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Alexandr Ceasovschih,1,2,* Victorita Sorodoc,1,2 Annabelle Shor,1,* Raluca Ecaterina Haliga,1,2,* Lynn Roth,3 Catalina Lionte,1,2 Viviana Onofrei Aursulesei,4,* Oana Sirbu,1,2,* Nicolae Culis,5 Albina Shapieva,6 Mohammed AR Tahir Khokhar,1 Cristian Statescu,7 Radu A Sascau,7 Adorata Elena Coman,1 Alexandra Stoica,1,2 Elena-Daniela Grigorescu,1 Maciej Banach,8 Costas Thomopoulos,9 Laurentiu Sorodoc1,2 1Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, 700115, Romania; 2 2nd Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, Iasi, 700111, Romania; 3Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, 2610, Belgium; 4Department of Cardiology, Clinical Emergency Hospital “Sfantul Spiridon”, Iasi, 700106, Romania; 5Nottingham University Hospitals NHS Trust, Queen’s Medical Center, Nottingham, NG72UH, UK; 6Cardiac Electrophysiology Department, Petrovsky National Research Center of Surgery, Moscow, 119991, Russia; 7Department of Cardiology, Cardiovascular Diseases Institute “Prof. Dr. George I.M. Georgescu”, Iasi, 700503, Romania; 8Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, 93338, Poland; 9Department of Cardiology, Elena Venizelou General Hospital, Athens, GR-11522, Greece*These authors contributed equally to this workCorrespondence: Victorita Sorodoc, 2nd Internal Medicine Department, Sf. Spiridon Clinical Emergency Hospital, Independentei 1 Street, Iasi, 700111, Romania, Tel +40232 240 822, Email vivisorodoc@yahoo.com Lynn Roth, Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Wilrijk, 2610, Belgium, Email lynn.roth@uantwerpen.beAbstract: The Coronavirus Disease 2019 (COVID-19) pandemic was declared in early 2020 after several unexplained pneumonia cases were first reported in Wuhan, China, and subsequently in other parts of the world. Commonly, the disease comprises several clinical features, including high temperature, dry cough, shortness of breath, and hypoxia, associated with findings of interstitial pneumonia on chest X-ray and computer tomography. Nevertheless, severe forms of acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) are not limited to the respiratory tract but also may be extended to other systems, including the cardiovascular system. The bi-directional relationship between atherosclerosis and COVID-19 is accompanied by poor prognosis. The immune response hyperactivation due to SARS-CoV-2 infection causes an increased secretion of cytokines, endothelial dysfunction, and arterial stiffness, which promotes the development of atherosclerosis. Also, due to the COVID-19 pandemic, access to healthcare amenities was reduced, resulting in increased morbidity and mortality in patients at risk. Furthermore, as lockdown measures were largely adopted worldwide, the sedentary lifestyle and the increased consumption of processed nutrients or unhealthy food increased, and in the consequence, we might observe even 70% of overweight and obese population. Altogether, with the relatively low ratio of vaccinated people in many countries, and important health debt appeared, which is now and will be for next decade a large healthcare challenge. However, the experience gained in the COVID-19 pandemic and the new methods of patients’ approaching have helped the medical system to overcome this crisis and will hopefully help in the case of new possible epidemics.Keywords: vascular diseases, COVID-19, SARS-CoV-2, endothelial dysfunction, atherosclerosis, arterial stiffness, vaccines

Accidental hypothermia (AH) presents a significant mortality risk, even in individuals with good health. Early recognition of the parameters associated with negative prognosis could save more lives.

Alexandr Ceasovschih,1,2,* Victorița Șorodoc,1,2 Serghei Covantsev,3,* Anastasia Balta,1,2,* Jamol Uzokov,4,* Sergio E Kaiser,5 Abdallah Almaghraby,6 Cătălina Lionte,1,2 Cristian Stătescu,1,7 Radu A Sascău,1,7 Viviana Onofrei,1,8 Raluca Ecaterina Haliga,1,2,* Alexandra Stoica,1,2,* Cristina Bologa,1,2 Ștefan Ailoaei,7 Yusuf Ziya Şener,9 Nicholas G Kounis,10 Laurențiu Șorodoc1,2 1Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania; 2 2nd Internal Medicine Department, “Sf. Spiridon” Clinical Emergency Hospital, Iasi, Romania; 3Department of Research and Clinical Development, Botkin Hospital, Moscow, Russia; 4Department of Cardiology, Republican Specialized Scientific Practical Medical Center of Therapy and Medical Rehabilitation, Tashkent, Uzbekistan; 5Discipline of Clinical and Experimental Pathophysiology, Rio de Janeiro State University, Rio de Janeiro, Brazil; 6Department of Cardiology, Ibrahim Bin Hamad Obaidallah Hospital, Ras Al Khaimah, United Arab Emirates; 7Department of Cardiology, “Prof. Dr. George I.M. Georgescu” Cardiovascular Diseases Institute, Iasi, Romania; 8Department of Cardiology, “Sf. Spiridon” Clinical Emergency Hospital, Iasi, Romania; 9Department of Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkiye; 10Department of Internal Medicine, Division of Cardiology, University of Patras Medical School, Patras, Greece*These authors contributed equally to this workCorrespondence: Victorița Șorodoc, 2nd Internal Medicine Department, “Sf. Spiridon” Clinical Emergency Hospital, Independentei 1 Street, Iasi, 700106, Romania, Tel +40232 240 822, Email vivisorodoc@yahoo.com Viviana Onofrei, Cardiology Department, “Sf. Spiridon” Clinical Emergency Hospital, Independentei 1 Street, Iasi, 700106, Romania, Email onofreiviviana@gmail.comAbstract: Despite the noteworthy advancements and the introduction of new technologies in diagnostic tools for cardiovascular disorders, the electrocardiogram (ECG) remains a reliable, easily accessible, and affordable tool to use. In addition to its crucial role in cardiac emergencies, ECG can be considered a very useful ancillary tool for the diagnosis of many non-cardiac diseases as well. In this narrative review, we aimed to explore the potential contributions of ECG for the diagnosis of non-cardiac diseases such as stroke, migraine, pancreatitis, Kounis syndrome, hypothermia, esophageal disorders, pulmonary embolism, pulmonary diseases, electrolyte disturbances, anemia, coronavirus disease 2019, different intoxications and pregnancy.Keywords: electrocardiography, electrocardiogram, features, non-cardiac diseases, ECG

