Coffee and Microbiota: A Narrative Review.

Coffee is one of the most widely consumed beverages in the world, which has important repercussions on the health of the individual, mainly because of certain compounds it contains. Coffee consumption exerts significant influences on the entire body, including the gastrointestinal tract, where a central role is played by the gut microbiota. Dysbiosis in the gut microbiota is implicated in the occurrence of numerous diseases, and knowledge of the microbiota has proven to be of fundamental importance for the development of new therapeutic strategies. In this narrative review, we thoroughly investigated the link between coffee consumption and its effects on the gut microbiota and the ensuing consequences on human health. We have selected the most significant articles published on this very interesting link, with the aim of elucidating the latest evidence about the relationship between coffee consumption, its repercussions on the composition of the gut microbiota, and human health. Based on the various studies carried out in both humans and animal models, it has emerged that coffee consumption is associated with changes in the gut microbiota, although further research is needed to understand more about this link and the repercussions for the whole organism.

Ursodeoxycholic acid does not affect the clinical outcome of SARS-CoV-2 infection: A retrospective study of propensity score-matched cohorts.

BACKGROUND: Ursodeoxycholic acid (UDCA) has been recently proposed as a modulator of angiotensin-converting enzyme 2 (ACE2) receptor expression, with potential effects on COVID-19. AIM AND STUDY DESIGN: We retrospectively evaluated the clinical course and outcome of subjects taking UDCA admitted to the hospital for COVID-19 compared with matched infected subjects. Differences regarding the severity and outcome of the disease between treated and non-treated subjects were assessed. The Kaplan-Meier survival analysis and log-rank test were used to evaluate the effect of UDCA on all-cause intra-hospital mortality. RESULTS: Among 6444 subjects with confirmed COVID-19 admitted to the emergency department (ED) from 1 March 2020 to 31 December 2022, 109 subjects were taking UDCA. After matching 629 subjects were included in the study: 521 in the no UDCA group and 108 in the UDCA group. In our matched cohort, 144 subjects (22.9%) died, 118 (22.6%) in the no-UDCA group and 26 (24.1%) in the UDCA group. The Kaplan-Meier analysis showed no significant difference in survival between groups. In univariate regression analysis, the presence of pneumonia, National Early Warning Score (NEWS) score, and Charlson Comorbidity Index (CCI) were significant independent predictors of death. At multivariate Cox regression analysis, age, NEWS, pneumonia and CCI index were confirmed significant independent predictors of death. UDCA treatment was not a predictor of survival both in univariate and multivariate regressions. CONCLUSIONS: UDCA treatment does not appear to have significant effects on the outcome of COVID-19. Specially designed prospective studies are needed to evaluate efficacy in preventing infection and severe disease.

PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications.

Sepsis is a serious organ dysfunction caused by a dysregulated immune host reaction to a pathogen. The innate immunity is programmed to react immediately to conserved molecules, released by the pathogens (PAMPs), and the host (DAMPs). We aimed to review the molecular mechanisms of the early phases of sepsis, focusing on PAMPs, DAMPs, and their related pathways, to identify potential biomarkers. We included studies published in English and searched on PubMed® and Cochrane®. After a detailed discussion on the actual knowledge of PAMPs/DAMPs, we analyzed their role in the different organs affected by sepsis, trying to elucidate the molecular basis of some of the most-used prognostic scores for sepsis. Furthermore, we described a chronological trend for the release of PAMPs/DAMPs that may be useful to identify different subsets of septic patients, who may benefit from targeted therapies. These findings are preliminary since these pathways seem to be strongly influenced by the peculiar characteristics of different pathogens and host features. Due to these reasons, while initial findings are promising, additional studies are necessary to clarify the potential involvement of these molecular patterns in the natural evolution of sepsis and to facilitate their transition into the clinical setting.

Cervical spine injury: clinical and medico-legal overview.

Spinal trauma is an important cause of disability worldwide. Injury to the cervical spine (CS) occurs frequently after major trauma. 5-10% of patients with blunt trauma have a cervical spine injury. The cervical spine accounts for ~ 50% of all spinal injuries. Determination of CS stability is a common challenge in the acute care setting of patients with trauma. Several issues, indeed, are of particular concern: who needs CS imaging; what imaging should be obtained; when should computed tomography (CT), magnetic resonance imaging (MRI), or flexion/extension (F/E) radiographs be obtained; and how is significant ligamentous injury excluded in the comatose patient. CT and MRI both have roles to play. This article aims to present the different imaging to frame techniques to be used with greater precision in the acute event also for the purpose of planning the next therapeutic process. An overview of the applicability of the same methods in forensic pathology is also provided highlighting possible future biomarker to ease in diagnosis of acute TBI.

