The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis.

INTRODUCTION: The effects of combustible cigarettes (CCs) and electronic nicotine delivery systems (ENDS) on immune cell-driven colon inflammation and intestinal healing of patients with ulcerative colitis (UC) are still unknown and, therefore, were examined in this study. METHODS: Intracellular staining and flow cytometry analysis of immune cells isolated from UC patients who used ENDS (UCENDS), CCs (UCCC) and who were non-smokers (UCAIR) were performed to elucidate cellular mechanisms which were responsible for CCs and ENDS-dependent modulation of immune response during UC progression. Additionally, dextran sulfate sodium (DSS)-colitis was induced in ENDS/CC/air-exposed mice (DSSENDS/ DSSCC/DSSAIR groups) to support clinical findings. RESULTS: Significantly increased number of immunosuppressive, IL-10, TGF-ß and IL-35-producing, FoxP3-expressing CD3+CD4+T regulatory cells (Tregs) was observed in the blood of UCENDS patients while reduced presence of inflammatory, TNF-α and IFN-γ-producing, Tbx21-expressing CD3+CD4+ Th1, IL-4-producing Gata3-expresing Th2 and IL-17, IL-22-producing, RORγT, IL-23R-expressing Th17 cells were noticed in the blood of UCCC patients. Exposure to either CCs or ENDS was associated with enhanced mucosal healing, ameliorated spontaneous recovery and improved survival of DSS-treated mice. An expansion of immunosuppressive cells (IL-10-producing tolerogenic CD11c+ dendritic cells, alternatively activated CD206, Arginase 1-expressing, IL-10-producing F4/80+macrophages, IL-10-producing FoxP3-expressing Tregs) was noticed in the colons of DSSENDS-treated mice, while reduced number of inflammatory, IL-17- and IL-4-producing T lymphocytes was observed in the colons of DSSCC-compared to DSSAIR-treated mice. CONCLUSIONS: Despite different mechanisms of action, both ENDS and CCs attenuated on-going colon inflammation, enhanced healing and ameliorated recovery of injured intestines of DSS-treated mice and UC patients. IMPLICATIONS: This is the first study that compared the effects of CCs and ENDS on immune cells of patients suffering from ulcerative colitis, providing new information about molecular and cellular mechanisms which were responsible for ENDS and CCs-dependent modulation of immune cell-driven colon injury and inflammation. Obtained results showed that both ENDS and CCs had capacity to attenuate detrimental immune response, enhanced healing and ameliorated recovery of injured intestines.

Effects of Combustible Cigarettes and Heated Tobacco Products on Systemic Inflammatory Response in Patients with Chronic Inflammatory Diseases.

Smoke derived from combustible cigarettes (CCs) contains numerous harmful chemicals that can impair the viability, proliferation, and activation of immune cells, affecting the progression of chronic inflammatory diseases. In order to avoid the detrimental effects of cigarette smoking, many CC users have replaced CCs with heated tobacco products (HTPs). Due to different methods of tobacco processing, CC-sourced smoke and HTP-derived aerosols contain different chemical constituents. With the exception of nicotine, HTP-sourced aerosols contain significantly lower amounts of harmful constituents than CC-derived smoke. Since HTP-dependent effects on immune-cell-driven inflammation are still unknown, herein we used flow cytometry analysis, intracellular staining, and an enzyme-linked immunosorbent assay to determine the impact of CCs and HTPs on systemic inflammatory response in patients suffering from ulcerative colitis (UC), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Both CCs and HTPs significantly modulated cytokine production in circulating immune cells, affecting the systemic inflammatory response in COPD, DM, and UC patients. Compared to CCs, HTPs had weaker capacity to induce the synthesis of inflammatory cytokines (IFN-γ, IL-1ß, IL-5, IL-6, IL-12, IL-23, IL-17, TNF-α), but more efficiently induced the production of immunosuppressive IL-10 and IL-35. Additionally, HTPs significantly enhanced the synthesis of pro-fibrotic TGF-ß. The continuous use of CCs and HTPs aggravated immune-cell-driven systemic inflammation in COPD and DM patients, but not in UC patients, suggesting that the immunomodulatory effects of CC-derived smoke and HTP-sourced aerosols are disease-specific, and need to be determined for specific immune-cell-driven inflammatory diseases.

