[This corrects the article DOI: 10.1055/s-0045-1808060.].

Objectives:To characterize the prevalence and clinical profile of neurological dysfunction and pure sepsis-associated encephalopathy (SAE) in adults presenting to the emergency department (ED) with sepsis, and to identify early clinical, laboratory, and brain imaging parameters associated with these phenotypes. Materials:This retrospective study included 226 adults with sepsis (Sepsis-3 criteria) at a tertiary emergency hospital. Neurological dysfunction was defined as an acute mental status change, and pure SAE was diagnosed after systematic exclusion of other identifiable causes of encephalopathy. Demographic, clinical, laboratory, and brain computed tomography (CT) data were collected from medical records. Methods:Group comparisons were made using Mann-Whitney U, chi-square, or Fisher's exact tests. Multivariable binary logistic regression identified predictors of neurological dysfunction and pure SAE. Results:Neurological dysfunction was present in 79.6% of patients, and pure SAE in 24.8%. In the multivariate model, red cell distribution width (RDW) independently predicted pure SAE (OR 1.20, 95% CI 1.05-1.36; p = 0.005), while creatinine was inversely associated (OR 0.77, 95% CI 0.60-0.99; p = 0.038), consistent with the exclusion of patients with metabolic causes of encephalopathy from the pure SAE category. Frontal cortical atrophy on brain CT was the only imaging parameter linked to pure SAE (p = 0.022). Neurological dysfunction and pure SAE were associated with lower survival at discharge (26% vs. 67.3% and 19.6% vs. 39.4%, respectively). Conclusions:Neurological dysfunction is common in ED sepsis patients. RDW and frontal cortical atrophy may help identify pure SAE early. These markers could aid rapid risk stratification and management.

Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction that occurs in patients with sepsis in the absence of direct central nervous system infection or other causes of encephalopathy. SAE is common, occurring in up to 70% of patients with sepsis, and is linked to various clinical manifestations and significantly poorer outcomes. The diagnosis of SAE usually relies on clinical examination, which is often difficult due to confounding factors in critically ill patients. Other diagnostic tools used include electroencephalography, neuroimaging, and biomarkers. We performed a systematic search and review to synthesize all available evidence on biomarkers used for SAE diagnosis in clinical practice and highlight future directions for research. The literature search in MEDLINE identified 18 eligible studies. Biomarkers reflecting inflammation, endothelial activation and damage, astrocytic and microglial activation, neuronal injury, and metabolism changes were described, demonstrating their usefulness and potential in diagnosing and evaluating SAE. However, among different studies, the reported sensitivity and specificity of the biomarkers for diagnosing SAE varied based on the populations studied and the cutoff levels considered for each biomarker. In conclusion, biomarkers may be useful for diagnosing and predicting outcomes in SAE, but their usefulness in clinical practice remains limited for the moment. More research is needed to identify biomarkers that can improve SAE diagnosis.

Background: Fibrinolytic impairment is one of the key factors involved in the pathogenesis of hemostasis disturbances in sepsis, significantly contributing to microthrombosis, organ dysfunction, and mortality rates. While hemostatic assessment in sepsis typically focuses on coagulation activation, evaluating fibrinolytic activity remains challenging due to methodological limitations and a lack of standardization of the currently available methods. Objectives: This comprehensive review examines current methods for assessing fibrinolytic activity in bacterial sepsis, their clinical applications, strengths and limitations, and future perspectives for improved diagnostic approaches. Methods: We conducted a systematic literature search and identified 52 studies that investigated fibrinolysis assessment in adult patients with bacterial sepsis using biomarkers or global tests. Studies included mainly observational cohorts examining various fibrinolytic assessment methods. Results: Fibrinolytic shutdown, primarily mediated by the overproduction of plasminogen activator inhibitor-1 (PAI-1), occurs early in sepsis and correlates with disease severity and mortality. Current assessment methods include plasma biomarker measurements (PAI-1, plasmin-antiplasmin complexes, D-dimer), global plasma-based tests (clot lysis time, plasmin generation assays), and whole-blood viscoelastic testing (rotational thromboelastometry, ROTEM; thromboelastography, TEG). Modified viscoelastic tests incorporating tissue plasminogen activators demonstrate enhanced sensitivity for detecting fibrinolytic resistance. Despite efforts, standardization is still limited, and routine clinical implementation has not been achieved yet. Conclusions: Fibrinolytic assessment provides important prognostic information in sepsis, despite methodological challenges. The integration of point-of-care viscoelastic testing with modified protocols shows promise for real-time evaluation. Future research should focus on developing standardized, automated assays suitable for routine clinical practice, enabling personalized therapeutic interventions that target fibrinolytic dysfunction in sepsis.

