Concomitant Type Research Articles

PROGNOSTIC VALUE OF ENDOTHELIAL MONOCYTE ACTIVATING POLYPEPTIDE – ІІ ON THE DEVELOPMENT OF ACUTE LEFT VENTRICULAR FAILURE IN HOSPITAL PERIOD OF ACUTE MYOCARDIAL INFARCTION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Introduction. 20% of patients with acute myocardial infarction are diagnosed as having type 2 diabetes: this is much higher than in the entire population. In the presence of this comorbid disease, the incidence of acute left ventricular failure with cardiogenic shock is also much higher than could be predicted based on the size of the infarction zone that poses a challenge for modern cardiology. Endothelial dysfunction is known to underlay the etiopathogenesis of acute myocardial infarction and concomitant type 2 diabetes. Endothelial monocyte activating polypeptide – ІІ is a multifunctional peptide with proinflammatory and angiogenesis properties, it activates a number of proinflammatory cytokines, inducing inflammatory changes in blood vessels. It plays a significant role in the process of myocardial tissue revascularization in acute myocardial infarction (AMI). The aim of this study is to investigate the relationship between the activity of endothelial monocyte activating polypeptide – ІІ and acute left ventricular failure in patients with acute myocardial infarction in hospital period and type 2 diabetes mellitus, as well as to evaluate the prognostic properties of endothelial monocytactating peptide II in this cohort of patients with following design of prognostic model. Material and methods. The study involved 120 patients (60 men and 60 women) with AMI, whose mean age was 66.35 ± 0.91 years, (p <0.05). The participants were divided into 2 groups: group 1 patients with concomitant type 2 diabetes (n = 70), group 2 patients with isolated AMI (n = 50). The control group included 20 healthy individuals. All participants underwent standard routine clinical and instrumental examinations. According to the objectives of this study, on the 1st day after AMI diagnosis was confirmed, the level of EMARII was evaluated in all participants using a commercial test system "Human Endothelial monocyte activating polypeptide – ІІ ELISA KIT". The findings data obtained were processed by the software package "Statistica 6.0" (StatSoft Inc, USA). Results. The patients of the 1 group had higher level of endothelial monocytic peptide-II 1.65 times than the patients of the 2nd group (4.54 ± 0.331 ng / ml vs. 2.74 ± 0.21 ng / ml, respectively, (p <0,05). In the control group, the average value of this indicator was 1.1 ± 0.037 ng / ml. Class IV by the Killip scale was detected in 44% of the patients included in the group of the 3rd tertile according to the level of endothelial monocyte activating polypeptide – ІІ. The value of endothelial monocyte activating polypeptide – ІІ > 6.45 ng / ml in patients of the 1 group and > 3.31 ng / ml in the patients of the 2 group is a predictor for occurrence of left-ventricular failure resulting in cardiogenic shock. Based on the results of the study, a multifactor logistic regression model for the prognosis of acute left-ventricular cardiac failure with cardiogenic shock in the hospital course of AMI in patients with type 2 diabetes was developed. Conclusions. Thus, endothelial monocyte activating polypeptide – ІІ acts as a predictor for acute left ventricular failure resulting in cardiogenic shock in the hospital period of acute myocardial infarction in patients with type 2 diabetes.

