Efficacy and safety of bempedoic acid in acute coronary syndrome. Design of the clinical trial ES-BempeDACS.

INTRODUCTION AND OBJECTIVES: Only about 1 out of every 3 patients with acute myocardial infarction (AMI) achieve low-density lipoprotein cholesterol (LDL-C) values <55mg/dL in the first year. The present study aims to evaluate the impact of early intensive therapy on lipid control after an AMI. METHODS: An independent, prospective, pragmatic, controlled, randomized, open-label, evaluator-blinded clinical trial (PROBE design) will analyze the efficacy and safety of an oral lipid-lowering triple therapy: high-potency statin+bempedoic acid (BA) 180mg+ezetimibe (EZ) 10mg versus current European-based guidelines (high-potency statin±EZ 10mg), in AMI patients. LDL-C will be determined within the first 48hours. Patients with LDL-C ≥ 115mg/dL (without previous statin therapy), ≥ 100mg/dL (with previous low-potency or high-potency statin therapy at submaximal dose), or ≥ 70mg/dL (with previous high-potency statin therapy at high dose) will be randomly assigned 1:1 between 24 and 72hours post-AMI to the BA/EZ combination or to statin±EZ, without BA. The primary endpoint is the proportion of patients reaching LDL-C <55mg/dL at 8 weeks after treatment. RESULTS: The results of this study will provide novel information for post-AMI LDL-C control by evaluating the usefulness of an early intensive lipid-lowering strategy based on triple oral therapy. CONCLUSIONS: Early intensive lipid-lowering triple oral therapy vs the treatment recommended by current clinical practice guidelines could facilitate the achievement of optimal LDL-C levels in the first 2 months after AMI (a high-risk period). IDENTIFICATION NUMBER: EudraCT 2021-006550-31.

Nitrosyl-Heme and Heme Iron Intake from Processed Meats in Subjects from the EPIC-Spain Cohort.

BACKGROUND: The consumption of processed meats (PMs) and red meats are linked to the likelihood of developing colorectal cancer. Various theories have been proposed to explain this connection, focusing on nitrosyl-heme and heme iron intake. We hypothesized that differences in nitrosyl-heme and heme iron intakes will be associated with various sociodemographic and lifestyle factors. METHODS: The study included 38,471 healthy volunteers (62% females) from five Spanish regions within the EPIC-Spain cohort. High-Performance Liquid Chromatography (HPLC) determined nitrosyl-heme and heme iron levels in the 39 most consumed PMs. Food intake was assessed using validated questionnaires in interviews. Nitrosyl-heme and heme iron intakes, adjusted for sex, age, body mass index (BMI), center, and energy intake, were expressed as geometric means due to their skewed distribution. Variance analysis identified foods explaining the variability of nitrosyl-heme and heme iron intakes. RESULTS: The estimated intakes were 528.6 µg/day for nitrosyl-heme and 1676.2 µg/day for heme iron. Significant differences in nitrosyl-heme intake were found by sex, center, energy, and education level. Heme iron intake varied significantly by sex, center, energy, and smoking status. "Jamón serrano" and "jamón cocido/jamón de York" had the highest intake values, while "morcilla asturiana" and "sangrecilla" were key sources of nitrosyl-heme and heme iron. CONCLUSIONS: This is the first study to estimate levels of nitrosyl-heme intake directly in PMs for a large sample, revealing variations based on sex, BMI, smoking, and activity. Its data aids future exposure estimations in diverse populations.

Oral health-related quality of life in a group of patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) and periodontitis (PD) are chronic diseases that are associated with connective tissue and bone destruction, which affects the quality of life of the people suffering from these conditions. The identification of social conditions and the determinants of RA and PD would permit the elaboration of policies and strategies based on social reality. OBJECTIVES: The aim of the present study was to identify the relationship between oral health-related quality of life (OHRQoL) and the indicators of general health and oral health in patients with RA. MATERIAL AND METHODS: A cross-sectional study involving 59 patients with RA was conducted between 2019 and 2020. Demographic, general health, periodontal, and oral health parameters were collected. In addition, the Oral Health Impact Profile-14 (OHIP-14) questionnaire was administered to each patient. A description of the OHIP-14 dimensions according to different variables was performed. The relationship between OHRQoL and general/oral health indicators was analyzed with logistic and linear regression analyses. RESULTS: The highest OHIP-14 scores were found in people that were 60 years of age and over, single, had low educational achievements, a low socioeconomic status, were unemployed, and had no health affiliation. In the adjusted model, the prevalence of the impact on OHRQoL was 1.34 (1.10-5.29) times greater in those with erosive RA than in those without, and 2.22 (1.16-29.50) times greater in those who self-reported morning stiffness. Regarding the stage of PD, those with stage IV had a prevalence of the impact on the OHRQoL of 70%, an average extent of 3.4 ±4.5 and a severity score of 11.5 ±22.0, with statistically significant differences. CONCLUSIONS: The dimensions with the greatest impact on the OHRQoL of patients were physical pain, discomfort and psychological disability. The type of RA and the severity of PD are indicators of worse scores on the OHRQoL scale.

