N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction - a randomized trial: The NICE study.

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.98; p = 0.048), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance [Correction added on 29 April 2024, after first online publication: In the preceding sentence, "95% CI 0.02 - 0.09" has been corrected to "95% CI 0.02 - 0.98; p = 0.048" in this version.]. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Serum Vitamins A and E at Mid-Pregnancy and Their Relationships with Both Maternal and Cord Blood Antioxidant Status and Perinatal Conditions: The NELA Cohort.

INTRODUCTION: Most of the pregnant women do not achieve the recommended dietary intake of vitamins A and E. These vitamins may counteract oxidative stress involved in some adverse perinatal outcomes. We aimed to assess the associations between maternal vitamin A and E at mid-pregnancy with both maternal and fetal outcomes and to identify possible early biomarkers during pregnancy to predict and prevent oxidative stress in the offspring. METHODS: Data on dietary and serum levels of vitamins A and E were collected from 544 pregnant women from the Nutrition in Early Life and Asthma (NELA) study, a prospective mother-child cohort set up in Spain. RESULTS: There were large discrepancies between low dietary vitamin E intake (78% of the mothers) and low serum vitamin E levels (3%) at 24 weeks of gestation. Maternal serum vitamins A and E at mid-pregnancy were associated with higher antioxidant status not only in the mother at this time point (lower hydroperoxides and higher total antioxidant activity [TAA]) but also with the newborn at birth (higher TAA). Gestational diabetes mellitus (GDM) was negatively associated with maternal serum vitamin A (OR: 0.95 CI: 0.91-0.99, p = 0.009) at mid-pregnancy. Nevertheless, we could not detect any association between GDM and oxidative stress parameters. CONCLUSIONS: In conclusion, maternal vitamin A and E serum levels may be used as an early potential biomarker of antioxidant status of the neonate at birth. Control of these vitamins during pregnancy could help avoid morbid conditions in the newborn caused by oxidative stress in GDM pregnancies.

Dietary Patterns in Pregnancy and Biomarkers of Oxidative Stress in Mothers and Offspring: The NELA Birth Cohort.

Background: Although adherence to the Mediterranean and antioxidant-rich diets during pregnancy is suggested to improve maternal-fetal health by reducing oxidative stress, yet there is no study available. Objective: We examined whether maternal dietary patterns in pregnancy impact the biomarkers of oxidative stress in mothers and their offspring. Methods: Study population included 642 mothers and 335 newborns of the "Nutrition in Early Life and Asthma" (NELA) birth cohort. Maternal diet during pregnancy was assessed by a validated food frequency questionnaire and a priori-defined dietary indices (relative Mediterranean Diet [rMED], alternative Mediterranean Diet [aMED], Dietary Approach to Stop Hypertension [DASH], Alternate Healthy Index [AHEI], and AHEI-2010) were calculated. Biomarkers measured were: hydroperoxides, carbonyl groups, and 8-hydroxydeoxyguanosine (8OHdG) determined in maternal blood and newborn cord blood, and urinary maternal and offspring 15-F2t-isoprostane. Multivariate linear regression models were performed. Results: Maternal rMED score was inversely associated with the maternal levels of 8OHdG at mid-pregnancy (beta per 1-point increase = -1.61; 95% CI -2.82, -0.39) and the newborn levels of hydroperoxides (beta per 1-point increase = -4.54; 95% CI -9.32, 0.25). High vs. low maternal rMED score was marginally associated with the decreased levels of 8OHdG in newborns (beta = -9.17; 95% CI -19.9, 1.63; p for trend 0.079). Maternal DASH score tended to be inversely associated with maternal urinary 15-F2t-isoprostane (beta per 1-point increase = -0.69; 95% CI, -1.44, 0.06). High vs. low maternal AHEI score was associated with reduced offspring urinary levels of 15-F2t-isoprostane (beta = -20.2; 95% CI -38.0, -2.46; p for trend 0.026). Conclusion: These results suggest that maternal adherence to healthy dietary patterns during pregnancy may reduce DNA damage and lipid oxidation in mothers and offspring.

Exhaled volatilome analysis as a useful tool to discriminate asthma with other coexisting atopic diseases in women of childbearing age.

