"Primum, non nocere": The Epidemiology of Toxigenic Clostridioides difficile Strains in the Antibiotic Era-Insights from a Prospective Study at a Regional Infectious Diseases Hospital in Eastern Europe.

Clostridioides difficile infection (CDI), though identified nearly five decades ago, still remains a major challenge, being associated with significant mortality rates. The strains classified as hypervirulent, notably 027/NAP1/BI, have garnered substantial attention from researchers and clinicians due to their direct correlation with the severity of the disease. Our study aims to elucidate the significance of toxigenic Clostridioides difficile (CD) strains in the clinical and therapeutic aspects of managing patients diagnosed with CDI. We conducted a single-center prospective study, including patients with CDI from north-eastern Romania. We subsequently conducted molecular biology testing to ascertain the prevalence of the presumptive 027/NAP1/BI strain within aforementioned geographic region. The patients were systematically compared and assessed both clinically and biologically, employing standardized and comparative methodologies. The study enrolled fifty patients with CDI admitted between January 2020 and June 2020. Among the investigated patients, 43 (86%) exhibited infection with toxigenic CD strains positive for toxin B genes (tcdB), binary toxin genes (cdtA and cdtB), and deletion 117 in regulatory genes (tcdC), while the remaining 7 (14%) tested negative for binary toxin genes (cdtA and cdtB) and deletion 117 in tcdC. The presence of the presumptive 027/NAP1/BI strains was linked to a higher recurrence rate (35.56%, p = 0.025), cardiovascular comorbidities (65.1% vs. 14.2%, p = 0.016), and vancomycin treatment (55.8% vs. 14.3%, p = 0.049). The findings of our investigation revealed an elevated incidence of colitis attributed to presumptive 027/NAP1/BI. Despite the prevalence of the presumptive 027 strain and its associated heightened inflammation among the patients studied, no significant differences were observed regarding the clinical course or mortality outcomes.

The Impact of Urinary Catheterization on the Antibiotic Susceptibility of ESBL-Producing Enterobacterales: A Challenging Duo.

INTRODUCTION: Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations tailored to local susceptibility patterns. RESULTS: We found a high prevalence of ESBL-producing strains (36.9%), with Escherichia coli and Klebsiella spp. being the most prevalent isolated bacteria. Among the catheterized patients, Klebsiella spp. emerged as the primary etiology, with a significant correlation between catheterization and Proteus spp. (p = 0.02) and Providencia stuartii (p < 0.0001). We observed significant correlations between urinary catheterization and older age (68.9 ± 13.7 years vs. 64.2 ± 18.1 years in non-catheterized patients, p = 0.026) and with the presence of an isolate with extensive drug resistance (p < 0.0001) or even pandrug resistance (p < 0.0001). Susceptibility rates significantly decreased for almost all the tested antibiotics during the study period. Notably, susceptibility was markedly lower among catheterized patients, with the most pronounced differences observed for carbapenems (59.6% versus 83.4%, p < 0.0001) and aminoglycosides (37.1% versus 46.9%, p = 0.0001). MATERIALS AND METHODS: We conducted a retrospective study analyzing the susceptibility profiles of 724 extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales isolated from urine cultures. Our focus was on highlighting susceptibility profiles among isolates associated with urinary catheterization and assessing the shifts in the susceptibility rates over time. CONCLUSIONS: The constant rise in AMR rates among Enterobacterales presents significant challenges in treating severe infections, particularly among urinary catheterized patients. This trend leaves clinicians with limited or no effective treatment options. Consequently, the development and implementation of personalized treatment protocols are imperative to ensure efficient empirical therapies.

Harmony in Chaos: Deciphering the Influence of Ischemic Cardiomyopathy and Non-Cardiac Comorbidities on Holter ECG Parameters in Chronic Heart Failure Patients: A Pilot Study.