Myocarditis related SARS-CoV-2 infection or vaccination: an expert consensus statement on its diagnosis and management.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revealed several cardiovascular complications, including myocarditis caused by SARS-CoV-2 infection (COVID-19) or after messenger RNA vaccine administration. Because of the high prevalence of COVID-19, the expansion of vaccination programs, and the appearance of new information on myocarditis in these contexts, there is a need to condense the knowledge acquired since the start of the pandemic. To meet this need, this document was drafted by the Myocarditis Working Group of the Heart Failure Association of the Spanish Society of Cardiology, with the collaboration of the Spanish Agency for Medicines and Health Products (AEMPS). The document aims to address the diagnosis and treatment of cases of myocarditis associated with SARS-CoV-2 infection or messenger RNA vaccine administration.

[Myocarditis related SARS-CoV-2 infection or vaccination: an expert consensus statement on its diagnosis and management]. / Consenso de expertos sobre el diagnóstico y el tratamiento de la miocarditis asociada con infección o vacunación contra el SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revealed several cardiovascular complications, including myocarditis caused by SARS-CoV-2 infection (COVID-19) or after messenger RNA vaccine administration. Because of the high prevalence of COVID-19, the expansion of vaccination programs, and the appearance of new information on myocarditis in these contexts, there is a need to condense the knowledge acquired since the start of the pandemic. To meet this need, this document was drafted by the Myocarditis Working Group of the Heart Failure Association of the Spanish Society of Cardiology, with the collaboration of the Spanish Agency for Medicines and Health Products (AEMPS). The document aims to address the diagnosis and treatment of cases of myocarditis associated with SARS-CoV-2 infection or messenger RNA vaccine administration.

Tana, a Healthcare Chatbot to Help Patients During the COVID-19 Pandemic at a University Hospital in Argentina.

A Chatbot or Conversational Agent is a computer application that simulates the conversation with a human person (by text or voice), giving automated responses to people's needs. In the healthcare domain, chatbots can be beneficial to help patients, as a complement to care by health personnel, especially in times of high demand or constrained resources such as the COVID-19 Pandemic. In this paper we share the design and implementation of a healthcare chatbot called Tana at the Hospital Italiano de Buenos Aires. Considering best practices and being aware of possible unintended consequences, we must take advantage of information and communication technologies, such as chatbots, to analyze and promote useful conversations for the health of all people.

Bipolar Disorder and Cardiovascular Risk in Rural versus Urban Populations in Colombia: A Comparative Clinical and Epidemiological Evaluation.

Background: Various multifactorial elements may contribute toward the urban and rural disparities in cardiovascular disease (CVD) risk, particularly among patients with psychiatric diseases. Objective: To investigate whether rural patients diagnosed and treated for Bipolar Disorder (BD) have different risk profiles and outcomes of CVD compared to urban (BD) patients. Methods: We conducted a case-control study that included 125 BD patients (cases) from rural Filadelfia, Colombia and 250 BD patients (controls) treated in Bogotá, Colombia. Cases and controls were 2:1, matched by age and sex. We applied the Framingham Heart Study (FHS) risk calculator to assess risk. Differences by rural/urban status (i.e., case-control status) were assessed by chi-square, paired t-tests, and logistic regression. Findings: Rural BD patients were found to have lower education (p = 1.0 × 10-4), alcohol consumption (p = 3.0 × 10-4), smoking (p = 0.015), psychiatric (p = 1.0 × 10-4) and CV family history (p = 0.0042) compared to urban BD patients. Rural BD patients were 81% more likely to have a more favorable CVD risk profile (OR: 0.19, 95% CI [0.06-0.62]) than urban BD patients, despite rural BD patients having increased CVD morbidity (p = 1.0 × 10-2). Conclusion: Based on increase in morbidity but lower predictive risk in the rural population, our study suggests that the FHS-CVD calculator may not be optimal to assess CVD risk in this population.

