Initial Respiratory System Involvement in Juvenile Idiopathic Arthritis with Systemic Onset Is a Marker of Interstitial Lung Disease: The Results of Retrospective Cohort Study Analysis.

Background: Pulmonary involvement in systemic juvenile idiopathic arthritis (SJIA) is a rare but dangerous complication. The main risk factors are already known, such as macrophage activation syndrome, a refractory course of systemic juvenile arthritis, infusion reaction to interleukin 1 and/or interleukin 6 blockers, trisomy 21, and eosinophilia. However, information about respiratory system involvement (RSI) at the onset of SJIA is scarce. Our study aimed to evaluate the specific features of children with SJIA with RSI and their outcomes. Methods: In a single-center retrospective cohort study, we compared the information from the medical records of 200 children with SJIA according to ILAR criteria or SJIA-like disease (probable/possible SJIA) with and without signs of RSI (dyspnea, shortness of breath, pleurisy, acute respiratory distress syndrome, and interstitial lung disease (ILD)) at the disease onset and evaluated their outcomes (remission, development of chronic ILD, clubbing, and pulmonary arterial hypertension). Results: A quarter (25%) of the SJIA patients had signs of the RSI at onset and they more often had rash; hepato- and splenomegaly; heart (pericarditis, myocarditis), central nervous system, and kidney involvement; hemorrhagic syndrome; macrophage activation syndrome (MAS, 44.4% vs. 9.0%, p = 0.0000001); and, rarely, arthritis with fewer active joints, compared to patients without RSI. Five patients (10% from the group having RSI at the onset of SJIA and 2.5% from the whole SJIA cohort) developed fibrosing ILD. All of them had a severe relapsed/chronic course of MAS; 80% of them had a tocilizumab infusion reaction and further switched to canakinumab. Unfortunately, one patient with Down's syndrome had gone. Conclusion: Patients with any signs of RSI at the onset of the SJIA are required to be closely monitored due to the high risk of the following fibrosing ILD development. They required prompt control of MAS, monitoring eosinophilia, and routine checks of night oxygen saturation for the prevention/early detection of chronic ILD.

Contemporary Approaches to Immunotherapy of Solid Tumors.

In recent years, the arrival of the immunotherapy industry has introduced the possibility of providing transformative, durable, and potentially curative outcomes for various forms of malignancies. However, further research has shown that there are a number of issues that significantly reduce the effectiveness of immunotherapy, especially in solid tumors. First of all, these problems are related to the protective mechanisms of the tumor and its microenvironment. Currently, major efforts are focused on overcoming protective mechanisms by using different adoptive cell therapy variants and modifications of genetically engineered constructs. In addition, a complex workforce is required to develop and implement these treatments. To overcome these significant challenges, innovative strategies and approaches are necessary to engineer more powerful variations of immunotherapy with improved antitumor activity and decreased toxicity. In this review, we discuss recent innovations in immunotherapy aimed at improving clinical efficacy in solid tumors, as well as strategies to overcome the limitations of various immunotherapies.

Systemic juvenile idiopathic arthritis-associated lung disease: A retrospective cohort study.