Background and Objective: In the landscape of heart failure, non-cardiac comorbidities represent a formidable challenge, imparting adverse prognostic implications. Holter ECG monitoring assumes a supplementary role in delineating myocardial susceptibility and autonomic nervous system dynamics. This study aims to explore the potential correlation between Holter ECG parameters and comorbidities in individuals with ischemic cardiomyopathy experiencing heart failure (HF), with a particular focus on the primary utility of these parameters as prognostic indicators. Materials and Methods: In this prospective inquiry, a cohort of 60 individuals diagnosed with heart failure underwent stratification into subgroups based on the presence of comorbidities, including diabetes, chronic kidney disease, obesity, or hyperuricemia. Upon admission, a thorough evaluation of all participants encompassed echocardiography, laboratory panel analysis, and 24 h Holter monitoring. Results: Significant associations were uncovered between diabetes and unconventional physiological indicators, specifically the Triangular index (p = 0.035) and deceleration capacity (p = 0.002). Pertaining to creatinine clearance, notable correlations surfaced with RMSSD (p = 0.026), PNN50 (p = 0.013), and high-frequency power (p = 0.026). An examination of uric acid levels and distinctive Holter ECG patterns unveiled statistical significance, particularly regarding the deceleration capacity (p = 0.045). Nevertheless, in the evaluation of the Body Mass Index, no statistically significant findings emerged concerning Holter ECG parameters. Conclusions: The identified statistical correlations between non-cardiac comorbidities and patterns elucidated in Holter ECG recordings underscore the heightened diagnostic utility of this investigative modality in the comprehensive evaluation of individuals grappling with HF. Furthermore, we underscore the critical importance of the thorough analysis of Holter ECG recordings, particularly with regard to subtle and emerging parameters that may be overlooked or insufficiently acknowledged.

Could Endothelin-1 Be a Promising Neurohormonal Biomarker in Acute Heart Failure?

Acute heart failure (AHF) is a life-threatening condition with high morbidity and mortality. Even though this pathology has been extensively researched, there are still challenges in establishing an accurate and early diagnosis, determining the long- and short-term prognosis and choosing a targeted therapeutic strategy. The use of reliable biomarkers to support clinical judgment has been shown to improve the management of AHF patients. Despite a large pool of interesting candidate biomarkers, endothelin-1 (ET-1) appears to be involved in multiple aspects of AHF pathogenesis that include neurohormonal activation, cardiac remodeling, endothelial dysfunction, inflammation, atherosclerosis and alteration of the renal function. Since its discovery, numerous studies have shown that the level of ET-1 is associated with the severity of symptoms and cardiac dysfunction in this pathology. The purpose of this paper is to review the existing information on ET-1 and answer the question of whether this neurohormone could be a promising biomarker in AHF.

T-Wave Analysis on the 24 h Holter ECG Monitoring as a Predictive Assessment of Major Adverse Cardiovascular Events in Patients with Myocardial Infarction: A Literature Review and Future Perspectives.

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.

Pulmonary Embolism Risk Assessment Using Blood Copeptin Concentration and Pulmonary Arteries Thrombotic Burden Evaluated by Computer Tomography.

(1) Background: Pulmonary embolism (PE) represents the third most important cardiovascular cause of death after myocardial infarction and stroke. The proper management of this condition is dependent on adequate risk stratification, due to the life-threatening complications of more aggressive therapies such as thrombolysis. Copeptin is a surrogate marker of vasopressin which is found increased in several cardiovascular conditions. The Mastora score is an imagistic evaluation of the degree of pulmonary arteries thrombotic burden based on computed tomography angiography. In this study, we aimed to evaluate the diagnostic and prognostic role of copeptin in patients with acute PE. Furthermore, we analyzed the relationship between copeptin and Mastora score and their role in PE risk profiling. (2) Methods: We conducted a single center prospective study that included 112 patients with PE and 53 healthy volunteers. Clinical and paraclinical parameters, together with plasma levels of copeptin and the Mastora score, were evaluated in all patients after admission. (3) Results: Copeptin levels were significantly increased in PE patients compared with the general population (26.05 vs. 9.5 pmol/L, p < 0.001), while receiver operating characteristic (ROC) analysis revealed an AUC of 0.800 (95% CI 0.728−0.873, p < 0.001). Copeptin directly correlated with the Mastora score (r = 0.535, p = 0.011) and both parameters were strong predictors for adverse clinical events and death. Receiver operating characteristic (ROC) analysis for death within 30 days revealed a copeptin cut-off of 38.36 pmol/L, which presented a specificity of 79.6% and a sensitivity of 88.9%, and a Mastora score cut-off of 82 points, which presented a specificity of 74.8% and a sensitivity of 77.8%. (4) Conclusions: Our results showed that copeptin and the Mastora score are both correlated with adverse cardiovascular events and mortality in PE patients, and this may pave the way for their use in clinical practice, helping physicians to select the best therapeutical management.