A Different View for an Old Disease: NEDDylation and Other Ubiquitin-Like Post-Translational Modifications in Chronic Lymphocytic Leukemia.

Despite the enormous amount of molecular data obtained over the years, the molecular etiology of chronic lymphocytic leukemia (CLL) is still largely unknown. All that information has enabled the development of new therapeutic approaches that have improved life expectancy of the patients but are still not curative. We must increase our knowledge of the molecular alterations responsible for the characteristics common to all CLL patients. One of such characteristics is the poor correlation between mRNA and protein expression, that suggests a role of post-translational mechanisms in CLL physiopathology. Drugs targeting these processes have indeed demonstrated an effect either alone or in combination with other aimed at specific pathways. A recent article unveiled an increment in ubiquitin-like modifications in CLL, with many protein members of relevant pathways affected. Interestingly, the inhibition of the NEDD8-activating protein NAE reverted a substantial number of those modifications. The present review gets the scarce data published about the role of NEDDylation in CLL together and establishes connections to what is known from other neoplasias, thus providing a new perspective to the underlying mechanisms in CLL.

Mitochondrial LonP1 protease is implicated in the degradation of unstable Parkinson's disease-associated DJ-1/PARK 7 missense mutants.

DJ-1/PARK7 mutations are linked with familial forms of early-onset Parkinson's disease (PD). We have studied the degradation of untagged DJ-1 wild type (WT) and missense mutants in mouse embryonic fibroblasts obtained from DJ-1-null mice, an approach closer to the situation in patients carrying homozygous mutations. The results showed that the mutants L10P, M26I, A107P, P158Δ, L166P, E163K, and L172Q are unstable proteins, while A39S, E64D, R98Q, A104T, D149A, A171S, K175E, and A179T are as stable as DJ-1 WT. Inhibition of proteasomal and autophagic-lysosomal pathways had little effect on their degradation. Immunofluorescence and biochemical fractionation studies indicated that M26I, A107P, P158Δ, L166P, E163K, and L172Q mutants associate with mitochondria. Silencing of mitochondrial matrix protease LonP1 produced a strong reduction of the degradation of the mitochondrial-associated DJ-1 mutants A107P, P158Δ, L166P, E163K, and L172Q but not of mutant L10P. These results demonstrated a mitochondrial pathway of degradation of those DJ-1 missense mutants implicated in PD pathogenesis.

Criptococosis y linfocitopenia T CD4 idiopática: Reporte de un caso / Cryptococcosis and idiopathic CD4 T lymphocytopenia: A case report

Resumen La linfocitopenia T CD4 idiopática (LCI) es un síndrome clínico inusual que se caracteriza por un déficit de células T CD4+ circulantes en ausencia de infección por VIH u otra condición de inmunosupresión. Los pacientes con dicha enfermedad pueden presentarse asintomáticos o con infecciones oportunistas, las más frecuentes son por criptococo, micobacterias o virales como herpes zoster. Presentamos el caso de un hombre de 32 años, sin antecedentes, en quien se descartó infección por retrovirus, con recuento de linfocitos T CD4+ menor a 300 células/m3; se diagnosticó LCI posterior al diagnóstico de criptococomas cerebrales mediante hallazgos imagenológicos los cuales fueron congruentes con estudios microbiológicos.

Summary Idiopathic CD4 T lymphocytopenia (ICL) is an unusual clinical syndrome characterized by a deficit of circulating CD4 + T cells in the absence of HIV infection or another immunosuppression condition. Patients with this disease may present asymptomatic or with opportunistic infections, the most frequent are cryptococcus, mycobacteria or viral such as herpes zoster. We present a case of a 32-year-old man with no prior disease, in whom retrovirus infection was discarded, with CD4 + T lymphocyte count less than 300 cells/m3; ICL was diagnosed after the diagnosis of brain cryptococomas by imaging findings which were consistent with microbiological studies.

Unusual high 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) tracer deposition on a heart scintigraphy in a patient with AL amyloidosis: A case report.