Therapeutic Potential of Palmitoylethanolamide in Gastrointestinal Disorders.

Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA's effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.

Nurses' Perception of Tension, Stress, and Pressure before and during the COVID-19 Pandemic: A Multicenter Serbian Study.

The mental health of healthcare workers, especially the nursing staff in intensive care units, is crucial for the optimal functioning of healthcare systems during medical emergencies. This study implements a cross-sectional design to investigate the associations between nurses' personal characteristics, workplace challenges, and job satisfaction with the increased perception of tension, stress, and pressure at the workplace (TSPW) before and during the COVID-19 pandemic. In 2021, we surveyed 4210 nurses from 19 intensive healthcare facilities in the capital of Serbia, Belgrade, and, at that time, collected data about their perceived TSPW before and during the COVID-19 pandemic. Our study identified six predictors of the increase in TSPW, as perceived by nurses: their work in COVID-19 infectious zones (OR = 1.446), exhaustion due to work under protective equipment (OR = 1.413), uncertainty and fear of infection (OR = 1.481), a high degree of superiors' appreciation and respect (OR = 1.147), a high degree of patients' attitudes (OR = 1.111), and a low degree of work autonomy (OR = 0.889). The study's findings suggest that a solution to this issue is necessary to ensure that nurses are safe and able to alleviate the physical and mental strain that comes with prolonged use of protective equipment. Nurses on the frontline of the pandemic require better health protection, better conditions, and respect for their role. Strategies to promote mental health would help reduce nurses' stress and increase job satisfaction.

Traditional risk factors and premature acute coronary syndromes in South Eastern Europe: a multinational cohort study.

Background: The age-standardized death rates under 65 years from ischemic heart disease in South Eastern Europe are approximately twice as high than the Western Europe average, but the reasons are not completely recognized. The aim of the present study was to address this issue by collecting and analyzing data from a large, multinational cohort. Methods: We enrolled 70,953 Caucasian patients with first acute coronary syndrome, from 36 urban hospital in 7 South Eastern European countries and assessed their life expectancy free of acute coronary syndrome and mortality within 30 days after hospital admission from acute coronary syndrome as estimated in relation to dichotomous categories of traditional risk factors (current smoking, hypertension, diabetes and hypercholesterolemia) stratified according to sex. Findings: Compared with patients without any baseline traditional risk factors, the presence of all four risk factors was associated with a 5-year shorter life expectancy free of acute coronary syndrome (women: from 67.1 ± 12.0 to 61.9 ± 10.3 years; r = -0.089; p < 0.001 and men: from 62.8 ± 12.2 to 58.9 ± 9.9 years; r = -0.096; p < 0.001). Premature acute coronary syndrome (women <67 years and men <63 years) was remarkably related to current smoking and hypercholesterolemia among women (RRs: 3.96; 95% CI: 3.72-4.20 and 1.31; 95% CI: 1.25-1.38, respectively) and men (RRs: 2.82; 95% CI: 2.71-2.93 and 1.39; 95% CI: 1.34-1.45, respectively). Diabetes was most strongly associated with death from premature acute coronary syndrome either in women (RR: 1.52; 95% CI: 1.29-1.79) or men (RR: 1.63; 95% CI: 1.41-1.89). Interpretation: Public health policies in South Eastern Europe should place significant emphasis on the four traditional risk factors and the associated lifestyle behaviors to reduce the epidemic of premature ischemic heart disease. Funding: None.

Clinical Review of Hypertensive Acute Heart Failure.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year (from 20% to 36%) mortality. Considering the high rate of rehospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Beta-blockers in Hypertensive Left Ventricular Hypertrophy and Atrial Fibrillation Prevention.

