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Abstract The diagnosis of acute appendicitis and concurrent surgery referral is primarily based on clinical presentation, laboratory and radiological imaging. However, utilizing such an approach results in as much as 10–15% of negative appendectomies. Hence, in the present study, we aimed to develop a machine learning (ML) model designed to reduce the number of negative appendectomies in pediatric patients with a high clinical probability of acute appendicitis. The model was developed and validated on a registry of 551 pediatric patients with suspected acute appendicitis that underwent surgical treatment. Clinical, anthropometric, and laboratory features were included for model training and analysis. Three machine learning algorithms were tested (random forest, eXtreme Gradient Boosting, logistic regression) and model explainability was obtained. Random forest model provided the best predictions achieving mean specificity and sensitivity of 0.17 ± 0.01 and 0.997 ± 0.001 for detection of acute appendicitis, respectively. Furthermore, the model outperformed the appendicitis inflammatory response (AIR) score across most sensitivity–specificity combinations. Finally, the random forest model again provided the best predictions for discrimination between complicated appendicitis, and either uncomplicated acute appendicitis or no appendicitis at all, with a joint mean sensitivity of 0.994 ± 0.002 and specificity of 0.129 ± 0.009. In conclusion, the developed ML model might save as much as 17% of patients with a high clinical probability of acute appendicitis from unnecessary surgery, while missing the needed surgery in only 0.3% of cases. Additionally, it showed better diagnostic accuracy than the AIR score, as well as good accuracy in predicting complicated acute appendicitis over uncomplicated and negative cases bundled together. This may be useful in centers that advocate for the conservative treatment of uncomplicated appendicitis. Nevertheless, external validation is needed to support these findings.

Acutely decompensated heart failure is one of the leading causes of hospitalisation worldwide, with a significant majority of these cases attributed to congestion. Although congestion is commonly mistaken for volume overload, evidence suggests that decompensation can occur without significant water accumulation, being attributed to volume redistribution. Yet, the distinction between intravascular and extravascular congestion in heart failure often blurs, as patients frequently exhibit overlapping features of both, and as patients may transition between phenotypes over time. Considering that differentiation between intravascular and extravascular congestion can lead to different management strategies, the aim of this review was to delineate the pathophysiological nuances between the two, as well as their correlation with clinical, biochemical and imaging indices.

Background: Radial forearm free flap (RFFF) is considered one of the workhorses in modern head and neck reconstruction surgery due to its technical simplicity, versatility and less time-consuming harvest. Methods: In this report, we present the case of a 56-year-old woman with sublingual squamous cell carcinoma (SCC) who underwent surgical resection and reconstruction of the defect with a RFFF. Results: The preoperative Allen test showed normal blood flow, and the ultrasound did not recognize any blood vessel abnormalities in the left arm. However, during the RFFF harvest, when the dissection of the pedicle came to the cubital fossa, there was no brachial artery bifurcation. While trying to find the bifurcation, the dissection almost came to the axillary region. Hence, the RFFF was converted to a pedicle flap and was pulled through to the intraoral defect where it was used for reconstruction. Conclusions: Hence, during the preoperative radiological ultrasound, besides the usual characteristics such as the radial artery diameter, flow and possible obstructions, it is also important to explore if there are any other anatomical abnormalities that could influence the operation.

Obesity is one of the leading causes of chronic diseases, and its prevalence is still rising in children and adolescent populations. Chronic cardiovascular complications result in metabolic syndrome (MS) and type 2 diabetes mellitus. Key factors in the development of MS are insulin resistance and low-grade inflammation. The disorder of glucose and insulin metabolism has not been fully elucidated so far, and an oral glucose tolerance test (OGTT) has been the only tool used to look into the complex metabolism disorder in children and adolescents with obesity. Continuous glucose monitoring (CGM) has become commercially available for over two decades and is primarily used to manage type 1 diabetes mellitus in pediatric populations. This review aims to present the current knowledge about the use of CGM in children and adolescent populations with obesity. CGM systems have the potential to serve as valuable tools in everyday clinical practices, not only in the better diagnosis of chronic complications associated with obesity, but CGM can also assist in interventions to make better adjustments to nutritional and therapeutic approaches based on real-time glucose monitoring data. Despite these promising benefits, further research is needed to fully understand the role of CGM in metabolic disorders in pediatric populations with obesity, which will additionally strengthen the importance of CGM systems in everyday clinical practices.

Background: Oral squamous cell carcinoma (OSCC) causes considerable morbidity and mortality rates, posing a major global health burden. The management of the OSCC is multidisciplinary, but still the gold standard is surgical resection and reconstruction of the postablative defect. The appearance of secondary primary OSCC is not uncommon; however, it is quite rare that it appears on the skin of the flap that was used for reconstruction during the previous surgical therapy. Methods: We present three cases in which a secondary primary OSCC appeared on the skin of two radial forearm free flaps and two on regional pectoralis major flaps. Results: Our case series show that, although relatively rare, there is a chance of a secondary primary tumor on the flap used for intraoral reconstruction after the first oncological reconstruction. According to the latest and available literature, there is still no explanation of the underlying mechanism that leads to this occurrence. Conclusions: The learning point of this case series should be that, aside from the neck metastasis or recurrence of the primary oral cancer, the clinicians should also bear in mind that the flap itself should be physically examined in detail.

The literature describes niacinamide, but also postbiotics and peptides, as ingredients that improve skin barrier function, but also affect melanin and sebum levels in individuals. However, the combined effects of these ingredients in a single cosmetic serum have not been sufficiently investigated. Therefore, the aim of this randomized controlled study, conducted at the University of Split School of Medicine (Croatia), was to evaluate the effects of cosmetic products containing these active ingredients. This study was registered with ClinicalTrials.gov (NCT06189105) and has been completed. Primary outcomes were the levels of trans epidermal water loss, skin hydration, erythema, melanin, and sebum, all measured in 25 healthy Caucasian participants. Significant differences between hydration levels were observed at week 4 (61.0 ± 11.2 vs. 68.6 ± 13.3 AU, control and intervention). Moreover, a significant decrease in erythema values from the first to last measurement in the intervention group was observed, (379.9 ± 106.8 vs. 333.6 ± 73.5 AU, baseline values and week 4, intervention group). Interestingly, both the increase in skin hydration levels and the decrease in skin erythema after niacinamide serum application were significant in study participants who did not use sun protection products. It is well known that ultraviolet radiation has detrimental effects on human skin, and our results suggest that niacinamide could help counteract these effects.