Severe Trauma-Induced Coagulopathy: Molecular Mechanisms Underlying Critical Illness.

Trauma remains one of the leading causes of death in adults despite the implementation of preventive measures and innovations in trauma systems. The etiology of coagulopathy in trauma patients is multifactorial and related to the kind of injury and nature of resuscitation. Trauma-induced coagulopathy (TIC) is a biochemical response involving dysregulated coagulation, altered fibrinolysis, systemic endothelial dysfunction, platelet dysfunction, and inflammatory responses due to trauma. The aim of this review is to report the pathophysiology, early diagnosis and treatment of TIC. A literature search was performed using different databases to identify relevant studies in indexed scientific journals. We reviewed the main pathophysiological mechanisms involved in the early development of TIC. Diagnostic methods have also been reported which allow early targeted therapy with pharmaceutical hemostatic agents such as TEG-based goal-directed resuscitation and fibrinolysis management. TIC is a result of a complex interaction between different pathophysiological processes. New evidence in the field of trauma immunology can, in part, help explain the intricacy of the processes that occur after trauma. However, although our knowledge of TIC has grown, improving outcomes for trauma patients, many questions still need to be answered by ongoing studies.

The Interplay between Helicobacter pylori and Gut Microbiota in Non-Gastrointestinal Disorders: A Special Focus on Atherosclerosis.

The discovery of Helicobacter pylori (H. pylori) in the early 1980s by Nobel Prize winners in medicine Robin Warren and Barry Marshall led to a revolution in physiopathology and consequently in the treatment of peptic ulcer disease. Subsequently, H. pylori has also been linked to non-gastrointestinal diseases, such as autoimmune thrombocytopenia, acne rosacea, and Raynaud's syndrome. In addition, several studies have shown an association with cardiovascular disease and atherosclerosis. Our narrative review aims to investigate the connection between H. pylori infection, gut microbiota, and extra-gastric diseases, with a particular emphasis on atherosclerosis. We conducted an extensive search on PubMed, Google Scholar, and Scopus, using the keywords "H. pylori", "dysbiosis", "microbiota", "atherosclerosis", "cardiovascular disease" in the last ten years. Atherosclerosis is a complex condition in which the arteries thicken or harden due to plaque deposits in the inner lining of an artery and is associated with several cardiovascular diseases. Recent research has highlighted the role of the microbiota in the pathogenesis of this group of diseases. H. pylori is able to both directly influence the onset of atherosclerosis and negatively modulate the microbiota. H. pylori is an important factor in promoting atherosclerosis. Progress is being made in understanding the underlying mechanisms, which could open the way to interesting new therapeutic perspectives.

Are Short-Stay Units Safe and Effective in the Treatment of Non-Variceal Upper Gastrointestinal Bleeding?