BACKGROUND: Lung damage in systemic juvenile arthritis (sJIA) is one of the contemporary topics in pediatric rheumatology. Several previous studies showed the severe course and fatal outcomes in some patients. The information about interstitial lung disease (ILD) in the sJIA is scarce and limited to a total of 100 cases. AIM: To describe the features of sJIA patients with ILD in detail. METHODS: In the present retrospective cohort study, information about 5 patients less than 18-years-old with sJIA and ILD were included. The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019. ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement. Macrophage activation syndrome (MAS) was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement. RESULTS: The onset age of sJIA ranged from 1 year to 10 years. The time interval before ILD ranged from 1 mo to 3 years. The disease course was characterized by the prevalence of the systemic features above articular involvement, intensive rash (100%), persistent and very active MAS (hScore range: 194-220) with transaminitis (100%), and respiratory symptoms (100%). Only 3 patients (60%) developed a clubbing phenomenon. All patients (100%) had pleural effusion and 4 patients (80%) had pericardial effusion at the disease onset. Two patients (40%) developed pulmonary arterial hypertension. Infusion-related reactions to tocilizumab were observed in 3 (60%) of the patients. One patient with trisomy 21 had a fatal disease course. Half of the remaining patients had sJIA remission and 2 patients had improvement. Lung disease improved in 3 patients (75%), but 1 of them had initial deterioration of lung involvement. One patient who has not achieved the sJIA remission had the progressed course of ILD. No cases of hyper-eosinophilia were noted. Four patients (80%) received canakinumab and one (20%) tocilizumab at the last follow-up visit. CONCLUSION: ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset. Extensive rash, serositis (especially pleuritis), full-blown MAS with transaminitis, lymphopenia, trisomy 21, eosinophilia, and biologic infusion reaction are the main predictors of ILD. The following studies are needed to find the predictors, pathogenesis, and treatment options, for preventing and treating the ILD in sJIA patients.

Influence of Extracellular Matrix Components on the Differentiation of Periodontal Ligament Stem Cells in Collagen I Hydrogel.

Regeneration of periodontal tissues requires an integrated approach to the restoration of the periodontal ligament, cementum, and alveolar bone surrounding the teeth. Current strategies in endogenous regenerative dentistry widely use biomaterials, in particular the decellularized extracellular matrix (dECM), to facilitate the recruitment of populations of resident cells into damaged tissues and stimulate their proliferation and differentiation. The purpose of our study was to evaluate the effect of the exogenous components of the extracellular matrix (hyaluronic acid, laminin, fibronectin) on the differentiation of periodontal ligament stem cells (PDLSCs) cultured with dECM (combinations of decellularized tooth matrices and periodontal ligament) in a 3D collagen I hydrogel. The immunohistochemical expression of various markers in PDLSCs was assessed quantitatively and semi-quantitatively on paraffin sections. The results showed that PDLSCs cultured under these conditions for 14 days exhibited phenotypic characteristics consistent with osteoblast-like and odontoblast-like cells. This potential has been demonstrated by the expression of osteogenic differentiation markers (OC, OPN, ALP) and odontogenic markers (DSPP). This phenomenon corresponds to the in vivo state of the periodontal ligament, in which cells at the interface between bone and cementum tend to differentiate into osteoblasts or cementoblasts. The addition of fibronectin to the dECM most effectively induces the differentiation of PDLSCs into osteoblast-like and odontoblast-like cells under 3D culture conditions. Therefore, this bioengineered construct has a high potential for future use in periodontal tissue regeneration.

Carotid total plaque area as an independent predictor of short-term subclinical polyvascular atherosclerosis progression and major adverse cardiac and cerebrovascular events.

BACKGROUND: The use of ultrasound-based methods for imaging of subclinical atherosclerosis, including measurement of carotid plaque burden (cPB), is a promising direction for further improvement of major adverse cardiac and cerebrovascular events (MACCE) prediction. OBJECTIVES: The aim of the study was to research the prognostic values' significance of cPB indicators with regard to the short-term progression of polyvascular subclinical atherosclerosis and the long-term onset of MACCE. DESIGN: Single-center prospective cohort study. METHODS: The study included patients 40-64 years of age. All patients underwent duplex scanning (DS) of the carotid and lower limb arteries. The following cPB indicators were determined: carotid plaque score (cPS), maximum carotid plaque thickness (cPTmax), and carotid total plaque area (cTPA). The combined endpoint included the following components: cardiovascular death; nonfatal myocardial infarction; nonfatal stroke or transient ischemic attack (TIA); revascularization of the coronary and/or peripheral arteries. RESULTS: The study included 387 patients, among whom 142 (36.7%) patients underwent repeated DS after 12-24 months. The median follow-up time was 20.0 (13.0; 36.5) months. MACCE were recorded in 33 (8.52%) of patients. cTPA and cPTmax, but not cPS, were independently associated with the progression of subclinical polyvascular atherosclerosis over a period of 13.9 months of follow-up. cTPA, but not cPTmax and cPS, was independently associated with the development of MACCE over a period of 20.0 months of follow-up. Only a cTPA > 42.0 mm2 proved to be an independent predictor of both the progression of subclinical polyvascular atherosclerosis and MACCE. CONCLUSION: In patients from 40 to 64 years of age with various cardiovascular risks, among the indicators of the cPB, only an increase in cTPA > 42.0 mm2 was shown to be independently associated with an increase in the relative risk (RR) of progression of subclinical polyvascular atherosclerosis by 2.38 (1.08-5.25) times, as well as with the development of MACCE by 3.10 (1.54-6.26) times.