Background: During pregnancy, significant cardiovascular changes occur to accommodate fetal growth, and catestatin may play a role in these changes. Evidence suggests that catestatin, a pleiotropic sympathoinhibitory peptide, is involved in multiple cardiovascular pathologies, including hypertensive disorders. The objective of this study was to compare serum catestatin levels between first-trimester pregnant women and non-pregnant women, aiming to investigate catestatin’s role in blood pressure regulation during early pregnancy. Methods: This cross-sectional study included 72 first-trimester pregnant women and 57 age-matched non-pregnant controls, all without known cardiovascular or metabolic disorders. Results: Serum catestatin concentrations were significantly higher in pregnant women compared to controls (12.4 (9.9–21.2) ng/mL vs. 7.1 (4.5–10.9) ng/mL, p < 0.001). However, there was no significant difference in serum catestatin levels between those with a normal and abnormal uterine artery pulsatility index (17.8 (8.3-22.3) ng/mL vs. 12.5 (9.9–22.4) ng/mL, p = 0.962). Similarly, catestatin concentrations did not significantly differ between primiparous and multiparous women (14.0 (11.5–22.4) ng/mL vs. 10.7 (8.8–19.0) ng/mL). A positive correlation was observed between systolic blood pressure and serum catestatin levels in the control group (r = 0.335, p = 0.011) but not in pregnant women. Conclusions: Research on catestatin in pregnancy is still in its early stages, necessitating further studies to fully elucidate its roles and potential therapeutic applications.

Background/Objectives: Renal artery stenosis (RAS) is associated with coronary artery disease (CAD), exacerbation of arterial hypertension, and progression to heart failure, but remains frequently unrecognized in clinical practice. Methods: We conducted a systematic review and meta-analysis of studies by pooling data of patients undergoing CAG due to suspected or stable CAD that received a bilateral renal artery angiography. Results: A total of 31 studies with 31,689 patients were included (mean age 63.2 ± 8.7 years, 20.9% were female). Overall, 13.4% (95%CI 10.5–16.7%) of patients undergoing coronary angiography had significant RAS, with 6.5% (95% CI 4.5–8.9%) and 3.7% (95%CI 2.5–5.2%) having severe and bilateral RAS. The mean weighted proportion of patients with three-vessel coronary disease (3VD) was 25.1 (95%CI 19.6–30.9%) while 4.2% (95%CI 2.6–6.2%) had left main (LM) coronary disease. Patients with RAS compared to those without RAS were significantly older (mean difference, MD 4.2 years (95%CI 3.8–4.6)). The relative risk of RAS was greater for the female sex (risk ratio, 95%CI; RR 1.3, 1.03–1.57), presence of diabetes (RR 1.2, 1.10–1.36), arterial hypertension (RR 1.3, 1.21–1.46), dyslipidemia (RR 1.1, 1.06–1.14), peripheral artery disease (PAD) (RR 2.1, 1.40–3.16), chronic kidney disease (CKD) (RR 2.6, 2.04–3.37), 3VD (RR 1.6, 1.30–1.87), and LM disease (RR 1.8, 1.28–2.47). Smoking had a neutral effect on the risk of RAS occurrence (RR 1.0, 0.94–1.06). Conclusions: RAS is common in patients undergoing coronary angiography. CKD, PAD, older age, and severe CAD were among the strongest predictors for the presence of significant RAS.

Nephrotic syndrome is a clinical syndrome characterized by massive proteinuria, called nephrotic range proteinuria (over 3.5 g per day in adults or 40 mg/m2 per hour in children), hypoalbuminemia, oncotic edema, and hyperlipidemia, with an increasing incidence over several years. Nephrotic syndrome carries severe morbidity and mortality risk. The main pathophysiological event in nephrotic syndrome is increased glomerular permeability due to immunological, paraneoplastic, genetic, or infective triggers. Because of the marked increase in the glomerular permeability to macromolecules and the associated urinary loss of albumins and hormone-binding proteins, many metabolic and endocrine abnormalities are present. Some of them are well known, such as overt or subclinical hypothyroidism, growth hormone depletion, lack of testosterone, vitamin D, and calcium deficiency. The exact prevalence of these disorders is unknown because of the complexity of the human endocrine system and the differences in their prevalence. This review aims to comprehensively analyze all potential endocrine and hormonal complications of nephrotic syndrome and, vice versa, possible kidney complications of endocrine diseases that might remain unrecognized in everyday clinical practice.

Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.

Contact dermatitis is a common inflammatory skin disease that often requires prescription therapy and is associated with adverse reactions. Omega fatty acids have been recognized for their anti-inflammatory effect and could serve as a safer option in contact dermatitis treatment. Therefore, the aim of this randomized controlled study, conducted at the University of Split School of Medicine, was to evaluate the efficacy and safety of omega fatty acids containing topical products in an experimental model of irritant contact dermatitis. This study was registered with ClinicalTrials (NCT06189144) and is closed. The primary outcomes were levels of transepidermal water loss, skin hydration, and skin erythema, all measured using an MPA6 device in 25 healthy participants. A significant difference was observed between the hydration values of the intervention (45.7 ± 12.4) and control groups (31.6 ± 12.3) (p < 0.05) on final measurements (day 10). Moreover, higher erythema levels were observed in participants who were smokers, compared to non-smokers. No adverse drug reactions were observed during the study period. In conclusion, omega fatty acids topical product use shows promise in the treatment of irritant contact dermatitis, and further studies are needed to evaluate efficacy in a larger sample of patients.

Despite the abundance of preclinical data, cardiovascular effects of cannabidiol (CBD) in humans remain controversial. HYPER-H21-4 trial was designed as a randomized, placebo-controlled, crossover trial aimed to explore the effects of chronic CBD dosing on ambulatory blood pressure (BP) and vascular stiffness in hypertensive individuals. In this pre-specified analysis of the trial we aimed to elucidate the anti-inflammatory effects of CBD by measuring the dynamic of serum cytokines. Specifically, interleukin 1β (IL-1β), IL-8, IL-6, IL-10, IL-18, Plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNF-α) and lectin-type oxidized LDL receptor 1 (LOX-1) were measured. A total of 65 patients with primary hypertension were included. After five weeks of oral CBD administration, but not of placebo, serum concentrations of IL-8, IL-10 and IL-18 were significantly lower in comparison to baseline concentrations (p = 0.044, p

Antimicrobial resistance is recognised as one of the top threats healthcare is bound to face in the future. There have been various attempts to preserve the efficacy of existing antimicrobials, develop new and efficient antimicrobials, manage infections with multi-drug resistant strains, and improve patient outcomes, resulting in a growing mass of routinely available data, including electronic health records and microbiological information that can be employed to develop individualised antimicrobial stewardship. Machine learning methods have been developed to predict antimicrobial resistance from whole-genome sequencing data, forecast medication susceptibility, recognise epidemic patterns for surveillance purposes, or propose new antibacterial treatments and accelerate scientific discovery. Unfortunately, there is an evident gap between the number of machine learning applications in science and the effective implementation of these systems. This narrative review highlights some of the outstanding opportunities that machine learning offers when applied in research related to antimicrobial resistance. In the future, machine learning tools may prove to be superbugs’ kryptonite. This review aims to provide an overview of available publications to aid researchers that are looking to expand their work with new approaches and to acquaint them with the current application of machine learning techniques in this field.

