Baseline NT-proBNP levels as a predictor of short-and long-term prognosis in COVID-19 patients: a prospective observational study.

BACKGROUND: Up to 20% of COVID-19 patients can suffer COVID-19-related myocardial injury. Elevated cardiac biomarkers, such as hs-cTnT and NT-proBNP, have been related to worse short-term prognosis. However, data on NT-proBNP and long-term prognosis are scarce. We have evaluated the potential association of baseline age-adjusted NT-proBNP levels and outcomes at one-year follow-up in COVID-19 patients. METHODS: This was a single-center prospective study of 499 COVID-19 patients in whom NT-proBNP was assessed at hospital admission. NT-proBNP levels were age-adjusted and patients were classified as high or low NT-proBNP. Clinical and demographic characteristics, comorbidities, laboratory results, and in-hospital complications and mortality were compared between the two groups. Survivors of the acute phase of COVID-19 were followed up for one year from admission to detect readmissions and mortality. RESULTS: The 68 patients with high NT-proBNP levels at hospital admission were older, with more cardiovascular risk factors, cardiovascular disease, comorbidities, myocardial injury, and higher levels of inflammatory markers than patients with low NT-proBNP levels. They also had more in-hospital complications and a higher acute-phase mortality rate (60.3% vs. 10.2%, p < 0.001). High NT-proBNP levels were an independent marker of death during hospitalization (HR 1.95; CI 1.07-3.52). At one-year follow-up, high NT-proBNP levels were independently associated with mortality (HR 2.69; CI 1.47-4.89). Among survivors of the acute phase of COVID-19, there were no differences in hospital readmissions between those with high vs. low NT-proBNP levels, but survivors with high baseline NT-proBNP levels showed a higher 1-year mortality rate (7.4% vs. 1.3%, p = 0.018). CONCLUSIONS: High age-adjusted NT-proBNP levels at the time of hospital admission for COVID-19 are associated with poor short and long-term prognosis. High NT-proBNP seems also to be related to worse prognosis in survivors of the acute phase of COVID-19. A closer follow-up on these patients may be crucial.

Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients.

OBJECTIVE: Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRß2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. METHODS: 109 EC patients were included. The expression of the ADRß2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. RESULTS: ADRß2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). CONCLUSION: DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.

The natural history of QTc interval and its clinical impact in coronavirus disease 2019 survivors after 1 year.

Background and objective: Prolonged QTc interval on admission and a higher risk of death in SARS-CoV-2 patients have been reported. The long-term clinical impact of prolonged QTc interval is unknown. This study examined the relationship in COVID-19 survivors of a prolonged QTc on admission with long-term adverse events, changes in QTc duration and its impact on 1-year prognosis, and factors associated with a prolonged QTc at follow-up. Methods: We conducted a single-center prospective cohort study of 523 SARS-CoV-2-positive patients who were alive on discharge. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval and repeated in 421 patients 7 months after discharge. Mortality, hospital readmission, and new arrhythmia rates 1 year after discharge were reviewed. Results: Thirty-one (6.3%) survivors had a baseline prolonged QTc. They were older, had more cardiovascular risk factors, cardiac disease, and comorbidities, and higher levels of terminal pro-brain natriuretic peptide. There was no relationship between prolonged QTc on admission and the 1-year endpoint (9.8% vs. 5.5%, p = 0.212). In 84% of survivors with prolonged baseline QTc, it normalized at 7.9 ± 2.2 months. Of the survivors, 2.4% had prolonged QTc at follow-up, and this was independently associated with obesity, ischemic cardiomyopathy, chronic obstructive pulmonary disease, and cancer. Prolonged baseline QTc was not independently associated with the composite adverse event at 1 year. Conclusions: Prolonged QTc in the acute phase normalized in most COVID-19 survivors and had no clinical long-term impact. Prolonged QTc at follow-up was related to the presence of obesity and previously acquired chronic diseases and was not related to 1-year prognosis.

