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In order to obtain new compounds with antitumoural action the N-(metaacylaminobenzoyl)-α-acylaminobenzoyl)-α-aminoacids 4-9 were prepared. Thesecompounds were subsequently converted into the corresponding δ2-oxazolin-5-ones 10-15,which in turn were submitted to a ring opening reaction with di-(β-chloroethyl)amine toafford the peptide supported N-mustards 16-21, which showed low toxicity and cytostaticactivity similar to that of sarcolisine against the Ehrlich ascite and Walker 253carcinosarcoma.

Amiodarone, a bi-iodinated benzofuran derivative, is among the most commonly used antiarrhythmic drugs due to its high level of effectiveness. Though initially categorized as a class III agent, amiodarone exhibits antiarrhythmic properties across all four classes of antiarrhythmic drugs. Amiodarone is highly effective in maintaining sinus rhythm in patients with paroxysmal atrial fibrillation while also playing a crucial role in preventing a range of ventricular arrhythmias. Amiodarone has a complex pharmacokinetic profile, characterized by a large volume of distribution and a long half-life, which can range from several weeks to months, resulting in prolonged effects even after discontinuation. Side effects may include thyroid dysfunction, pulmonary fibrosis, and hepatic injury, necessitating regular follow-ups. Additionally, amiodarone interacts with several drugs, including anticoagulants, which must be managed to prevent adverse effects. Therefore, a deep understanding of both oral and intravenous formulations, as well as proper dosage adjustments, is essential. The aim of this paper is to provide a comprehensive and updated review on amiodarone's indications, contraindications, recommended dosages, drug interactions, side effects, and monitoring protocols.

Despite being one of the most debilitating conditions encountered in the field of toxicology, there is a lack of neutralization measures for the toxins involved in acute corrosive poisoning, and this promotes progressive contact injury of deep tissues after poisoning has occurred. Multiple controversies still surround management strategies during the acute phase of poisoning and the long-term follow-up of the patient. Here, we report a severe case of intentional poisoning with nitric acid complicated by extensive injury of the upper digestive tract, multiple stricture formation, and complete dysphagia. Serial endoscopic dilation and insertion of a jejunostomy feeding tube were necessary, and underlying psychiatric illness negatively affected the outcome of the patient. We conclude that an interdisciplinary approach is necessary to properly reduce the extent of lesions and sequelae induced by corrosion. Early endoscopic mapping of injuries is of major importance to better predict the evolution and possible complications of poisoning. Interventional and reconstructive surgical procedures may significantly improve the life expectancy and quality of life of patients following intoxication with corrosive substances.

Myocardial ischemia is a pathophysiological state characterized by inadequate perfusion of the myocardium, resulting in an imbalance between myocardial oxygen demand and supply. It is most commonly caused by coronary artery disease, in which atherosclerotic plaques lead to luminal narrowing and reduced blood flow to the heart. Myocardial ischemia can manifest as angina pectoris or silent myocardial ischemia and can progress to myocardial infarction or heart failure if left untreated. Diagnosis of myocardial ischemia typically involves a combination of clinical evaluation, electrocardiography and imaging studies. Electrocardiographic parameters, as assessed by 24 h Holter ECG monitoring, can predict the occurrence of major adverse cardiovascular events in patients with myocardial ischemia, independent of other risk factors. The T-waves in patients with myocardial ischemia have prognostic value for predicting major adverse cardiovascular events, and their electrophysiological heterogeneity can be visualized using various techniques. Combining the electrocardiographic findings with the assessment of myocardial substrate may offer a better picture of the factors that can contribute to cardiovascular death.

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.

Hyponatremia is commonly encountered in the setting of heart failure, especially in decompensated, fluid-overloaded patients. The pathophysiology of hyponatremia in patients with heart failure is complex, including numerous mechanisms: increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system, high levels of arginine vasopressin and diuretic use. Symptoms are usually mild but hyponatremic encephalopathy can occur if there is an acute decrease in serum sodium levels. It is crucial to differentiate between dilutional hyponatremia, where free water excretion should be promoted, and depletional hyponatremia, where administration of saline is needed. An inappropriate correction of hyponatremia may lead to osmotic demyelination syndrome which can cause severe neurological symptoms. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. The aim of this review is to summarize the principal mechanisms involved in the occurrence of hyponatremia, to present the main guidelines for the treatment of hyponatremia, and to collect and analyze data from studies which target new treatment options, such as vaptans.

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.

Electrocardiogram (ECG) still remains a very useful diagnostic method in modern cardiology. Its broad availability, noninvasiveness and good sensitivity explain why it plays a capital role in the very beginning of the process of diagnosis for every patient, with or without cardiac-related complaints. For the practitioner, good training in ECG interpretation is mandatory. Sometimes, the ECG trace reveals particular aspects that may cause confusion and complicate decision-making. In this article, we present several less common situations underlying the general context and ECG features. The syndromes studied have a high pathological significance and may range from acute emergencies that call for a rapid therapeutical response to chronic syndromes that require prolonged observation, monitoring and risk stratification.

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.

Acute coronary syndrome (ACS) is a spectrum of clinical and paraclinical disorders arising from an imbalance of oxygen demand and supply to the myocardium. The most common cause is atherosclerosis; however, other rare causes such as carbon monoxide (CO) poisoning should be considered. Through tissue hypoxia and direct cell injury, CO poisoning can lead to a broad spectrum of cardiac disorders, especially ACS. Materials and Methods. We have conducted a retrospective study in the Toxicology Department of Saint Spiridon Emergency University Hospital, including all patients admitted through the emergency department with CO poisoning. We divided the cohort into event group (myocardial injury) and non-event group (patients without myocardial injury) and performed a subset analysis of the former. Results. A total of 65 patients were included, 22 in the event and 43 in the non-event group. The severity of poisoning did not correlate with myocardial injury; however, 50% of the event group had severe poisoning with carboxyhaemoglobin ≥ 20%. Cardiac enzyme markers (troponin and creatin-kinase MB) had a statistically significant increase in the event group compared to the non-event group (p < 0.05). Most of the patients in the STEMI (50%) and NSTEMI (66.7%) groups had severe CO intoxication. The STEMI group had a mean age of 27.7 years old and no comorbidities. Conclusions. Myocardial injury can develop in CO poisoning irrespective of the severity of poisoning, and it can be transient, reversible, or permanent. Our study introduces new information on adverse cardiac events in patients with CO poisoning, focusing on the ACS. We found that the severity of CO poisoning plays an important role in developing myocardial injury, as 50% of patients in the event group were severely intoxicated. While in-hospital mortality in our study was low, further prospective studies should investigate the long-term mortality in these patients.

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.

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

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.