Acute exposure to systemic poisons represents an important challenge in clinical toxicology. We aimed to analyze the potential role of cardiac biomarkers, routine laboratory tests, and clinical scores as morbidity and in-hospital mortality predictors in patients intoxicated with various systemic poisons. We conducted a prospective study on adults acutely exposed to systemic poisons. We determined the PSS, Glasgow Coma Scale (GCS), and we performed electrocardiogram, laboratory tests, lactate and cardiac biomarkers (which were reassessed 4 h, respectively 6 h later). Of 120 patients included, 45% developed complications, 19.2% had a poor outcome, and 5% died. Multivariate logistic regression sustained lactate (odds ratio (OR) 1.58; confidence interval (CI) 95%: 0.97–2.59; p 0.066), MB isoenzyme of creatine kinase (6h-CKMB; OR 1.08; CI 95%: 1.02–1.16; p 0.018) as predictors for a poor outcome. A GCS < 10 (OR 0.113; CI 95%: 0.019–0.658; p 0.015) and 4h-lactate (OR 4.87; CI 95%: 0.79–29.82; p 0.087) predicted mortality after systemic poisons exposure. Receiver operating characteristic analysis showed that brain natriuretic peptide (area under the curve (AUC), 0.96; CI 95%: 0.92–0.99; p < 0.001), lactate (AUC, 0.91; CI 95%: 0.85–0.97; p < 0.001), and 6h-CKMB have good discriminatory capacity for predicting a poor outcome. In conclusion, these biomarkers, lactate, and GCS can be used to predict morbidity and mortality after systemic poisons exposure. [ABSTRACT FROM AUTHOR]

A case of respiratory failure in a domestic fire victim presenting with 1-3-degree skin burns on 10% of the total body surface, is reported. Forty-eight hours after admission to hospital, the patient developed severe respiratory failure that did not respond to mechanical ventilation. Severe obstruction of the airway had resulted from secretions and deposits of soot forming bronchial casts. The patient required repeated bronchoscopies to separate and remove the bronchial secretions and soot deposits. An emergency bronchial endoscopic exam was crucial in the patient’s survival and management. The patient was discharged from the hospital after twenty-four days.

Objectives: The objective of this study was to assess the pattern and outcome of acute cholinesterase inhibitors substances (CIS) poisoning cases, in a cohort from a regional tertiary care hospital. Methods: cases admitted in the Toxicology Clinic of “Sf. Spiridon” Emergency Clinic Hospital Iasi, Romania between 1983 and 2013 were studied. Results: a total number of 606 patients were included. The reason for exposures was intentional in 70% of cases and the commonest route of poisoning was oral in 92.2%. The highest percent of cases was females (56.4), the age group 20-29 (25.4%) and the majority (66.7%) coming from rural areas, 28.2% being agricultural workers. 36.6% of cases were severe clinical forms. Overall mortality rates were 3.8%, more than half of the death patients (65.2%) had concomitant alcohol intake. It was a significant statistical association between decrease level of serum cholinesterase on admittance and severe forms (p 0.000) and between survival and deaths groups (p 0.000). The pattern of poisoning described by our retrospective study suggests that CIS poisoning are mainly preventable. The main effective goals for prevention are restriction in free accessibility to toxic pesticides, together with sustained efforts in education concerning the life-threatening danger of pesticide poisoning.