BACKGROUND:Peripheral artery disease (PAD) refers to the extracardiac localization of atherosclerotic disease, generally in arteries that vascularize the lower limbs. More than 50% of patients with PAD also have coronary artery disease (CAD). There are concerns about possible differences in mortality rates among hospitalized patients and the need for immediate revascularization during hospital stay across different types of acute coronary syndrome (ACS) when PAD is present. METHODS:This was a retrospective study that included 100 patients admitted with ACS between October 2019 and May 2022. Participants were divided into two groups: those with ACS and PAD (n=32) and those without PAD (n=68). We used the SYNTAX score to evaluate the severity of coronary artery disease, the amount of contrast and dose area product (DAP) dosage per patient during the procedure and how these factors vary. RESULTS:There was a 6.8 higher average SYNTAX score among patients with ACS and PAD (p=0.034), which could negatively affect their prognosis. In addition, there was a 12.7-point increase in the SYNTAX score for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) and PAD (p=0.008). Patients with ACS and concomitant PAD were more likely to require complete revascularization of the left main disease. CONCLUSION:Patients with PAD and concomitant ACS have more severe CAD, with more frequent involvement of the left main artery than those without PAD.

Background: Peripheral artery disease is a condition that causes narrowing of the arteries, impairing circulation to the extremities. Globally, it affects millions of people and is more prevalent in older adults and those with diabetes, high blood pressure, or high cholesterol. There is an overlap specific to polyvascular patients, and almost 50% of patients with PAD have coronary artery disease. Compelling evidence reveals a noteworthy association between PAD and major adverse cardiovascular events (MACEs) in individuals experiencing acute coronary syndrome (ACS) but limited knowledge exists regarding the influence of PAD on left ventricular systolic function during ACS. Methods: In a retrospective case–control study, we examined 100 participants who presented with ACS (mean age = 61.03 years, 80 [80%] males). The patients were divided into two groups: the ACS-PAD group (32 subjects, 74% of them with STEMI, 10% with NSTEMI, and 16% with NSTEACS) and the ACS-nonPAD group (68 participants). Results: This study highlighted that PAD negatively impacts patients with non-ST-segment elevation myocardial infarction (NSTEMI). These patients were likely to experience a decline of approximately 19.3% in their left ventricular ejection fraction (LVEF) compared to the ACS-nonPAD group (p = 0.003) and presented a worse clinical status (the PAD group correlated with Killip class IV, p = 0.049). Conclusion: Our analysis indicates that patients diagnosed with NSTEACS and PAD tend to have a higher LVEF of over 55% and a lower HEART score. Patients with PAD tend to have a functionally higher EF but clinically present with more unstable scenarios (pulmonary edema and cardiogenic shock). This is mainly driven by a higher prevalence of HFpEF in the PAD group. Looking closer at the PAD group, they have a higher incidence of comorbidities such as diabetes, hypertension, high cholesterol, CAD, and stroke, as well as being more active smokers.

Introduction:Sepsis-associated encephalopathy (SAE) is one of the most common complications seen both in early and late stages of sepsis, with a wide spectrum of clinical manifestations ranging from mild neurological dysfunction to delirium and coma. The pathophysiology of SAE is still not completely understood, and the diagnosis can be challenging especially in early stages of sepsis and in patients with subtle symptoms. Aim of the study:The objective of this study was to assess the coagulation profile in patients with early SAE and to compare the hemostatic parameters between septic patients with and without SAE in the first 24 hours from sepsis diagnosis. Material and methods:This retrospective observational study included 280 patients with sepsis in the first 24 hours after sepsis diagnosis. A complete blood count was available in all patients; a complex hemostatic assessment including standard coagulation tests, plasmatic levels of coagulation factors, inhibitors, D-dimers, and Rotation thromboelastometry (ROTEM, Instrumentation Laboratory) was performed in a subgroup of patients. Results:Early SAE was diagnosed in 184 patients (65.7%) and was correlated with a higher platelet count, after adjusting for age and leucocyte count. Compared to patients without neurological dysfunction, patients with early SAE presented a more active coagulation system revealed by faster propagation phase, increased clot firmness and elasticity with a higher platelet contribution to clot strength. The initiation of coagulation and clot lysis were not different between the groups. Conclusion:In the early stages of sepsis, the development of SAE is correlated with increased systemic clotting activity where platelets seem to have an important role. More research is needed to investigate the role of platelets and the coagulation system in relation to the development of early SAE.

A long term operation of Multi-Strip Multi-Gap Resistive Plate Chambers (MSMGRPC) with gas mixtures based on C2H2F4 and SF6 leads to aging effects observed as depositions on the surface of the resistive electrodes, especially in the region of the spacers used for defining the gas gaps between the resistive electrodes. The observed higher noise rate and dark current has a negative impact on the performance of the chamber and leads to an increase of the data volume in a free running readout mode operation. MSMGRPC prototypes designed with a direct gas flow through the gas gaps and minimization of the number of spacers in the active area were developed as mitigation solution. Three new prototypes of different granularities were assembled using fishing line as spacers and investigated for aging effects. Although a significant reduction in the dark current and dark counting rate was evidenced, noise rate localized around the fishing line spacers, even though reduced, still remains. In this paper, a new generation of direct flow chambers based on discrete spacers is presented. The results of their aging investigations show that, even at lower gas flows, the aging effects become negligible.

Background: Time intervals related to ST-segment myocardial infarction (STEMI) revascularization are central determinants for patient outcomes. The current capability of the Romanian STEMI program to meet guideline-recommended time intervals is largely unknown. Aims: The present study aims to assess the ability of a regional STEMI network to obtain guideline-recommended time intervals for primary percutaneous coronary intervention (pPCI) and to measure the occurrence and the extent of time delays. Materials and Methods: This prospective study included 500 consecutive patients with STEMI at the "Prof. Dr. C.C. Iliescu" Emergency Institute for Cardiovascular Diseases, Bucharest, Romania during a period of 14 months. Complete ischemic timelines were created using several key timepoints. Results: A secondary route (transfer from another hospital) was noted in most cases. The main time intervals were the following: patient delay 209 min, emergency medical system delay 66 min, and PCI center delay at 70 min, totaling an ischemic time of 6.4 h. A provisional stop at another hospital involved the addition of 113 min (1.8 h) until STEMI diagnosis and an additional 83 min (1.3 h) from diagnosis to revascularization, totaling a supplementary ischemic time of 3.1 h. In total, 41.5% of the patients were revascularized between 2 and 6 h from symptoms onset. The objective of revascularization in less than 120 min (from first medical contact) was accomplished in 35.5% of the patients. Prehospital thrombolysis was performed in 6.4% of the cases, although its potential benefits could have been expected in 64.5% of the patients. Conclusions: Patients with STEMI arrive predominantly via secondary routes to the PCI center, which implies significantly increased ischemic times. The ambulance alert system and primary routes represent by far the most efficient, albeit still imperfect methods of pre-hospital approach. Prehospital thrombolysis did not compensate for the gaps existing in the performance of the current system.

The multi-strip, multi-gap resistive plate chambers (MSMGRPCs) of the Time of Flight (TOF) wall of the Compressed Baryonic Matter (CBM) experiment will be exposed to challenging counting rates, up to 50 kHz/cm2. The unprecedented requirement to the CBM-TOF chambers to keep their performance (efficiency over 90% and system time resolution better than 80 ps) at these high counting rates has triggered the development of a new generation of MSMGRPCs with increased counting rate capabilities and suppression of aging effect in high irradiation environment. The MSMGRPCs designed for the low polar angles region of the CBM-TOF wall, besides performing in high counting rate, should also maintain their performance over the lifetime of the experiment. Detailed aging investigation evidenced mainly a gas pollution effect for the chambers with gas exchange via diffusion, enhanced around the spacers. In order to mitigate this phenomenon, a MSMGRPC prototype with a direct gas flow through the gas gaps and a reduced number of spacers in the electric field was developed. Assembling and tests of such prototypes as well as the results of the first aging investigations performed exposing the chamber to a high intensity X-ray flux at different gas flow rates and gas mixtures are reported.