Innate and Adaptive Immunity-Related Markers as Predictors of the Short-Term Progression of Subclinical Atherosclerosis in Middle-Aged Patients.

Assessment of inflammation is a promising approach to monitoring the progression of asymptomatic atherosclerosis. The aim of the present study was to investigate the predictive value of innate and adaptive immunity-related markers, in relation to the short-term progression of subclinical atherosclerosis. The study included 183 patients aged 40-64 years who underwent duplex scanning of the carotid and lower limb arteries at two visits with an interval of 12-24 months between examinations. Phenotyping of circulating lymphocytes and monocytes subpopulations were performed through flow cytometry. An increase in the number of circulating TLR4-positive intermediate monocytes (>447.0-467.0 cells/µL) was an independent predictor of the short-term progression of lower limb artery atherosclerosis (p < 0.0001) and polyvascular atherosclerosis (p = 0.003). The assessment of TLR4-positive monocytes significantly improved the prognostic model for the progression of lower limb arterial atherosclerosis (C-index 0.728 (0.642-0.815) versus 0.637 (0.539-0.735); p = 0.038). An increase in the number of circulating TLR4-positive intermediate monocytes was an independent predictor of the short-term progression of lower limb artery and polyvascular atherosclerosis. Their inclusion into models containing conventional risk factors significantly improved their prognostic effectiveness regarding lower limb artery atherosclerosis progression.

Decellularized Matrix Induced Spontaneous Odontogenic and Osteogenic Differentiation in Periodontal Cells.

The regeneration of periodontal tissues is a decisive factor in the treatment of periodontitis. Currently, to achieve complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized tissue-engineered constructs on periodontal regeneration. We studied the possibilities of osteogenic and odontogenic differentiation of periodontal progenitor and stem cells (SCs) of the periosteum and periodontal ligament, in decellularized tooth matrix (dTM) and periodontal ligament (dPDL), in 2D and 3D culture. The cell culture of periodontal cells without decellularized matrices was used as control. On the 14th day of cultivation of PDLSCs, PSCs, and PDLSCs + PSCs on dTM and/or dPDL scaffolds in 2D conditions, in all scaffold variants, a dense monolayer of spindle-shaped cells was intensely stained for markers of osteogenic differentiation, such as osteopontin and osteocalcin. Periodontal cells in the collagen I hydrogel (3D-dimensional culture) were more diverse in shape and, in combination of dTM and dPDL, in addition to osteogenic expression, expressed dentin sialophosphoprotein, an odontogenic differentiation marker. Thus, collagen I hydrogel contributed to the formation of conditions similar to those in vivo, and the combination of dTM with dPDL apparently formed a microenvironment that promoted osteogenic and odontogenic differentiation of periodontal cells.

Pancreatic ductal adenocarcinoma: tumor microenvironment and problems in the development of novel therapeutic strategies.