BACKGROUND: Hypertensive left ventricular hypertrophy (HTN LVH) is a key risk factor for atrial fibrillation (AF). OBJECTIVE: To evaluate the possible role of beta-blockers (BBs) in addition to a renin-angiotensinaldosterone system (RAAS) blocker in AF prevention in patients with HTN LVH. METHODS: We performed a PubMed, Elsevier, SAGE, Oxford, and Google Scholar search with the search items 'beta blocker hypertension left ventricular hypertrophy patient' from 2013-2023. In the end, a 'snowball search', based on the references of relevant papers as well as from papers that cited them was performed. RESULTS: HTN LVH is a risk factor for AF. In turn, AF substantially complicates HTN LVH and contributes to the genesis of heart failure (HF) with preserved ejection fraction (HFpEF). The prognosis of HFpEF is comparable with that of HF with reduced EF (HFrEF), and, regardless of the type, HF is associated with five-year mortality of 50-75%. The antiarrhythmic properties of BBs are wellrecognized, and BBs as a class of drugs are - in general - recommended to decrease the incidence of AF in HTN. CONCLUSION: BBs are recommended (as a class) for AF prevention in several contemporary guidelines for HTN. LVH regression in HTN - used as a single criterion for the choice of antihypertensive medication - does not capture this protective effect. Consequently, it is worth studying how meaningful this antiarrhythmic action (to prevent AF) of BBs is in patients with HTN LVH in addition to a RAAS blocker.

The 'peptide for life' initiative in the emergency department study.

AIMS: Natriuretic peptide (NP) uptake varies in Emergency Departments (EDs) across Europe. The 'Peptide for Life' (P4L) initiative, led by Heart Failure Association, aims to enhance NP utilization for early diagnosis of heart failure (HF). We tested the hypothesis that implementing an educational campaign in Western Balkan countries would significantly increase NP adoption rates in the ED. METHODS AND RESULTS: This registry examined NP adoption before and after implementing the P4L-ED study across 10 centres in five countries: Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, and Serbia. A train-the-trainer programme was implemented to enhance awareness of NP testing in the ED, and centres without access received point-of-care instruments. Differences in NP testing between the pre-P4L-ED and post-P4L-ED phases were evaluated. A total of 2519 patients were enrolled in the study: 1224 (48.6%) in the pre-P4L-ED phase and 1295 (51.4%) in the post-P4L-ED phase. NP testing was performed in the ED on 684 patients (55.9%) during the pre-P4L-ED phase and on 1039 patients (80.3%) during the post-P4L-ED phase, indicating a significant absolute difference of 24.4% (95% CI: 20.8% to 27.9%, P < 0.001). The use of both NPs and echocardiography significantly increased from 37.7% in the pre-P4L-ED phase to 61.3% in the post-P4L-ED phase. There was an increased prescription of diuretics and SGLT2 inhibitors during the post-P4L-ED phase. CONCLUSIONS: By increasing awareness and providing resources, the utilization of NPs increased in the ED, leading to improved diagnostic accuracy and enhanced patient care.

Principal components analysis to evaluate complex association of polymorphisms in ACE and ACTN3 genes and the extent of cardiovascular adaptive changes in elite athletes.

BACKGROUND: Present article aims at clarifying the association of ACE and ACTN3 polymorphisms with adaptive heart changes in elite athletes from power, endurance and mixed sport disciplines using the principal component analysis (PCA). METHODS: Overall, 281 elite male athletes are divided into three groups: strength-type sports, endurance and mixed sports. After anthropometric measurements, physical and ultrasound examination of the heart, the athletes were exposed to a physical load test. All groups were analyzed for functional ACE and ACTN3 polymorphisms. In order to convert a set of examined, possibly correlated adaptive cardiovascular changes into a set of values of linearly uncorrelated variables we used principal component analysis (PCA). RESULTS: The type of sport significantly affects not only the athlete's anthropometric characteristics, but also on the scope and specificity of the investigated adaptive cardiovascular changes. Athletes from the mixed group of sports showed the best working efficiency of the heart. PCA showed that the type of sport, but not genetic predisposition affects the co-adaptation of complex traits. CONCLUSIONS: Effect of genotype, type of sport and their interaction on observed variability in morpho-functional cardiovascular adaptive changes in elite athletes can be used for a better understanding of the clinical phenomenon of athlete's heart and sudden cardiac death syndrome.

Antiphospholipid Antibodies and Vascular Thrombosis in Patients with Severe Forms of COVID-19.