The prevalence of asthma is considerably high among women of childbearing age. Most asthmatic women also often have other atopic disorders. Therefore, the differentiation between patients with atopic diseases without asthma and asthmatics with coexisting diseases is essential to avoid underdiagnosis of asthma and to design strategies to reduce symptom severity and improve quality of life of patients. Hence, we aimed for the first time to conduct an analysis of volatile organic compounds in exhaled breath of women of childbearing age as a new approach to discriminate between asthmatics with other coexisting atopic diseases and non-asthmatics (with or without atopic diseases), which could be a helpful tool for more accurate asthma detection and monitoring using a noninvasive technique in the near future. In this study, exhaled air samples of 336 women (training set (n = 211) and validation set (n = 125)) were collected and analyzed by thermal desorption coupled with gas chromatography-mass spectrometry. ASCA (ANOVA (analysis of variance) simultaneous component analysis) and LASSO + LS (least absolute shrinkage and selection operator + logistic regression) were employed for data analysis. Fifteen statistically significant models (p-value < 0.05 in permutation tests) that discriminated asthma with other coexisting atopic diseases in women of childbearing age were generated. Acetone, 2-ethyl-1-hexanol and a tetrahydroisoquinoline derivative were selected as discriminants of asthma with other coexisting atopic diseases. In addition, carbon disulfide, a tetrahydroisoquinoline derivative, 2-ethyl-1-hexanol and decane discriminated asthma disease among patients with other atopic disorders. Results of this study indicate that refined metabolomic analysis of exhaled breath allows asthma with other coexisting atopic diseases discrimination in women of reproductive age.

Self-Reported DHA Supplementation during Pregnancy and Its Association with Obesity or Gestational Diabetes in Relation to DHA Concentration in Cord and Maternal Plasma: Results from NELA, a Prospective Mother-Offspring Cohort.

Maternal supplementation of docosahexaenoic acid (DHA) during pregnancy has been recommended due to its role in infant development, but its effect on materno-fetal DHA status is not well established. We evaluated the associations between DHA supplementation in pregnant women with obesity or gestational diabetes mellitus (GDM) and maternal and neonatal DHA status. Serum fatty acids (FA) were analyzed in 641 pregnant women (24 weeks of gestation) and in 345 venous and 166 arterial cord blood samples of participants of the NELA cohort. Obese women (n = 47) presented lower DHA in serum than those lean (n = 397) or overweight (n = 116) before pregnancy. Linoleic acid in arterial cord was elevated in obese women, which indicates lower fetal retention. Maternal DHA supplementation (200 mg/d) during pregnancy was associated with enhanced maternal and fetal DHA levels regardless of pre-pregnancy body mass index (BMI), although higher arterial DHA in overweight women indicated an attenuated response. Maternal DHA supplementation was not associated with cord venous DHA in neonates of mothers with GDM. The cord arteriovenous difference was similar for DHA between GDM and controls. In conclusion, maternal DHA supplementation during pregnancy enhanced fetal DHA status regardless of the pre-pregnancy BMI while GDM may reduce the effect of DHA supplementation in newborns.

Diagnostic Application of Postmortem Cardiac Troponin I Pericardial Fluid/Serum Ratio in Sudden Cardiac Death.

In approximately 5% of unexpected deaths, establishing a conclusive diagnosis exclusively on the basis of anatomo-pathological findings in a classic autopsy is difficult. Postmortem biomarkers have been actively investigated as complementary indicators to help to reach valid conclusions about the circumstances of death. Several studies propose either the pericardial fluid or peripheral veins as a location for troponin determination, but the optimum sampling site is still a matter of debate. Our objective was to evaluate the association between the ratio of troponin values in the pericardial fluid and serum (determined postmortem) and the diagnosis of acute myocardial infarction (AMI) in the context of sudden cardiac death. We included 175 forensic cases. Two groups were established: AMI deaths (48; 27.4%) and the control group (127; 72.6%). The cardiac Troponin I (cTnI) values in the pericardial fluid and the troponin ratio were found to be associated with the cause of death. Univariate regression analyses showed that both age and the cTnI ratio were significantly associated with the diagnosis of AMI death. In a multivariate analysis, adjusting for confounding factors, the age and cTnI ratio were independent predictors of death from myocardial infarction. We performed a receiver operating characteristic (ROC) curve for the cTnI ratio for AMI death and selected a cut-off point. Our biomarker was found to be a valuable and highly effective tool for use in the forensic field as a complementary method to facilitate diagnosis in nonconclusive autopsies.

