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In modern cardiology, sodium‐glucose cotransporter 2 (SGLT2) inhibitors are critical components of heart failure (HF) treatment algorithms and exert their effects primarily by preventing glucose reabsorption and facilitating its urinary excretion. The objective was to systematically review randomized controlled trials (RCTs) assessing the effects of SGLT2 inhibitors, particularly canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, sotagliflozin (dual SGLT inhibitor), and their use in HF. Systematic searches of PubMed/Medline, The Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were performed. There were no restrictions imposed on the date and status of publication; however, there were restrictions on language for the searched studies. A total of 1139 records were identified in the bibliographic searches from both databases and the register of choice for this systematic review. Following duplicate removal, screening for titles and abstracts, and thorough assessment of full‐text articles, 12 RCTs met the inclusion criteria. Altogether, 83 878 patients were included in this review. Among the included studies, two RCTs, with six respective reports, investigated canagliflozin, four RCTs with 13 derived reports investigated dapagliflozin, three RCTs with 12 separate reports studied the effects of empagliflozin, one RCT and its three respective reports assessed ertugliflozin's effects, and two RCTs with one added report investigated the dual inhibitor sotagliflozin. Pooled meta‐analytic effects of SGLT2 inhibitors were as follows: on atrial fibrillation odds ratio (OR) = 0.83, 95% confidence interval (CI): 0.68–1.01, prediction interval (PI): 0.57–1.19; on HF hospitalization OR = 0.69, 95% CI: 0.60–0.78, PI: 0.60–0.78; on cardiovascular death OR = 0.82, 95% CI: 0.58–1.15, PI: 0.42–1.60; and on major adverse cardiovascular events OR = 0.90, 95% CI: 0.77–1.06, PI: 0.71–1.15. SGLT2 inhibitors significantly improve the quality of life in HF patients. Their beneficial effects on HF, especially in left ventricular dysfunction, have made their use possible irrespective of diabetes mellitus or atrial fibrillation status.

M. Halilčević, E. Begić, A. Džubur, A. Džubur, B. Aziri, A. Durak-Nalbantić, A. Begić, Ammar Brkić et al.

Aim To examine a relation of thyroid function, neutrophil-lymphocyte ratio (NLR) with left ventricular function measured through the left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction treated with percutaneous coronary intervention (PCI). Methods This prospective research involved 160 consecutive patients with acute myocardial infarction. Patients were divided into those with normal thyroid hormone status (n=80) and those with hypothyroidism (newly diagnosed) (n=80). Inflammatory parameters and parameters of hormonal status were taken for analysis: thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3). All patients underwent transthoracic echocardiographic examination (TTE) five days upon admission, and left ventricular ejection fraction (LVEF) was analysed. Results Significant difference between the two groups was verified in values of T3, T4, erythrocytes, haemoglobin, haematocrit, neutrophil, lymphocytes, NLR, C-reactive protein (CRP) and sedimentation rate. Patients with euthyroidism had a higher frequency of coronary single-vessel disease (p=0.035) and a significantly lower frequency of triple vessel disease (p=0.046), as well as a higher median value of LVEF (p=0.003). There was a significant correlation between LVEF with haemoglobin values (p=0.002), NLR (p=0.001), and CRP (p=001). Conclusion The altered status of the thyroid gland in acute myocardial infarction is associated with the severity of the coronary blood vessel lesion, LVEF and correlates with inflammatory response.

BACKGROUND: Heat-not-burn (HNB) technology by the U.S. Food and Drug Administration has been classified as a modified risk tobacco product, which can be a better option for those populations who cannot give up the habit of smoking. The outlook on the effects of these products is quite controversial in the scientific world. OBJECTIVE: To present the effect of HNB tobacco products on the cardiovascular system, with reference to the existence of possible benefits of the technology. METHODS: The literature search was conducted in PubMed/Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases, with reliance on a well-defined guiding research statement. Quality appraisal was performed using the CASP checklist for randomized controlled trials. RESULTS: The search of three databases identified 167 records, and after selection process, 25 randomized controlled trials were eligible for our study’s criteria. Twenty studies investigated the effects of HNB products on biomarkers of clinical relevance. Five studies evaluated other functional heart parameters rather than biomarkers. CONCLUSION: With HNB tobacco products, significant reductions were found in biomarkers of exposure and biological effect related to pathways involved in cardiovascular disease, including inflammation, oxidative stress, lipid metabolism, platelet function, and endothelial dysfunction.

Sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors) represent a therapeutic modality option for type 2 diabetes mellitus. This group of drugs includes dapagliflozin, empagliflozin, canagliflozin, ertugliflozin and sotagliflozin. Given their proven benefit in the scope of heart failure through clinical studies, they have also gained their place in patients with reduced, moderately reduced, or preserved systolic function of the left ventricle. Due to the effect on both the systolic and diastolic function of the left ventricle, and the neurohumoral activity itself, their range of use has been expanded in patients without a history of diabetes mellitus, and empagliflozin in a dose of 10 mg, as well as dapagliflozin in a dose of 10 mg, have been implemented in patients without diabetes mellitus. New directions for the expansion of the use of SGLT2 inhibitors have pointed towards their applicability in acute heart failure (sotagliflozin) and type 1 diabetes (sotagliflozin). Recently, clinical studies concerning the use of empagliflozin and dapagliflozin in acute coronary syndrome (ACS), appeared. The aim of this paper was to highlight the possible benefit of including SGLT2 inhibitors in patients with ACS.

Cardiotoxicity is one of the most important side effects of first-line chemotherapy medications. It is influenced by genetic variation, whereby the relationship between the chemotherapeutic dose and the risk of cardiotoxicity can be altered. The incidence of cardiotoxicity depends on the substance used in the therapeutic modality of cancer and can reach an incidence of 30% during a three-year follow-up. The main element of the clinical picture is systolic dysfunction of the left ventricle, with symptoms of heart failure, which can change or stop oncological therapy, along with pharmacological treatment of heart failure. These symptoms can occur during prolonged use of cancer therapies, monitoring the patient is advisable. Considering the increasing success of oncology therapy and the extension of life, as well as the improvement of the quality of life, a multidisciplinary approach, as well as the symbiosis of the work of cardiologists and oncologists, is imperative. Patient stratification concerning oncological treatment modality is imposed as part of a cardiologist's daily work from the beginning of cancer treatment.

Cardiomyopathies are diseases of the heart muscle, and present a heterogeneous group of myocardial diseases with mechanical or electrical dysfunction, characterized by ventricular hypertrophy or dilatation. They can be strictly related to the heart muscle (primary), or as part of a systemic disease (secondary), and represent a factor that leads to a reduced quality of life, the occurrence of heart failure and mortality. The primary ones are those that are genetic conditioning, the mixed ones include dilated and restrictive cardiomyopathy, and the acquired ones are caused by myocarditis, stress-induced, peripartum, tachycardia-induced and those caused by endocrine pathology (primarily in newborns of mothers with a diagnosis of diabetes mellitus). Etiologically, they can arise as a result of a genetic mutation, an inflammatory process, and they are also divided into metabolic, toxic and those caused by some other cause. The aim of the article was to present the characteristics of cardiomyopathies themselves in relation to the etiological factor, with review of the diagnostic and therapeutic modality.

Abstract Aim: The study aimed to evaluate the acute effect of ultrafiltration on the mechanical properties of the aorta using brachial-ankle pulse wave velocity (PWV) before and after hemodialysis (HD). Patients and Methods: This study included 80 patients who were on a long-term HD program. The input variables were anamnestic data, body composition monitor (BCM) parameters, and echocardiography findings. The assessment of hydration status was determined by BCM, whose work is based on the principle of multifrequency bioimpedance spectroscopy. Another diagnostic procedure was the use of an arteriograph apparatus to assess PWV and Augmentation Index (AIx). All measurements were performed before and after dialysis on the middle dialysis day of the week. Results: The participants were divided into two groups based on hydration status: the experimental group consisted of 40 overhydrated participants and the control group consisted of 40 normovolemic participants. Statistically, the following BCM parameters correlated significantly positively with PWV: total body fat (r = 0.222; P < 0.05), overhydration (r = 0.290; P < 0.001), and relative overhydration (r = 0.290; P < 0.001). From echocardiography findings, only left atrial diameter correlated statistically significantly positively with PWV (r = 0.359; P < 0.001). Comparison of the mean PWV values within the experimental group before and after HD showed a statistically significant decrease from 14.32 ± 2.34 m/s to 8.72 ± 1.52 m/s (Z = 3.254; P = 0.0001). Mean PWV values within the control group did not decrease significantly from 13.39 ± 1.32 m/s to 10.39 ± 1.18 m/s (Z = 0.524; P = 0.742). If we compare the mean values of PWV between groups, then before HD treatment, there was no statistically significant difference between groups with PWV values in the experimental group of 14.32 ± 2.34 m/s and the control group of 13.39 ± 1.32 m/s (Z = 0.762; P = 0.852). According to the results of univariate regression analysis before and after HD treatment, only overhydration showed an absolute effect on PWV before and after HD. Conclusion: Overhydration showed an effect on brachial-ankle PWV before and after HD, and brachial-ankle PWV should be followed in HD patients.