Diagnosis and treatment of carcinoma of the exocrine part of the pancreas is a serious problem for modern medicine. Despite the identification of a large number of aberrant mutations in pancreatic ductal adenocarcinoma (PDAC), attempts to create effective therapeutic agents based on identified genetic or epigenetic variations have not been succesful. The role of the tumor microenvironment (TME) in tumor progression is currently a popular topic. Cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) are the main components of the tumor stroma and play an important role in the proliferation, invasiveness and metastasis of cancer. However, the mechanisms underlying the effect of CAFs and ECM on cancer progression are still unclear. Recent studies on stromal components and blockage of signaling pathways have brought some optimism to this area. New information on the role of TME will lead to the development of targeted therapies or combinations with modern chemotherapy for PDAC.

Achilles tendon thickness normalized to body surface area as a marker of asymptomatic peripheral arterial disease.

OBJECTIVES: The normalisation of Achilles tendon thickness (ATT) to anthropometric parameters may increase the diagnostic efficiency of the assessment of ATT. The aim of this study was to compare the diagnostic value of AT dimensions depending on their normalization to body surface area (BSA) in patients with asymptomatic peripheral arterial disease (PAD). METHODS: All patients underwent duplex scanning of the carotid arteries and the lower limb arteries. Asymptomatic PAD was defined as the presence of ≥50% stenosis in the carotid and/or lower limb arteries. ATT was measured using a longitudinal scan, width (ATW) and cross-sectional area (AT CSA), which was determined during a cross-sectional scan. RESULTS: The study included 369 patients, among whom asymptomatic PAD was detected in 18 (4.88%) patients. Only the ATT demonstrated diagnostic value for asymptomatic PAD. After normalizing the size of the AT to the BSA, the diagnostic performance of ATT, ATW and AT CSA became statistically significant. Among the studied parameters, only an increase in ATT/BSA >0.29 cm/m2 was associated with a significant increase in the odds ratio (OR) of asymptomatic PAD by 4.11 times (95% CI 1.08-15.7; p = .038) after adjustments. CONCLUSION: An increase in ATT/BSA >0.29 cm/m2 predicted the presence of asymptomatic PAD with a sensitivity of 61.1% and a specificity of 77.9%. ATT/BSA values of less than 0.29 cm/m2 made it possible to exclude asymptomatic PAD with a probability of 97.5%. An increase in ATT/BSA >0.29 cm/m2 was associated with a 4.11-fold increase in the OR of asymptomatic PAD (95% CI 1.08-15.7).

Liver Stiffness Is Associated with the Burden of Carotid and Systemic Atherosclerosis in an Unorganized Cohort of Patients 40-64 Years Old.

Background: The aim of the study is to research the relationship between the severity of liver fibrosis and the burden of carotid and systemic atherosclerosis. Methods: The study includes 163 patients 40 to 64 years of age without atherosclerotic CVD or liver disease. All patients underwent duplex scanning of the carotid and lower limb arteries. All patients underwent transient liver elastometry using the FibroScan (Echosens, France). Results: Carotid plaque was detected in 110 (67.5%) patients. Based on the results of linear regression analysis, relationships between liver stiffness and carotid total plaque area (r = 0.21; p = 0.025) were found. Significant relationships were established between liver stiffness and atherosclerosis burden score based on the results of linear regression (r = 0.17; p = 0.029). Liver stiffness showed moderate diagnostic performance (AUC 0.666; p = 0.01) with regard to generalized atherosclerosis. An increase in liver stiffness >4.5 kPa was associated with an odds ratio of generalized atherosclerosis of 3.48 (95% CI 1.07−11.3; p = 0.038) after adjusting confounding factors. Conclusion: Among patients 40−64 years of age without established atherosclerotic CVD and liver disease, liver stiffness directly correlates with the burden of carotid and systemic atherosclerosis. Liver stiffness showed moderate diagnostic performance (AUC 0.666; p = 0.01) with regard to generalized atherosclerosis.