Proteomics in Deaths by Drowning: Diagnostic Efficacy of Apolipoprotein A1 and α-1Antitrypsin, Pilot Study.

Drowning is one of the leading causes of death worldwide. The pathophysiology of drowning is complex and, sometimes, interpretation of the circumstances of death in the autopsy becomes the main source of information in its diagnosis. New advances in medical research, such as proteomics, especially in forensic pathology, are still in the development. We proposed to investigate the application of Mass Spectrometry-based technologies, to identify differentially expressed proteins that may act as potential biomarkers in the postmortem diagnosis of drowning. We performed a pilot proteomic experiment with the inclusion of two drowned and two control forensic cases. After applying restrictive parameters, we identified apolipoprotein A1 (ApoA1) and α-1 antitrypsin as differentially expressed between the two diagnostic groups. A validation experiment, with the determination of both proteins in 25 forensic cases (16 drowned and 9 controls) was performed, and we corroborated ApoA1 higher values in the drowning group, whereas α-1 antitrypsin showed lower levels. After adjusting by confounder factors, both remained as predictive independent factors for diagnosis of drowning (p = 0.010 and p = 0.022, respectively). We constructed ROC curves for biomarkers' levels attending at the origin of death and established an ApoA1 cut-off point of 100 mg/dL. Correct classification based on the diagnosis criteria was reached for 73.9% of the cases in a discriminant analysis. We propose apolipoprotein A1 (with our cutoff value for correct classification) and α-1 antitrypsin as valuable biomarkers of drowning. Our study, based on forensic cases, reveals our proteomic approach as a new complementary tool in the forensic diagnosis of drowning and, perhaps, in clinical future implications in drowned patients. However, this is a pilot approach, and future studies are necessary to consolidate our promising preliminary data.

Impact of pre-hospital renal function on the detection of acute kidney injury in acute decompensated heart failure.

BACKGROUND: Acute kidney injury (AKI) is a serious complication in patients hospitalized for decompensated heart failure (HF). Currently, AKI definitions consider creatinine levels at admission as reference of baseline renal function (RF). However, renal impairment may already be present at admission. We aimed to study the impact on AKI detection of considering outpatient RF as reference. METHODS: In a cohort of 458 patients hospitalized for decompensated HF, we studied the occurrence of AKI using the standardized KDIGO criteria and grading (stages: 1, 2, 3), and considering two different definitions according to the RF used as reference or baseline: the latest outpatient measurement prior to admission vs. the first measurement at admission. We compared the prevalence, timing and prognostic value for both AKI definitions. RESULTS: The definition based on outpatient RF was associated with an increase in overall AKI detection from 20.1% to 33.8% (p < 0.001), and from 3.1% to 5.0% for advanced stages (2-3) (p < 0.001); additionally, 12.5% of patients already had criteria of AKI at admission (36.8% of AKI cases). Both definitions were associated with longer hospital stay. However, only AKI already present at admission, as based on pre-hospital creatinine, was independently associated with all-cause death, in-hospital and after discharge, and death or HF readmission in the follow-up: 1 stage (HR 2.72, 95%CI 1.83-4.06, p < 0.001) and 2-3 stage (HR 7.29, 95%CI, 3.02-17.64, p < 0.001). CONCLUSIONS: Evaluation of AKI in patients admitted with HF should consider pre-hospital RF, since it improves early identification of AKI and has implications for risk assessment.

Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1ß release.

The nucleotide-binding domain and leucine-rich repeat-containing receptor with a pyrin domain 3 (NLRP3) inflammasome is a sensor for different types of infections and alterations of homeostatic parameters, including abnormally high levels of the extracellular nucleotide ATP or crystallization of different metabolites. All NLRP3 activators trigger a similar intracellular pathway, where a decrease in intracellular K+ concentration and permeabilization of plasma membrane are key steps. Cationic amphipathic antimicrobial peptides and peptide toxins permeabilize the plasma membrane. In fact, some of them have been described to activate the NLRP3 inflammasome. Among them, the bee venom antimicrobial toxin peptide melittin is known to elicit an inflammatory reaction via the NLRP3 inflammasome in response to bee venom. Our study found that melittin induces canonical NLRP3 inflammasome activation by plasma membrane permeabilization and a reduction in the intracellular K+ concentration. Following melittin treatment, the apoptosis-associated speck-like protein, an adaptor protein with a caspase recruitment domain (ASC), was necessary to activate caspase-1 and induce IL-1ß release. However, cell death induced by melittin prevented the formation of large ASC aggregates, amplification of caspase-1 activation, IL-18 release and execution of pyroptosis. Therefore, melittin-induced activation of the NLRP3 inflammasome results in an attenuated inflammasome response that does not result in caspase-1 dependent cell death.

