Environmental exposure to manganese and health risk assessment from personal sampling near an industrial source of airborne manganese.

Manganese (Mn), despite being a trace element necessary in small quantities for the correct functioning of the organism, at higher concentrations can induce health disorders, mainly in motor and cognitive functions, even at levels found in non-occupational environments. For this reason, US EPA guidelines define safe reference doses/concentrations (RfD/RfC) for health. In this study, the individualised health risk of exposure to Mn through different media (air, diet, soil) and routes of entry into the organism (inhalation, ingestion and dermal absorption) was assessed according to the procedure defined by the US EPA. Calculations related to Mn present in ambient air were made on the basis of data obtained from size-segregated particulate matter (PM) personal samplers carried by volunteers recruited in a cross-sectional study conducted in the Santander Bay (northern Spain), where an industrial source of airborne Mn is located. Individuals residing in the vicinity of the main Mn source (within 1.5 km) were found to have a hazard index (HI) higher than 1, indicating that there is a potential risk for these subjects to develop health alterations. Also, people living in Santander, the capital of the region, located 7-10 km from the Mn source, may have some risk (HI > 1) under some wind conditions (SW). In addition, a preliminary study of media and routes of entry into the body confirmed that inhalation of PM2.5-bound Mn is the most important route contributing to the overall non-carcinogenic health risk related to environmental Mn.

Short- and long-term exposure to trace metal(loid)s from the production of ferromanganese alloys by personal sampling and biomarkers.

The environmental exposure to trace metal(loid)s (As, Cd, Cu, Fe, Mn, Pb, and Zn) was assessed near a ferromanganese alloy plant using filters from personal particulate matter (PM) samplers (bioaccessible and non-bioaccessible fine and coarse fractions) and whole blood as short-term exposure markers, and scalp hair and fingernails as long-term biomarkers, collected from volunteers (n = 130) living in Santander Bay (northern Spain). Bioaccessible and non-bioaccessible metal(loid) concentrations in coarse and fine PM from personal samplers were determined by ICP-MS after extraction/digestion. Metal(loid) concentration in biomarkers was measured after alkaline dilution (whole blood) and acid digestion (fingernails and scalp hair) by ICP-MS as well. Results were discussed in terms of exposure, considering the distance to the main Mn source, and sex. In terms of exposure, significant differences were found for Mn in all the studied fractions of PM, As in whole blood, Mn and Cu in scalp hair and Mn and Pb in fingernails, with all concentrations being higher for those living closer to the Mn source, with the exception of Cu in scalp hair. Furthermore, the analysis of the correlation between Mn levels in the studied biomarkers and the wind-weighted distance to the main source of Mn allows us to conclude that scalp hair and mainly fingernails are appropriate biomarkers of long-term airborne Mn exposure. This was also confirmed by the significant positive correlations between scalp hair Mn and bioaccessible Mn in coarse and fine fractions, and between fingernails Mn and all PM fractions. This implies that people living closer to a ferromanganese alloy plant are exposed to higher levels of airborne metal(loid)s, mainly Mn, leading to higher levels of this metal in scalp hair and fingernails, which according to the literature, might affect some neurological outcomes. According to sex, significant differences were observed for Fe, Cu and Pb in whole blood, with higher concentrations of Fe and Pb in males, and higher levels of Cu in females; and for Mn, Cu, Zn, Cd and Pb in scalp hair, with higher concentrations in males for all metal(loid)s except Cu.

Understanding how methodological aspects affect the release of trace metal(loid)s from urban dust in inhalation bioaccessibility tests.

The bioaccessibility of metal(loid)s in ambient particulate matter (PM) has been recently used to represent the risk of inhalation exposure. Nevertheless, different methodological factors affect the bioaccessibility values; among these, the type and composition of surrogate biological fluids and the liquid to solid ratio have been revealed to be the most important. To better understand how these methodological aspects affect the bioaccessibility, a reference material corresponding to urban dust (SRM1648a) was contacted with synthetic biological fluids commonly used in the literature representing surrogate fluids that may interact with fine (Gamble's solutions, artificial lysosomal fluid (ALF)) and coarse particles (gastric fluid), for liquid to solid (L/S) ratios ranging from 500 to 20,000. Visual MINTEQ 3.1. was used to enhance the discussion on how the solubility of metals in the leaching solution depends on the composition of the simulated fluids and the speciation of metals. The results obtained indicate that a small change in the composition of Gamble's solution (the presence of glycine) may increase significantly the bioaccessibility at a L/S ratio of 5,000. The highest bioaccessibility of most of the studied metal(loid)s at a L/S ratio of 5,000 was found for ALF fluid. The study of the effect of the L/S ratio showed that metal(loid)s bioaccessibility in Gamble's fluid increased logarithmically with increasing L/S ratio, while it remained practically constant in ALF and gastric fluid. This different behavior is explained assuming that the leaching of metal(loid)s in Gamble's solution is solubility-controlled, while in ALF and gastric fluid is availability-controlled.