Circulating Ageing Neutrophils as a Marker of Asymptomatic Polyvascular Atherosclerosis in Statin-Naïve Patients without Established Cardiovascular Disease.

BACKGROUND: Current data on the possible involvement of aging neutrophils in atherogenesis are limited. This study aimed to research the diagnostic value of aging neutrophils in their relation to subclinical atherosclerosis in statin-naïve patients without established atherosclerotic cardiovascular diseases (ASCVD). METHODS: The study was carried out on 151 statin-naïve patients aged 40-64 years old without ASCVD. All patients underwent duplex scanning of the carotid arteries, lower limb arteries and abdominal aorta. Phenotyping and differentiation of neutrophil subpopulations were performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). RESULTS: The number of CD62LloCXCR4hi-neutrophils is known to be significantly higher in patients with subclinical atherosclerosis compared with patients without atherosclerosis (p = 0.006). An increase in the number of CD62LloCXCR4hi-neutrophils above cut-off values makes it possible to predict atherosclerosis in at least one vascular bed with sensitivity of 35.4-50.5% and specificity of 80.0-92.1%, in two vascular beds with sensitivity of 44.7-84.4% and specificity of 80.8-33.3%. CONCLUSION: In statin-naïve patients 40-64 years old without established ASCVD with subclinical atherosclerosis, there is an increase in circulating CD62LloCXCR4hi-neutrophils. It was also concluded that the increase in the number of circulating CD62LloCXCR4hi-neutrophils demonstrated moderate diagnostic efficiency (AUC 0.617-0.656) in relation to the detection of subclinical atherosclerosis, including polyvascular atherosclerosis.

Associations between Circulating VEGFR2hi-Neutrophils and Carotid Plaque Burden in Patients Aged 40-64 without Established Atherosclerotic Cardiovascular Disease.

Background: Neutrophils expressing vascular endothelial growth factor receptor (VEGFR) represent a distinct subtype of neutrophils with proangiogenic properties. The purpose of this study was to identify the interrelations between circulating CD16hiCD11bhiCD62LloCXCR2hiVEGFR2hi-neutrophils and indicators of carotid plaque burden in patients without atherosclerotic cardiovascular diseases (ASCVD). Methods: The study included 145 patients, 51.7% men and 48.3% women, median age-49.0 years. All patients underwent carotid duplex ultrasound scanning. The maximal carotid plaque thickness was used as an indicator of carotid plaque burden. Also, carotid intima-media thickness (cIMT) and femoral IMT were measured. The phenotyping of neutrophil subpopulations was executed by the flow cytometry via the Navios 6/2. Results. The subpopulation of VEGFR2hi-neutrophils accounted for about 5% of the total pool of circulating neutrophils. A decrease in VEGFR2hi-neutrophils with an increase in carotid plaque burden was statistically significant (p = 0.036). A decrease in VEGFR2hi-neutrophils < 4.52% allowed to predict the presence of plaque with a maximum height > 2.1 mm (Q4), with sensitivity of 78.9% and specificity of 61.5% (AUC 0.693; 95% CI 0.575-0.811; p = 0.007). Inverse correlations were established between the carotid and femoral IMT and the absolute and relative number of VEGFR2hi-neutrophils (p < 0.01). Conclusion: In patients aged 40-64 years without established ASCVD, with an increase in indicators of the carotid plaque burden, a significant decrease in the proportion of circulating VEGFR2hi-neutrophils was noticed. A decrease in the relative number of VEGFR2hi-neutrophils of less than 4.52% made it possible to predict the presence of extent carotid atherosclerosis with sensitivity of 78.9% and specificity of 61.5%.

Prognostic Significance of Hypertriglyceridemia in Patients at High and Very High Cardiovascular Risk Depending on the Concentration of Highsensitivity C-reactive Protein.