The Importance of HDL-Cholesterol and Fat-Free Percentage as Protective Markers in Risk Factor Hierarchy for Patients with Metabolic Syndrome.

This research focused on establishing a hierarchy concerning the influence of various biological markers and body composition parameters on preventing, diagnosing and managing Metabolic Syndrome (MetS). Our cross-sectional cohort study included 104 subjects without any atherosclerotic antecedent pathology, organized in two groups (with and without MetS). All participants underwent clinical and anthropometric measurements, DEXA investigation and blood tests for all MetS criteria, together with adiponectin, leptin, insulin, uric acid and CRP. Based on mathematical logic, we calculated a normalized sensitivity score to compare the predictive power of biomarkers and parameters associated with MetS, upon the prevalence of MetS. Patients with MetS report higher levels of uric acid (p = 0.02), CRP (p = 0.012) and lower levels of adiponectin (p = 0.025) than patients without MetS. The top three biological markers with the highest predictive power of the prevalence of the disease are HDL, insulin, and adiponectin:leptin ratio, and the top three body composition parameters are trunk fat-free percentage, waist-height ratio and trunk fat percentage. Their high sensitivity scores differentiate them from all the other markers analysed in the study. Our findings report relevant scores for estimating the importance of cardiometabolic risks in the prevalence of MetS. The high rank of protective markers, HDL and trunk fat-free percentage, suggest that positive effects have a stronger association with the prevalence of MetS, than negative ones do. Therefore, this risk stratification study provides important support for prevention and management programs regarding MetS.

Myocardial Ischemia in Patients with COVID-19 Infection: Between Pathophysiological Mechanisms and Electrocardiographic Findings.

Given the possible pathophysiological links between myocardial ischemia and SARS-CoV-2 infection, several studies have focused attention on acute coronary syndromes in order to improve patients' morbidity and mortality. Understanding the pathophysiological aspects of myocardial ischemia in patients infected with SARS-CoV-2 can open a broad perspective on the proper management for each patient. The electrocardiogram (ECG) remains the easiest assessment of cardiac involvement in COVID-19 patients, due to its non-invasive profile, accessibility, low cost, and lack of radiation. The ECG changes provide insight into the patient's prognosis, indicating either the worsening of an underlying cardiac illnesses or the acute direct injury by the virus. This indicates that the ECG is an important prognostic tool that can affect the outcome of COVID-19 patients, which important to correlate its aspects with the clinical characteristics and patient's medical history. The ECG changes in myocardial ischemia include a broad spectrum in patients with COVID-19 with different cases reported of ST-segment elevation, ST-segment depression, and T wave inversion, which are associated with severe COVID-19 disease.

Cardiopulmonary Exercise Testing and Cardiac Biomarker Measurements in Young Football Players: A Pilot Study.