Abstract Catestatin (CST) is an important peptide that influences various inflammatory diseases. Our goal was to investigate CST concentrations in patients with RA compared to healthy subjects. This cross-sectional observational study included 80 patients with RA and 80 healthy control subjects. Demographic characteristics and laboratory parameters were recorded. Serum CST levels were determined by an enzyme-linked immunosorbent assay (ELISA). Serum CST levels were significantly higher in RA patients than in the control group (10.53 ± 3.90 vs 5.24 ± 2.37 ng/mL, p

Background and Objectives: Anticoagulants are a well-known risk factor for gastrointestinal bleeding (GIB). In recent years, direct oral anticoagulants (DOACs) have taken a leading role in the treatment and prevention of thromboembolic incidents. The aim of this study was to investigate the prevalence of DOAC-treated patients with GIB whose plasma drug concentrations exceeded the cut-off values reported in the literature and to evaluate their clinical characteristics. Materials and Methods: Patients who were admitted to the Intensive Care Unit in the period 2/2020–3/2022 due to GIB were prospectively included in the study and classified into three groups according to the prescribed type of DOAC (apixaban, rivaroxaban, and dabigatran). For all participants, it was determined if the measured plasma drug levels exceeded the maximum serum concentration (Cmax) or trough serum concentration (Ctrough) obtained from the available data. A comparison of clinical parameters between the patients with and without excess drug values was performed. Results: There were 90 patients (54.4% men) included in the study, of whom 27 were treated with dabigatran, 24 with apixaban, and 39 with rivaroxaban. According to Cmax, there were 34 (37.8%), and according to Ctrough, there were 28 (31.1%) patients with excess plasma drug values. A statistically significant difference regarding excess plasma drug values was demonstrated between DOACs according to both Cmax (p = 0.048) and Ctrough (p < 0.001), with the highest rate in the group treated with dabigatran (55.6% for Cmax and 59.3% for Ctrough). Multivariate logistic regression showed that age (OR 1.177, p = 0.049) is a significant positive and glomerular filtration rate (OR 0.909, p = 0.016) is a negative predictive factor for excess plasma drug values. A total of six (6.7%) patients had fatal outcomes. Conclusions: Plasma drug concentrations exceed cut-off values reported in the literature in more than one-third of patients with GIB taking DOAC, with the highest rate in the dabigatran group. Clinicians should be more judicious when prescribing dabigatran to the elderly and patients with renal failure. In these patients, dose adjustment, plasma drug monitoring, or substitution with other, more appropriate DOACs should be considered.

The clonal hematopoiesis of indeterminate potential (CHIP) is a term used to describe individuals who have detectable somatic mutations in genes commonly found in individuals with hematologic cancers but without any apparent evidence of such conditions. The mortality rate in individuals with CHIP is remarkably higher than the influence ascribed to hematologic malignancies, and it is plausible that cardiovascular diseases (CVD) could elucidate the apparent disparity. Studies have shown that the most frequently altered genes in CHIP are associated with the increased incidence of CVDs, type 2 diabetes mellitus (T2DM) and myeloid malignancies, as well as obesity. Additionally, multiple research studies have confirmed that obesity is also independently associated with these conditions, particularly the development and progression of atherosclerotic CVD. Considering the shared pathogenetic mechanisms of obesity and CHIP, our objective in this review was to investigate both preclinical and clinical evidence regarding the correlation between obesity and CHIP and the resulting implications of this interaction on the pathophysiology of CVDs and malignancies. The pro-inflammatory condition induced by obesity and CHIP enhances the probability of developing both diseases and increases the likelihood of developing CVDs, T2DM and malignancies, suggesting that a dangerous vicious loop may exist. However, it is vital to conduct additional research that will suggest targeted treatment options for obese individuals with CHIP in order to reduce harmful effects connected to these conditions.

We wanted to investigate whether students who study within biomedical fields (i.e., medicine, pharmacy science) differ from those whose studies are not connected to the biomedical field in terms of their attitudes and behaviors related to urinary tract infections (UTIs). This was a cross-sectional survey-based study conducted among 392 female students, of whom 243 attended a biomedical school and 149 (38.0%) attended a non-biomedical school, using a previously published tool. The survey was distributed as an online link via student representatives at different faculties. Only 22 (5.6%) of women felt that they could not recognize a UTI. A greater proportion of biomedical students wiped front to back, while significantly more non-biomedical students chose cotton underwear and avoided daily sanitary pads compared to biomedical students. As many as 215 (54.8%) women stated that they used cranberry preparations. Biomedical students showed greater awareness about possible resistance to repeated treatment (p = 0.002) and greater knowledge of possible interactions of antibiotics (p < 0.001). This study reveals that young women are confident in recognizing an UTIs, are open to alternative treatments, and would consider UTI management in a pharmacy setting. However, it reveals that there might be gaps in their knowledge regarding antibiotic resistance risks, possible interactions, and efficacy of available preparations, as participants from the group of biomedical students showed greater knowledge and different behaviors.

Abstract Aims Soluble suppression of tumourigenicity 2 (sST2) and catestatin (CST) reflect myocardial fibrosis and sympathetic overactivity during the acute worsening of heart failure (AWHF). We aimed to determine serum levels and associations of sST2 and CST with in‐hospital death as well as the association between sST2 and CST among AWHF patients. Methods and results A total of 96 AWHF patients were consecutively enrolled, while levels of sST2 and CST were determined and compared between non‐survivors and survivors. Predictive values of sST2 and CST for in‐hospital death were determined by the penalized multivariable Firth logistic regression. The diagnostic ability of sST2 and CST for in‐hospital death was assessed by the receiver operating characteristic analysis and examined with respect to the N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin I, and C‐reactive protein. The in‐hospital death rate was 6.25%. Serum sST2 and CST levels were significantly higher among non‐survivors than survivors [146.6 (inter‐quartile range, IQR 65.9–156.2) vs. 35.3 (IQR 20.6–64.4) ng/mL, P

Abstract Adropin is a novel peptide mostly associated with energy homeostasis and vascular protection. To our knowledge, there are no studies that investigated its relationship with inflammatory bowel diseases (IBD). The aim of this study was to compare serum adropin levels between 55 patients with IBD (30 Ulcerative colitis (UC) patients, 25 Crohn’s disease (CD) patients) and 50 age/gender matched controls. Furthermore, we explored adropin correlations with IBD severity scores, hsCRP, fecal calprotectin, fasting glucose and insulin levels. Serum adropin levels were significantly lower in patients with IBD in comparison with the control group (2.89 ± 0.94 vs 3.37 ± 0.60 ng/mL, P = 0.002), while there was no significant difference in comparison of UC patients with CD patients (P = 0.585). Furthermore, there was a negative correlation between adropin and fecal calprotectin (r = −0.303, P = 0.025), whereas in the total study population, we found a significant negative correlation with fasting glucose levels (r = −0.222, P = 0.023). A multivariable logistic regression showed that serum adropin was a significant predictor of positive IBD status when enumerated along with baseline characteristics (OR 0.455, 95% CI 0.251–0.823, P = 0.009). Our findings imply that adropin could be involved in complex pathophysiology of IBD, but further larger scale studies are needed to address these findings.