Background and Objectives: Available data with regard to the outcomes of patients with severely calcified left main (LM) lesions after revascularization by percutaneous coronary intervention (PCI) when compared to non-calcified LM lesions is unclear. Materials and Methods: The present study sought to retrospectively investigate in hospital and 1 year post-intervention outcomes of patients with extremely calcified LM lesions after PCI facilitated by calcium-dedicated devices (CdD). Seventy consecutive patients with LM PCI were included. CdD requirement was based on suboptimal results after balloon angioplasty. Results: Twenty-two patients (31.4%) required at least one CdD, while nine patients (12.8%) required at least two. Intravascular lithotripsy and rotational atherectomy were the predominantly used methods(59.1% and 40.9% respectively, for in-group ratios), while ultra-high pressure and scoring balloons contributed the least to lesion preparation (9%). In 20 patients (28.5%), severe or moderate calcifications were angiographically identified, but non-compliant balloon predilation was adequate and CdD were not necessary. Total procedural time was significantly higher in CdD group (p-value 0.02). Procedural and clinical success were obtained in 100% of cases. There were no major adverse cardiac and cerebrovascular events (MACCE) recorded during hospitalization. MACCE at 1 year post-procedure were recorded in three patients (4.2% overall). All three events were documented in the control group (6.2%), and no events were recorded in CdD group (p-value 0.23). There was one cardiac death at 10 months and two target lesion revascularizations for side-branch restenosis. Conclusions: Patients with extremely calcified LM lesions treated by PCI present a favorable prognosis if angioplasty is facilitated by more aggressive lesion debulking using calcium-dedicated devices.

There are a number of devastating complications associated with peripheral artery disease, including limb amputations and acute limb ischemia. Despite the overlap, atherosclerotic diseases have distinct causes that need to be differentiated and managed appropriately. In coronary atherosclerosis, thrombosis is often precipitated by rupture or erosion of fibrous caps around atheromatous plaques, which leads to acute coronary syndrome. Regardless of the extent of atherosclerosis, peripheral artery disease manifests itself as thrombosis. Two-thirds of patients with acute limb ischemia have thrombi associated with insignificant atherosclerosis. A local thrombogenic or remotely embolic basis of critical limb ischemia may be explained by obliterative thrombi in peripheral arteries of patients without coronary artery-like lesions. Studies showed that thrombosis of the above-knee arteries was more commonly due to calcified nodules, which are the least common cause of luminal thrombosis associated with acute coronary events in patients with acute coronary syndrome. Cardiovascular mortality was higher in peripheral artery disease without myocardial infarction/stroke than in myocardial infarction/stroke without peripheral artery disease. The aim of this paper is to gather published data regarding the disparities of acute coronary syndrome with and without peripheral artery disease in terms of pathophysiology and mortality.