Neural plasticity of the uterus: New targets for endometrial cancer?

Endometrial carcinoma is the most common gynecological malignancy in Western countries and is expected to increase in the following years because of the high index of obesity in the population. Recently, neural signaling has been recognized as part of the tumor microenvironment, playing an active role in tumor progression and invasion of different solid tumor types. The uterus stands out for the physiological plasticity of its peripheral nerves due to cyclic remodeling brought on by estrogen and progesterone hormones throughout the reproductive cycle. Therefore, a precise understanding of nerve-cancer crosstalk and the contribution of the organ-intrinsic neuroplasticity, mediated by estrogen and progesterone, of the uterine is urgently needed. The development of new and innovative medicines for patients with endometrial cancer would increase their quality of life and health. This review compiles information on the architecture and function of autonomous uterine neural innervations and the influence of hormone-dependent nerves in normal uterus and tumor progression. It also explores new therapeutic possibilities for endometrial cancer using these endocrine and neural advantages.

Effect of statin therapy on SARS-CoV-2 infection-related mortality in hospitalized patients.

AIM: Assessing the effect of statin therapy (ST) at hospital admission for COVID-19 on in-hospital mortality. METHODS AND RESULTS: Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients [1234 men, 923 women; age: 67 y/o (IQR 54-78)] admitted to the hospital were retrieved from the clinical records in anonymized manner. Three hundred and fifty-three deaths occurred. Five hundred and eighty-one patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on ST than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: P = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared with the GM non-statin group (17.4%; P = 0.045). The Cox model applied to the CSH function [HR = 0.58(CI: 0.39-0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39-0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality. CONCLUSIONS: A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.

Long-term exposure to PM10 above WHO guidelines exacerbates COVID-19 severity and mortality.

BACKGROUND: Age, sex, race and comorbidities are insufficient to explain why some individuals remain asymptomatic after SARS-CoV-2 infection, while others die. In this sense, the increased risk caused by the long-term exposure to air pollution is being investigated to understand the high heterogeneity of the COVID-19 infection course. OBJECTIVES: We aimed to assess the underlying effect of long-term exposure to NO2 and PM10 on the severity and mortality of COVID-19. METHODS: A retrospective observational study was conducted with 2112 patients suffering COVID-19 infection. We built two sets of multivariate predictive models to assess the relationship between the long-term exposure to NO2 and PM10 and COVID-19 outcome. First, the probability of either death or severe COVID-19 outcome was predicted as a function of all the clinical variables together with the pollutants exposure by means of two regularized logistic regressions. Subsequently, two regularized linear regressions were constructed to predict the percentage of dead or severe patients. Finally, odds ratios and effects estimates were calculated. RESULTS: We found that the long-term exposure to PM10 is a more important variable than some already stated comorbidities (i.e.: COPD/Asthma, diabetes, obesity) in the prediction of COVID-19 severity and mortality. PM10 showed the highest effects estimates (1.65, 95% CI 1.32-2.06) on COVID-19 severity. For mortality, the highest effect estimates corresponded to age (3.59, 95% CI 2.94-4.40), followed by PM10 (2.37, 95% CI 1.71-3.32). Finally, an increase of 1 µg/m3 in PM10 concentration causes an increase of 3.06% (95% CI 1.11%-4.25%) of patients suffering COVID-19 as a severe disease and an increase of 2.68% (95% CI 0.53%-5.58%) of deaths. DISCUSSION: These results demonstrate that long-term PM10 burdens above WHO guidelines exacerbate COVID-19 health outcomes. Hence, WHO guidelines, the air quality standard established by the Directive 2008/50/EU, and that of the US-EPA should be updated accordingly to protect human health.

Influence of PACE score and conduction disturbances in the incidence of early new onset atrial fibrillation after typical atrial flutter ablation.