Heart rate (HR) lowering during acute coronary syndrome (ACS) is beneficial as it reduces myocardial oxygen consumption. However, the role of ivabradine as an HR-lowering agent in the setting of ACS is not clear. We aimed to systematically review and synthesize the current evidence on the role of ivabradine use in the ACS. A systematic review was conducted for eligible randomized clinical trials and quasi-experimental studies, between 2009 and 2020, that investigated the use of ivabradine in ACS. Various clinical endpoints were evaluated such as major adverse cardiovascular events, efficacy in HR control, impact on left ventricular (LV) dimensions and function, and overall safety. Eleven publications were included encompassing a total of 1833 patients. The mean age of the examined cohort was 57 ± 11 years and 80 % were men. Seven studies were in the setting of ST-segment elevation myocardial infarction (MI) while the remaining studies also included patients with unstable angina and non-ST-segment elevation MI. Ivabradine was administered as a peroral drug with dosing from 2.5 to 7.5 mg b.i.d. Overall, the addition of ivabradine was superior to the control arm concerning HR control with a good safety profile. Beneficial effects on LV function and potential impact on infarct size reduction were observed as well. The use of ivabradine appeared to not affect short-term mortality. In conclusion, the use of ivabradine for HR control is safe, feasible, and efficacious for HR control in the ACS. Further studies are required to elucidate other potentially beneficial effects of ivabradine.

Obstructive sleep apnea (OSA) has become major public concern and is continuously investigated in new aspects of pathophysiology and management. Urotensin II (UII) is a powerful vasoconstrictor with a role in cardiovascular diseases. The main goal of this study was to evaluate serum UII levels in OSA patients and matched controls. A total of 89 OSA patients and 89 controls were consecutively enrolled. A medical history review and physical examination of the participants was conducted, with polysomnography performed in the investigated group. UII levels and other biochemical parameters were assessed according to the standard laboratory protocols. The median AHI in the OSA group was 39.0 (31.4–55.2) events/h, and they had higher levels of hsCRP when compared to control group (2.87 ± 0.71 vs. 1.52 ± 0.68 mg/L; p < 0.001). Additionally, serum UII levels were significantly higher in the OSA group (3.41 ± 1.72 vs. 2.18 ± 1.36 ng/mL; p < 0.001), while positive correlation was found between UII levels and hsCRP (r = 0.450; p < 0.001) and systolic blood pressure (SPB) (r = 0.317; p < 0.001). Finally, multiple regression analysis showed significant association of UII levels with AHI (0.017 ± 0.006, p = 0.013), SBP (0.052 ± 0.008, p < 0.001) and hsCRP (0.538 ± 0.164, p = 0.001). As UII levels were associated with blood pressure and markers of inflammation and OSA severity, it might play an important role in the complex pathophysiology of OSA and its cardiometabolic complications.

Cannabidiol (CBD) is a non-psychoactive cannabinoid, and available evidence suggests potential efficacy in the treatment of many disorders. DehydraTECH™2.0 CBD is a patented capsule formulation that improves the bioabsorption of CBD. We sought to compare the effects of CBD and DehydraTECH™2.0 CBD based on polymorphisms in CYP P450 genes and investigate the effects of a single CBD dose on blood pressure. In a randomized and double-blinded order, 12 females and 12 males with reported hypertension were given either placebo capsules or DehydraTECH™2.0 CBD (300 mg of CBD, each). Blood pressure and heart rate were measured during 3 h, and blood and urine samples were collected. In the first 20 min following the dose, there was a greater reduction in diastolic blood pressure (p = 0.025) and mean arterial pressure MAP (p = 0.056) with DehydraTECH™2.0 CBD, which was probably due to its greater CBD bioavailability. In the CYP2C9*2*3 enzyme, subjects with the poor metabolizer (PM) phenotype had higher plasma CBD concentrations. Both CYP2C19*2 (p = 0.037) and CYP2C19*17 (p = 0.022) were negatively associated with urinary CBD levels (beta = −0.489 for CYP2C19*2 and beta = −0.494 for CYP2C19*17). Further research is required to establish the impact of CYP P450 enzymes and the identification of metabolizer phenotype for the optimization of CBD formulations.

Because heart failure (HF) is more lethal than some of the common malignancies in the general population, such as prostate cancer in men and breast cancer in women, there is a need for a cost-effective prognostic biomarker in HF beyond natriuretic peptides, especially concerning congestion, the most common reason for the hospitalisation of patients with worsening of HF. Furthermore, despite diuretics being the mainstay of treatment for volume overload in HF patients, no randomised trials have shown the mortality benefits of diuretics in HF patients, and appropriate diuretic titration strategies in this population are unclear. Recently, carbohydrate antigen (CA) 125, a well-established marker of ovarian cancer, emerged as both a prognostic indicator and a guide in tailoring decongestion therapy for patients with HF. Hence, in this review the authors present the molecular background regarding the role of CA125 in HF and address valuable clinical aspects regarding the relationship of CA125 with both prognosis and therapeutic management in HF.

The autonomic nervous system is crucial in initiating and maintaining atrial fibrillation (AF). Catestatin is a multipurpose peptide that regulates cardiovascular systems and reduces harmful, excessive activity of the sympathetic nervous system by blocking the release of catecholamines. We aimed to determine whether serum catestatin concentrations are associated with AF severity, duration indices, and various clinical and laboratory indicators in these individuals to better define the clinical value of catestatin in patients with AF. The present single center study enrolled 73 participants with AF and 72 healthy age-matched controls. Serum catestatin concentrations were markedly higher in AF patients than controls (14.11 (10.21–26.02) ng/mL vs. 10.93 (5.70–20.01) ng/mL, p = 0.013). Furthermore, patients with a more severe form of AF had significantly higher serum catestatin (17.56 (12.80–40.35) vs. 10.98 (8.38–20.91) ng/mL, p = 0.001). Patients with higher CHA2DS2-VASc scores (17.58 (11.89–37.87) vs. 13.02 (8.47–22.75) ng/mL, p = 0.034) and higher NT-proBNP levels (17.58 (IQR 13.91–34.62) vs. 13.23 (IQR 9.04–22.61), p = 0.036) had significantly higher serum catestatin concentrations. Finally, AF duration correlated negatively with serum catestatin levels (r = −0.348, p = 0.003). The results of the present study implicate the promising role of catestatin in the intricate pathophysiology of AF, which should be explored in future research.

It has been well established that diabetes mellitus (DM) is considered as a core risk factor for the development of cardiovascular diseases. However, what is less appreciated is the fact that DM may affect cardiac function irrespective of cardiac pathologies to which it contributes, such as coronary artery disease and hypertension. Although echocardiography provides accurate and reproducible diagnostic and prognostic data in patients with DM, its use in these patients is still underappreciated, resulting in progression of DM-related heart failure in many patients. Hence, in the present review, we aimed to discuss the role of echocardiography in the contemporary management of diabetic cardiomyopathy (DCM), as well as the role of emerging echocardiographic techniques, which may contribute to earlier diagnosis and more appropriate management of this complication of DM. In order to improve outcomes, focus must be placed on early diagnosis of this condition using a combination of echocardiography and emerging biomarkers, but perhaps the more important thing is to change perspective when it comes to the clinical importance of DCM.