Background. Alcohol ingestion can induce either a hypoglycemia or a hyperglycemia, in patients with acute and chronic ethanol poisoning, unknown with diabetes mellitus. Aim. The aim of this study was to evaluate whether 5 hours prolonged oral glucose tolerance test (5h-OGTT) is useful in evaluating the abnormalities of glucose metabolism in acute and chronic ethanol poisoning, in comparison with standard methods (fasting blood glucose - FBG, and/or 2h-OGTT). Methods. 497 consecutive patients were enrolled in a 34 months cross sectional study. In all cases, glucose tolerance was assessed by a 75-g oral glucose tolerance, OGTT 2 hours, prolonged to 5 hours. The relationship between clinical and biochemical variables of ethanol poisoning (liver status, lipid profile, metabolic syndrome) and glucose tolerance was investigated. Risk factors for hypoglycemia in ethanol poisoning were identified. Results. 349 subjects presented acute ethanol poisoning, and 148 subjects had chronic ethanol poisoning. 254 patients (51.10%) had documented alcoholic liver disease (ALD - clinical, biochemical and imagistic criteria). Glucose metabolism abnormalities were recorded in 143 subjects with chronic ethanol poisoning and ALD (96.63%), and in 207 cases with acute alcohol poisoning (59.31%). 371 patients (74.65%) showed normal FBG, diabetes mellitus (DM) was diagnosed in 54 subjects (10.86%), impaired glucose tolerance (IGT) in 43 subjects (8.65%), delayed hypoglycemia in 172 subjects (34.60%) and normal glucose tolerance (NGT) in 147 subjects (29.57%) using OGTT and ADA diagnosis criteria. Hypoglycemia was recorded in more than two thirds of acutely poisoned patients, when alcohol level was 0.5-1.5 g/L. Impaired glucose tolerance (IGT) were recorded in half of patients with blood ethanol levels > 2.5 g/L. Conclusions. OGTT 2 hours and OGTT 5 hours revealed the same number of patients with diabetes mellitus. Frequent co morbidities in patients with ethanol poisoning influence the prolonged OGTT and revealed .especially delayed hypoglycemia, and IGT, as an indicator of alcoholic liver disease (ALD). [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) usually represents the clinical manifestation of atherothrombotic coronary artery disease (CAD) resulting from atherosclerotic plaque rupture. However, there are cases in which coronary angiography or coronary computed tomography angiography reveals patients with acute coronary syndrome with non-obstructive CAD. This clinical entity is defined as myocardial infarction with non-obstructive coronary arteries (MINOCA) and often considered as a clinical dynamic working diagnosis that needs further investigations for the establishment of a final etiologic diagnosis. The main causes of a MINOCA working diagnosis include atherosclerotic, non-atherosclerotic (vessel-related and non-vessel-related), and thromboembolic causes This literature review aimed to investigate the major thromboembolic causes in patients presenting with MINOCA regarding their etiology and pathophysiologic mechanisms, as well as diagnostic and treatment methods., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

According to the latest international resuscitation guidelines, extracorporeal cardiopulmonary resuscitation (ECPR) involves the utilization of extracorporeal membrane oxygenation (ECMO) in specific patients experiencing cardiac arrest, and it can be considered in situations where standard cardiopulmonary resuscitation efforts fail if they have a potentially reversible underlying cause, among which we can also find hypothermia. In cases of cardiac arrest, both witnessed and unwitnessed, hypothermic patients have higher chances of survival and favorable neurological outcomes compared to normothermic patients. ECPR is a multifaceted procedure that requires a proficient team, specialized equipment, and comprehensive multidisciplinary support within a healthcare system. However, it also carries the risk of severe, life-threatening complications. With the increasing use of ECPR in recent years and the growing number of centers implementing this technique outside the intensive care units, significant uncertainties persist in both prehospital and emergency department (ED) settings. Proper organization is crucial for an ECPR program in emergency settings, especially given the challenges and complexities of these treatments, which were previously not commonly used in ED. Therefore, within a narrative review, we have incorporated the initial case of ECPR in an ED in Romania, featuring a successful resuscitation in the context of severe hypothermia (20 °C) and a favorable neurological outcome (CPC score of 1)., Competing Interests: The authors declare no conflict of interest.

Background: Upper gastrointestinal (GI) bleeding is a life-threatening condition with high mortality rates., Aim: To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes: In-hospital mortality, intervention (endoscopic or surgical) and length of admission (≥ 7 d)., Methods: We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021. We calculated and compared the area under the receiver operating characteristics curves (AUROCs) of Glasgow-Blatchford score (GBS), pre-endoscopic Rockall score (PERS), albumin, international normalized ratio, altered mental status, systolic blood pressure, age older than 65 (AIMS65) and age, blood tests and comorbidities (ABC), including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts. We subsequently analyzed through a logistic binary regression model, if addition of lactate increased the score performance., Results: All scores had discriminative ability in predicting in-hospital mortality irrespective of study group. AIMS65 score had the best performance in the variceal bleeding group (AUROC = 0.772; P < 0.001), and ABC score (AUROC = 0.775; P < 0.001) in the non-variceal bleeding group. However, ABC score, at a cut-off value of 5.5, was the best predictor (AUROC = 0.770, P = 0.001) of in-hospital mortality in both populations. PERS score was a good predictor for endoscopic treatment (AUC = 0.604; P = 0.046) in the variceal population, while GBS score, (AUROC = 0.722; P = 0.024), outperformed the other scores in predicting surgical intervention. Addition of lactate to AIMS65 score, increases by 5-fold the probability of in-hospital mortality ( P < 0.05) and by 12-fold if added to GBS score ( P < 0.003). No score proved to be a good predictor for length of admission., Conclusion: ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population. PERS and GBS should be used to determine need for endoscopic and surgical intervention, respectively. Lactate can be used as an additional tool to risk scores for predicting in-hospital mortality., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Infective endocarditis is a severe infective heart disease, commonly involving native or prosthetic valves. It frequently presents with univalvular involvement and simultaneous double valve or multivalvular involvement is rarely described. The third leading cause of infective endocarditis worldwide is Enterococcus faecalis , which is associated with high mortality rates despite important advances in antimicrobial therapy. It develops secondary to enterococcal bacteremia, with its origin from the gastrointestinal or genitourinary tract and predominantly affecting the elderly population with multiple comorbidities. Clinical presentation is usually less typical, and the treatment is challenging. It can be marked by antibiotic resistance, side effects, and subsequent complications. Surgical treatment can be considered if deemed appropriate. To the best of our knowledge, we present the first case-based narrative review of Enterococcus faecalis double valve endocarditis involving both the aortic native and prosthetic mitral valve, highlighting the clinical characteristics, treatment, and complications of this condition.