BACKGROUND: It has been established that an increase in triglyceride-rich lipoprotein levels is associated with the development of systemic low-grade inflammation. Data on the prognostic role of hypertriglyceridemia (HTG) dependent on the state of low-grade inflammation are limited. OBJECTIVE: The study's objective was to evaluate the predictive value of mild-to-moderate HTG (2.3- 11.2 mmol/L) regarding the development of cardiovascular events in patients at high and very high cardiovascular risk (CVR), depending on the high-sensitivity C-reactive protein (hsCRP) values. METHODS: The study included 185 patients with high and very high CVR. The concentration of hsCRP in blood serum was measured using an enzyme-linked immunosorbent assay kit. The combined endpoint was cardiovascular death, nonfatal myocardial infarction or unstable angina (which required hospitalization), nonfatal stroke, and coronary revascularization. RESULTS: HTG was revealed in 17.3% of the patients. An increase in hsCRP ≥2.0 mg/L was observed in 51.9% of the patients. The event-free survival of patients with HTG was not statistically different from that in patients with TG <2.3 mmol/L (RR 1.61; 95% CI 0.86-3.00; p=0.133). In the subgroup of patients with hsCRP <2.0 mg/L, patients with HTG were not significantly different from patients without HTG. In the subgroup of patients with hsCRP≥2.0 mg/L, the presence of HTG was associated with a 4.63 times increase in the RR of adverse cardiovascular events (95% CI 1.35-15.8; p=0.015) after adjusting for potential confounders. CONCLUSION: In patients with high and very high CVR, an increase in TG ≥2.3 mmol/L was associated with the development of adverse cardiovascular events only in the subgroup of patients with an increase in hsCRP ≥2.0 mg/L. The presence of HTG was associated with a 4.63 times increase in RR of adverse cardiovascular events (95% CI 1.35-15.8; p=0.015).

Modern Approaches to Acellular Therapy in Bone and Dental Regeneration.

An approach called cell-free therapy has rapidly developed in regenerative medicine over the past decade. Understanding the molecular mechanisms and signaling pathways involved in the internal potential of tissue repair inspires the development of new strategies aimed at controlling and enhancing these processes during regeneration. The use of stem cell mobilization, or homing for regeneration based on endogenous healing mechanisms, prompted a new concept in regenerative medicine: endogenous regenerative medicine. The application of cell-free therapeutic agents leading to the recruitment/homing of endogenous stem cells has advantages in overcoming the limitations and risks associated with cell therapy. In this review, we discuss the potential of cell-free products such as the decellularized extracellular matrix, growth factors, extracellular vesicles and miRNAs in endogenous bone and dental regeneration.

Claudins as biomarkers of differential diagnosis and prognosis of tumors.

Claudins are a superfamily of transmembrane proteins, the optimal expression and localization of which are important for the normal physiological function of the epithelium and any imbalance may have pathological consequences. Not only insufficient but also excessive production of claudins in cancer cells, as well as their aberrant localization, equally manifest the formation of a malignant phenotype. Many works are distinguished by contradictory data, which demonstrate the action of the same claudins both in the role of tumor-growth suppressors and promoters in the same cancers. The most important possible causes of significant discrepancies in the results of the works are a considerable variability of sampling and the absence of a consistent approach both to the assessment of the immune reactivity of claudins and to the differential analysis of their subcellular localization. Combined, these drawbacks hinder the histological assessment of the link between claudins and tumor progression. In particular, ambiguous expression of claudins in breast cancer subtypes, revealed by various authors in immunohistochemical analysis, not only fails to facilitate the identification of the claudin-low molecular subtype but rather complicates these efforts. Research into the role of claudins in carcinogenesis has undoubtedly confirmed the potential value of this class of proteins as significant biomarkers in some cancer types; however, the immunohistochemical approach to the assessment of claudins still has limitations, needs standardization, and, to date, has not reached a diagnostic or a prognostic value.

Associations between Hypertriglyceridemia and Circulating Neutrophil Subpopulation in Patients with Dyslipidemia.