Advanced glycation end products (AGEs) represent an endogenously produced or exogenously derived group of compounds derived from nonenzymatic glycation. Recent experimental studies are suggesting that AGEs could play an important role in the skin’s quality and its aging process. Hence, the aim of this study was to clinically evaluate the AGEs and skin quality parameters across different age groups in the general population. The study included 237 participants. Melanin, erythema, hydration, friction and transepidermal water loss (TEWL) were evaluated using noninvasive probes, while AGEs were evaluated using a skin autofluorescence reader. There was a significant positive correlation between AGEs and the amount of melanin (p < 0.001), erythema (p < 0.001) and TEWL (p < 0.001), while there was a significant negative correlation between AGEs and hydration (p < 0.001) and friction (p < 0.001). After dividing the sample into three groups depending on their age, in all three groups, there was a significant positive correlation between AGEs and the melanin count (p < 0.001) and TEWL (p < 0.001), while there was a significant negative correlation between AGEs and skin hydration (p < 0.001). Multiple linear regression analysis showed that the level of AGEs as a dependent variable retained a significant association with age (p < 0.001), melanin (p < 0.001), erythema (p = 0.005) and TEWL (p < 0.001) as positive predictors. Moreover, AGEs retained a significant association with skin hydration (p < 0.001) and friction (p = 0.017) as negative predictors. These outcomes imply that AGEs could be linked with the complex physiology of the skin and its aging process.

Obstructive sleep apnea (OSA) is a chronic, sleep-related breathing disorder. It is characterized by a nocturnal periodic decrease or complete stop in airflow due to partial or total collapse of the oropharyngeal tract. Surgical treatment of OSA is constantly evolving and improving, especially with the implementation of new technologies, and this is needed because of the very heterogeneous reasons for OSA due to the multiple sites of potential airway obstruction. Moreover, all of these surgical methods have advantages and disadvantages; hence, patients should be approached individually, and surgical therapies should be chosen carefully. Furthermore, while it is well-established that oromaxillofacial surgery (OMFS) provides various surgical modalities for treating OSA both in adults and children, a new aspect is emerging regarding the possibility that some of the surgeries from the OMFS domain are also causing OSA. The latest studies are suggesting that surgical treatment in the head and neck region for causes other than OSA could possibly have a major impact on the emergence of newly developed OSA, and this issue is still very scarcely mentioned in the literature. Both oncology, traumatology, and orthognathic surgeries could be potential risk factors for developing OSA. This is an important subject, and this review will focus on both the possibilities of OMFS treatments for OSA and on the OMFS treatments for other causes that could possibly be triggering OSA.

Background: The aim of this study was to explore community pharmacy service users’ attitudes and opinions towards vaccination programs in pharmacy conducted by a doctor of medicine or a pharmacist. Methods: The questionnaire used in this study comprised 40 items about demographics, sources of information, attitudes about vaccination, attitudes about vaccination in community pharmacies, and willingness to pay for such a service. Results: A total of 385 people participated in this study. Injection was the preferred route of administration of vaccine for more than half of study participants (50.6%). Univariate analysis showed that those who had a healthcare worker as a family member and those familiar with the HPV vaccine had better attitudes; however, those results were no longer significant after factoring in other variables in multivariate analysis. More than half (59.2%) of the study population would consider vaccination service in community pharmacies only if it were free or covered by the national health insurance. Conclusions: More than half of the participants believed that providing vaccination services in community pharmacies would result in greater vaccination rates for seasonal illnesses. However, around half would prefer that it were conducted exclusively by a physician. Less than 10% of the study participants would pay out of their pocket for such a service.

The increase in antibiotic resistance to Helicobacter pylori (H. pylori) is associated with a decrease in the effectiveness of eradication therapy. Although some success has been achieved by adjusting therapeutic regimens according to local data on resistance to certain antibiotics, a new approach is needed to ensure a better therapeutic response. Tailored therapy, based on sensitivity tests to antibiotics, is increasingly proving to be a superior therapeutic option, even as a first-line therapy. Moreover, the recently published Maastricht VI guidelines emphasize utilizing a susceptibility-guided strategy in respect to antibiotic stewardship as the first choice for eradication therapy. In addition, polymerase chain reaction (PCR) technology is becoming a standard tool in the diagnosis of H. pylori infections through non-invasive testing, which further optimizes the eradication process. We provide a review regarding the current position of the individualized approach in eradication therapy and its future prospects. Based on novel understandings, the personalized approach is an effective strategy to increase the successful eradication of H. pylori infections.

Abstract Background Adverse drug reaction (ADR) reporting practices by health care professionals remain poor. Over-the-counter (OTC) drugs are perceived as safe; however, they can also cause ADRs. The objective of this study was to analyze ADR reporting for OTC drugs in a 10-year period, in order to evaluate frequency of ADRs, population that ADRs most affect and reporters of ADRs of OTC drugs in Croatia. Methods Spontaneously reported ADRs of non-analgesic OTC drugs, collected from January 2008 to December 2017 were analyzed. Data was obtained from Agency for Medicinal Products and Medical Devices of Croatia (HALMED). Results There were 547 ADRs of OTC drugs reported in total and an increase in number of reports through the years was observed. Pharmacists reported 45.4% of all ADRs, and were most frequent reporters (p

Although the role of inflammation and adverse cardiac remodeling in myocardial infarction (MI) have been extensively explored, gaps in knowledge on the complex interaction between these processes still exist. Data suggest that DNAX accessory molecule-1 (DNAM-1), an activating receptor implicated in NK cell education, may be involved in cardiac remodeling following coronary artery occlusion. In the present study, we aimed to explore the dynamic of DNAM-1+ monocytes and NK cells in peripheral blood in the early phase following reperfusion in patients with ST-elevation MI (STEMI). The study enrolled 49 patients older than 18 years of age diagnosed with STEMI, referred to primary percutaneous coronary intervention (pPCI). Blood samples were obtained at three distinct points (at admission, 3 h, and 24 h after pPCI) and analyzed using flow cytometry. The number of circulating DNAM-1+ monocytes (CD16++ and CD14++) and CD56dimCD16++NK cells was significantly reduced 3 h after pPCI and subsequently returned to initial levels 24 h after procedure (p = 0.003, p < 0.001, and p = 0.002, respectively). Notably, such dynamic was dependent on age of patients. A positive correlation between high sensitivity troponin I levels and number of CD16++DNAM-1+ monocytes in peripheral blood 3 h after pPCI was observed (r = 0.431, p = 0.003). In conclusion, in the present study we delineated the post-reperfusion dynamic of DNAM-1-expresing leukocytes. Additionally, we demonstrated that the number of CD16++ DNAM-1+ monocytes correlate with the extent of myocardial injury.

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated beneficial renoprotective effects, which culminated in the recent approval of their use for patients with chronic kidney disease (CKD), following a similar path to one they had already crossed due to their cardioprotective effects, meaning that SGLT2i represent a cornerstone of heart failure therapy. In the present review, we aimed to discuss the pathophysiological mechanisms operating in CKD that are targeted with SGLT2i, either directly or indirectly. Furthermore, we presented clinical evidence of SGLT2i in CKD with respect to the presence of diabetes mellitus. Despite initial safety concerns with regard to euglycemic diabetic ketoacidosis and transient decline in glomerular filtration rate, the accumulating clinical data are reassuring. In summary, although SGLT2i provide clinicians with an exciting new treatment option for patients with CKD, further research is needed to determine which subgroups of patients with CKD will benefit the most, and which the least, from this therapeutical option.