Introduction: Emergency Department (ED) overcrowding is a health, political, and economic problem of concern worldwide. The causes of overcrowding are an aging population, an increase in chronic diseases, a lack of access to primary care, and a lack of resources in communities. Overcrowding has been associated with an increased risk of mortality. The establishment of a Short Stay Unit (SSU) for conditions that cannot be treated at home but require treatment and hospitalization for up to 72 h may be a solution. SSU can significantly reduce hospital length of stay (LOS) for certain conditions but does not appear to be useful for other diseases. Currently, there are no studies addressing the efficacy of SSU in the treatment of non-variceal upper gastrointestinal bleeding (NVUGIB). Our study aims to evaluate the efficacy of SSU in reducing the need for hospitalization, LOS, hospital readmission, and mortality in patients with NVUGIB compared with admission to the regular ward. Materials and Methods: This was a retrospective, single-center observational study. Medical records of patients presenting with NVUGIB to ED between 1 April 2021, and 30 September 2022, were analyzed. We included patients aged >18 years who presented to ED with acute upper gastrointestinal tract blood loss. The test population was divided into two groups: Patients admitted to a normal inpatient ward (control) and patients treated at SSU (intervention). Clinical and medical history data were collected for both groups. The hospital LOS was the primary outcome. Secondary outcomes were time to endoscopy, number of blood units transfused, readmission to the hospital at 30 days, and in-hospital mortality. Results: The analysis included 120 patients with a mean age of 70 years, 54% of whom were men. Sixty patients were admitted to SSU. Patients admitted to the medical ward had a higher mean age. The Glasgow-Blatchford score, used to assess bleeding risk, mortality, and hospital readmission were similar in the study groups. Multivariate analysis after adjustment for confounders found that the only factor independently associated with shorter LOS was admission to SSU (p < 0.0001). Admission to SSU was also independently and significantly associated with a shorter time to endoscopy (p < 0.001). The only other factor associated with a shorter time to EGDS was creatinine level (p = 0.05), while home treatment with PPI was associated with a longer time to endoscopy. LOS, time to endoscopy, number of patients requiring transfusion, and number of units of blood transfused were significantly lower in patients admitted to SSU than in the control group. Conclusions: The results of the study show that treatment of NVUGIB in SSU can significantly reduce the time required for endoscopy, the hospital LOS, and the number of transfused blood units without increasing mortality and hospital readmission. Treatment of NVUGIB at SSU may therefore help to reduce ED overcrowding but multicenter randomized controlled trials are needed to confirm these data.

Five Level Triage vs. Four Level Triage in a Quaternary Emergency Department: National Analysis on Waiting Time, Validity, and Crowding-The CREONTE (Crowding and RE-Organization National TriagE) Study Group.

Background and Objectives: Triage systems help provide the right care at the right time for patients presenting to emergency departments (EDs). Triage systems are generally used to subdivide patients into three to five categories according to the system used, and their performance must be carefully monitored to ensure the best care for patients. Materials and Methods: We examined ED accesses in the context of 4-level (4LT) and 5-level triage systems (5LT), implemented from 1 January 2014 to 31 December 2020. This study assessed the effects of a 5LT on wait times and under-triage (UT) and over-triage (OT). We also examined how 5LT and 4LT systems reflected actual patient acuity by correlating triage codes with severity codes at discharge. Other outcomes included the impact of crowding indices and 5LT system function during the COVID-19 pandemic in the study populations. Results: We evaluated 423,257 ED presentations. Visits to the ED by more fragile and seriously ill individuals increased, with a progressive increase in crowding. The length of stay (LOS), exit block, boarding, and processing times increased, reflecting a net raise in throughput and output factors, with a consequent lengthening of wait times. The decreased UT trend was observed after implementing the 5LT system. Conversely, a slight rise in OT was reported, although this did not affect the medium-high-intensity care area. Conclusions: Introducing a 5LT improved ED performance and patient care.

Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers.

Our digestive system, particularly our intestines, harbors a vast amount of microorganisms, whose genetic makeup is referred to as the microbiome. Clostridium difficile is a spore-forming Gram-positive bacterium, which can cause an infection whose symptoms range from asymptomatic colonization to fearsome complications such as the onset of toxic megacolon. The relationship between gut microbiota and Clostridium difficile infection has been studied from different perspectives. One of the proposed strategies is to be able to specifically identify which types of microbiota alterations are most at risk for the onset of CDI. In this article, we understood once again how crucial the role of the human microbiota is in health and especially how crucial it becomes, in the case of its alteration, for the individual's disease. Clostridium difficile infection is an emblematic example of how a normal and physiological composition of the human microbiome can play a very important role in immune defense against such a fearsome disease.

Gastrointestinal Involvement in Extra-Digestive Disease: Which Is the Role of Fecal Calprotectin?

Fecal calprotectin (FC) is a very sensitive marker of inflammation of the gastrointestinal tract. Its clinical utility can be appreciated in both intestinal and extraintestinal diseases. Recent evidence suggests a link between intestinal inflammation and dermatological, rheumatic and neurological diseases. This review focuses on the role of FC in non-gastrointestinal disease, such as rheumatic, dermatologic, neurologic and last but not least SARS-CoV-2 infection.

Energy drinks: a narrative review of their physiological and pathological effects.