PURPOSE: Patients undergoing cavotricuspid isthmus (CTI) ablation for typical flutter (AFL) have a high incidence of new onset atrial fibrillation (AF). We aimed to analyze the influence of PACE score to predict new onset AF in this subset of patients to stratify thromboembolic risk. METHODS: Between 2017 and 2019, patients undergoing CTI ablation for AFL and without history of AF were prospectively included. All patients were monitored continuously by implantable loop recorder and followed by remote monitoring. RESULTS: Overall 48 patients were included. New onset AF rate at 12 months was 56.3%. We observed two very strong independent predictors for new onset AF: a PACE score ≥ 30 (HR:6.9; 95% CI:1.71-27.91; p = 0.007) and an HV interval ≥ 55 (HR:11.86; 95% CI:2.57-54.8; p = 0.002). CONCLUSIONS: The incidence of newly diagnosed AF is high in patients with AFL after CTI ablation, and can occur early. A high PACE score and/or long HV interval predict even higher risk, and may be useful in the decision for empiric long-term anticoagulation.

Myocardial Injury as a Prognostic Factor in Mid- and Long-Term Follow-Up of COVID-19 Survivors.

Myocardial injury, which is present in >20% of patients hospitalized for COVID-19, is associated with increased short-term mortality, but little is known about its mid- and long-term consequences. We evaluated the association between myocardial injury with one-year mortality and readmission in 172 COVID-19 patients discharged alive. Patients were grouped according to the presence or absence of myocardial injury (defined by hs-cTn levels) on admission and matched by age and sex. We report mortality and hospital readmission at one year after admission in all patients and echocardiographic, laboratory and clinical data at six months in a subset of 86 patients. Patients with myocardial injury had a higher prevalence of hypertension (73.3% vs. 50.0%, p = 0.003), chronic kidney disease (10.5% vs. 2.35%, p = 0.06) and chronic heart failure (9.3% vs. 1.16%, p = 0.03) on admission. They also had higher mortality or hospital readmissions at one year (11.6% vs. 1.16%, p = 0.01). Additionally, echocardiograms showed thicker walls in these patients (10 mm vs. 8 mm, p = 0.002) but without functional disorder. Myocardial injury in COVID-19 survivors is associated with poor clinical prognosis at one year, independent of age and sex, but not with echocardiographic functional abnormalities at six months.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Case Report: Clinical and Pharmacokinetic Profile of Lithium Monotherapy in Exclusive Breastfeeding. A Follow-Up Case Series.

Background: Most guidelines advise that women taking lithium should not breastfeed. The variation in transfer is just one reason behind this advice. Objectives: To present clinical and pharmacokinetic data of nine mother-infant pairs exposed to lithium monotherapy during late pregnancy and exclusive breastfeeding at the Perinatal Psychiatric Unit (2006-2018). Methods: We obtained sociodemographic data, medical risk factors, obstetric variables, and family and personal psychiatric history by semi-structured interview, and assessed maternal psychopathology with the Hamilton Depression Rating Scale and Young Mania Rating Scale. A senior neonatologist reviewed neonatal outcomes at birth using the Peripartum Events Scale. Paired maternal and cord blood and infant venous blood samples were collected. During the breastfeeding period, we monitored serum lithium and creatinine concentrations in mother-infant pairs at delivery, and at days 1-5, 7-11, 30, and 60 postpartum, and monthly until 6-months. Results: Lithium equilibrated completely across the placenta [1.13 (0.10), range (1.02-1.30)]. No women presented symptoms of postpartum lithium intoxication, two of the neonates presented transient hypotonia (22%). Lithium exposure was significantly less during breastfeeding than during late pregnancy, and serum lithium concentrations decreased up to 44% overtime from delivery to the first-month, and up to 60% to the third-month postpartum. There was no growth or developmental delay in the follow-up period. One woman had a manic episode with psychotic features at 45 days postpartum. Conclusions: In carefully selected women with bipolar disorder, lithium therapy when breastfeeding can be an appropriate option if coupled with close monitoring of the mother-infant pair.