Etiology of bloodstream infections at a population level during 2013-2017 in the Autonomous Community of Valencia, Spain.

OBJECTIVE: Bloodstream Infections has become in one of the priorities for the antimicrobial stewardship teams due to their high mortality and morbidity rates. Usually, the first antibiotic treatment for this pathology must be empirical, without microbiology data about the microorganism involved. For this reason, the population studies about the etiology of bacteremia are a key factor to improve the selection of the empirical treatment, because they describe the main microorganisms associated to this pathology in each area, and this data could facilitate the selection of correct antibiotic therapy. METHODS: This study describes the etiology of bloodstream infections in the Southeast of Spain. The etiology of bacteremia was analysed by a retrospective review of all age-ranged patients from every public hospital in the Autonomous Community of Valencia (approximately 5,000,000 inhabitants) for five years. RESULTS: A total of 92,097 isolates were obtained, 44.5% of them were coagulase-negative staphylococci. Enterobacteriales was the most prevalent group and an increase in frequency was observed along the time. Streptococcus spp. were the second microorganisms more frequently isolated. Next, the most prevalent were Staphylococcus aureus and Enterococcus spp., both with a stable incidence along the study. Finally, Pseudomonas aeruginosa was the fifth microorganism more frequently solated. CONCLUSIONS: These data constitute a useful tool that can help in the choice of empirical treatment for bloodstream infections, since the knowledge of local epidemiology is key to prescribe a fast and appropriate antibiotic therapy, aspect capital to improve survival.

Aspectos proteómicos y genéticos de la resistencia a la aspirina / Proteomics and genetics aspects of aspirin resistance

Objetivo: Analizar si existe alguna asociación entre la resistencia a aspirina (RA) y la presencia de polimorfismos genéticos de un único nucleótido (SNPs) en el gen de la COX-1, así como su relación con modificaciones en la expresión de proteínas plasmáticas en pacientes con enfermedad isquémica estable y tratamiento continuado de aspirina. Materiales y métodos: Analizamos el proteoma plasmático de 19 pacientes sensibles, 19 resistentes. RA se definió mediante el sistema PFA-100. Se realizó electroforesis bidimensional (IPG 17cm, pH(4-7), geles SDS-PAGE 10%) y tinción con plata. Se analizaron cambios en tres SNPs (A-842G, C22T y C50T) en 50 pacientes sensibles, 33 resistentes y 83 controles mediante PCR a tiempo real. Resultados: La expresión de cuatro isoformas de alfa1-antitripsina estaba aumentada en los pacientes resistentes. No encontramos diferencias en la expresión de ceruloplasmina, precursor de haptoglobina, apolipoproteína AI y precursor de albúmina entre ambos tipos de pacientes. Ningún paciente presentó cambios en el SNP A-842G. La frecuencia de cambio en C22T y C50T fue relativamente baja con respecto a la población total. Conclusiones: No encontramos asociación entre la presencia de polimorfismos en el gen de la COX-1 y la peor respuesta a la aspirina. Los cambios en observados alfa1-antitripsina podrían estar relacionados con un diferente estado inflamatorio entre ambos tipos de pacientes (AU)

Aim: To evaluate the existence of a possible association between Aspirin resistance (AR), COX-1 single-nucleotide polymorphisms (SNPs) and the modifications in the plasma proteome of clinically stable coronary patients. Materials and methods: AR was defined according to the PFA-100 assay. AR-sensitive and AR-resistant patients had been taken aspirin for the last 9 months. The proteomic study (19 AR-sensitive, 19 AR-resistant) was performed using IPG strips (17cm, pH 4-7), SDS-PAGE gels (10%) and silver staining. We study three SNPs (A- 842G, C22T y C50T) in 50 AR-sensitive patients, 33 AR-resistant and 83 controls using a real-time PCR. Results: The expression of four alpha1-antitripsin isoforms was increased in the aspirin-resistant patients. No differences were found in the expression of ceruloplasmin, haptoglobin-precursor, apolipoprotein-AI and albumin- precursor between both groups of patients. The A-842G SNP was undetectable in all subjects. The remaining two SNPs (C22T y C50T) showed a low frequency with respect the global population. Conclusions: The low SNPs frequencies were unlikely to explain the difference in aspirin responsiveness between both groups of patients. The changes in alpha1-antitripsin could be linked with a different inflammatory state in these patients (AU)