The consumption of energy drinks (Edks) has increased significantly in past years, with a growing market that is estimated to reach $61 billion by 2021 worldwide. Several studies demonstrated the physiological and pathological effects of these substances contained in Edks. The most common ingredient contained in Edks is caffeine, which is commonly mixed with taurine, and B-group vitamins. Scientific evidence of potentially serious adverse health effects are known, but it would be better to acquire more information regarding these beverages. We systematically checked Medical literature on MEDLINE-Pubmed from inception to January 2020 to find studies and reports on Edks and adverse events. Edks consumption is specially related to cardiovascular effects as malignant arrhythmias. We found a significant focus on arrhythmogenic risk in patients affected by long QT syndrome or other predisposing conditions for QT elongation. Other pathological effects are known as gastrointestinal, vascular and neurological disorders. Edks, as well as all caffeinated beverages, should be taken with caution or avoided in select populations, such as patients suffering from cardiovascular or neurological illnesses; their use can unmask a sleepy life-threatening disease.

Interaction between Lipopolysaccharide and Gut Microbiota in Inflammatory Bowel Diseases.

Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.

Microbiota and Probiotics: The Role of Limosilactobacillus Reuteri in Diverticulitis.

The microbiota is the set of commensal microorganisms, residing in the organism, helping proper functioning of organs and systems. The role that the microbiota plays in maintaining the health of vertebrates is widely accepted, particularly in the gastrointestinal system, where it is fundamental for immunity, development, and conversion of nutrients. Dysbiosis is an alteration of the microbiota which refers to a disturbed balance, which can cause a number of pathologies. Probiotics have proven to be effective in modulating the microbiota of the gastrointestinal system and, therefore, in promoting the health of the individual. In particular, Lactobacilli are a group of Gram-positive bacteria, which are able to produce lactic acid through glucose metabolism. They are present in different microenvironments, ranging from the vagina, to the mouth, to different tracts of the small intestine. In the present review, we will discuss the use of Limosilactobacillus in human health in general and more specifically in diverticulitis. In particular we analyze the role of Limosilactobacillus reuteri and its anti-inflammatory action. For this review, articles were identified using the electronic PubMed database through a comprehensive search, conducted by combining key terms such as "diverticulitis", "Limosilactobacillus reuteri", "human health and disease", "probiotics". We selected all the articles published in the last 10 years and screened 1017 papers. Articles referenced in the screened papers were evaluated if considered interesting for our topic. Probiotics have proven to be effective in modulating the microbiota of the gastrointestinal system and, therefore, in promoting the health of the individual. The importance of probiotics in treating diverticular disease and acute diverticulitis can be further understood if taking into consideration some pathophysiological aspects, associated to the microbiota. L. reuteri plays an important role in human health and disease. The effectiveness of L. reuteri in stimulating a correct bowl motility partly explains its effectiveness in treating diverticulitis. The most important action of L. reuteri is probably its immunomodulating activity. Levels of IL-6, IL-8, and Tumor necrosis factor (TNF-alpha) are reduced after supplementation with different strands of Lactobacilli, while T-regulatory cells increase in number and activity. Anyway, new mechanisms of action of probiotics come to light from the many investigations currently taking place in numerous centres around the world and to improve how exactly probiotic administration could make the difference in the management of diverticular disease and acute diverticulitis.

Factors Associated with ICU Admission in Patients with COVID-19: The GOL2DS Score.

Background and Objectives: The COVID-19 pandemic has been shaking lives around the world for nearly two years. The discovery of highly effective vaccines has not been able to stop the transmission of the virus. SARS-CoV-2 shows completely different clinical manifestations. A large percentage (about 40%) of admitted patients require treatment in an intensive care unit (ICU). This study investigates the factors associated with admission of COVID-19 patients to the ICU and whether it is possible to obtain a score that can help the emergency physician to select the hospital ward. Materials and Methods: We retrospectively recorded 313 consecutive patients who were presented to the emergency department (ED) of our hospital and had a diagnosis of COVID-19 confirmed by polymerase chain reaction (PCR) on an oropharyngeal swab. We used multiple logistic regression to evaluate demographic, clinical, and laboratory data statistically associated with ICU admission. These variables were used to create a prognostic score for ICU admission. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver-operating characteristic curve (ROC) of the score for predicting ICU admission during hospitalization were calculated. Results: Of the variables evaluated, only blood type A (p = 0.003), PaO2/FiO2 (p = 0.002), LDH (p = 0.004), lactate (p = 0.03), dyspnea (p = 0.03) and SpO2 (p = 0.0228) were significantly associated with ICU admission after adjusting for sex, age and comorbidity using multiple logistic regression analysis. We used these variables to create a prognostic score called GOL2DS (group A, PaO2/FiO2, LDH, lactate and dyspnea, and SpO2), which had high accuracy in predicting ICU admission (AUROC 0.830 [95% CI, 0.791-0.892). Conclusions: In our single-center experience, the GOL2DS score could be useful in identifying patients at high risk for ICU admission.