Low HDL and high triglycerides predict COVID-19 severity.

Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.

Prognostic Implications of Chronic Heart Failure and Utility of NT-proBNP Levels in Heart Failure Patients with SARS-CoV-2 Infection.

BACKGROUND: The prevalence and prognostic value of chronic heart failure (CHF) in the setting of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has seldom been studied. The aim of this study was to analyze the prevalence and prognosis of CHF in this setting. METHODS: This single-center study included 829 consecutive patients with SARS-CoV-2 infection from February to April 2020. Patients with a previous history of CHF were matched 1:2 for age and sex. We analyze the prognostic value of pre-existing CHF. Prognostic implications of N terminal pro brain natriuretic peptide (NT-proBNP) levels on admission in the CHF cohort were explored. RESULTS: A total of 129 patients (43 CHF and 86 non-CHF) where finally included. All-cause mortality was higher in CHF patients compared to non-CHF patients (51.2% vs. 29.1%, p = 0.014). CHF was independently associated with 30-day mortality (hazard ratio (HR) 2.3, confidence interval (CI) 95%: 1.26-2.4). Patients with CHF and high-sensitivity troponin T < 14 ng/L showed excellent prognosis. An NT-proBNP level > 2598 pg/mL on admission was associated with higher 30-day mortality in patients with CHF. CONCLUSIONS: All-cause mortality in CHF patients hospitalized due to SARS-CoV-2 infection was 51.2%. CHF was independently associated with all-cause mortality (HR 2.3, CI 95% 1.26-4.2). NT-proBNP levels could be used for stratification risk purposes to guide medical decisions if larger studies confirm this finding.

Epidemiological approximation of the enteric manifestation and possible fecal-oral transmission in COVID-19: a preliminary systematic review.

The recent appearance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has led to the publication of the first evidence on gastrointestinal symptoms (GIS), the possible enteric involvement of the virus and the detection of RNA in stool, with its possible implication in the fecal-oral transmission of coronavirus disease 2019 (COVID-19). We aimed to conduct a systematic review to describe the epidemiological scientific evidence on GIS, enteric involvement and fecal excretion of SARS-CoV-2 viral RNA and to discuss the possible fecal-oral transmission pathway of COVID-19.

[Markers of myocardial injury in the prediction of short-term COVID-19 prognosis]. / Marcadores de daño miocárdico en la predicción del pronóstico a corto plazo de los pacientes con COVID-19.

INTRODUCTION AND OBJECTIVES: COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19. METHODS: We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT > 14 ng/L, the upper 99th percentile. Levels of NT-proBNP > 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV). RESULTS: Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87). CONCLUSIONS: Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.

Markers of myocardial injury in the prediction of short-term COVID-19 prognosis.

INTRODUCTION AND OBJECTIVES: COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19. METHODS: We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT> 14ng/L, the upper 99th percentile. Levels of NT-proBNP> 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV). RESULTS: Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87). CONCLUSIONS: Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.

Características clínicas y riesgo de agudizaciones asociados con diferentes criterios diagnósticos del solapamiento asma-EPOC / Clinical Characteristics and Risk of Exacerbations Associated With Different Diagnostic Criteria of Asthma-COPD Overlap