Nontrombotic pulmonary embolism represents the embolization of different types of materials (cells, organisms, gas, foreign material) into pulmonary circulation. The disease is uncommon, and clinical presentation together with laboratory findings are nonspecific. Its pathology is usually misdiagnosed based on imaging findings as pulmonary thromboembolism, but the correct diagnosis is essential because different therapeutic approaches are required. In this context, knowledge of the risk factors associated with nontrombotic pulmonary embolism and specific clinical symptoms is fundamental. Our objective was to discuss the specific features of the most common etiologies of nontrombotic pulmonary embolism, gas, fat, amniotic fluid, sepsis and tumors, to provide assistance for a rapid and correct diagnosis. Because the most common etiologies are iatrogenic, knowledge of the risk factors could be an important tool for prevention or rapid treatment if the disease develops during different procedures. The diagnosis of nontrombotic pulmonary embolisms represent a laborious challenge, and endeavors should be made to prevent development and increase awareness of this disease., Competing Interests: The authors declare no conflict of interest.

In recent years, direct oral anticoagulants (DOAC) have accumulated evidence of efficacy and safety in various clinical scenarios and are approved for a wide spectrum of indications. Still, they are currently used off-label for left ventricular thrombus owing to a paucity of evidence. For the same reason, there is a lack of guideline indication as well. Our work is based on an exhaustive analysis of the available literature and provides a structured and detailed update on the use of DOACs in patients with left ventricle thrombus. The safety and efficacy of DOACs were analyzed in particular clinical scenarios. As far as we know, this is the first paper that analyzes DOACs in this approach.

Serotonin syndrome (SS) is a clinical toxidrome with high variability in clinical practice. It develops due to increased serotonin levels in the central nervous system. With an underestimated frequency, SS can develop following an overdose, a therapeutic dose increase, or drug to drug interaction of at least one serotonergic agent. It can present with autonomic signs, neuromuscular changes and an altered mental status. However, history and clinical examination are key features to formulate the diagnosis. Treatment options consist of supportive measures, discontinuation of the offending agent and certain therapeutic agents previously reported to improve outcomes. Physicians have limited experience with SS, partially due to the lack of its identification in clinical practice. Therefore, we have integrated, in a narrative review, the case of a young male with SS following an atypical antipsychotic overdose superimposed on chronic treatment with agents previously known to produce SS.

Background: The ongoing COVID-19 pandemic has put a constant strain on hospital resources, so there is a dire need for investigation methods that are widely available and that can predict mortality and the need for critical care. Hematological indices, which can be easily calculated from a complete blood count (CBC), are useful in determining a patient’s inflammatory response to infectious diseases. Aim: This was a prospective cohort study that aimed to assess the prognostic value of scores based on CBCs in hospitalized patients with mild or moderate COVID-19 and medical comorbidities regarding the need for intensive care unit (ICU) therapy and short-term mortality. Methods: We included 607 patients with confirmed COVID-19, followed up for the need for ICU admission (15.5%) and 30 day mortality post-discharge (21.7%). CBC-derived scores were tested upon emergency department (ED) admission and after a median of 8 days. Results: In a multivariate model, elevated followed-up neutrophil-to-lymphocyte ratio (NLR) predicted increased odds for ICU admission (OR: 1.14 [95%CI: 1.06−1.22], p < 0.001) and short-term mortality (OR: 1.30 [95%CI: 1.09−1.57], p = 0.005). Monocyte-to-lymphocyte ratio (MLR) predicted 2.5-fold increased odds for ICU admission and 2.2-fold increased odds for mortality. Conclusion: NLR and MLR followed up 8 days post-admission are predictive for adverse outcomes in mild or moderate COVID-19 patients.