Associations between oxidative stress biomarkers in different body fluids and reproductive parameters in male partners of subfertile couples / Asociaciones entre biomarcadores de estrés oxidativo en diferentes fluidos biológicos y parámetros reproductivos en varones de parejas subfértiles

Objective. To evaluate the relationships between oxidative stress (OS) biomarkers and total antioxidant capacity (TAC) in blood serum and seminal plasma, and their associations with semen quality and serum reproductive hormone concentrations in potential subfertile men. Material and method. A cross-sectional study was conducted on men (n = 122) attending an infertility clinic in the Murcia Region (Southern Spain) between 2012 and 2013. Concentrations of malondialdehyde (MDA), nitric oxide (NO) and TAC were measured in blood and semen. Follicle-stimulating hormone, luteinising hormone, testosterone, prolactin and oestradiol concentrations were measured in serum. Semen analyses were performed according to World Health Organization criteria. Correlation analysis and multiple linear regression models were performed, controlling for important covariates. Results. There was a significant inverse association between serum MDA concentrations and all sperm parameters, except for seminal volume. Serum TAC concentrations were positively related to sperm count and motility. A positive association was observed between seminal plasma NO levels and the percentage of morphologically normal sperm. With regard to reproductive hormones, serum MDA concentrations were positively related to FSH and LH levels, and TAC inversely associated with FSH levels. Conclusions. Our results suggest that oxidative stress may be associated with semen parameters and reproductive hormone levels in male partners of couples seeking infertility treatment. However, further studies are needed to confirm and extend these findings, in particular, with regard to serum reproductive hormones (AU)

Objetivo. Evaluar las correlaciones entre marcadores de estrés oxidativo (OS) y capacidad antioxidante total (TAC) en suero sanguíneo y plasma seminal, y sus asociaciones con calidad seminal y hormonas reproductivas en varones potencialmente subfértiles. Material y método. Estudio transversal realizado en varones (n = 122) que acudían a un servicio de infertilidad de Murcia entre 2012-2013. Las concentraciones de malondialdehído (MDA), óxido nítrico (NO) y TAC se midieron en sangre y semen. Se analizaron los niveles séricos de las hormonas foliculoestimulante, luteinizante, testosterona, prolactina y estradiol. Los análisis espermáticos se llevaron a cabo siguiendo las normas de la Organización Mundial de la Salud. Se utilizaron análisis de correlación y modelos de regresión lineal múltiple ajustando por covariables importantes. Resultados. Se mostró una asociación inversa significativa entre las concentraciones séricas de MDA y todos los parámetros espermáticos, excepto el volumen seminal. Las concentraciones séricas de TAC se relacionaron positivamente con el recuento y la movilidad espermática. Los niveles de NO en plasma seminal se asociaron directamente con el porcentaje de espermatozoides morfológicamente normales. Con respecto a las hormonas reproductivas, las concentraciones séricas de MDA se asociaron positivamente con los niveles de FSH y LH, y las de TAC se asociaron inversamente con los niveles de FSH. Conclusiones. Nuestros resultados sugieren que el estrés oxidativo estaría asociado con los parámetros seminales y hormonales en varones de parejas que consultan por problemas de infertilidad. Sin embargo, son necesarios más estudios para confirmar estos hallazgos, en particular con respecto al papel de las hormonas reproductivas (AU)