Antiphospholipid antibodies (aPLA) are a laboratory criterion for the classification of antiphospholipid syndrome (APS) and are known to cause clinical symptoms such as vascular thrombosis or obstetric complications. It is suggested that aPLA may be associated with thromboembolism in severe COVID-19 cases. Therefore, we aimed to combine clinical data with laboratory findings of aPLA at four time points (admission, worsening, discharge, and 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. In 111 patients with COVID-19 pneumonia, current and past history of thrombosis and pregnancy complications were recorded. Nine types of aPLA were determined at four time points: anticardiolipin (aCL), anti-ß2-glycoprotein I (anti- ß2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG, or IgA isotypes. During hospitalization, seven patients died, three of them due to pulmonary artery thromboembolism (none were aPLA positive). Only one of the five who developed pulmonary artery thrombosis was aPLA positive. Out of 9/101 patients with a history of thrombosis, five had arterial thrombosis and none were aPLA positive at admission and follow-up; four had venous thrombosis, and one was aPLA positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPLA positive at discharge only, compared to 26.1% without a history of thrombosis (p = 0.041). Patients with severe forms of COVID-19 and positive aPLA should receive the same dose and anticoagulant medication regimen as those with negative aPLA because those antibodies are mostly transiently positive and not linked to thrombosis and fatal outcomes.

Coronary Microvascular Dysfunction and Hypertension: A Bond More Important than We Think.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-induced morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly that with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD and also to investigate and guide the treatment of additional complications that can affect further prognosis. This comprehensive review provides insight into the main pathophysiological mechanisms of CMD in hypertensive patients, offering an integrated diagnostic approach as well as an overview of currently available therapeutical modalities.

Galectin-3 as a Prognostic Biomarker in Patients with First Acute Myocardial Infarction without Heart Failure.

BACKGROUND: Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and quality of life. METHODS: Our study included 59 patients with AMI and a preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 h of chest pain onset from the aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACEs) were evaluated at six months follow-up. RESULTS: MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from the aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p = 0.038; OR 3.438; 95%CI: 1.275-9.265; p = 0.015). ROC analysis identifies the Gal-3 plasma concentration from the aortic root as a better predictor of MACE or death (cut-off ≥ 10.86 ng/mL; AUC 0.858; 95%CI: 0.744-0.973; p < 0.001) than Gal-3 plasma concentration from the femoral/radial artery (cut-off ≥ 10.18 ng/mL; AUC 0.742; 95%CI: 0.596-0.888; p = 0.006). CONCLUSION: the Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 h after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2-3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. METHODS: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. RESULTS: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). CONCLUSION: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. CLINICAL TRIAL REGISTRATION: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité - Universitätsmedizin Berlin.

Update on Myocarditis: From Etiology and Clinical Picture to Modern Diagnostics and Methods of Treatment.

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic methods. The multitude of different etiological factors, the diversity of the clinical picture, and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated with diseases that in their natural course can lead to myocardial involvement, as well as the iatrogenic cause of myocarditis, which is due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, such as changes in ECG and echocardiography readings, has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive and is the gold standard for diagnosis and clinical follow-up of these patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening cases with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support, and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Redox Status and Telomere-Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2•-), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere-telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The "cholesterol-protein factor" and "oxidative-telomere factor" were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the "oxidative-telomere factor" (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length.

The Predictive Value of Risk Factors and Prognostic Scores in Hospitalized COVID-19 Patients.