Background: Biomarkers, electrocardiogram (ECG) and Holter ECG are basic, accessible and feasible cardiac investigations. The combination of their results may lead to a more complex predictive model that may improve the clinical approach in acute heart failure (AHF). The main objective was to investigate which ECG parameters are correlated with the usual cardiac biomarkers (prohormone N-terminal proBNP, high-sensitive cardiac troponin I) in patients with acute heart failure, in a population from Romania. The relationship between certain ECG parameters and cardiac biomarkers may support future research on their combined prognostic value. Methods: In this prospective case-control study were included 49 patients with acute heart failure and 31 participants in the control group. For all patients we measured levels of prohormone N-terminal proBNP (NT-proBNP), high-sensitive cardiac troponin I (hs-cTnI) and MB isoenzyme of creatine phosphokinase (CK-MB) and evaluated the 12-lead ECG and 24 h Holter monitoring. Complete clinical and paraclinical evaluation was performed. Results: NT-proBNP level was significantly higher in patients with AHF (p < 0.001). In patients with AHF, NT-proBNP correlated with cQTi (p = 0.027), pathological Q wave (p = 0.029), complex premature ventricular contractions (PVCs) (p = 0.034) and ventricular tachycardia (p = 0.048). Hs-cTnI and CK-MB were correlated with ST-segment modification (p = 0.038; p = 0.018) and hs-cTnI alone with complex PVCs (p = 0.031). Conclusions: The statistical relationships found between cardiac biomarkers and ECG patterns support the added value of ECG in the diagnosis of AHF. We emphasize the importance of proper ECG analysis of more subtle parameters that can easily be missed. As a non-invasive technique, ECG can be used in the outpatient setting as a warning signal, announcing the acute decompensation of HF. In addition, the information provided by the ECG complements the biomarker results, supporting the diagnosis of AHF in cases of dyspnea of uncertain etiology. Further studies are needed to confirm long-term prognosis in a multi-marker approach.

Background: Data regarding the combined prognostic role of biomarkers and risk scores in relation with the history of atherosclerotic cardiovascular disease (ASCVD) in COVID-19 patients are lacking., Methods: The aim of this observational cohort study was to evaluate the combined prognostic value of N-terminal pro B-type natriuretic peptide (NT-pro BNP), troponin and risk scores in relation with ASCVD history in hospitalized COVID-19 patients. The primary composite endpoint was Intensive Care Unit (ICU) admission and death., Results: From April 2020 to June 2022, 1066 consecutive COVID-19 patients with available biomarkers upon admission were included. During a median follow-up period of 12 days, 176 patients (16.5%) died. Independent predictors of ICU admission and death in patients with ASCVD were NT-pro BNP (HR 2.63; 95% CI, 1.65-4.18) and troponin (HR 1.51; 95% CI, 1.13-2.03). In patients without ASCVD, only NT-pro BNP was predictive for the primary endpoint (HR 1.66; 95% CI, 1.10-2.53). This remained significant after adjustment for other relevant covariates (HR 3.54; 95% CI, 1.98-6.33) in patients with ASCVD and in patients without ASCVD (HR 1.82; 95% CI, 1.02-3.26)., Conclusions: These data showed the combined prognostic accuracy of NT-pro BNP and troponin in relation with ASCVD history for ICU admission and death in COVID-19 patients.

In cancer survivors, cardiac dysfunction is the main cause of mortality. Cardiotoxicity represents a decline in cardiac function associated with cancer therapy, and the risk factors include smoking, dyslipidemia, an age of over 60 years, obesity, and a history of coronary artery disease, diabetes, atrial fibrillation, or heart failure. Troponin is a biomarker that is widely used in the detection of acute coronary syndromes. It has a high specificity, although it is not exclusively associated with myocardial ischemia. The aim of this paper is to summarize published studies and to establish the role of troponin assays in the diagnosis of cardiotoxicity associated with various chemotherapeutic agents. Troponin has been shown to be a significant biomarker in the diagnosis of the cardiac dysfunction associated with several types of chemotherapeutic drugs: anthracyclines, anti-human epidermal growth factor receptor 2 treatment, and anti-vascular endothelial growth factor therapy. Based on the data available at this moment, troponin is useful for baseline risk assessment, the diagnosis of cardiotoxicity, and as a guide for the initiation of cardioprotective treatment. There are currently clear regulations regarding the timing of troponin surveillance depending on the patient's risk of cardiotoxicity and the type of medication administered, but data on the cut-off values of this biomarker are still under investigation.

Background: Biomarkers were correlated with mortality in critically ill COVID-19 patients. No prediction tools exist for noncritically ill COVID-19 patients. We aimed to compare the independent prognostic value of inflammation and cardiac biomarkers for post-acute COVID-19 patients and the 30-day mortality rate in noncritically ill COVID-19 patients, as well as the relation with the virus variant involved., Methods: This observational cohort study was conducted at an emergency clinical hospital between 1 October 2020 and 31 December 2021. We included consecutive patients with biomarkers determined within 24 h of presentation, followed up at least 30 days postdischarge., Results: Post-acute COVID-19 was diagnosed in 20.3% of the cases and the all-cause 30-day mortality rate was 35.1% among 978 patients infected with variants of concern. Neutrophil-to-lymphocyte ratio (1.06 [95%CI, 1.01-1.11], p = 0.015) and NT-pro BNP were correlated with 30-daymortality, while the monocyte-to-lymphocyte ratio (2.77 [95%CI, 1.10-6.94], p = 0.03) and NT-pro BNP (1.68 [95%CI, 1.00-2.84], p = 0.05) were correlated with post-acute COVID-19. High-sensitivity to troponin was associated with 30-day mortality (1.55 [95%CI, 1.00-2.42], p = 0.05). A Cox proportional-hazards model confirmed that NT-pro BNP was independently associated with mortality. NT-pro BNP remained independently associated with 30-day mortality during follow-up (1.29 [95%CI, 1.07-1.56], p = 0.007) after adjustment for confounders., Conclusion: Inflammation and cardiac biomarkers, determined upon admission and predischarge, in a cohort of hospitalized noncritically ill COVID-19 patients throughout successive pandemic waves, showed a predictive value for post-acute COVID-19 and 30-day mortality.