INTRODUCCIÓN: En la actualidad no disponemos de una definición de solapamiento asma-EPOC (ACO) universalmente aceptada. OBJETIVO: Comparar la prevalencia del ACO en pacientes con asma o EPOC, valorar sus características clínicas y la capacidad predictiva de riesgo de agudización de las diferentes definiciones. MÉTODO: Estudio prospectivo observacional con seguimiento de 12 meses sobre una cohorte de asma y otra con EPOC. Se comparan 4 criterios diagnósticos: A) el consenso español del 2012; B) el consenso internacional del 2016; C) el consenso entre la guía española de la EPOC (GesEPOC) y la del asma (GEMA) del 2017; y D) el criterio único de ≥ 300 eosinófilos/μl, propuesto por GOLD 2019. En cada grupo se evaluó el riesgo de agudizaciones. RESULTADOS: Se incluyeron 345 pacientes, 233 (67,5%) con EPOC y 112 (32,5%) con asma, con una edad de 63 ± 14 años; el 70,4% eran hombres. Quince (4,3%) pacientes cumplían criterios de ACO con criterios A; 30 (8,7%) con los B; 118 (34,2%) con los C; y 97 (28,1%) con el criterio D. El subtipo ACO-EPOC presentó más edad, peor función pulmonar y mayor riesgo de agudización que los ACO-asma. De todas las definiciones evaluadas, las que presentaron mayor riesgo de agudizaciones fueron la del consenso GesEPOC-GEMA y la propuesta de GOLD. CONCLUSIONES: La prevalencia de ACO varía enormemente en función del criterio diagnóstico utilizado. La población de ACO es heterogénea, con un subtipo ACO-EPOC muy diferente al ACO-asma. Las definiciones que incluyen la eosinofilia identifican a los ACO de más riesgo de agudización

INTRODUCTION: There is currently no universally accepted definition of asthma-COPD overlap (ACO). OBJECTIVE: To compare the prevalence of ACO in patients with asthma or COPD, and to assess their clinical characteristics and the capacity of the different definitions to predict the risk of exacerbation. METHOD: Prospective observational study with a 12-month follow-up in an asthma cohort and a COPD cohort. Four diagnostic criteria were compared: A) the Spanish 2012 consensus; B) the 2016 international consensus; C) the 2017 consensus between the Spanish COPD guidelines (GesEPOC) and GEMA asthma guidelines; and D) the single criterion of ≥ 300 eosinophils/μL, proposed by GOLD 2019. The risk of exacerbations was evaluated in each group. RESULTS: A total of 345 patients were included, 233 (67.5%) with COPD and 112 (32.5%) with asthma, aged 63 ± 14 years, 70.4% men. Fifteen (4.3%) patients met the criteria for ACO according to the criteria described under A above; 30 (8.7%) with the criteria of B; 118 (34.2%) with the criteria of C; and 97 (28.1%), with the D criterion. The ACO-COPD subtype were older, had worse lung function, and an increased risk of exacerbation compared with the ACO-asthma group. Of all the definitions evaluated, those which distinguished a higher risk of exacerbations were the GesEPOC-GEMA consensus and the GOLD proposal. CONCLUSIONS: The prevalence of ACO varies enormously depending on the diagnostic criteria used. The ACO population is heterogeneous, and the ACO-COPD subtype is very different from the ACO-asthma subtype. The definitions that include eosinophilia identify ACO patients with a greater risk of exacerbation

Behavioural cardiovascular risk factors and prevalence of diabetes in subjects with familial hypercholesterolaemia.

A low prevalence of type 2 diabetes mellitus has been reported in familial hypercholesterolaemia. Whether a healthier lifestyle could explain it has not been explored. This cross-sectional study determines the prevalence of lifestyle-related cardiovascular risk factors in heterozygous familial hypercholesterolaemia (HeFH) from the Dyslipidaemia Registry of the Spanish Atherosclerosis Society and in the ENRICA study, a representative sample of the adult Spanish general population, weighted to match the age and sex distribution of the HeFH sample. A total of 2185 HeFH patients and 11,856 individuals from ENRICA were included. HeFH had lower body mass index and fewer of them were smokers than in the reference population. A model adjusted for age, sex and body mass index showed that HeFH more frequently had cardiovascular disease (odds ratio (OR) 23.98; 95% confidence interval (CI) 18.40-31.23) and hypertension (OR 1.20; 95% CI 1.07-1.35), and took anti-hypertensive medication (OR 1.36; 95% CI 1.18-1.56) and anti-diabetic medication (OR 1.25; 95% CI 1.00-1.56), but less frequently were smokers (OR 0.79; 95% CI 0.71-0.89). In a HeFH subsample (n = 513) with complete blood glucose information, those patients without cardiovascular disease showed lower prevalence of smoking and type 2 diabetes mellitus, lower body mass index and glucose, and higher diastolic blood pressure than the Spanish population. The differences in type 2 diabetes mellitus were justified mostly by the difference in body mass index. Body mass index adjustment also showed higher prevalence of hypertension and use of anti-hypertensive drugs in HeFH. In summary, HeFH patients had lower body mass index, which may contribute to explaining the lower prevalence of diabetes, and lower current smoking but higher hypertension.