INTRODUCTION: Risk stratification in patients with COVID-19 is a challenging task. Early warning scores (EWSs) are commonly used tools in the initial assessment of critical patients. However, their utility in patients with COVID-19 is still undetermined. AIM: This study aimed to discover the most valuable predictive model among existing EWSs for ICU admissions and mortality in COVID-19 patients. MATERIALS AND METHODS: This was a single-center cohort study that included 3608 COVID-19 patients admitted to the University Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia, between 23 June 2020, and 14 April 2021. Various demographic, laboratory, and clinical data were collected to calculate several EWSs and determine their efficacy. For all 3608 patients, five EWSs were calculated (MEWS, NEWS, NEWS2, REMS, and qSOFA). Model discrimination performance was tested using sensitivity, specificity, and positive and negative predictive values. C statistic, representing the area under the receiver operating characteristic (ROC) curve, was used for the overall assessment of the predictive model. RESULTS: Among the evaluated prediction scores for 3068 patients with COVID-19, REMS demonstrated the highest diagnostic performance with the sensitivity, PPV, specificity, and NPV of 72.1%, 20.6%, 74.9%, and 96.8%, respectively. In the multivariate logistic regression analysis, aside from REMS, age (p < 0.001), higher CT score (p < 0.001), higher values of urea (p < 0.001), and the presence of bacterial superinfection (p < 0.001) were significant predictors of mortality. CONCLUSIONS: Among all evaluated EWSs to predict mortality and ICU admission in COVID-19 patients, the REMS score demonstrated the highest efficacy.

Takotsubo Cardiomyopathy Occurring Simultaneously with Acute Myocardial Infarction.

INTRODUCTION: Takotsubo cardiomyopathy (TCM) is a reversible form of cardiomyopathy characterized by transient regional systolic dysfunction of the left ventricle. CASE OUTLINE: A 78-year-old woman was admitted to the general hospital due to acute inferior STEMI late presentation. Two days after admission, the patient reported intense chest pain and an ECG registered diffuse ST-segment elevation in all leads with ST-segment denivelation in aVR. The patient also showed clinical signs of cardiogenic shock and was referred to a reference institution for further evaluation. Echocardiography revealed akinesia of all medioapical segments, dynamic obstruction of the left ventricular outflow tract (LVOT), moderate mitral regurgitation, and pericardial effusion. Coronary angiography showed the suboccluded right coronary artery, and a primary percutaneous coronary intervention was performed, which involved implanting a drug-eluting stent. The patient's condition worsened as pericardial effusion increased and led to tamponade. Pericardiocentesis was performed, resulting in the patient's stabilization. At this point, significant gradients at the LVOT and pericardial effusion were not registered. After eight days without symptoms and stable status, the patient was discharged. CONCLUSIONS: The simultaneous presence of AMI and TCM increases the risk of developing cardiogenic shock. The cardio-circulatory profile of these patients is different from those with AMI.

Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID-19 and Preexisting Cardiovascular Disease.

Background Empiric antimicrobial therapy with azithromycin is highly used in patients admitted to the hospital with COVID-19, despite prior research suggesting that azithromycin may be associated with increased risk of cardiovascular events. Methods and Results This study was conducted using data from the ISACS-COVID-19 (International Survey of Acute Coronavirus Syndromes-COVID-19) registry. Patients with a confirmed diagnosis of SARS-CoV-2 infection were eligible for inclusion. The study included 793 patients exposed to azithromycin within 24 hours from hospital admission and 2141 patients who received only standard care. The primary exposure was cardiovascular disease (CVD). Main outcome measures were 30-day mortality and acute heart failure (AHF). Among 2934 patients, 1066 (36.4%) had preexisting CVD. A total of 617 (21.0%) died, and 253 (8.6%) had AHF. Azithromycin therapy was consistently associated with an increased risk of AHF in patients with preexisting CVD (risk ratio [RR], 1.48 [95% CI, 1.06-2.06]). Receiving azithromycin versus standard care was not significantly associated with death (RR, 0.94 [95% CI, 0.69-1.28]). By contrast, we found significantly reduced odds of death (RR, 0.57 [95% CI, 0.42-0.79]) and no significant increase in AHF (RR, 1.23 [95% CI, 0.75-2.04]) in patients without prior CVD. The relative risks of death from the 2 subgroups were significantly different from each other (Pinteraction=0.01). Statistically significant association was observed between AHF and death (odds ratio, 2.28 [95% CI, 1.34-3.90]). Conclusions These findings suggest that azithromycin use in patients with COVID-19 and prior history of CVD is significantly associated with an increased risk of AHF and all-cause 30-day mortality. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05188612.

HDL Subclasses and the Distribution of Paraoxonase-1 Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction.

The aim of this multicentric study was to assess the impacts of oxidative stress, inflammation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins' subclasses were separated using polyacrylamide gradient (3-31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL.