Background and Methods: This prospective observational study investigated the prognostic value of the hemoglobin-to-red cell distribution width ratio (HRR) in 278 patients hospitalized with decompensated heart failure (HF). The primary endpoint was a composite of all-cause mortality or HF rehospitalization at 12 months. Multivariable Cox regression was employed to adjust for risk factors including age, sex, NT-proBNP, LVEF, and eGFR. Results: The median HRR was 0.89. During follow-up, the primary endpoint occurred in 167 (60.1%) patients. Unadjusted analysis showed a lower HRR was significantly associated with reduced event-free survival (log-rank p = 0.027). However, after multivariable adjustment, this association was no longer statistically significant (p = 0.240). Older age and male sex remained independent predictors. Conclusions: In patients with decompensated HF, a lower baseline HRR correlates with increased risk but does not maintain independent prognostic value after adjusting for powerful confounders. HRR may serve as a simple, initial marker of risk rather than an independent predictor.

Background/Objectives: Heart failure (HF) in patients with conventional right ventricular pacing with significant pacing percentages is still a subject of concern, and management of HF in this population has historically been difficult; however, novel HF pillar medications, such as SGLT2 inhibitors (SGLT2i) and angiotensin receptor/neprilysin inhibitors (ARNi), have fundamentally transformed contemporary pharmacological HF management. The aim of this study was to assess left ventricular (LV) function after current guideline-directed medical therapy (GDMT) in patients with chronic right ventricular (RV) pacing and HF. Methods: Patients with a lifetime ventricular pacing percentage > 20% (Vp > 20%) and HF diagnosed according to ESC guideline criteria were included. Device interrogation and transthoracic echocardiography (TTE), including assessment of left ventricular ejection fraction (LVEF) and mitral annular plane systolic excursion (MAPSE), were performed at GDMT initiation and during subsequent follow-up. Changes in LVEF and MAPSE were assessed overall and according to baseline HF phenotype. Multivariable linear regression analyses were performed to identify independent predictors of changes in LVEF and MAPSE. Results: Among 550 conventionally paced patients screened for HF, 127 (23.1%) met the inclusion criteria and underwent GDMT initiation. Mean age was 68.2 ± 12.1 years, and mean follow-up duration was 10.2 ± 6.3 months. Baseline LVEF and MAPSE were 48.7 ± 6.3% and 12.0 ± 2.4 mm, respectively. All patients received SGLT2i therapy, while 24 (18.9%) received ARNi. Overall, LVEF increased by 1.94 ± 2.47% and MAPSE by 0.84 ± 0.96 mm (both p < 0.001). Patients with HFrEF (n = 25) showed an increase in LVEF of 5.84 ± 2.53% and MAPSE of 1.72 ± 1.21 mm. In patients with HFmrEF, LVEF increased by 2.50 ± 1.54% and MAPSE by 0.83 ± 0.92 mm, whereas in HFpEF, LVEF increased by 0.67 ± 0.78% and MAPSE by 0.58 ± 0.71 mm. NYHA functional class improved by at least one class in 100 patients (78.7%). In multivariable analysis, ARNi use was independently associated with greater improvement in LVEF and MAPSE, while lower baseline LV function was associated with greater subsequent improvement. Conclusions: In patients with HF and chronic RV pacing, GDMT was associated with modest but statistically significant improvements in LV systolic function, assessed by LVEF and MAPSE, across the HF spectrum. The greatest improvements were observed in patients with HFrEF. However, given the observational design, absence of a control group, and universal use of SGLT2i, these findings do not establish a causal treatment effect or demonstrate superiority of any specific GDMT combination. Prospective controlled studies are warranted to determine the clinical significance of these changes and the independent contribution of individual therapies.

Abstract Chronic obstructive pulmonary disease (COPD) is frequently complicated by cardiovascular diseases (CVDs), worsening patient outcomes. Recognising COPD as a multimorbid and syndemic condition, we developed this position paper to provide evidence-based recommendations for reducing cardiopulmonary (CP) risk through integrated, guideline-directed management in Romania. In June–September 2025, the multidisciplinary task force (pulmonologists/cardiologists/internal medicine specialists/general practitioners GPs), with expertise in diagnosis and treatment of patients with COPD and CVDs, engaged in working groups and developed algorithms for COPD management, focusing on CP risk reduction. Expert recommendations were formulated using current guidelines, scientific literature evidence and clinical expertise as follows: (i) prioritise early COPD diagnosis in at-risk populations; (ii) address CP risk assessment at every visit, with urgent pulmonology referral for severe COPD symptoms and cardiology referral for severe dyspnoea with abnormal electrocardiogram; (iii) ensure adequate assessment and management of mild-moderate COPD exacerbations, with urgent emergency referral/hospitalisation when severity cannot be reliably determined; (iv) refer all patients with severe COPD exacerbations to emergency care and/or hospitalisation; (v) implement standardised COPD hospital discharge protocol; (vi) optimise pharmacotherapy by initiating long-acting β 2 -agonist (LABA) + long-acting muscarinic antagonist (LAMA) and escalating to triple therapy (LABA/LAMA/inhaled corticosteroid) when indicated and ensure structured follow-up as per GOLD guidelines. This expert opinion paper calls for urgent action to bridge the gap between guideline-directed recommendations and routine practice, with a strict policy of zero tolerance for treatment delays.