Patients poisoned with drugs and nonpharmaceutical substances are frequently admitted from the emergency department (ED) to a medical or ICU department. We hypothesized that biomarkers of inflammation and inflammation-related indexes based on the complete blood cell (CBC) count can identify acutely poisoned patients at increased risk for ICU hospitalization and death. We performed a 6-year prospective cohort study on 1548 adult patients. The demographic data, the levels of hs-CRP (high-sensitivity C-reactive protein), CBC, and inflammation-related indexes based on CBC counts were collected upon admission and compared between survivors and nonsurvivors, based on the poison involved. Both a multivariate logistic regression model with only significant univariate predictors and a model including univariate predictors plus each log-transformed inflammation-related indexes for mortality were constructed. The importance of the variables for mortality was graphically represented using the nomogram. hs-CRP (odds ratio (OR), 1.38; 95% CI, 1.16-1.65, p < 0.001 for log-transformed hs-CRP), red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were significantly associated with the risk of ICU hospitalization, after multivariable adjustment. Only RDW, NLR, and monocyte-lymphocyte ratio (MLR) were significantly associated with mortality. The predictive accuracy for mortality of the models which included either NLR (AUC 0.917, 95% CI 0.886-0.948) or MLR (AUC 0.916, 95% CI 0.884-0.948) showed a high ability for prognostic detection. The use of hs-CRP, RDW, NLR, and MLR upon ED admission are promising screening tools for predicting the outcomes of patients acutely intoxicated with undifferentiated poisons., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Catalina Lionte et al.)

Thank you for the opportunity to respond to the issues raised by Ferrés-Padró et al. in their recent letter to the editor [...].

Background and objectives: The connections between the imidazoline system and multiple other neurotransmitter systems in the brain (adrenergic, dopaminergic, serotoninergic, glutamatergic, opioid) indicate the complexity of the mechanisms underlying motor activity and behavior. The aim of the present research was to investigate the effects of the combination of ephedrine (EPD) and imidazoline antagonists idazoxan (IDZ) and efaroxan (EFR) on the endurance performance in the treadmill test in rats. Materials and Methods: We used Wistar rats distributed as follows: Group 1 (Control) receiving distilled water 0.3 mL/100 g body weight; Group 2 (EPD) receiving 20 mg/kg ephedrine; Group 3 (EPD + IDZ) receiving 20 mg/kg ephedrine + 3 mg/kg idazoxan; Group 4 (EPD + EFR) receiving 20 mg/kg ephedrine + 1 mg/kg efaroxan. An additional group (C) of animals receiving 0.3 mL/100 g body weight distilled water (but not subjected) to effort was used. Endurance capacity was evaluated using a treadmill running PanLAB assay. The evaluation of the substances' influence on oxidative stress was performed by spectrophotometric determination of superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity. Results: Treatment with EPD-IDZ and EPD-EFR were correlated with a longer distance traveled on the belt and with a decrease in the necessary electric shocks to motivate the animal to continue running in the forced locomotion test. Additionally, an increase in the activity of antioxidant enzymes was found. Conclusions: Idazoxan and efaroxan potentiated the physical effort-related effects of ephedrine with regard to endurance capacity and antioxidant activity in rats.

The prognostic value of multiple glycemic parameters in poisoned patients was never assessed. We aim to explore the effects of glucose variability on short-term outcomes in nondiabetic and diabetic patients acutely poisoned with undifferentiated xenobiotics. We performed a prospective observational study in a tertiary center for toxicology in northeastern Romania. Over the course of 3 years, we included 1076 adults, older than 18 years, admitted for acute poisoning with a xenobiotic. The mortality rate was 4.1%. The admission blood glucose level (BGL) predicted mortality (OR 1.015, 95% CI 1.011-1.019, p < 0.001) and complications (OR 1.005, 95% CI 1.001-1.009, p 0.02). The mean glucose level (MGL) after admission (OR 1.007, 95% CI 1.000-1.013, p 0.034) and coefficient of glucose variability (CV) were predictive for complications (OR 40.58, 95% CI 1.35-1220.52, p 0.033), using the same multivariable model. The receiver operating characteristic curve (ROC) analysis revealed that BGL had good predictive value for in-hospital mortality (area under the curve (AUC) = 0.744, 95% CI = 0.648-0.841, p < 0.001), and complications (AUC = 0.618, 95% CI = 0.584-0.653, p < 0.001). In patients acutely poisoned with xenobiotics, the BGL, MGL and CV can be useful as mortality and short-outcome predictors.