Accumulating data suggest that various neurologic manifestations are reported in critically-ill COVID-19 patients. Although low testosterone levels were associated with poor outcomes, the relationship between testosterone levels and indices of brain injury are still poorly understood. Therefore, we aimed to explore whether testosterone levels are associated with glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), biomarkers of brain injury, in patients with a severe form of COVID-19. The present study was conducted on 65 male patients aged 18–65 with severe COVID-19. Blood samples were collected at three time points: upon admission to ICU, 7 days after, and 14 days after. In patients with neurological sequels (n = 20), UCH-L1 serum concentrations at admission were markedly higher than in patients without them (240.0 (155.4–366.4) vs. 146.4 (92.5–243.9) pg/mL, p = 0.022). GFAP concentrations on admission did not differ between the groups (32.2 (24.2–40.1) vs. 29.8 (21.8–39.4) pg/mL, p = 0.372). Unlike GFAP, UCH-L1 serum concentrations exhibited a negative correlation with serum testosterone in all three time points (r = −0.452, p < 0.001; r = −0.430, p < 0.001 and r = −0.476, p = 0.001, respectively). The present study suggests that the traumatic brain injury biomarker UCH-L1 may be associated with neurological impairments seen in severe COVID-19. Moreover, a negative correlation between UCH-L1 and serum testosterone concentrations implies that testosterone may have a role in the development of neurological sequels in critically-ill COVID-19 patients.

Accumulating data suggests that catestatin, an eclectic neuroendocrine peptide, is involved in the pathophysiology of primary hypertension (PH). Nevertheless, clinical studies concerning its role in PH are still scarce. Therefore, in the present study, we aimed to explore an association between serum catestatin levels, ambulatory blood pressure (BP) and arterial stiffness in patients with PH and healthy controls. In this single-center study, 72 patients aged 40–70 diagnosed with PH, and 72 healthy controls were included. In patients with PH, serum catestatin concentrations were significantly higher in comparison to the healthy controls (29.70 (19.33–49.48) ng/mL vs. 5.83 (4.21–8.29) ng/mL, p < 0.001). Untreated patients had significantly higher serum catestatin than patients treated with antihypertensive drugs (41.61 (22.85–63.83) ng/mL vs. 24.77 (16.41–40.21) ng/mL, p = 0.005). Multiple linear regression analysis showed that serum catestatin levels retained a significant association with mean arterial pressure (β ± standard error, 0.8123 ± 0.3037, p < 0.009) after model adjustments for age, sex and body mass index. Finally, catestatin levels positively correlated with pulse wave velocity (r = 0.496, p < 0.001) and central augmentation index (r = 0.441, p < 0.001), but not with peripheral resistance. In summary, increased serum catestatin concentration in PH, predominantly in the untreated subgroup, and its association with ambulatory BP and arterial stiffness address the role of this peptide in PH.

Background: The utilization of pharmacogenomics in everyday practice has shown several notable benefits. Keeping in mind the rising trend of applicability of pharmacogenomics and personalized medicine, we sought to compare the attitudes of future healthcare workers in different branches of the healthcare system. Methods: The present study was conducted as a questionnaire-based cross-sectional study in October of 2020. Students eligible to participate were all the students of the University of Split School of Medicine enrolled in the academic year 2020/2021. Results: The number of students that participated in the study was 503. Students were most interested in clinical examples of pharmacogenomics (31.4%) and the benefits of pharmacogenomics in clinical practice (36.4%). Furthermore, 72.6% of all students agreed that they should be able, in their future practice, to identify patients that could benefit from genetic testing. Conclusion: At the present time, the lack of education and appropriate clinical guidelines appear to be the major barriers to the clinical application of pharmacogenomics, especially in Croatia. Hence, in order to support health care professionals’ evidence-based therapeutic recommendations with patients’ pharmacogenomic data, universities should offer more pharmacogenomics education in their curricula.

Abstract Background The aim of this study was to investigate whether marketed antibiotics package sizes are in accordance with treatment durations recommended in guidelines for prescribing antibiotics in sore throat and urinary tract infections. Methods National drug database was searched with limitation to Antibacterials for systemic use. Formulations which did not have pre-specified dosage unit by the manufacturer were excluded (e.g. powders for oral solutions). The final list contained 94 drugs with 23 different active substances. This list was then cross-referenced with selected antimicrobial prescribing guidelines provided by Intersectoral Society for Antibiotic Resistance Control (ISKRA), National Institute for Health and Care Excellence (NICE) and The Infectious Diseases Society of America (IDSA). Results Seven packages matched ISKRA guidelines on sore throat while 16 were mismatched. Considering drug packages under reimbursement, 3 matched ISKRA guidelines and 8 were mismatched. Only 3 packages matched IDSA guidelines for comparable indications, and 18 were mismatched. When considering NICE guidelines there were 5 mismatched and only one package that was in accordance with the guidelines. ISKRA guidelines for urinary tract infections matched 23 packages and mismatched 58 packages. IDSA guidelines for urinary tract infections matched one package and were mismatched in 15 cases. Conclusions One of the causes of leftover antibiotics is poor accordance of antibiotic package size with treatment recommendation duration. This should be identified as a potential target for reduction of excess antibiotics in the community. Measures that promote patient adherence to therapy and patient education should be considered essential to manage proper handling of leftover antibiotics.

Background: Urotensin-II (U-II) is a short cyclic peptide that is widely recognized as one of the most potent vasoconstrictors. U-II plays a role in the pathophysiology of MS, participating in the development of essential hypertension, insulin resistance, hyperglycemia, and a proinflammatory state. Methods: This study comprised 52 obese children and adolescents with a body mass index (BMI) z score > 2, aged 10 to 18 years. Serum levels of U-II were assessed using an enzyme-linked immunosorbent assay along with other standard biochemical parameters. Results: Elevated serum levels of U-II were recorded in the group of obese subjects with MS when compared with the group of obese subjects without MS (4.99 (8.97–3.16) vs. 4.17 (5.17–2.03) ng/mL, median and IQR, p = 0.026). Furthermore, a subgroup of study subjects with high blood pressure had significantly higher U-II levels in comparison with the normotensive subgroup (4.98 (7.19–3.22) vs. 3.32 (5.06–1.97) ng/mL, p = 0.027), while the subgroup with a positive family history of high blood pressure had significantly higher U-II levels when compared with subjects who had a negative family history of elevated blood pressure (5.06 (6.83–4.45) vs. 3.32 (6.13–2.21) ng/mL, p = 0.039). Conclusions: To the best of the author’s knowledge, this is the first study on the levels of U-II in obese children and adolescents, including a possible link to MS.

Adropin is a secretory protein that mainly modulates metabolic homeostasis and endothelial function. There is growing evidence supporting association of adropin with various inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to compare serum adropin levels between 70 patients with RA and 70 matched healthy controls. Furthermore, we explored adropin correlations with RA disease activity, glucose metabolism parameters and inflammatory biomarkers. Serum adropin levels were determined by a competitive enzyme-linked immunosorbent assay. Serum adropin levels were significantly lower in RA patients than in the control group (2.85 ± 0.91 vs. 4.02 ± 0.99 ng/mL, p < 0.001). In the RA group, serum adropin levels had a significant negative correlation with total cholesterol (r = −0.172, p = 0.043), HbA1c (r = −0.406, p < 0.001), fasting glucose (r = −0.377, p < 0.001) and HOMA-IR (the homeostasis model assessment-estimated insulin resistance; (r = −0.315, p = 0.008)). Multiple linear regression analysis showed that serum adropin levels retained a significant association with levels of fasting glucose (β ± SE, −0.450 ± 0.140, p = 0.002) and HbA1c (−0.528 ± 0.223, p = 0.021) after model adjustments. These findings imply that adropin could have an impact on metabolic homeostasis in RA, although further well-designed studies are warranted in order to establish this.