Background/Objectives: Paraneoplastic syndromes (PNS), characterized by a large diversity of symptoms, may sometimes be the first clinical feature of a severe underlying disorder such as cancer. Methods: We report the case of a middle-aged male patient with no significant previous medical history, a nonsmoker or alcohol heavy drinker, complaining about generalized, recently onset itch. Given no reasonable explanation of pruritus after dermatological consultation and the unsatisfactory response to treatment, the patient was referred to gastroenterology with the suspicion of a cholestatic liver disease. Results: The abdominal ultrasound examination revealed gallstones and no dilation of the biliary tree. Numerous tests were run and came out negative, except for the slight elevation of C-reactive protein, mild dyslipidemia, and positivity for H. pylori antigen. The gut microbiota displayed important dysbiosis with a significant increase in the histamine-producing bacteria. Given this chronic pruritus became suspicious, thorax and abdominal CT were recommended and performed soon after. A large right mid-thoracic tumor image was found. Bronchoscopy came out negative for a tumor. After the CT-guided biopsy, the tumor turned out not to be a lymphoma, but a non-small cell lung carcinoma (NSCLC). Conclusions: Chronic pruritus was not associated with cholestasis in a patient with gallstone disease, but rather with a PNS, as the first clinical manifestation of NSCLC, triggering many diagnostic and therapeutic challenges.

The study aimed to assess the link between procalcitonin (PCT) and gut dysbiosis in patients with nonalcoholic fatty liver disease (NAFLD). A total of 125 research participants, 100 patients with NAFLD (59% women and 41% men) age between 43 and 84 years and 25 healthy controls, joined this observational study. Patients were consecutively enrolled into two groups: 50 with gut dysbiosis and 50 without gut dysbiosis, after several conditions have been ruled out. Patients from dysbiotic group displayed significantly lesser use of biguanides and statins and elevation of fatty liver index (FLI), PCT, C-reactive protein (CRP), and alanine aminotransferase (ALT). Their gut microbiome was characterized by Bacteroides and Prevotella sp. dominant enterotype (74%) and by Ruminococcus sp. in only 26% of cases. The decrease of H index of biodiversity was observed in 64% of patients as well as of Firmicutes/Bacteroidetes (F/B) ratio and Akkermansia muciniphila in 60%. The increase of lipopolysaccharide positive bacteria was noted in 62% of patients. PCT strongly correlated with the level of CRP and ALT as well as to stool’s H index of biodiversity and F/B ratio. Dysbiotic patients with NAFLD exhibited significant elevation of PCT that correlated well with the H index of stool’s microbiota biodiversity, F/B ratio, CRP level, and severity of cytolytic syndrome.

Despite the notable advancements witnessed in the past decade in medical and health research domain, cancer remains a prominent global cause of mortality. Moreover, the conventional treatments employed to combat this disease have been found to considerably compromise the quality of life experienced by patients due to its severe side effects. Recent in vitro studies revealed encouraging findings on the potential beneficial effects of probiotics as adjuvants of anticancer therapy, and even as possible agents for the prevention and treatment of various types of malignancies. From this standpoint, the primary objective of this work was to investigate the anticancer properties of Lactiplantibacillus plantarum (LP) and elucidate its underlying mechanism of action. In order to investigate this matter, several doses of LP (ranging from 105 to 1010 CFU/mL) were examined in relation to melanoma cancer cell lines (A375) and breast cancer cell line (MCF-7). The cell viability findings, which were substantiated by morphological investigations and annexin V/PI assay, indicated that LP exerted inhibitory effects on cellular activity and triggered apoptosis. Additionally, upon further investigation into its mechanism, it was observed through the apoptosis assay and Western blot analysis that the administration of LP resulted in an elevation of pro-apoptotic BAX protein levels and an upregulation of cleaved poly-ADP-ribose polymerase (PARP) protein expression. Conversely, the levels of anti-apoptotic Bcl-2 protein were found to decrease in the A375 and MCF-7 cell lines. These findings provide insight into the pro-apoptotic mechanism of action of LP in these specific cell lines.

Purpose:This study aimed to explore inflammatory biomarkers, stool's functional bacterial groups and their possible link to portal vein thrombosis (PVT) in patients with liver cirrhosis (LC).Materials and Methods:An observational study of 300 participants: 200 inhospital cirrhotic patients, who met inclusion criteria, equally assigned into two groups, based on the presence or absence of PVT and 100 healthy controls was carried out.Results:The PVT group displayed significant differences related to older age, cigarettes smoking history, emergency admission, higher Child-Pugh score, metabolic related disorders and nonalcoholic fatty liver disease, as well as non-obstructive aspects, with chronic thrombi. The PVT group exhibited significant differences related to biomarkers such as tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), D-dimers (D-D), as well as gut overall dysbiosis (DB) and alteration of different functional bacterial groups of the gut microbiota. Strong positive correlations were observed between PVT severity, and TNF-alpha, CRP, D-D as well as lipopolysaccharide (LPS) positive bacteria. Esophageal varices, age and abdominal pain were independent predictors for PVT severity as well as CRP, TNF-alpha and D-D.Conclusion:Patients with LC and PVT displayed elevation of TNF-alpha, CRP, D-D alterations of the functional gut microbiota, as well as several morphological and clinical particularities. Although the LPS positive gut microbiota was linked to inflammatory biomarkers and PVT severity, it was not proven to be an independent predictor of the PVT severity like CRP, TNF-alpha and D-D.

Objectives:This national representative survey sought to assess hypertension's prevalence, awareness, treatment and control in Romania.Methods:A representative sample (by age, sex and residence) of 1477 Romanian adults (51.19 & PLUSMN; 16.61 years, range 18-80 years, 59.9% women) was multimodally evaluated during two study visits. Hypertension was defined as SBP at least 140 mmHg and/or DBP at least 90 mmHg or previously diagnosed hypertension, regardless of BP. Awareness was defined by knowledge of previous hypertension diagnosis or of current use of antihypertensive treatment. Treatment was defined by antihypertensive medication taken at least 2 weeks prior to enrolment. Control was defined as SBP less than 140 mmHg and DBP less than 90 mmHg at both visits in treated hypertensive patients.Results:Hypertension prevalence was 46% (n = 680) consisting of 81.02% (n = 551) known hypertensive patients and 18.98% (n = 129) newly diagnosed hypertensive patients. Awareness, treatment and control of hypertension were: 81% (n = 551), 83.8% (n = 462) and 39.2% (n = 181).Conclusion:Despite numerous pandemic-related obstacles in conducting a national survey, SEPHAR IV updates hypertension epidemiological data of a high-cardiovascular-risk Eastern-European population. This study confirms previous predictions of hypertension prevalence, treatment and control, which remain unfavourable because of unsatisfactory control of promoting factors.

The future waves of COVID 19 infections will continue to raise serious problems in patients with severe forms of the disease. Bacterial infections associated with SARS-CoV-2 disease may complicate the progress of hospitalized patients with COVID-19. The present study aimed to evaluate the etiological spectrum of superinfection in adult patients with COVID-19 and to investigate the correlation between superinfection with multidrug-resistant (MDR) bacteria and serum procalcitonin (PCT). A total of 82 COVID-19 hospitalized patients with COVID-19 and bacterial superinfection were included. The superinfections were classified into early infections (3-7 days from admission) and late infections (>7 days from admission). Bacterial superinfection etiological spectrum, MDR bacteria profile and levels of serum PCT were studied. The most frequently isolated bacteria were Klebsiella pneumoniae, Acinetobacter baumannii and Enterococcus spp. MDR bacteria were involved in 73.17% of COVID-19 patients with bacterial superinfections. Most MDR bacteria superinfections (73.52%) occurred in the late infection period. Klebsiella pneumoniae, Enterococcus spp. and Methicillin-resistant Staphylococcus aureus were the most common MDR bacteria identified in late infections after hospitalization in 20.43, 4.30 and 4.30% of all infections, respectively. Serum PCT values were significantly higher in patients with MDR bacteria superinfection compared with patients with sensitive bacteria superinfection (P=0.009). The principal findings of the present study were the high prevalence of superinfection with MDR bacteria among the COVID-19 patients with bacterial superinfections and the presence of a statistically significant association between serum PCT levels and the presence of superinfection with MDR bacteria. The most effective way to fight against microbial resistance to antibiotics, whether it occurs independently or overlaps with viral infections, is to pursue a national policy for the rational use of antibiotics.