EXPERIMENTAL AND CLINICAL JUSTIFICATION OF THE USE OF COLLAGEN-FIBRIN ADHESIVE COMPOSITION FOR CLOSING A COLON DEFECT

Relevance: The aim of our study was to assess the degree of penetration of the intestinal area by connective tissue when using a collagen plate in rats with a colon defect. Increasing the efficiency of surgical treatment of pararectal fistulas.
 An experimental morphological study was carried out on laboratory rats of the Wistar line, which were divided into two groups consisting of 20 animals each, depending on the method of closure of the intestinal wall defect: group 1 main and group 2 comparison.
 The average weight of animals in each group was 180 ± 220 g.
 For the purpose of anesthesia, a sodium thiopental solution was used, which was prepared as follows: 1 g of sodium thiopental was diluted in 20 ml of 0.9% sodium chloride solution. Each animal was injected with 0.7 ml of a 0.5% solution.
 In the main group, the operation of closing the defect of the intestinal wall was carried out using a collagen-fibrin adhesive composition. In the comparison group, the operation of closing the defect of the intestinal wall was performed with interrupted sutures.
 At the end of the experiment, the animals were euthanized in equal numbers from each group, subject to the conditions of euthanasia, 10, 30, 60 days after surgery.
 As a result of the experimental study, the animals of the main group and the comparison group were all alive on day 10 after surgery.
 Morphological changes in histological samples of the large intestine with the closure of the intestinal wall defect with a collagen-fibrin adhesive composition consisted in pronounced leuko-lymphocytic cell infiltration. Individual infiltrates were observed that formed lymphoid follicles.
 An objective assessment of the immunohistological analysis of the samples of the operated intestine in animals from the comparison group at the same time showed the presence of a defect in the muscle layer with fragments of granuloma formed around the suture material. Filaments, multinucleated giant cells of a foreign body, epithelioid cells, mature dense connective tissue, and coarse collagen fibers were visualized in the samples. Also, in the samples of the intestine near the site of the defect, one can see the absence of complete restoration of the mucous-producing function of the glandular epithelium at the border with the site of damage, as evidenced by the uneven staining of vacuoles with mucin, a decrease in their number. These results indicate the advantage of proliferative inflammation processes with the formation of formed granulomas, foreign bodies around the surgical suture material. Morphological signs are characteristic of the surgical recurrent course of the inflammatory process in the intestinal wall, which was additionally provoked and supported by suture material. The use of the technique of nodular suturing of the intestinal wall defect in the experiment led to uneven germination of connective tissue around the suture material with foci of pronounced productive inflammation.
 Immunohistological studies have shown that the use of a collagen-fibrin adhesive composition minimizes the inflammatory reaction in the intestinal wall, accelerates regeneration processes and contributes to the anatomical restoration of the integrity of all layers in the defect zone. The postoperative results showed that among the patients of the main group, after three months of surgery, the recurrence of the perrectal fistula occurred in 1 patient with a collagen-fibrin adhesive composition (1.6%) concomitant type 2 diabetes mellitus. Among the patients of the comparison group, 5 patients (8.3%) had recurrent-prolonged wound infection.
 The introduction of a collagen-fibrin adhesive composition into the surgical treatment of pararectal fistulas increases the effect of treatment, namely, a decrease in the recurrence rate of 1.6% versus 8.3% in the comparison group.

Clinical and Anamnestic Characteristics of Acute Coronary Syndrome after Suffering COVID-19

Background. COVID-19 increases the risk of developing thromboembolic complications, including acute myocardial infarction, in the acute period of the disease. The long-term consequences of COVID-19 are poorly understood. At the same time, the available data on an increased risk of acute coronary syndrome after infectious diseases allow us to make an assumption about a similar risk in COVID-19. The aim of the study was to study the anamnestic and laboratory diagnostic data in patients with acute coronary syndrome after COVID-19. Methods. The study included 185 patients with acute coronary syndrome who were admitted to the State Clinical Hospital No. 13 in Moscow in the period from May to December 2020. 2 groups were identified: group 1 109 patients with ACS who had previously suffered COVID-19, group 2 76 patients with ACS without COVID-19 in the past. The patients were collected anamnesis, including: the fact of smoking and alcohol consumption, heredity, previous diseases, including diabetes mellitus, acute myocardial infarction, previously performed PCI. Information about the COVID-19 infection has been collected (the duration of the disease, the course of the disease). A clinical and laboratory examination was conducted, including the determination of body mass index (BMI), examination for antibodies to COVID-19, determination of the lipid profile level (total cholesterol, LDL, HDL, triglycerides), blood glucose level, C-RB. The analysis was performed on automatic biochemical analyzers Hitachi-902, 912 (Roche Diagnostics, Japan). All patients underwent coronary angiography. Results. In patients with ACS with previously transferred COVID-19, the development of the disease occurred at a younger age compared to patients without transferred COVID-19. Among the patients with COVID-19, body weight was significantly lower, there were fewer smokers, concomitant type 2 diabetes mellitus and transferred ONMC were less common. In laboratory parameters, lower triglyceride levels were observed in patients with ACS with COVID-19 compared with those of patients without COVID-19. In the laboratory parameters of blood clotting in patients with ACS with COVID-19, higher APTT, thrombin time, fibrinogen level, D-dimer were noted. The indicated laboratory parameters in the groups had statistically significant differences. In ACS patients with a previous COVID-19, compared with patients without COVID-19, the lesion of 2 or more coronary vessels was more common in the anamnesis. Conclusion. According to the results of our study, it was revealed that multivessel coronary artery damage in patients after COVID-19 in comparison with patients without COVID-19 develops significantly more often, while these patients are significantly less likely to have DM and previously suffered ONMC, the level of TG is significantly lower.