As early commencement of inflammatory bowel disease (IBD) treatment has been shown to substantially improve outcomes, it is of utmost importance to make a timely diagnosis of this disease. Despite undisputed sensitivity of fecal calprotectin, the most widely accepted IBD biomarker, in discriminating between irritable bowel syndrome (IBS) and IBD, as well as recognized role in monitoring disease activity and response to therapy, perhaps the biggest setback of calprotectin use in IBD is lack of specificity. Therefore, an additional biomarker in IBD is warranted. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, recently emerged as a viable candidate for this role. So far, overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus, where BAFF-inhibitor belimumab was approved for treatment. As BAFF levels were also shown to correlate with indices of IBD, in this review we aimed to summarize the current evidence with respect to the role of BAFF in diagnosis and assessing the activity of IBD, as well as putative therapeutic implications that may arise from exploring of this relation.

Accounting for almost one-third of the global mortality, cardiovascular diseases (CVDs) represent a major global health issue. Emerging data suggest that most of the well-established mechanistic explanations regarding the cardiovascular pathophysiology are flawed, and cannot fully explain the progression and long-term effects of these diseases. On the other hand, dysregulation of the sympathetic nervous system (SNS) has emerged as an important player in the pathophysiology of CVDs. Even though upregulated SNS activity is an essential compensatory response to various stress conditions, in the long term, it becomes a major contributor to both cardiac dysfunction and vascular damage. Despite the fact that the importance of SNS hyperactivity in the setting of CVDs has been well-appreciated, its exact quantification and clinical application in either diagnostics or therapy of CVDs is still out of reach. Nevertheless, in recent years a number of novel laboratory biomarkers implicated in the pathophysiology of SNS activation have been explored. Specifically, in this review, we aimed to discuss the role of catestatin, a potent physiological inhibitor of catecholamine spillover that offers cardioprotective effects. Limited data indicate that catestatin could also be a reliable indirect marker of SNS activity and it is likely that high CST levels reflect advanced CV disease burden. Consequently, large-scale studies are required to validate these observations in the upcoming future.

Although a large amount of data supports the crucial role of endothelial dysfunction (ED) in cardiovascular diseases (CVDs), there is a large bench-to-bedside chasm between basic and clinical research of ED, limiting the implementation of these findings in everyday clinical settings. Hence, it is important to further investigate the pathophysiological mechanisms underlying ED and find modalities that will alleviate its clinical implementation. Adropin, a highly conserved peptide hormone secreted primarily by the liver, recently emerged as an important regulatory component of the vascular endothelium. Specifically, the vasoprotective role of adropin is achieved mainly by affecting endothelial NO synthesis. Thus, in this review, we aimed to summarize the current knowledge regarding the role of adropin in physiological processes and address the protective role of adropin in endothelium with consequent implications to CV pathologies. We focused on data regarding the role of adropin in the clinical setting, with concurrent implications to future clinical use of adropin. Studies suggest that plasma levels of adropin correlate with indices of ED in various pathologies and enhanced disease progression, implying that adropin may serve as a useful biomarker of ED in the upcoming future. On the other hand, despite notable results with respect to therapeutic potential of adropin in preliminary experiments, further well-designed studies are warranted in order to establish if adropin might be beneficial in this setting.

With the rising prevalence of Inflammatory bowel disease (IBD) worldwide, and the rising cost of treatment with novel biological drugs, there is an increasing interest in various diets and natural foods as a potential way to control/modulate IBD. As recent data indicates that diet can modify the metabolic responses essential for the resolution of inflammation, and as wine compounds have been shown to provide substantial anti-inflammatory effect, in this review we aimed to discuss the current evidence concerning the impact of biological compounds present in wine on IBD. A number of preclinical studies brought forth strong evidence on the mechanisms by which molecules in wine, such as resveratrol or piceatannol, provide their anti-inflammatory, anti-oxidative, anti-tumor, and microbiota-modulation effects. However, concerning the effects of alcohol, it is still unclear how the amount of ethanol ingested within the framework of moderate wine consumption (1–2 glasses a day) affects patients with IBD, as human studies regarding the effects of wine on patients with IBD are scarce. Nevertheless, available evidence justifies the conductance of large-scale RCT trials on human subjects that will finally elucidate whether wine can offer real benefits to the IBD population.

BackgroundThe primary objective of this study was to compare concomitant and hybrid therapy in the first line eradication treatment of Helicobacter pylori infection in Split-Dalmatia County, Croatia, in which clarithromycin resistance is above 20%. The secondary objective of the study was to determine and compare compliance and adverse events rate between these therapeutic protocols.Materials and methodsIn an open-label, randomised clinical trial 140 patients total with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 g, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or hybrid (esomeprazole 40 mg and amoxicillin 1 g twice daily during 14 days with adding metronidazole 500 mg and clarithromycin 500 mg twice daily, in the last 7 days,) treatment group.ResultsEradication rates for concomitant group and hybrid therapy group were 84.1% (58/69) and 83.1% (59/71) respectively in the intention-to-treat analysis and 96.7% (58/60) and 95.2% (59/62) in per-protocol analysis. There was no significant difference between the groups (ITT analysis: P = 0.878; PP analysis: P = 0.675). Adverse events were more frequent in the concomitant group (33.3% vs 18.3%, P = 0.043). There was no difference among groups regarding compliance rate.ConclusionHybrid therapy has similar eradication rate as concomitant therapy, with lower adverse events rate. In the era of increasing antibiotic resistance, eradication regime with less antibiotic's usage, as hybrid therapy, should be reasonable first line treatment choice for H. pylori infection. Clinical Trials, gov: NCT03572777.

Background and Objectives: Helicobacter pylori (H. pylori) infection impairs quality of life. However, whether eradication therapy ameliorates gastrointestinal symptoms remains questionable. The main objective of this study was to evaluate the influence of H. pylori eradication therapy on gastrointestinal symptoms. Materials and Methods: A total of 140 patients, 59 women and 81 men, with a mean age of 61 and suffering from H. pylori infection in the University Hospital of Split, Croatia, were enrolled in the study. Patients were randomly assigned to either concomitant or hybrid therapies. The Gastrointestinal Symptom Rating Scale (GSRS) questionnaire was completed by patients prior to and after the eradication therapy. Results: In both groups, the total GSRS score improved significantly after therapy. In the concomitant group, the abdominal pain score, reflux symptoms score and indigestion score decreased significantly after therapy. In the group with hybrid therapy, all five groups of symptoms (abdominal pain, reflux symptoms, indigestion, diarrhea and constipation) significantly decreased after therapy. Patients with adverse events had significantly higher total GSRS scores after eradication therapy. Conclusions: H. pylori eradication therapy could alleviate gastrointestinal symptoms regardless of the treatment used, but the favorable effect seemed to be more pronounced after hybrid therapy.