E. Begić, Berina Hasanović, Ada Đozić, B. Aziri

The use of anticoagulant therapy is a part of the daily work of clinicians and a reason for fear, primarily due to the risk of bleeding. The use of anticoagulant drugs in rheumatology remains a challenge. first, a large number of clinicians consider rheumatic conditions as a hypercoagulable state, which often leads to wrong decisions. second, the use of drugs in the treatment of rheumatic diseases may be associated with an increased risk of venous thromboembolism (vte), and they can have effect on dose of anticoagulant agent. The aim of this paper is to present the properties of anticoagulant therapy through the prism of rheumatological pathology.

Aislin Fields, Koray N. Potel, Rhandel Cabuhal, B. Aziri, I. Stewart, B. Schock

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is rare, poorly understood, with heterogeneous characteristics resulting in difficult diagnosis. We aimed to systematically review evidence of soluble markers in peripheral blood or bronchoalveolar lavage fluid (BALF) as biomarkers in SSc-ILD. Method Five databases were screened for observational or interventional, peer-reviewed studies in adults published between January 2000 and September 2021 that assessed levels of biomarkers in peripheral blood or BALF of SSc-ILD patients compared with healthy controls. Qualitative assessment was performed using Critical Appraisal Skills Programme (CASP) checklists. Standardised mean difference (SMD) in biomarkers were combined in random-effects meta-analyses where multiple independent studies reported quantitative data. Results 768 published studies were identified; 38 articles were included in the qualitative synthesis. Thirteen studies were included in the meta-analyses representing three biomarkers: KL6, SP-D and IL-8. Greater IL-8 levels were associated with SSc-ILD in both peripheral blood and BALF, overall SMD 0.88 (95% CI 0.61 to 1.15; I2=1%). Greater levels of SP-D and KL-6 were both estimated in SSc-ILD peripheral blood compared with healthy controls, at an SMD of 1.78 (95% CI 1.50 to 2.17; I2=8%) and 1.66 (95% CI 1.17 to 2.14; I2=76%), respectively. Conclusion We provide robust evidence that KL-6, SP-D and IL-8 have the potential to serve as reliable biomarkers in blood/BALF for supporting the diagnosis of SSc-ILD. However, while several other biomarkers have been proposed, the evidence of their independent value in diagnosis and prognosis is currently lacking and needs further investigation. PROSPERO registration number CRD42021282452.

A. Fields, K. Potel, Rhandel Cabuhal, B. Aziri, I. Stewart, B. Schock

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is rare, poorly understood, with heterogeneous characteristics resulting in difficult diagnosis. We aimed to systematically review evidence of soluble markers in peripheral blood or bronchoalveolar lavage fluid (BALF) as biomarkers in SSc-ILD. Method Five databases were screened for observational or interventional, peer-reviewed studies in adults published between January 2000 and September 2021 that assessed levels of biomarkers in peripheral blood or BALF of SSc-ILD patients compared with healthy controls. Qualitative assessment was performed using Critical Appraisal Skills Programme (CASP) checklists. Standardised mean difference (SMD) in biomarkers were combined in random-effects meta-analyses where multiple independent studies reported quantitative data. Results 768 published studies were identified; 38 articles were included in the qualitative synthesis. Thirteen studies were included in the meta-analyses representing three biomarkers: KL6, SP-D and IL-8. Greater IL-8 levels were associated with SSc-ILD in both peripheral blood and BALF, overall SMD 0.88 (95% CI 0.61 to 1.15; I2=1%). Greater levels of SP-D and KL-6 were both estimated in SSc-ILD peripheral blood compared with healthy controls, at an SMD of 1.78 (95% CI 1.50 to 2.17; I2=8%) and 1.66 (95% CI 1.17 to 2.14; I2=76%), respectively. Conclusion We provide robust evidence that KL-6, SP-D and IL-8 have the potential to serve as reliable biomarkers in blood/BALF for supporting the diagnosis of SSc-ILD. However, while several other biomarkers have been proposed, the evidence of their independent value in diagnosis and prognosis is currently lacking and needs further investigation. PROSPERO registration number CRD42021282452.

Aim To determine the value of IFN (intzerferon)-α in the patients with systemic lupus erythematosus (SLE) and to correlate IFN-α with values of non-specific biochemical parameters of inflammation (C-reactive protein, leukocytes values, erythrocyte sedimentation rate, albumins and globulins). Methods Research included 55 patients with SLE diagnosis and a control group consisted of 25 healthy subjects (during period 2019-2020). IFN (Interferon)-α and non-specific biochemical parameters of inflammation were obtained using standard protocols. Results IFN-α values were independent of gender (p=0.95). The difference in serum IFN-α values in relation with the age in the SLE group was statistically significant (p=0.036). Only serum globulin was significantly higher (p=0.0023) in IFN-α positive compared to IFN-α negative SLE patients. A statistically significant correlation between the values of IFN-α and globulin was proved (r=0.315; p=0.019). No significant correlation was found between other non-specific biochemical parameters and IFN-α values. Conclusion Increased IFN-α values were observed in younger patients, and the correlation between IFN and globulin was proved.

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