sST2 levels are associated with all-cause mortality in anticoagulated patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with high morbidity and mortality, even despite the use of oral anticoagulation (OAC). Soluble suppression of tumorigenicity-2 (sST2) is a member of the interleukin-1 receptor family [interleukin-1 receptor-like 1 (IL1RL1)], which has been associated with an increased risk of mortality and morbidity in heart failure or acute coronary syndrome. We assessed the predictive value of sST2 levels in an unselected 'real-world' cohort of anticoagulated AF patients. METHODS: We included 562 patients (49% male; median age 77 [IQR: 71-82]) with permanent AF who were stable (for at least 6 months) on OAC (INRs 2.0-3.0). sST2 levels were quantified by ELISA. Patients were followed-up for up to 4 years, and cardiovascular events and all-cause mortality were recorded. RESULTS: Median (IQR) of sST2 levels was 51.23 (39.09-67.40) µg/L. Median follow-up was 1587 days [IQR 1482-1617], and during this period, 91 patients died (16.2%, 3.72%/year). The c-statistic for predicting mortality with sST2 was 0.58 + 0.03; P = 0.017). On multivariate analysis, age [hazard ratio (HR) 1.09 (1.05-1.13); P < 0.001], diabetes mellitus [1.76 (1.08-2.88); P = 0.023], previous stroke [2.16 (1.29-3.60); P = 0.003] and sST2 levels [1.008 (1.002-1.14); P = 0.008] were independently associated with mortality. Concentrations of sST2 were also significantly associated with the risk of mortality, even after adjusting for the CHA2 DS2 -VASc score [HR: 1.007 (1.001-1.013); P = 0.014]. CONCLUSIONS: In an anticoagulated AF patient's cohort, sST2 levels are an independent predictive factor of all-cause mortality. sST2 levels could be a biomarker used to improve clinical risk assessment in anticoagulated AF patients.

Associations between urinary organophosphate pesticide metabolite levels and reproductive parameters in men from an infertility clinic.

Organophosphate (OP) pesticides are compounds used for pest control at home or in agriculture activities. Almost all OP pesticides are metabolized to at least one of six possible dialkylphosphates (DAPs). Despite wide use, their potential effects on human reproductive health have not yet been fully characterized. The aim of this study was to evaluate the associations between urinary concentrations of six DAP metabolites and reproductive parameters in men. All men were attended an infertility clinic and provided urine, serum and semen samples on the same day. Six DAP metabolites were measured in urine (dimethylphosphate [DMP], dimethylthiophosphate [DMTP], dimethyldithiophosphate [DMDTP], diethylphosphate [DEP], diethylthiophosphate [DETP], and diethyldithiophosphate [DEDTP]). Sperm quality was assessed by measuring volume, concentration, total sperm count (TSC), motility and morphology, and serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin and estradiol. Pearson correlations were used for unadjusted analyses, and multiple linear regression analysis was performed controlling for appropriate covariates. All men presented detectable concentrations of at least one urinary OP metabolite. After adjustment by important covariates, there was a significant positive association between DEDTP concentrations and LH [(ß)=11.4; 95% CI 0.81-22.1] as well as FSH levels [(ß)=3.2; 95% CI 0.08-6.2]. Sperm concentration and TSC were both significantly inversely associated with DMP, DMDP, DMDTP and ∑DAP in multivariate analysis. Besides, there was a significant inverse association between percentage of motile sperm and DMTP, DMDTP and DEP metabolite concentrations. Our results suggest that exposure to OP pesticides may be associated with decreased sperm counts and motility and altered reproductive hormone levels in male partners of couples seeking for infertility treatment. However, further studies are warranted to confirm and extent these findings.

The real role of prediagnostic high-density lipoprotein cholesterol and the cancer risk: a concise review.

BACKGROUND: In several observational and clinical studies, the association between serum cholesterol levels and cancer is still unsettled although serum total cholesterol has been associated with increased mortality from cancer. Moreover, the importance of abnormal levels of serum lipid components as the main features of dyslipidemia and the risk of individual cancers is unclear. The prevalence of dyslipidemia is increasing worldwide but, the precise aetiology of the link between risk of cancer and the behaviour of lipid profile, prior diagnosis, has yet to be determinated. Low levels of high-density lipoprotein cholesterol (HDL) at baseline of many of the studies analyzed has to be taken into account, and continued low levels of HDL without explanation should be considered by clinicians. AIMS: The main aim of this review was to undertake the assessment of the most recent studies implying the lipid profile and cancer risk, and focused on low HDL levels at baseline and follow up, and also analyzing this behaviour on the different cancer types. MATERIAL AND METHODS: A literature search was performed to identify publications. The most recent prospective and case-control studies with multivariate Cox models were analyzed and also were considered some recent meta-analyses. RESULTS AND CONCLUSIONS: The findings exposed in this review suggest that the association with low HDL levels at baseline of different studies of cancer risk is shared among many types of cancer, and it is mainly linked to obesity and inflammation, suggesting a common pathway.

Kidney stones in a Mediterranean population from the south of Spain.