Background and Objectives : During the coronavirus disease 2019 (COVID-19) pandemic, patients with chronic diseases suffering exacerbations have required acute medical care. The purpose of our study was to determine useful criteria for the differentiation of patients with acute clinical syndromes and suspicion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Materials and Methods : This was an observational retrospective study, conducted in an internal medicine clinic from April to May 2020. We collected clinical, biological, and computed tomography (CT) data on patients with exacerbations of chronic diseases and clinical suspicion of SARS-CoV-2 infection. Patients with an already-positive real-time reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 on presentation at the emergency department were excluded from our study. Results : Of 253 suspected cases, 20 were laboratory-confirmed as having SARS-CoV-2 infection by RT-PCR, whereas COVID-19 diagnosis was ruled out in the remaining 233. Venous thromboembolism (VTE) correlated significantly with COVID-19 diagnosis in suspected patients, while laboratory markers were not significantly different between the two groups. Of the suspected patients, significantly higher percentages of dry cough, fever, myalgias, sore throat, loss of smell and appetite, and ground-glass opacities (GGOs) on CT were found in SARS-CoV-2-positive individuals. Conclusions : The study demonstrated that, until receiving the result of an RT-PCR test for SARS-CoV-2 (usually 12-24 h), association with VTE as a comorbidity, fever, dry cough, and myalgia as clinical features, and GGO on CT are the main markers for the identification of COVID-19 patients among those suspected with acute clinical syndromes. Our results also provide evidence for doctors not to rely solely on biological markers in the case of suspected SARS-CoV-2 infection in patients with exacerbations of chronic diseases. These data are useful for faster decision-making with regard to suspected COVID-19 patients before receiving RT-PCR test results, thus avoiding keeping patients in crowded emergency departments.

Peripheral arterial disease (PAD) is a common manifestation of generalized atherosclerosis, which affects more than 200 million patients worldwide. Currently, there is no ideal biomarker for PAD risk stratification and diagnosis. The goal of this research was to investigate the levels of inflammation biomarkers and cystatin C and to explore their utility for the diagnosis of PAD. The study included 296 participants, distributed in two groups: 216 patients diagnosed with PAD and 80 patients without PAD as controls. All studied biomarker levels (C-reactive protein, CRP; fibrinogen; erythrocyte sedimentation rate, ESR; neopterin; beta 2-microglobulin, B2-MG; and cystatin C) were significantly higher in the PAD group and indirectly correlated with the ankle-brachial index (ABI). The final logistic regression model included an association of neopterin, fibrinogen, and cystatin C as the most efficient markers for the prediction of PAD diagnosis. When comparing the area under the curve (AUC) for all biomarkers, the value for neopterin was significantly higher than those of all the other analyzed biomarkers. In agreement with previous studies, this research shows that markers such as fibrinogen, CRP, ESR, B2-MG, and cystatin C have significant value for the diagnosis of PAD, and also clearly underlines the accuracy of neopterin as a leading biomarker in PAD prediction.

Background and objectives: The etiology of anemia associated with heart failure is not fully understood, but there are data suggesting the involvement of multiple mechanisms, including various drug therapies used in patients with heart failure. Our primary objective was to evaluate the impact of beta blockers, angiotensin-converting enzyme inhibitors, and calcium-channel blockers on iron metabolism in patients with heart failure. Materials and Methods: This was a prospective observational study that included patients diagnosed with heart failure and iron deficiency (defined by ferritin <100 μg/L, or 100-300 μg/L with transferrin saturation <20%). Patients with anemia secondary to a known cause were excluded. Results: We found a statistically significant correlation between beta-blocker treatment and ferritin values ( p = 0.02). Iron, hemoglobin, and hematocrit levels were significantly lower in the patients using calcium-channel blockers than those who were not. We also found a statistically significant indirect correlation ( p = 0.04) between the use of angiotensin-converting enzyme inhibitors and hematocrit levels. Conclusion: The contribution of our study arises from the additional data regarding the drug-induced etiology of iron deficiency. Practitioners should be aware of the potential impact of therapeutic recommendations and this should imply a close monitoring of the biochemical parameters of iron deficiency in this category of patients.

Anemia associated with heart failure is a frequent condition, which may lead to heart function deterioration by the activation of neuro-hormonal mechanisms. Therefore, a vicious circle is present in the relationship of heart failure and anemia. The consequence is reflected upon the patients' survival, quality of life, and hospital readmissions. Anemia and iron deficiency should be correctly diagnosed and treated in patients with heart failure. The etiology is multifactorial but certainly not fully understood. There is data suggesting that the following factors can cause anemia alone or in combination: iron deficiency, inflammation, erythropoietin levels, prescribed medication, hemodilution, and medullar dysfunction. There is data suggesting the association among iron deficiency, inflammation, erythropoietin levels, prescribed medication, hemodilution, and medullar dysfunction. The main pathophysiologic mechanisms, with the strongest evidence-based medicine data, are iron deficiency and inflammation. In clinical practice, the etiology of anemia needs thorough evaluation for determining the best possible therapeutic course. In this context, we must correctly treat the patients' diseases; according with the current guidelines we have now only one intravenous iron drug. This paper is focused on data about anemia in heart failure, from prevalence to optimal treatment, controversies, and challenges.