Clinical variables related with in-stent restenosis late regression after bare metal coronary stenting

In-stent restenosis (ISR) has an incidence between 20% and 30% using bare metal stents. ISR late regression phenomenon (ISRLR) has been previously described, but clinical variables related with this phenomenon remain unclear. The aim of the study was to identify the variables related with ISRLR. METHODS: We identified from our data base 30 patients between November 1995 and September 2002 that fulfilled the following criteria: 1) Documented ISR at follow-up angiography (CA-1); 2) treated medically; and 3) Referred for a second follow-up angiography (CA-2). at least 3 months after CA-1. ISRLR was defined as a > 0.2 mm increase in MLD between CA-1 and CA-2, calculated as the 2-fold of our inter-observer variability. ISR late progression was defined as a > 0.2 mm decrease in minimum lumen diameter (MLD) between CA-1 and CA-2. RESULTS: At the time of CA-2 only 2 patients (6.7%) had symptoms related with the previously stented vessel. We found a mean MLD of 1.03+/-0.34 mm and 1.54+/-0.48 mm at CA-1 and CA-2 respectively (AMLD = 0.51 +/-0.34 mm; p < 0.001). Twenty four patients (80.0%) had ISRLR. Two variables were related to the presence or absence ISRLR: Current smoking at the time of coronary stenting (70.8% vs 20.0% respectively, p = 0.026) and acute coronary syndrome as clinical indication for coronary stenting (and 83.5% vs 40.0% respectively, p = 0.029). CONCLUSION: ISRLR is a frequent phenomenon in patients with ISR treated medically, probably contributing to the benign long-term clinical outcome that has been previously described in patients with asymptomatic or mildly symptomatic ISR. Current smoking at the time of coronary stenting and acute coronary syndrome as clinical indication for coronary stenting are associated with this phenomenon.

Predictors of failure in direct stenting in the real world.

INTRODUCTION: Stent implantation without predilation simplifies a large proportion of coronary intervention procedures, with a significant reduction in costs and procedure time. OBJECTIVES: To determine the variables associated with a higher probability of failure in direct stent implantation in daily practice in a wide range of clinical contexts and types of lesions. POPULATION AND METHODS: Over a period of 28 months, direct implantation of 931 stents was attempted in our Center (811 patients, 83% male, mean age 62 +/- 12 years; 1.1 stent per patient). In 59 patients (7.3%), balloon predilation was necessary, and the factors associated with direct implant failure were determined. RESULTS: The vessels treated were: anterior descending (373 lesions: 40.1%), right coronary artery (306 lesions: 32.9%, circumflex (210 lesions: 22.6%), saphenous vein (35 lesions: 3.8%), left main (5 lesions: 0.4%) and internal mammary artery (2 lesions: 0.2%). 54% of the lesions were of type B2/C (ACC/AHA classification). The characteristics significantly associated with, or with statistical tendency towards, a lower success rate in direct stent implantation were: Lesion in the circumflex (11% vs. 5.5%, p = 0.012); reference vessel diameter less than 3.0 mm (9.8% vs. 6.2%, p = 0.097); age over 65 years (8.5% vs. 4.5%, p = 0.017); left main disease, irrespective of the vessel treated (23.5%% vs. 6.5%, p = 0.023); B2/C lesion (7.8%, vs. 4.8%, p = 0.086); calcification (9.9% vs. 4.9%, p = 0.012); vessel angulation greater than 45 degrees (9.9% vs. 4.9%, p = 0.009); and Express stent implant (19.6% vs. 6.0%, p < 0.001). On multivariate analysis, independent predictors of failure in direct stent implantation were: left main lesion (RR 6.6; 95% CI 1.73-24.93; p = 0.013), presence of calcium (RR 1.9; 95% CI 1.02-3.37; p = 0.049), vessel curvature (RR 2.0; 95% CI 1.13-3.64; p = 0.018), reference vessel diameter less than 3 mm (RR 2.2; 95% CI 1.15-4.32; p = 0.023), lesion type B2/C (RR 1.9; 95% CI 1.0-3.52; p = 0.044) and Express stent (RR 2.7; 95% CI 1.07-6.79; p = 0.05). CONCLUSION: In a large and heterogeneous series of patients, direct stenting was not possible in 7.3% of cases, which required balloon predilation. Certain clinical and angiographic features can predict when this is more like to occur.