BACKGROUND: There is strong evidence to suggest that the negative influence of triglyceride-rich lipoproteins (TRLs) on atherosclerosis development and progression is at least partially mediated by their proinflammatory effects. However, the effect of hypertriglyceridemia (HTG) on the subpopulation composition of circulating neutrophils has not been studied so far. The aim of this study was to examine correlations between the level of triglycerides (TGs) and the subpopulation composition of circulating neutrophils in middle-aged patients with dyslipidemia without established atherosclerotic cardiovascular diseases (ASCVDs). METHODS: Ninety-one patients with dyslipidemia, including 22 (24.2%) patients with HTG, were enrolled in the study. Phenotying of neutrophil subpopulations was performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). For phenotyping of neutrophil subpopulations, conjugated monoclonal antibodies were used: CD16, PE-Cyanine7 (Invitrogen, USA); CD11b-FITC (Beckman Coulter, USA); CD62L-PE (Beckman Coulter, USA); and CD184 (CXCR4)-PE-CF594 (BD Biosciences, USA). RESULTS: Following the correlation analysis, the TG level directly correlated with the number of circulating leukocytes (r = 0.443; p < 0.0001) and neutrophils (r = 0.311; p=0.008). HTG patients displayed a significantly high number of circulating neutrophils with CD16hiCD11bhiCD62Lhi and CD16hiCD11bloCD62Lbr phenotypes. TG levels directly correlated with the number of circulating neutrophils having CD16hiCD11bhiCD62Lhi and CD16hiCD11bloCD62Lbr phenotypes. Following the linear regression analysis, statistically significant correlations between TG levels and neutrophil subpopulations having CD16hiCD11bloCD62Lbr and CD16hiCD11bbrCD62LloCXCR4hi phenotypes were established. Changes in TG levels could explain up to 19.1% of the variability in the number of studied neutrophil subpopulations. CONCLUSION: Among middle-aged patients without established ASCVDs, patients with HTG demonstrated a significantly higher overall number of neutrophils and neutrophils having CD16hiCD11bhiCD62Lhi (mature neutrophils) and CD16hiCD11bloCD62Lbr (immunosuppressive neutrophils) than patients with normal TG levels. The TG level was associated with an increase in the number of CD16hiCD11bloCD62Lbr and CD16hiCD11bbrCD62LloCXCR4hi (ageing neutrophils) neutrophils, adjusted for the sex and age of the patients.

Achilles Tendon Thickness Is an Independent Predictor of Carotid Atherosclerosis and Is Associated With a Carotid Plaque Burden.

The aim of the study was to research the relationship between carotid atherosclerosis markers and ultrasound parameters of Achilles tendons (AT). The study included 150 patients at high and very high cardiovascular risk (CVR). All patients underwent a carotid ultrasound scanning. We evaluated carotid plaque, carotid plaque score (cPS), carotid total plaque area (cTPA), and the percentage of stenosis. All patients underwent AT ultrasound with an assessment of thickness (Achilles tendon thickness [ATT]), width (Achilles tendon width), and cross-sectional area. An increase in the ATT ≥5.07 mm was associated with a 4.55-fold increase in the relative risk of carotid atherosclerosis (sensitivity 68.3% and specificity 62.5%). Direct correlations between the ATT and carotid stenosis (r = 0.277; P = .004), cPS (r = 0.225; P = .035), and cTPA (r = 0.305; P = .004) were determined. An increase in the mean ATT by 1 mm was associated with an increase in cTPA by 8.09 mm2 (95% CI: 2.26-13.9; P = .007) and carotid stenosis by 4.11% (95% CI: 0.64-7.60; P = .021). Thus, in patients with high and very high CVR, an increase in ATT is an independent predictor of carotid atherosclerosis. The ATT directly correlates with the markers of carotid plaque burden.

Osmoregulation in children with cystic fibrosis.