Proadrenomedullin in Sepsis and Septic Shock: A Role in the Emergency Department.

Sepsis and septic shock represent a leading cause of mortality in the Emergency Department (ED) and in the Intensive Care Unit (ICU). For these life-threating conditions, different diagnostic and prognostic biomarkers have been studied. Proadrenomedullin (MR-proADM) is a biomarker that can predict organ damage and the risk of imminent death in patients with septic shock, as shown by a large amount of data in the literature. The aim of our narrative review is to evaluate the role of MR-proADM in the context of Emergency Medicine and to summarize the current knowledge of MR-proADM as a serum indicator that is useful in the Emergency Department (ED) to determine an early diagnosis and to predict the long-term mortality of patients with sepsis and septic shock. We performed an electronic literature review to investigate the role of MR-proADM in sepsis and septic shock in the context of ED. We searched papers on PubMed®, Cochrane®, UptoDate®, and Web of Science® that had been published in the last 10 years. Data extracted from this literature review are not conclusive, but they show that MR-proADM may be helpful as a prognostic biomarker to stratify the mortality risk in cases of sepsis and septic shock with different degrees of organ damage, guiding emergency physicians in the diagnosis and the succeeding therapeutic workup. Sepsis and septic shock are conditions of high complexity and have a high risk of mortality. In the ED, early diagnosis is crucial in order to provide an early treatment and to improve patient survival. Diagnosis and prognosis are often the result of a combination of several tests. In our opinion, testing for MR-proADM directly in the ED could contribute to improving the prognostic assessment of patients, facilitating the subsequent clinical management and intensive treatment by the emergency physicians, but more studies are needed to confirm these results.

Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review.

The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria changed in 2016, replaced by the new criteria of SEPSIS-3 based on organ failure evaluation, early identification and consequent early appropriated therapy remain the primary goal of sepsis treatment. Unfortunately, currently there is a lack of a foolproof system for making early sepsis diagnosis because conventional diagnostic tools like cultures take a long time and are often burdened with false negatives, while molecular techniques require specific equipment and have high costs. In this context, biomarkers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT), are very useful tools to distinguish between normal and pathological conditions, graduate the disease severity, guide treatment, monitor therapeutic responses and predict prognosis. Among the new emerging biomarkers of sepsis, Presepsin (P-SEP) appears to be the most promising. Several studies have shown that P-SEP plasma levels increase during bacterial sepsis and decline in response to appropriate therapy, with sensitivity and specificity values comparable to those of PCT. In neonatal sepsis, P-SEP compared to PCT has been shown to be more effective in diagnosing and guiding therapy. Since in sepsis the P-SEP plasma levels increase before those of PCT and since the current methods available allow measurement of P-SEP plasma levels within 17 min, P-SEP appears a sepsis biomarker particularly suited to the emergency department and critical care.

Probiotic Bacterial Application in Pediatric Critical Illness as Coadjuvants of Therapy.

