Persistent malapposition was observed in nine patients (60.0%). Major coronary evaginations (46.7 vs. 0%; p = 0.001) and uncovered struts (6.3 vs. 1.0%; p < 0.001) were also more frequent in patients with malapposition than without malapposition. None of the patients had thin-cap fibroatheroma neoatherosclerosis. Contributing causes of late/very-late ST are diverse and have different healing patterns at 12 months. Patients with stent malapposition treated with intravascular imaging guided PCI showed poor re-healing; but patients with other causes of the ST showed optimal stent healing as assessed by OCT.