Clinical Characteristics and Risk of Exacerbations Associated With Different Diagnostic Criteria of Asthma-COPD Overlap. / Características clínicas y riesgo de agudizaciones asociados con diferentes criterios diagnósticos del solapamiento asma-EPOC.

INTRODUCTION: There is currently no universally accepted definition of asthma-COPD overlap (ACO). OBJECTIVE: To compare the prevalence of ACO in patients with asthma or COPD, and to assess their clinical characteristics and the capacity of the different definitions to predict the risk of exacerbation. METHOD: Prospective observational study with a 12-month follow-up in an asthma cohort and a COPD cohort. Four diagnostic criteria were compared: A) the Spanish 2012 consensus; B) the 2016 international consensus; C) the 2017 consensus between the Spanish COPD guidelines (GesEPOC) and GEMA asthma guidelines; and D) the single criterion of ≥300eosinophils/µL, proposed by GOLD 2019. The risk of exacerbations was evaluated in each group. RESULTS: A total of 345 patients were included, 233 (67.5%) with COPD and 112 (32.5%) with asthma, aged 63±14 years, 70.4% men. Fifteen (4.3%) patients met the criteria for ACO according to the criteria described under A above; 30 (8.7%) with the criteria of B; 118 (34.2%) with the criteria of C; and 97 (28.1%), with the D criterion. The ACO-COPD subtype were older, had worse lung function, and an increased risk of exacerbation compared with the ACO-asthma group. Of all the definitions evaluated, those which distinguished a higher risk of exacerbations were the GesEPOC-GEMA consensus and the GOLD proposal. CONCLUSIONS: The prevalence of ACO varies enormously depending on the diagnostic criteria used. The ACO population is heterogeneous, and the ACO-COPD subtype is very different from the ACO-asthma subtype. The definitions that include eosinophilia identify ACO patients with a greater risk of exacerbation.

Marcadores de daño miocárdico en la predicción del pronóstico a corto plazo de los pacientes con COVID-19 / Markers of myocardial injury in the prediction of short-term COVID-19 prognosis

INTRODUCCIÓN Y OBJETIVOS: La información sobre el daño miocárdico en la población con COVID-19 es muy escasa. Nuestro objetivo fue evaluar el daño cardiaco en pacientes con COVID-19 y determinar la correlación entre las concentraciones de troponina T ultrasensible (TnT-us) y fracción aminoterminal del propéptido natriurético cerebral (NT-proBNP) con la gravedad del COVID-19. MÉTODOS: Se incluyó a 872 pacientes consecutivos con COVID-19 confirmada desde febrero a abril de 2020. Se determinó al ingreso la TnT-us a 651 pacientes y la NT-proBNP a 506. El daño miocárdico se definió como una TnT-us> 14 ng/l,> percentil 99. La cifras de NT-proBNP> 300 pg/ml se consideraron relacionadas con daño miocárdico. El objetivo primario es muerte o ventilación mecánica (VM) a 30 días. RESULTADOS: Se observó daño miocárdico según la TnT-us en el 34,6%. Las tasas del evento muerte o VM fue superior en los pacientes con daño miocárdico (el 39,1 frente al 9,1%). Los valores de TnT-us y NT-proBNP fueron predictores independientes de muerte o VM (HR=2,18; IC95%, 1,23-3,83, y HR=1,87; IC95%, 1,05-3,36), y de mortalidad total (HR=2,91; IC95%, 1,211-7,04, y HR=5,47; IC95%, 2,10-14,26). Se observó que la NT-proBNP mejoró de manera significativa el modelo predictivo de la troponina para muerte o VM (estadístico C, 0,83-0,84) y mortalidad total (estadístico C, 0,85-0,87). CONCLUSIONES: El daño miocárdico analizado al ingreso se observó con frecuencia entre los pacientes con COVID-19 y es un potente predictor de muerte y necesidad de VM. La NT-proBNP mejoró la precisión pronóstica de la determinación de troponina