The use of probiotics in critically ill adult and children patients has been growing exponentially over the last 20 years. Numerous factors in pediatriac intensive care unit (PICU) patients may contribute to intestinal dysbiosis, which subsequently promotes the pathobiota's growth. Currently, lactobacillus and bifidobacterium species are mainly used to prevent the development of systemic diseases due to the subverted microbiome, followed by streptococcus, enterococcus, propionibacterium, bacillus and Escherichia coli, Lactobacillus rhamnosus GG, and Lactobacillus reuteri DSM 17938. The aim of this article is to review the scientific literature for further confirmation of the importance of the usage of probiotics in intensive care unit (ICU) patients, especially in the pediatric population. A progressive increase in nosocomial infections, especially nosocomial bloodstream infections, has been observed over the last 30 years. The World Health Organization (WHO) reported that the incidence of nosocomial infections in PICUs was still high and ranged between 5% and 10%. Petrof et al. was one of the first to demonstrate the efficacy of probiotics for preventing systemic diseases in ICU patients. Recently, however, the use of probiotics with different lactobacillus spp. has been shown to cause a decrease of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines. In addition, in some studies, the use of probiotics, in particular the mix of Lactobacillus and Bifidobacterium reduces the incidence of ventilator-associated pneumonia (VAP) in PICU patients requiring mechanical ventilation. In abdominal infections, there is no doubt at all about the usefulness of using Lactobacillus spp probiotics, which help to treat ICU-acquired diarrhoea episodes as well as in positive blood culture for candida spp. Despite the importance of using probiotics being supported by various studies, their use is not yet part of the standard protocols to which all doctors must adhere. In the meantime, while waiting for protocols to be drawn up as soon as possible for use in PICUs, routine use could certainly stimulate the intestine's immune defences. Though it is still too early to say, they could be considered the drugs of the future.

Intestinal Fibrogenesis in Inflammatory Bowel Diseases: Exploring the Potential Role of Gut Microbiota Metabolites as Modulators.

Fibrosis, sustained by the transformation of intestinal epithelial cells into fibroblasts (epithelial-to-mesenchymal transition, EMT), has been extensively studied in recent decades, with the molecular basis well-documented in various diseases, including inflammatory bowel diseases (IBDs). However, the factors influencing these pathways remain unclear. In recent years, the role of the gut microbiota in health and disease has garnered significant attention. Evidence suggests that an imbalanced or dysregulated microbiota, along with environmental and genetic factors, may contribute to the development of IBDs. Notably, microbes produce various metabolites that interact with host receptors and associated signaling pathways, influencing physiological and pathological changes. This review aims to present recent evidence highlighting the emerging role of the most studied metabolites as potential modulators of molecular pathways implicated in intestinal fibrosis and EMT in IBDs. These studies provide a deeper understanding of intestinal inflammation and fibrosis, elucidating the molecular basis of the microbiota role in IBDs, paving the way for future treatments.

Multi-Marker Approach in Patients with Acute Chest Pain in the Emergency Department.

BACKGROUND: Chest pain is a prevalent reason for emergency room referrals and presents diagnostic challenges. The physician must carefully differentiate between cardiac and noncardiac causes, including various vascular and extracardiovascular conditions. However, it is crucial not to overlook serious conditions such as acute coronary syndrome (ACS). Diagnosis of acute myocardial infarction (AMI) and early discharge management become difficult when traditional clinical criteria, ECG, and troponin values are insufficient. Recently, the focus has shifted to a "multi-marker" approach to improve diagnostic accuracy and prognosis in patients with chest pain. METHODS: This observational, prospective, single-center study involved, with informed consent, 360 patients presenting to the emergency department with typical chest pain and included a control group of 120 healthy subjects. In addition to routine examinations, including tests for hsTnI (Siemens TNIH kit), according to the 0-1 h algorithm, biochemical markers sST2 (tumorigenicity suppression-2) and suPAR (soluble urokinase plasminogen activator receptor) were also evaluated for each patient. A 12-month follow-up was conducted to monitor outcomes and adverse events. RESULTS: We identified two groups of patients: a positive one (112 patients) with high levels of hsTnI, sST2 > 24.19 ng/mL, and suPAR > 2.9 ng/mL, diagnosed with ACS; and a negative one (136 patients) with low levels of hsTnI, suPAR < 2.9 ng/mL, and sST2 < 24.19 ng/mL. During the 12-month follow-up, no adverse events were observed in the negative group. In the intermediate group, patients with hsTnI between 6 ng/L and the ischemic limit, sST2 > 29.1 ng/mL and suPAR > 2.9 ng/mL, showed the highest probability of adverse events during follow-up, while those with sST2 < 24.19 ng/mL and suPAR < 2.9 ng/mL had a better outcome with no adverse events at 12 months. CONCLUSION: Our data suggest that sST2 and suPAR, together with hsTnI, may be useful in the prognosis of cardiovascular patients with ACS, providing additional information on endothelial damage. These biomarkers could guide the clinical decision on further diagnostic investigations. In addition, suPAR and sST2 emerge as promising for event prediction in patients with chest pain. Their integration into the standard approach in PS could facilitate more efficient patient management, allowing safe release or timely admission based on individual risk.