Cancer remains a leading cause of death worldwide and, even though several advances have been made in terms of specific treatment, the late-stage detection and the associated side effects of the conventional drugs sustain the search for better treatment alternatives. Probiotics are live microorganisms that have been proven to possess numerous health benefits for human hosts, including anticancer effects. In the present study, the in vitro effect of the association of two probiotic strains (PBT), Lactobacillus sporogenes and Clostridium butyricum, were tested against colon (HT-29 and HCT 116), lung (A549), and liver (HepG2) cancer cell lines, alone or in combination with 5-fluorouracil (5FU). Moreover, the underlying mechanism of PBT and PBT-5FU against the HT-29 cell line was evaluated using the Hoechst 33342 staining, revealing characteristic apoptotic modifications, such as chromatin condensation, nuclear fragmentation, and membrane blebbing. Furthermore, the increase in the expression of pro-apoptotic Bax, Bid, Bad, and Bak proteins and the inhibition of the anti-apoptotic Bcl-2 and Bcl-XL proteins were recorded. Collectively, these findings suggest that the two strains of probiotic bacteria, alone or in association with 5FU, induce apoptosis in colon cancer cells and may serve as a potential anticancer treatment.

ObjectivesNonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease while flow mediated dilation (FMD) is an independent predictor of future cardiovascular events and death. The aim of this study is to evaluate endothelial dysfunction measured by flow mediated dilation in patients with nonalcoholic fatty liver disease and low cardiovascular risk (CV risk).MaterialsThis observational case-control study was designed to evaluate endothelial function in patients with documented NAFLD and low CV risk by assessing the FMD of the brachial artery. The study included 54 patients over 40 years of age, divided in two groups: 34 patients with NAFLD and a control group of 22 individuals without NAFLD. Exclusion criteria were diabetes mellitus type 2, history of cardiovascular, cerebrovascular or peripheral vascular disease, viral hepatitis, chronic liver disease, significant alcohol consumption, smoking, uncontrolled hypertension, body mass index ≥ 40 kg/m². NAFLD was diagnosed by ultrasound (bright liver with posterior attenuation) and quantified by Controlled attenuation parameter (CAP) implemented on the FibroScan device. FMD of the brachial artery was evaluated using B mode vascular ultrasound, measuring the maximum percentage variation of the brachial artery diameter before and after a 5-minute occlusion of the forearm blood flow induced by inflation and deflation of a proximal upper arm cuff. All patients underwent B-mode ultrasound, CAP and FMD assessment.ResultsThere were no significant differences between the two groups regarding age, gender and CV risk (assessed by SCORE risk calculator). FMD was significantly lower in the NAFLD group as compared to the control group (8.7±7.8% vs 11.5±6.5%, p=0.007). CAP was 306,1±38,7 dB/m in the NAFDL patients and 194,8±31,5 in the control group. In a multivariable regression analysis, we found that the severity of steatosis (evaluated by CAP) was independently associated with FMD (β=-0,44, p=0,022).ConclusionsEndothelial dysfunction is associated with nonalcoholic fatty liver disease in patients with low cardiovascular risk.

Study basis: As a byproduct of protein metabolism, serum uric acid is a controversial risk factor and is the focus of several recent studies in the field of cardiovascular disease. Whether serum uric acid is involved in the development of these pathologies alone or in conjunction with other factors is a matter of debate. Objective: The objective of this study is to assess the direct relationship between serum uric acid and the ejection fraction. Methods: A retrospective study of 303 patients with heart failure, classified according to the ESC guidelines, was conducted, and several parameters, along with the relationship between serum uric acid and ejection fraction, were characterized. Results: A direct relationship between the level of serum uric acid and the ejection fraction was established (p = 0.03); patients with higher uric acid had an increased risk of having a lower ejection fraction. Conclusions: Serum uric acid, even when asymptomatic, is linked with the level of the ejection fraction of the left ventricle.

Sleep plays an essential role in overall health. A negative impact of sleep deprivation has been recognized on physical performance, including reaction time, accuracy, vigor, submaximal strength, endurance, cognitive functions such as judgment and decision making. Professional athletes are often unable to achieve sleep recommendations during training or competition periods. Association of sleep breathing disorders (SBD) worsens physical performance and alter health status in athletes. Little is known about the incidence of SBD among athletes performing different sports. Objectives The aim of our study is to analyze published articles on SBD in athletes in order to investigate their prevalence in different sports, differences between genders and their impact on health and sport performance. We are also aiming to present methods used to evaluate the presence of SBD among professional athletes. Method The four major databases, PubMed, Google Academic, ScienceDirect, were searched for identifying articles targeting SBD in athletes. The search included all work published between 2010 and 2020. Randomized controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The main outcomes were: sleep breathing disorders, obstructive sleep apnea, athletes, sports, physical performance. Results and conclusions Sleep-breathing disorders are frequent among professional athletes, impacting physical performance and health status. High prevalence of sleep-breathing disorders was observed among swimmers, rugby and American-style football players. There is an urgent need to conduct sleep-breathing disorders identification through screening and diagnostic methods within the athletic community.