The literature indicates that the limited pharmacovigilance knowledge demonstrated by healthcare professionals is the main reason for the underreporting of adverse drug reactions. Therefore, the main objective of this study was to investigate pharmacy, dental and medical students’ knowledge and attitudes to pharmacovigilance and pharmacovigilance education. The cross-sectional questionnaire study was conducted at the University of Split School of Medicine in November 2020. In total, 350 students participated in the study. The results have shown that pharmacy students showed a significantly higher knowledge score compared to dental and medical students (P < 0.001). In total 92.2% of pharmacy, 21.8% of dental and 70.8% of medical students had knowledge of patients’ involvement in adverse drug reactions, reporting (P < 0.001). Interestingly, only 44.3% of all students knew that adverse drug reactions could be reported using a mobile application. Moreover, significantly more pharmacy students (74.4%) were aware of the adverse drug reactions monitoring center in Croatia, with 47.5% of dental and 39.2% of medical students correctly identifying it (P < 0.001). The results showed that most students felt that pharmacovigilance was not adequately covered in curricula; therefore, there is a great need to increase the knowledge and awareness of pharmacovigilance among students aspiring to become future healthcare professionals, and improve their reporting practice in clinical future.

The “Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines” (CRUSADE) score emerged as a predictor of major bleeding in patients presenting with the acute coronary syndrome. On the other hand, previous studies established the association of dephosphorylated-uncarboxylated Matrix Gla protein (dp-ucMGP) and vitamin K, as well as their subsequent impact on coagulation cascade and bleeding tendency. Therefore, in the present study, we explored if dp-ucMGP plasma levels were associated with CRUSADE bleeding score. In this cross-sectional study, physical examination and clinical data, including plasma dp-ucMGP levels, were obtained from 80 consecutive patients with acute myocardial infarction (AMI). A significant positive correlation was found between CRUSADE bleeding score and both dp-ucMGP plasma levels (r = 0.442, p < 0.001) and risk score of in-hospital mortality (r = 0.520, p < 0.001), respectively. In comparing the three risk groups of risk for in-hospital bleeding, the high/very high-risk group had significantly higher dp-ucMGP levels from both very low/low group (1277 vs. 794 pmol/L, p < 0.001) and the moderate group (1277 vs. 941 pmol/L, p = 0.047). Overall, since higher dp-ucMGP levels were associated with elevated CRUSADE score and prolonged hemostasis parameters, this may suggest that there is a biological link between dp-ucMGP plasma levels and the risk of bleeding in patients who present with AMI.

To replace mechanical ventilation (MV), which represents the cornerstone therapy in severe COVID-19 cases, high-flow nasal oxygen (HFNO) therapy has recently emerged as a less-invasive therapeutic possibility for those patients. Respecting the risk of MV delay as a result of HFNO use, we aimed to evaluate which parameters could determine the risk of in-hospital mortality in HFNO-treated COVID-19 patients. This single-center cohort study included 102 COVID-19-positive patients treated with HFNO. Standard therapeutic methods and up-to-date protocols were used. Patients who underwent a fatal event (41.2%) were significantly older, mostly male patients, and had higher comorbidity burdens measured by CCI. In a univariate analysis, older age, shorter HFNO duration, ventilator initiation, higher CCI and lower ROX index all emerged as significant predictors of adverse events (p < 0.05). Variables were dichotomized and included in the multivariate analysis to define their relative weights in the computed risk score model. Based on this, a risk score model for the prediction of in-hospital mortality in COVID-19 patients treated with HFNO consisting of four variables was defined: CCI > 4, ROX index ≤ 4.11, LDH-to-WBC ratio, age > 65 years (CROW-65). The main purpose of CROW-65 is to address whether HFNO should be initiated in the subgroup of patients with a high risk of in-hospital mortality.

Coronary artery disease (CAD) is widely recognized as one of the most important clinical entities. In recent years, a large body of accumulated data suggest that coronary artery calcification, a process highly prevalent in patients with CAD, occurs via well-organized biologic processes, rather than passively, as previously regarded. Matrix Gla protein (MGP), a vitamin K-dependent protein, emerged as an important inhibitor of both intimal and medial vascular calcification. The functionality of MGP hinges on two post-translational modifications: phosphorylation and carboxylation. Depending on the above-noted modifications, various species of MGP may exist in circulation, each with their respective level of functionality. Emerging data suggest that dysfunctional species of MGP, markedly, dephosphorylated-uncarboxylated MGP, might find its application as biomarkers of microvascular health, and assist in clinical decision making with regard to initiation of vitamin K supplementation. Hence, in this review we summarized the current knowledge with respect to the role of MGP in the complex network of vascular calcification with concurrent inferences to CAD. In addition, we discussed the effects of warfarin use on MGP functionality, with concomitant implications to coronary plaque stability.

Despite significant strides to mitigate the complications of acute coronary syndrome (ACS), this clinical entity still represents a major global health burden. It has so far been well-established that most of the plaques leading to ACS are not a result of gradual narrowing of the vessel lumen, but rather a result of sudden disruption of vulnerable atherosclerotic plaques. As most of the developed imaging modalities for vulnerable plaque detection are invasive, multiple biomarkers were proposed to identify their presence. Owing to the pivotal role of lipids and inflammation in the pathophysiology of atherosclerosis, most of the biomarkers originated from one of those processes, whereas recent advancements in molecular sciences shed light on the use of microRNAs. Yet, at present there are no clinically implemented biomarkers or any other method for that matter that could non-invasively, yet reliably, diagnose the vulnerable plaque. Hence, in this review we summarized the available knowledge regarding the pathophysiology of plaque instability, the current evidence on potential biomarkers associated with plaque destabilization and finally, we discussed if search for biomarkers could one day bring us to non-invasive, cost-effective, yet valid way of diagnosing the vulnerable, rupture-prone coronary artery plaques.

Adropin is a novel pleotropic peptide involved in energy homeostasis, with possible contribution to cardiovascular protection through production of nitric oxide and subsequent blood pressure regulation. Given that patients undergoing hemodialysis (HD) are related with high cardiovascular risk, hyperlipidemia, chronic low-grade inflammation, and malnutrition the aim of our study was to investigate serum adropin levels in HD patients to evaluate possible associations with nutritional status and other relevant clinical and laboratory parameters. The study included 70 patients on HD and 60 healthy controls. Serum adropin levels were determined by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit. Serum adropin levels were significantly lower in the HD group compared to the control group (2.20 ± 0.72 vs. 4.05 ± 0.93 ng/mL, p < 0.001). Moreover, there was a significant negative correlation with malnutrition-inflammation score (r = −0.476, p < 0.001), dialysis malnutrition score (r = −0.350, p = 0.003), HD duration (r = −0.305, p = 0.010), and high sensitivity C-reactive protein (hsCRP) (r = −0.646, p < 0.001). Additionally, there was a significant negative correlation between adropin levels and pre-dialysis systolic (r = −0.301, p = 0.011) and diastolic blood pressure (r = −0.299, p = 0.011). These results are implying that adropin is potentially involved in the pathophysiological mechanisms of chronic kidney disease (CKD)/HD and its complications. However, future larger scale longitudinal studies need to further address it.