Hyponatremia is not rare in cystic fibrosis and might be due to several mechanisms. An endocrine and renal imbalance in water and salt homeostasis was suggested. To address this hypothesis, we assessed the urinary concentrating and diluting ability in 12 cystic fibrosis patients (6 females, 6 males) and in two control groups: 14 children with pneumonia (9 females, 5 males) and in 13 healthy children (9 females, 4 males). Renal concentrating ability was evaluated following overnight water deprivation. Urine osmolality was not significantly different between groups. Renal diluting ability was assessed by means of a water-load test. This provoked a decrease in urine osmolality, as well as an increase in diuresis and solute-free water excretion. These changes were comparable among groups.Conclusion: Children with cystic fibrosis show a preserved renal concentrating and diluting capacity. A generalized endocrine and renal imbalance in water and salt homeostasis therefore appears unlikely.What is Known:•Hyponatremia sometimes occurs in cystic fibrosis.What is New:•Osmoregulation is normal in cystic fibrosis.

Multivessel spontaneous coronary artery dissection in a patient after mild COVID-19: A case report.

Coronavirus disease 2019 (COVID-19) is characterized by heterogeneity of possible cardiovascular manifestations. Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome, the development of which in patients with COVID-19 has been described and studied insufficiently. A 35-year-old male patient presented to our hospital with an acute coronary syndrome a few weeks after mild COVID-19. According to coronary angiography, a dissection of ramus intermedius was detected. Successful stenting was performed. Subsequently, the patient had relapses of chest pain, which led to two repeated coronary angiographies. The patient had been diagnosed with consecutive dissections of right coronary artery and distal branch of ramus intermedius. Repeated stenting of dissected segments of right coronary artery and ramus intermedius was not performed. Afterward, the patient's condition remained stable and he was successfully discharged. One of the main pathophysiological mechanisms of cardiovascular complications in COVID-19 is probably the virus-triggered hyperinflammation and massive release of cytokines. A systemic inflammatory response may initiate inflammation of the vascular wall and other target tissues. The results of histological studies confirm the direct infection of endothelial cells 2019-nCoV with the development of diffuse endothelial inflammation (endotheliitis). It is possible that in patients with a genetic predisposition to artery dissection, COVID-19 may be a trigger of spontaneous coronary artery dissection.

The prognostic value of various carotid ultrasound parameters in patients at high and very high cardiovascular risk.

BACKGROUND: According to the current guidelines the visualization of atherosclerotic plaques in the carotid arteries is the only option that carotid ultrasound provides for the assessment of cardiovascular risk (CVR). The direction devoted to the development and implementation of markers based on the quantification of atheroma, is promising. The aim of the study was to evaluate the prognostic value of various carotid ultrasound parameters in patients at high and very high CVR. METHODS: Patients at high and very high CVR were included. All patients underwent carotid ultrasound. We evaluated carotid intima-media thickness (cIMT), carotid plaque, carotid plaque score (cPS) and carotid total plaque area (cTPA). The combined endpoint was cardiovascular death, non-fatal myocardial infarction or unstable angina, non-fatal stroke and coronary revascularization. RESULTS: The study included 100 patients. The duration of the follow-up period was 24.4 (14.1-34.3) months. Endpoint events occurred in 34.0% patients. cIMT and cPS were not significantly associated with the risk of cardiovascular events. The presence of carotid plaque in accordance with Cox regression after adjusting for possible confounders was associated with an increase in the relative risk of cardiovascular events by 10.5 times (95% CI 1.27-86.5; p = 0.008). CTPA ≥69 mm2 according to adjusted analysis was associated with an increase in the risk of cardiovascular events by 5.86 times (95% CI 2.09-16.4; p = 0.001). CONCLUSION: In patients at high and very high CVR among carotid atherosclerosis markers only carotid plaque and cTPA had an independent predictive value regarding the development of adverse cardiovascular events.