[Leukocytoclastic vasculitis associated with ticlopidine]. / Vasculitis leucocitoclástica en relación con ticlopidina.

In the last five years the combination of ticlopidine plus aspirin has been the treatment of choice to avoid thrombi formation after the implantation of intracoronary stents. The adverse effects observed include the appearance of a maculopapulous, pruritic, painless, cutaneous rash. We present the case of a patient who developed leucocytoclastic vasculitis associated with the administration of ticlopidine.

Results (>6 months) of stenting of >1 major coronary artery in multivessel coronary artery disease.

Multivessel percutaneous transluminal coronary angioplasty (PTCA) is associated with a high requirement for further revascularization procedures. Although stenting can reduce restenosis and clinical events after 1-vessel intervention, little information is available after multivessel coronary stenting. We followed up 136 patients (9% of 1,481 undergoing stenting in our center) who had had stent implantation in at least 2 different major native coronary arteries and were followed-up for >6 months. Each patient had received a mean of 2.3 +/- 0.6 stents (1.13 +/- 0.4 stents per lesion) and procedural success was 95%. In-hospital complications included 1 death, 1 Q-wave infarction, 5 non-Q-wave myocardial infarctions, and 1 repeat PTCA. After a mean of 18 +/- 13 months, 7 patients died (3 of heart failure, 4 of noncardiac causes), 2 required coronary bypass surgery, 1 had a myocardial infarction, 13 target vessel repeat PTCA, and 4 non-target vessel PTCA. Survival free of major cardiac events was 75% at 3 years. A history of heart failure, dilation of a restenotic lesion, and 3-vessel dilation were independent negative predictors of event-free survival. Angiographic follow-up was available in 86 patients: 56 (65%) were restenosis free, 23 (27%) had 1-vessel restenosis, and 6 (7%) had 2-vessel and 1 patient 3-vessel restenosis. Restenosis per vessel was 23% (41 of 177). Reference diameter, past-PTCA minimal luminal diameter, and length of the stent were independent predictors of restenosis. We conclude that multivessel stenting provides good midterm results in selected patients with multivessel coronary artery disease. Midterm events are less frequent than previously reported after balloon PTCA.

Initial results and long-term clinical and angiographic implications of coronary stenting in elderly patients.

Results of 378 consecutive elderly patients (> or = 65 years) undergoing coronary stenting were compared with those of 601 younger patients. Although the restenosis rate was similar in the 2 groups, age > or = 65 years was an independent predictor of in-hospital mortality (relative risk 5.4, 95% confidence interval 1.2 to 20.1) and follow-up mortality (relative risk 2.8, 95% confidence interval 1.3 to 6.1).

Long-term clinical and echocardiographic follow-up after percutaneous mitral valvuloplasty with the Inoue balloon.

BACKGROUND: The objective of this study was to assess the long-term clinical outcome and valvular changes (area and regurgitation) after percutaneous mitral valvuloplasty (PMV). METHODS AND RESULTS: After PMV, 561 patients were followed up for 39 (+/-23) months and clinical/echocardiographic data obtained yearly. Kaplan-Meier and Cox regression analyses were performed to estimate event-free survival, its predictors, and the relative risks of several patient subgroups. There were several nonexclusive events: 19 (3.3%) cardiac deaths, 55 (9.8%) mitral replacements, 6 (1%) repeated PMVs, 56 (10%) cases of restenosis, and 108 (19%) cases of clinical impairment. Survival free of major events (cardiac death, mitral surgery, repeat PMV, or functional impairment) was 69% at 7 years, ranging from 88% to 40% in different subgroups of patients. Wilkins score was the best preprocedural predictor of mitral opening, but the procedural result (mitral area and regurgitation) was the only independent predictor of major event-free survival. Mitral area loss, though mild [0.13 (+/-0.21)cm2], increased with time and was >/=0.3 cm2 in 12%, 22%, and 27% of patients at 3, 5, and 7 years, respectively. Regurgitation did not progress in 81% of patients, and when it occurred it was usually by 1 grade. CONCLUSIONS: Seven years after PMV, more than two thirds of patients were in good clinical condition and free of any major event. The procedural result was the main determinant of long-term outcome, although a high score had also negative implications. Mitral area decreased progressively over time, whereas regurgitation did not tend to progress.