Since obesity and type 2 diabetes mellitus (DM) became almost pandemic, incidence and prevalence of associated nonalcoholic fatty liver disease (NAFLD) rose accordingly. Aim of the study was assessing whether there is a link between circulating C-reactive protein(CRP), gut microbiota dysbiosis and severity of liver disease in patients with NAFLD and confirmed type 2 DM. 50 patients diagnosed with type 2 DM were consecutively enrolled in this cross-sectional, pilot study, being evenly divided in two groups, as matched pairs, on the basis of presence or absence of NAFLD confirmed by abdominal and CT exam, after ruling out a lot of diseases and conditions. Patients underwent measurements of waist circumference, blood pressure (BP), body mass index (BMI) and thoroughly physical examination. Complete blood count (CBC), liver tests, CRP, fasting plasma glucose (FPG), low density lipoprotein(LDL) and high-density lipoprotein(HDL) cholesterol, triglycerides, creatinin and uric acid, micro proteinuria as well as stool microbiology were run, using standardized methods. Fatty liver index (FLI) was also calculated. Fibromax (BioPredictive) was performed in NAFLD (+) patients. NAFLD (+) group displayed significant differences of age and BMI, as well as lab biochemistry: ALT, GGT, LDL-cholesterol and triglycerides, CRP, microprotienuria and stool microbiology.. Strong positive correlation of CRP with gut dysbiosis (DB) severity, microproteinuria, as well as with nonalcoholic steatohepatitis (NASH) score, were observed. DB range correlated positively in NAFLD (+) group with age, BMI, BP, dyspepsia as well as with NASH scores. In conclusion patients with NAFLD and associated type 2 DM displayed a specific profile with significant differences of age, BMI, FLI, diabetic treatment, biochemistry and gut microbiological charts. Strong positive correlations between CRP, gut DB and NASH score suggest the possibility of link between inflammation, gut microbiota DB and severity of liver disease.

The aim of this study was to reveal the important role of CEUS in identifying correctly benign hepatic lesion vs a malignant one. We report a case of a diffuse hepatic steatosis particular sonographic aspect in a middle aged male presenting with general malaise. History revealed cardiac pathology, diabetes mellitus type 2 and chemotreated prostate neoplasia. The abdominal ultrasound (US) presented numerous hyperechoic lesions disseminated in the whole parenchyma. A contrast enhanced ultrasound (CEUS) of the lesions described an isoenhancement pattern of the lesions in the arterial phase, followed by the same aspect in the venous phase, with a high uptake pattern in the late phase. The CT and MRI also confirmed a diagnosis of a benign pathology. Hepatic steatosis may occur in chemotreated cancer patients, raising a suspicion of hepatic metastasis, but also due to the amount of lipid deposit distribution in the liver. Thus, CEUS was able to establish a correct diagnosis in a fast and reliable way.

Heart rate variability (HRV) is a simple measure that estimates cardiac autonomic modulation. Analysis in the time domain and frequency range of RR variability suggests that the negative prognosis of patients with acute myocardial infarction is related to the overall neuro-vegetative imbalance. The alteration of RR variability reflects the dysfunction of the autonomic nervous system and especially the reduction of parasympathetic tone. The results of this study confirm the association between the reduction of RR variability and the increased risk of adverse events and mortality after acute myocardial infarction. Moreover, it appears that RR variability is an independent predictor for atrial fibrillation.

Recent evidence shows that many vascular risk factors (VRFs) contribute to the cognitive decline. The aim of the study was to evaluate the cognitive decline, depression and the occurrence of subclinical atherosclerosis and the association between cognitive decline and subclinical atherosclerosis in patients with atrial fibrillation (AF) and VRFs versus patients without AF but with VRFs. After statistical analysis, we concluded that cognitive decline is more common in patients with AF and VRFs than in those without AF, but with VRFs, and we consider it is mandatory to identify and prevent cognitive changes. Our findings suggest a direct association between cognitive decline and AF, age, risk factors, cognitive parameters, hemodynamic changes (LVEF) and subclinical atherosclerosis (IMT).