Objective: The aim of the study was to assess the clinical particularities and the lab tests in patients hospitalized for SARS-COV2 infection, with new onset of hypertension on admission. Design and method: We performed a retrospective study on 217 patients admitted to a Clinical Emergency Hospital between January 2021 and October 2021. Results: We had 217 patients admitted in internal medicine clinic for infection with SARS-COV2 virus, most of them with moderate and severe form of disease. From them, 148 patients had hypertension, 83.78% with medical history of hypertension and 16.22% with new onset of high blood pressure on admission. Patients were aged between 23 and 99 years, with an average age of 65 years. In comparison, the patients with new onset of hypertension (subgroup 1) were aged between 37 and 90 years, with an average age of 66 years. The most affected group of age was 60–69 years. In subgroup 1, the gender distribution was: 58.33% male, 41.66% female. At admission, the stages of SARS-COV2 infection in subgroup 1, according to CT examination, were severe in 52.38%, moderate 19.04%, and mild 28.57% of patients. As comorbidities in subgroup 1: cancer in 8.33%, metabolic syndrome 54.16%, dyslipidemia 4.16%, obesity 50%, type II diabetes mellitus 45.83%, chronic heart failure in 12.5% of cases (37.5% NYHA I class, 54.16% NYHA II class and 8.3% NYHA III class), atrial fibrillation in 12.5%, atherosclerosis in 16.66%, anxiety disorders in 4.16% and dementia in 8.33% of cases. High levels of inflammatory markers in Subgroup 1: CRP in 95.83%, procalcitonin in 87.5%, ferritin 79.16%, D-dimers in 83.33%, troponin 4.16%, NT-proBNP in 50% of cases. Decreased GFR was found in 65.21% of patients. Microalbuminuria was present in 29.16% of patients. The antihypertensive medication during hospitalization was: diuretics in 45.83%% of cases, betablockers in 33.34%, calcium blockers in 8.33%, angiotensin converting enzyme inhibitors in 16.67%. Conclusions: Hypertension with new onset during SARS-COV2 infection and its persistence in post-covid syndrome may have complex pathogenic mechanisms and require personalized therapeutic decision.

Objective: The relationship between COVID-19 and blood pressure (BP) has raised great concern since the discovery of Angiotensin Convertase Enzyme 2 (ACE 2) – mediated mechanism of action for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV2). Hypertension (HTN) itself proved to be a risk factor for more severe Coronavirus Disease 19 (COVID -19). However less studies focus on the trend of blood BP for patients with COVID-19 during the initial phase of disease. Design and method: We present the case of a 71 years old woman with grade 2 HTN previously controlled with diuretic and betablocker therapy that came to our hospital with dyspnea, cough and debilitating fatigue progressively worsened in the last 10 days. The patient also related the first episode of syncope in her life the night before the presentation. Results: The clinical evaluation revealed a conscious, euvolemic, with polypnea and a peripheral saturation in oxygen of 86%, corrected to 95% with 9 liters oxygen/minute via simple face mask and a BP of 110/70 mmHg with a ventricular rate of 45 beats per minute in supine position. The assessment of BP values while standing showed a value of 78/60 mmHg after 1 minute and 58/40 mmHg after 3 minutes, while the ventricular rate increased overall to 65 beats per minute. ECG was remarkable only for mild bradycardia and computed tomography pulmonary angiogram excluded pulmonary embolism. The patient was admitted with severe COVID-19 accompanied by severe orthostatic hypotension and bradycardia. Continuous telemonitoring showed only mild bradycardia. Under standard COVID 19 treatment, after 10 days, her symptoms had resolved with no residual orthostatic hypotension or bradycardia. Conclusions: In conclusion this case reflects the life-threatening dysautonomia caused by SARS-COV 2 infection. More concern should be placed on this type of fragile patients, taking into account both the macroscopic implications of being confined to bed for a long period of time and the microscopic butterfly effect caused by the binding of the virus on the widespread ACE 2 in the lungs, heart, kidneys and digestive tract.

Detailed tests and analysis of ageing effects of high irradiation dose on Multi-Strip Multi-Gap Resistive Plate Counters (MSMGRPC) based on low resistivity glass electrodes, foreseen to be used for the most forward polar angles covered by the Time-of Flight (ToF) sub-detector of the Compressed Baryonic Matter (CBM) experiment at Facility for Antiprotons and Ion Research (FAIR) - Darmstadt are reported. The tests were performed at a multi-purpose irradiation facility of IFIN-HH based on Co-60 source. MSMGRPC efficiency, cluster size, surface and volume resistivity of the glass electrodes after irradiation are measured and compared with their values before irradiation. The results of a comprehensive analysis of the composition and properties of the deposited layers on the glass electrodes, based on different methods, i.e. Scanning Electron Microscope (SEM), X-ray Photoelectron Spectroscopy (XPS), foil Elastic Recoil Detection Analysis (ERDA), Rutherford Backscattering Spectrometry (RBS), Atomic Force Microscopy (AFM) and Terahertz Time Domain Spectroscopy (THz-TDS), are presented.