BACKGROUND: Kidney stones have become increasingly prevalent in the developed countries over the past 100 years. The incidence of urolithiasis in a population depends on the geographical area, racial distribution, socio-economic status and dietary habits. During the past decades, these factors have changed affecting the incidence and also the chemical composition of calculi; nowadays in our region, the most common stones composition is calcium oxalate. The identification of the calculi composition enables superior treatment, lower (decreased) cost and a better quality of life for the patients. METHODS: We analyzed the composition and the evolution of all of the cases concerning calculi received at Biochemical Clinical Analysis Laboratory from 2007 to 2010, using Interferometry with Fourier transformation (FTIR). The relationship between composition, gender and age was studied for an aleatory group in 2010 (n=657, 431 men and 226 women). RESULTS: The stone composition obtained was mixtures 24.7% and only one component 75.3%. Calcium oxalate monohydrate (COM) 41.5%, calcium oxalate dihydrate (COD) 7.6%, anhydrous uric acid (AUA) 12.4%, uric acid dehydrate (UAD) 6.7%, urates 1.4%, carbonate-apatite (CA) 2.9%, and others 2.8%. The male to female ratio was 1.9 and the largest number of stones was found in patients between the ages of 40 and 49, for both men and women. CONCLUSIONS: The most common composition (relative percentage) was COM, mixtures and AUA. Presence of calculi is more common in men than in women with the exception of carbonate apatite stones. Stones follow a Gaussian distribution throughout the lifetime of a patient, with particular incidence in those between 40 to 49 years old.

Biochemical and immunologic features of an outbreak of Legionnaires disease: comparative study between community-acquired pneumonias.

Legionella pneumophila has been recognized as an important cause of community- and hospital-acquired pneumonia. This study evaluates the interrelationship between that patients group with Legionnaires disease (LD) and the possible factors that may predispose hosts to acquire this infection. Likewise, we search for preliminary biochemical and immunologic evidences that could help physicians to differentiate between LD and other pneumonias. We analyzed biochemical parameters and immunoglobulin levels in 61 LD patients and a control group (n = 30) who were non-Legionella pneumonia diagnosed. We observed statistically significant differences in LD patients versus control group in serum sodium, albumin, gamma-band, IgG levels, (P < .01) and for total proteins, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (P < .05). Our study shows a trend between the presence of LD and immunoglobulin deficiencies in the group studied. Deficit in IgG or IgG plus IgM, during the exposure period, may predispose individuals to suffer legionellosis (P < .05). Overall, hypoalbuminemia, hyponatremia, and high AST and LDH levels can represent a useful prognostic marker in patients with severe pulmonary infection suspected to be legionellosis.

[Usefulness of NTproBNP in the emergency management of patients with severe dyspnea and an uncertain heart failure diagnosis]. / Utilidad del NTproBNP en el manejo urgente del paciente con disnea severa y diagnóstico dudoso de insuficiencia cardíaca.

INTRODUCTION AND OBJECTIVES: Measurement of N-terminal pro-B-type natriuretic peptide (NTproBNP) helps in diagnosing heart failure (HF). The test's usefulness may be greatest in patients with severe dyspnea of uncertain origin. However, NTproBNP has not been evaluated specifically in this setting. PATIENTS AND METHOD: This prospective emergency department study included 70 patients with shortness of breath at rest as their chief complaint. In the attending physician's opinion, both HF and a non-cardiac cause were equally probable. Blinded NTproBNP measurement was carried out in blood samples collected on admission. Patients were monitored and their final diagnoses were based on clinical findings, therapeutic responses, and cardiac and noncardiac tests performed during hospitalization. RESULTS: The NTproBNP level was higher in the 49 patients (70%) with a final diagnosis of HF (P = .006); the area under the ROC curve was 0.72 (0.60-0.82). The optimum diagnostic cut-off value was 900 pg/mL, which had an accuracy of 87%, a sensitivity of 98%, and a negative predictive value of 92%. The NTproBNP level was significantly higher in the 6 patients (9%) who died during hospitalization (P = .009); the area under the ROC curve was 0.87 (0.76-0.93) and the optimum cut-off value for predicting death was 5500 pg/mL, which had an accuracy of 77%, a sensitivity of 100%, and a positive likelihood ratio of 4.2. CONCLUSIONS: In patients with severe dyspnea and an uncertain diagnosis of HF, an NTproBNP level < 900 pg/mL helps exclude the presence of HF, whereas a NTproBNP level > 5500 pg/mL identifies patients at an increased risk of death.