Acute poisonings represent a common cause of morbidity and mortality worldwide. The prognostic utility of the transthoracic echocardiography (TTE) parameters combined with brain natriuretic peptide (BNP) in acute poisoning with different xenobiotics, upon admission in the hospital, was not evaluated. This prospective observational cohort study included 229 acutely poisoned non-diabetic adults, with a median age of 44 years (range 18-90 years), 50.7% women, with an in-hospital mortality rate of 8.7%. Univariate logistic regression analysis showed that age, the left ventricle kinetic abnormalities, the E-wave deceleration time (EDT) and BNP correlated significantly with mortality in acutely poisoned patients. Multivariate logistic regression showed that only EDT [odds ratio (OR) 3.44, 95% confidence interval (CI) 1.54-7.69, p 0.003], BNP (OR 1.61, 95% CI: 1.02-2.55, p 0.04) and age (OR 2.66, 95% CI: 1.23-5.76, p 0.013) are predictive for mortality. The receiver-operating characteristic (ROC) analysis proved EDT [area under the ROC curve (AUC), 0.85; CI: 0.76-0.94; p 0.001], BNP (AUC, 0.83; CI: 0.75-0.91; p 0.001) and age (AUC, 0.82; CI: 0.74-0.90; p 0.001) as indicators for fatalities. In hospitalized patients acutely intoxicated with undifferentiated poisons, EDT as a parameter of left ventricle diastolic function and BNP are useful to early predict mortality., (© 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Acute poisoning with drugs and nonpharmaceutical agents represents an important challenge in the emergency department (ED).The objective is to create and validate a risk-prediction nomogram for use in the ED to predict the risk of in-hospital mortality in adults from acute poisoning with drugs and nonpharmaceutical agents.This was a prospective cohort study involving adults with acute poisoning from drugs and nonpharmaceutical agents admitted to a tertiary referral center for toxicology between January and December 2015 (derivation cohort) and between January and June 2016 (validation cohort). We used a program to generate nomograms based on binary logistic regression predictive models. We included variables that had significant associations with death. Using regression coefficients, we calculated scores for each variable, and estimated the event probability. Model validation was performed using bootstrap to quantify our modeling strategy and using receiver operator characteristic (ROC) analysis. The nomogram was tested on a separate validation cohort using ROC analysis and goodness-of-fit tests.Data from 315 patients aged 18 to 91 years were analyzed (n = 180 in the derivation cohort; n = 135 in the validation cohort). In the final model, the following variables were significantly associated with mortality: age, laboratory test results (lactate, potassium, MB isoenzyme of creatine kinase), electrocardiogram parameters (QTc interval), and echocardiography findings (E wave velocity deceleration time). Sex was also included to use the same model for men and women. The resulting nomogram showed excellent survival/mortality discrimination (area under the curve [AUC] 0.976, 95% confidence interval [CI] 0.954-0.998, P < 0.0001 for the derivation cohort; AUC 0.957, 95% CI 0.892-1, P < 0.0001 for the validation cohort).This nomogram provides more precise, rapid, and simple risk-analysis information for individual patients acutely exposed to drugs and nonpharmaceutical agents, and accurately estimates the probability of in-hospital death, exclusively using the results of objective tests available in the ED.

Aim: To assess the role of butyrylcholinesterase (BuChE) activity as a predictive biomarker in acute cholinesterase inhibitor poisoning in a cohort from a regional tertiary care hospital., Material and Methods: Plasma butyrylcholinesterase activity on admission and at regular intervals during admission and clinical outcomes of cases admitted to the Toxicology Clinic of "Sf. Spiridon" Emergency Hospital Iasi, Romania between 1983 and 2013 were evaluated., Results: A total number of 606 patients were included in the study. The mean BuChE-activity level on admission was 1.54 ml NaOH N/100. A correlation between the amount of ingested organophosphates/carbamates (OPs/CMs) and low cholinesterase activity on admission was found. 66.66% of the patients were admitted to hospital within 8 hours after poisoning. The initial, daily and mean total atropine doses administrated were 9.65 mg, 10.51 mg and 69.39 mg, respectively. 67.16% of the investigated patients received Toxogonin for 6.41 days showing a slow increase in BuChE activity afterwards. The average number of hospital days was 11.22. The study revealed that complications occurred in patients with BuChE-activity levels below 1.4 mL NaOH N/100. A positive correlation between mortality rate (3.8% of patients) and the lowest BuChE-activity level on admission (0.89 mL NaOH N/100) was found., Conclusions: BuChE activity on admission and its level during hospital stay represent an important predictive factor for acute cholinesterase inhibitors poisoning.

The main objective of this study was to investigate whether cardiac troponin (cTn) and N-terminal, protein B-type natriuretic peptide (NT-proBNP) can be useful as indicators for amitriptyline cardiotoxicity which is a known drug having sublethal toxic cardiac effects. At the same time, this study looked at detecting potential histopathological changes specific to irreversible cardiac injuries in a rat model of amitriptyline cardiotoxicity. Male Wistar rats were randomly divided into 2 groups, control (saline) group and amitriptyline group (100 mg/kg body weight intraperitoneally, equivalent for lethal dose at 50%). Blood was collected 30 minutes after the administration. The cTn was measured using 3 different methods (2 methods designed for human use and a sandwich enzyme immunoassay specific for rat cTnT). The brain natriuretic peptide was measured by 2 different methods (1 for human and 1 specific for rats). Electrocardiography showed that the QRS complex (P < .0001) and the QT interval (P = .002) were significantly prolonged for amitriptyline-treated animals. Troponin T and NT-proBNP had significantly increased levels in all the rats but showed positive results only when using rat-specific quantitative measurement. In certain rats, the histopathological examination identified a few small foci of acute myocardial necrosis. In conclusion, elevation of cTnT and NT-proBNP are early indicators of cardiotoxicity, yet the significance of irreversible myocardial damage in amitriptyline cardiotoxicity needs to be further understood.