We present a case of a 40-year-old Spanish man with cardiac amyloidosis in which a Tc-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-99m-DPD) scintigraphy was strongly suggestive of cardiac amyloidosis by transthyretin (ATTR) but endomyocardial biopsy (EB) analyzed by immunohistochemistry demonstrated a light chain amyloidosis (AL). Even though the Tc-99m-DPD has proven in different published papers that has high sensibility and specificity for differentiating AL and ATTR cardiac amyloidosis, we present an unusual case of an AL cardiac amyloidosis with a Perugini grade 3 on the scintigraphy. Diagnostic approach of cardiac amyloidosis following consensus documents is discussed to avoid diagnostic mistakes based on imaging techniques.

Congenital long QT syndrome: Should citric fruits be avoided? A case report of a cLQTS type 1 with unusual QTc prolongation with citric juices.

Congenital long QT syndromes (cLQTS) are relatively rare diseases in which QT interval is prolonged due to several mutations on ion channels involved in cardiac cell repolarization. This condition confers higher risk of malignant arrhythmias and sudden cardiac death, and it is widely accepted that substances that prolong QT interval should be avoided by these patients. Most of these substances are antibiotics and non-antibiotics drugs, but almost nothing is known about frequently consumed fruits and juices. We report the case of a patient with a previously asymptomatic cLQTS type 1 (cLQTS1) with unusual QT prolongation of 167 milliseconds (ms) related to the consumption of large amounts of citric juices (oranges and lemons). A literature review was done for better understanding of its influence on QT interval duration and to know the concentration of flavonoids on citric fruits. .

Correction: Inhibitors of lysosomal function or serum starvation in control or LAMP2 deficient cells do not modify the cellular levels of Parkinson disease-associated DJ-1/PARK 7 protein.

[This corrects the article DOI: 10.1371/journal.pone.0201152.].

Evaluating the Performance of a Terminology Search Engine Using Historical Data.

Clinical terms are noisy descriptions typed by healthcare professionals in Spanish language in the electronic health record system (EHR). Thus, an evaluation of terminology search engine that extends SNOMED CT and an approach that uses historical data of clinical terms is described. We show how to measure precision and recall using historical search data, and we show how the performance of the search engine can be improved significantly using the technology available in the search engine.

An Information Retrieval Approach to ICD-10 Classification.

ICD-10 (International Classification of Diseases 10th revision) is a classification code for diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases. This paper describes an automatic information retrieval approach to map free-text disease descriptions to ICD-10 codes. We use the Hospital Italiano de Buenos Aires (HIBA) terminology data mapped to ICD-10 codes as indexed data to find an appropriate ICD-10 code using search engine similarity metrics.

Pyroglutamic acidosis by glutathione regeneration blockage in critical patients with septic shock.

AIM: The aim of this study was to evaluate oxidative stress from glutathione depletion in critically ill patients with a septic shock through the abnormal presence of pyroglutamic acid (PyroGlu) in the urine (indirectly) and through its serum level (directly). METHODS: This was a prospective analytical study of 28 critically ill patients with a septic shock who were monitored from admission (initial) to 3 days of stay (final) in the intensive care unit (ICU). Data collected included PyroGlu and glutamic acid (Glu) using liquid chromatography/mass spectrometry, and glutathione peroxidase (GPX) activity with a colorimetric assay. The differences in Glu, PyroGlu, and GPX activity between the septic shock group and healthy control group serving as reference values were evaluated using the Mann-Whitney test. The correlations between Glu, PyroGlu, and GPX activity and clinical outcomes were determined using Spearman's correlation coefficient. RESULTS: In patients with septic shock, serum and urine PyroGlu levels were higher, erythrocyte GPX activity/gr Hb was lower, and urine Glu levels were lower compared to healthy control reference values, for both initial and final values. Initial serum Glu levels were also lower. Serum PyroGlu levels had a correlation with both initial and final serum Glu levels; levels also correlated in the urine. Initial serum Glu correlated with the days of mechanical ventilation (P = 0.016) and the days of ICU stay (P = 0.05). Urine Glu/mg creatinine correlated with APACHE II (P = 0.030). This positive correlation observed for serum Glu was not observed for PyroGlu. CONCLUSIONS: The current study found that septic patients have higher levels of PyroGlu, lower levels of Glu, and lower erythrocyte GPX activity, suggesting that these biomarkers could be used as an indicator of glutathione depletion. In addition, Glu is related to severity parameters. This study can guide future studies on the importance of monitoring the levels of pyroglutamic acidosis in critical patients with septic shock in order to preserve the oxidative status and its evolution during the stay in the ICU.