Utilidad del NTproBNP en el manejo urgente del paciente con disnea severa y diagnóstico dudoso de insuficiencia cardíaca / Usefulness of NTproBNP in the emergency management of patients with severe dyspnea and an uncertain heart failure diagnosis

Introducción y objetivos. El NTproBNP ayuda a identificar a los pacientes con insuficiencia cardíaca. Su utilidad podría ser máxima en pacientes con disnea severa de origen incierto; sin embargo, esta población no ha sido específicamente evaluada. Pacientes y método. Estudio prospectivo de 70 pacientes que acudieron a urgencias refiriendo disnea de reposo, cuyo diagnóstico clínico inicial fue establecido como dudoso, con probabilidad intermedia de insuficiencia cardíaca. A la llegada a urgencias se extrajeron las muestras analíticas y se determinó el valor de NTproBNP de forma ciega. Los pacientes fueron controlados y el diagnóstico final se estableció sobre la base de los hallazgos clínicos, la respuesta al tratamiento y las pruebas practicadas durante el curso hospitalario. Resultados. El NTproBNP fue mayor en los 49 pacientes (70%) con un diagnóstico final de insuficiencia cardíaca (p = 0,006), obteniendo un área bajo la curva ROC de 0,72 (0,60-0,82). El valor de corte diagnóstico óptimo fue 900 pg/ml, con una precisión del 87%, una sensibilidad del 98% y un valor predictivo negativo del 92%. En los 6 pacientes (9%) fallecidos durante la hospitalización, el NTproBNP fue significativamente mayor (p = 0,009), con un área bajo la curva ROC de 0,87 (0,76-0,93) y un valor de corte pronóstico óptimo de 5.500 pg/ml, con una precisión del 77%, una sensibilidad del 100% y una razón de probabilidad positiva de 4,2. Conclusiones. En una población con disnea severa que acude a urgencias con diagnóstico dudoso de insuficiencia cardíaca, un valor de NTproBNP 5.500 pg/ml identifica a los pacientes con un mayor riesgo de muerte hospitalaria

Introduction and objectives. Measurement of N-terminal pro-B-type natriuretic peptide (NTproBNP) helps in diagnosing heart failure (HF). The test's usefulness may be greatest in patients with severe dyspnea of uncertain origin. However, NTproBNP has not been evaluated specifically in this setting. Patients and method. This prospective emergency department study included 70 patients with shortness of breath at rest as their chief complaint. In the attending physician's opinion, both HF and a non-cardiac cause were equally probable. Blinded NTproBNP measurement was carried out in blood samples collected on admission. Patients were monitored and their final diagnoses were based on clinical findings, therapeutic responses, and cardiac and noncardiac tests performed during hospitalization. Results. The NTproBNP level was higher in the 49 patients (70%) with a final diagnosis of HF (P=.006); the area under the ROC curve was 0.72 (0.60-0.82). The optimum diagnostic cut-off value was 900 pg/mL, which had an accuracy of 87%, a sensitivity of 98%, and a negative predictive value of 92%. The NTproBNP level was significantly higher in the 6 patients (9%) who died during hospitalization (P=.009); the area under the ROC curve was 0.87 (0.76-0.93) and the optimum cut-off value for predicting death was 5500 pg/mL, which had an accuracy of 77%, a sensitivity of 100%, and a positive likelihood ratio of 4.2. Conclusions. In patients with severe dyspnea and an uncertain diagnosis of HF, an NTproBNP level 5500 pg/mL identifies patients at an increased risk of death

Heterophile antibodies produce spuriously elevated concentrations of cardiac Troponin I in patients with Legionella pneumophila.

We found an unusually high positive rate for cTnI in patients recently infected with Legionella pneumophila. The aim of this study was to examine the possible origin of increased cTnI levels and to test if it could be associated with the immune response to legionellosis. The cTnI was above the cut point in 46.7% of patients infected with legionellosis when measured with reagent lot number RF421A. A strong correlation between high cTnI measurements and positive serologic values for legionellosis was found. With a revised formulation of cTnI reagent, lot number RF421C, the positive rate decreased by over 10-fold to 3.3%. We conclude that the revised lot of cTnI reagent minimized interference by heterophilic antibodies produced in response to legionellosis.