Constant and intense physical activity causes physiological adaptive changes in the human body, but it can also become a trigger for adverse events, such as sudden cardiac arrest or sudden cardiac death. Our main objective was to assess the use of combined cardiopulmonary exercise testing (CPET) and cardiac biomarker determinants in young professional athletes. We conducted a study which involved the full examination of 19 football players, all male, aged between 18 and 20 years old. They underwent standard clinical and paraclinical evaluation, a 12-lead electrocardiogram (ECG), and transthoracic echocardiography (TTE). Afterwards, a tailored CPET was performed and peripheral venous blood samples were taken before and 3 h after the test in order to determine five biomarker levels at rest and post-effort. The measured biomarkers were cardiac troponin I (cTnI), myoglobin (Myo), the MB isoenzyme of creatine-kinase (CK-MB), the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and D-dimers. While cTnI and NT-proBNP levels were undetectable both at rest and post-effort in all subjects, the variations in Myo, CK-MB and D-dimers showed significant correlations with CPET parameters. This highlights the potential use of combined CPET and biomarker determinants to evaluate professional athletes, and encourages further research on larger study groups.

Beyond the Finish Line: The Impact and Dynamics of Biomarkers in Physical Exercise-A Narrative Review.

The research of biomarkers continues to emerge as a developing academic field which is attracting substantial interest. The study of biomarkers proves to be useful in developing and implementing new screening methods for a wide variety of diseases including in the sports area, whether for leisure activities or professional sports. Novel research has brought into question the immune system and the limitations it may impose on sports practicing. As the well-being of athletes is a priority, the state of their immune function offers valuable information regarding their health status and their ability to continue training. The assessment of various biomarkers may contribute to a more accurate risk stratification and subsequent prevention of some invalidating or even fatal pathologies such as the sudden cardiac death. Therefore, we have reviewed several studies that included sports-related pathology or specific morphofunctional alterations for which some immune biomarkers may represent an expression of the underlying mechanism. These include the defensins, immunoglobulin A (IgA), interleukin-6 (IL-6), the tumoral necrosis factor α (TNF-α), and the white blood cells (WBC) count. Similarly, also of significant interest are various endocrine biomarkers, such as cortisol and testosterone, as well as anabolic or catabolic markers, respectively. Literature data highlight that these values are greatly influenced not only by the duration, but also by the intensity of the physical exercise; moderate training sessions actually enhance the immune function of the body, while a significant increase in both duration and intensity of sports activity acts as a deleterious factor. Therefore, in this paper we aim to highlight the importance of biomarkers' evaluation in connection with sports activities and a subsequent more adequate approach towards personalized training regimens.

Insights into multidrug-resistant K. pneumoniae urinary tract infections: From susceptibility to mortality.

The incidence of urinary tract infections (UTIs) caused by Klebsiella pneumoniae has exhibited an increasing trend and has become a high burden for many public health systems, especially in hospital settings. Multidrug resistance associated with the production of extended-spectrum ß-lactamases (ESBL) among K. pneumoniae isolates is endemic in Southeastern Europe. We retrospectively analyzed 75 cases admitted to 'St. Parascheva' Clinical Hospital of Infectious Diseases in Iasi, Romania, during the first 6 months of 2019 (January 1 to June 30), who had a confirmed diagnosis of K. pneumoniae UTI at discharge. From a total of 75 patients, 34 (45.3%) presented ESBL+ K. pneumoniae. The mean age was 66 years (70.1 for the ESBL+ patients vs. 62.6 for the ESBL- patients, P=0.0365). There was a symmetrical sex distribution (37 men vs. 38 women). Of these, 22 men had ESBL+ K. pneumoniae UTIs, compared to only 15 with an ESBL- strain, P=0.0087. Another risk factor for ESBL+ K. pneumoniae UTIs was the presence of hospitalization in the past 6 months; 20 (58.82%) patients with ESBL+ infections were previously hospitalized, compared to only 5 (12.19%) patients with ESBL- strains, P<0.0001. The urinary catheter carriers presented an increased prevalence of ESBL+ infections (15/34 vs. 5/41, P=0.0012). Regarding mortality, ESBL+ infections caused 6 fatalities, compared to only 1 death in the ESBL- group, P=0.0166. ESBL+ K. pneumoniae strains represent an important cause of healthcare-related UTIs, with a significantly higher mortality rate compared to ESBL- strains. Early identification and adequate management of the risk factors incriminated in ESBL+ UTIs should be a priority for physicians in order to limit the dissemination of the ESBL-producing strains and thus to improve the outcome of these patients.