INTRODUCTION AND OBJECTIVES: COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19. METHODS: We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT> 14 ng/L, the upper 99th percentile. Levels of NT-proBNP> 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV). RESULTS: Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87). CONCLUSIONS: Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT

Management of severe strongyloidiasis attended at reference centers in Spain.

INTRODUCTION: Strongyloides stercoralis is a globally distributed nematode that causes diverse clinical symptoms in humans. Spain, once considered an endemic country, has experienced a recent increase in imported cases. The introduction of serology helps diagnosis and is currently replacing microbiological techniques in some settings, but its sensitivity is variable and can be low in immunocompromised patients. Diagnosis can only be confirmed by identification of larvae. Often, this "gold standard" can only be achieved in severe cases, such as disseminated S.stercoralis infection, or S.stercoralis hyperinfection syndrome, where parasite load is high. In addition, these clinical presentations are not well-defined. Our aim is to describe severe cases of S.stercoralis, their epidemiological profile, and their clinical details. METHODS: An observational retrospective study of disseminated S.stercoralis infection, or hyperinfection syndrome. Inclusion criteria: aged over 18, with a diagnosis of disseminated S.stercoralis infection, or hyperinfection syndrome, confirmed by visualization of larvae. Patients were identified through revision of clinical records for the period 2000-2015, in collaboration with eight reference centers throughout Spain. RESULTS: From the period 2000-2015, eighteen cases were identified, 66.7% of which were male, with a median age of 40 (range 21-70). Most of them were foreigners (94.4%), mainly from Latin America (82.3%) or Western Africa (17.6%). Only one autochthonous case was identified, from 2006. Immunosuppressive conditions were present in fourteen (77%) patients, mainly due steroids use and to retroviral coinfections (four HIV, two HTLV). Transplant preceded the clinical presentation in four of them. Other comorbidities were coinfection with HBV, Trypanosoma cruzi, Mycobacterium leprae or Aspergillus spp. All presented with digestive disorders, with 55.6% also presenting malaise. 44.4% of cases had fever, 27.8% skin complaints, and 16.7% respiratory or neurological disorders. One patient presented anemia, and one other nephrotic syndrome. Diagnosis was confirmed by identification of larvae in fresh stool samples (n = 16; 88.9%), concentration techniques (n = 6; 33.3%), larval culture (n = 5; 29.4%), or digestive biopsies (n = 8; 44%). S.stercoralis forms were identified during necropsy in one case. In addition, ten (55%) had a positive serology. All the cases were treated with ivermectin, six (33%) also received albendazole and one case received thiabendazole followed by ivermectin. All needed inpatient management, involving a mean hospitalization stay of 25 days (range 1-164). Two cases received intensive care and eventually died. CONCLUSIONS: Only eighteen cases of disseminated S.stercoralis infection/hyperinfection syndrome were identified from the 15-year period, most of which were considered to have been imported cases. Among those, immunosuppression was frequent, and mortality due to S.stercoralis was lower than previously described.