Hypertensive emergencies (HE) represent high cardiovascular risk situations defined by a severe increase in blood pressure (BP) associated with acute, hypertension mediated organ damage (A-HMOD) to the heart, brain, retina, kidneys, and large arteries. Blood pressure values alone do not accurately predict the presence of HE; therefore, the search for A-HMOD should be the first step in the management of acute severe hypertension. A rapid therapeutic intervention is mandatory in order to limit and promote regression of end-organ damage, minimize the risk of complications, and improve patient outcomes. Drug therapy for HE, target BP, and the speed of BP decrease are all dictated by the type of A-HMOD, specific drug pharmacokinetics, adverse drug effects, and comorbidities. Therefore, a tailored approach is warranted. However, there is currently a lack of solid evidence for the appropriate treatment strategies for most HE. This article reviews current pharmacological strategies while providing a stepwise, evidence based approach for the management of HE.

Polyvascular disease affects up to 20% of atherosclerotic patients and portends a significantly higher cardiovascular risk, especially in terms of ischemic events. Therapeutic options mainly focus on aggressive pharmacotherapy and risk factor control. We present the case of a male obese patient with coronary artery disease, chronic renal disease, and refractory hypertension who underwent serial contrast imaging to document the extent and severity of his systemic atherosclerosis and was consequently referred for cardiovascular surgery to address total occlusion of the abdominal aorta. We further discuss specific features complicating the medical management of patients with severe hypertension, extensive atherosclerosis, and renal disease.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class of anti-hyperglycaemic drugs that act by partially inhibiting glucose reabsorption from the renal filtrate and inducing glycosuria. However, they have several other benefits, independent of the glycaemic control. SGLT2i reduced major cardiovascular events, including new-onset heart failure, in patients with type 2 diabetes mellitus (T2DM), in large randomized clinical trials. These effects have been recently described in patients with HF with reduced ejection fraction, irrespective of their diabetic or glycated haemoglobin status, suggesting that their benefits are driven independently of their glucose lowering properties. This review summarizes the current evidence for their cardioprotective effects, and provides an overview of the possible mechanisms for the cardiovascular benefits. The alleged mechanisms that lead to improve cardiovascular outcome, even though still incompletely understood, include an association between improvement in cardiac pre- and after-load, partially explained by osmotic diuresis and natriuresis, prevention of cardiac remodelling, direct cardiac effects with improved cardiac energetics and ion handling, anti-inflammatory effects, and anti-fibrotic effects. Therefore, in the latest years, both mechanistic insights, as well as major trials data, have repurposed SGLT2i usage from only anti-diabetic to potent HF treatment drugs, and new indications have been attributed to these compounds in HF guidelines.

Resistant hypertension (R-HTN) implies a higher mortality and morbidity compared to non-R-HTN due to increased cardiovascular risk and associated adverse outcomes—greater risk of developing chronic kidney disease, heart failure, stroke and myocardial infarction. R-HTN is considered when failing to lower blood pressure below 140/90 mmHg despite adequate lifestyle measures and optimal treatment with at least three medications, including a diuretic, and usually a blocker of the renin-angiotensin system and a calcium channel blocker, at maximally tolerated doses. Hereby, we discuss the diagnostic and therapeutic approach to a better management of R-HTN. Excluding pseudoresistance, secondary hypertension, white-coat hypertension and medication non-adherence is an important step when diagnosing R-HTN. Most recently different phenotypes associated to R-HTN have been described, specifically refractory and controlled R-HTN and masked uncontrolled hypertension. Optimizing the three-drug regimen, including the diuretic treatment, adding a mineralocorticoid receptor antagonist as the fourth drug, a β-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when failing to achieve target blood pressure values are current recommendations regarding the correct management of R-HTN.

Abstract According to tradition, every year, at the Congress of the European Society of Cardiology new clinical guidelines, usefull for our daily pratice, are launched. This year a new guideline for the management of non-ST-segment elevation myocardial infarction (NSTEMI) was presented. Substantial resources had been invested to sustain the research efforts in order to improve the diagnosis and therapeutic tools for this disease. In this article we present the main differences between this guideline and the previous one, regarding the utility of the cardiac biomarkers, diagnosis and risk stratification algorithms, and last, but not least, medical and invasive treatment tools.