Asymmetric dimethylarginine – a marker of repeated cardiovascular events in patients with comorbid pathology

Annotation. Today, diseases of the cardiovascular system retain their leading position among the incidence in the world. The presence of comorbid pathology in the form of type 2 diabetes mellitus (DM) significantly complicates the course of these diseases, worsening its prognosis. The aim of the study: to analyze the prognostic value of asymmetric dimethylarginine (ADMA) as a marker of recurrent cardiovascular events in patients with acute myocardial infarction with type 2 diabetes for 6 months of follow-up. 120 patients were examined: group 1 – patients with acute myocardial infarction (AMI) in combination with type 2 diabetes mellitus (n=70), group 2 - patients with isolated AMI (n=50). The control group included 20 practically healthy individuals. All patients underwent general clinical and instrumental examinations, on the first day of AMI the level of ADMA was determined using a commercial test system "Human Asymmetrical Dimethylarginine ELISA". Statistical processing of the obtained data was performed using the software package StatSoft Inc, USA – "Statistica 6.0". The analysis of the average level of ADMA showed a significantly higher value of this indicator in patients with AMI in combination with type 2 DM than in patients without concomitant type 2 DM 2.57 times (1.57±0.11 μmol / l and 0.61±0.06 μmol / l, respectively), (p<0,05. ADMA level >1,72 μmol / l in patients with AMI in combination with type 2 DM and >0,69 μmol / l in patients with AMI without concomitant type 2 DM was identified as a predictor of recurrent acute myocardial infarction within 6 months of follow-up. Thus, the level of ADMA was higher in the presence of comorbid pathology in the form of type 2 DM in patients with AMI, reflecting endothelial dysfunction combining disease. It is advisable to further study this indicator of endothelial dysfunction as a predictor of the adverse course of AMI in combination with concomitant type 2 DM.

Abstract 13467: Using Data Analytics Toward Precision Warfarin Dosing in Children With Heart Disease

Introduction: Warfarin is the most common anticoagulant used in children with heart disease. Multiple factors make initial warfarin dose selection and management subjective and variable in children. This variability increases hospital length of stay and impacts efficacy and safety. We sought to develop a data-driven tool to optimize time to warfarin goal dose in children with heart disease. Methods: We collected all demographic and clinical data for all patients <18 years who received warfarin at our institution. We developed a warfarin sensitivity metric (Δ International Normalized Ratio (INR)/mg warfarin) to assess individual medication processing and characterize influential factors. Each inpatient interaction with warfarin was analyzed to assess the impact of concomitant medications, hepatic impairment, and procedure type on dosing, sensitivity, and resultant INR. A linear regression model was formulated to predict ending warfarin dose based on these influential factors. Results: A total of 714 patients were identified; 334 patients met inclusion criteria, and 447 unique encounters with warfarin were analyzed. Warfarin sensitivity was 94.3% higher in patients receiving major anticoagulation enhancing drugs and 13.6% higher in patients with minor liver injury. Patients undergoing a Fontan procedure had increased warfarin sensitivity compared to other procedures; 60% and 66% increase from ventricular assist device and valve replacement, respectively. A linear regression model was used to predict a patient’s warfarin ed dose based on age, baseline INR, other medications, liver injury, and Fontan procedure status. The Fontan binary indicator and age were the most impactful in predicting end dose with an adjusted R 2 of 0.1792. Conclusions: We have identified multiple factors that could affect individualized warfarin. Further analysis will refine our warfarin sensitivity metric and finalize and validate our tool to allow accurate and efficient warfarin dose prediction.

Thromboembolism, Bleeding, and Vascular Death Among Older and Younger Nonvalvular Atrial Fibrillation Patients with Type 2 Diabetes Receiving Rivaroxaban or Warfarin

Background: Advancing age and diabetes are common comorbidities among patients diagnosed with nonvalvular atrial fibrillation (NVAF). In separate subanalyses of the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), the relative efficacy and safety of rivaroxaban versus warfarin did not vary with by older (≥75 years old) or younger age (<75 years old) or with the presence or absence of diabetes. We sought to evaluate the impact of age on the comparative effectiveness and safety of rivaroxaban compared to warfarin in NVAF patients with comorbid diabetes treated in routine practiceMethods: We performed an analysis using Optum® De-Identified electronic health record (EHR) data from November 2010 to December 2019. This study included adults with NVAF and type 2 diabetes, newly started on either rivaroxaban or warfarin and who had ≥12-months of EHR activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. To allow for the assessment of statistical interaction in outcome rates across age groups, we propensity score-overlap weighted patients after stratification of eligible patients into older (≥80 years old) and younger (<80 years old) cohorts. Weighted incidence rates (%/year) of developing stroke or systemic embolism, or vascular death; hospitalization for major or clinically relevant nonmajor (CRNM) bleeding; and major adverse limb events (need for revascularization or major amputation of the lower limbs) for rivaroxaban and warfarin users with type 2 diabetes patients either ≥80 or <80 years old were reported. Propensity score-overlap weighted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox regression employing a robust sandwich estimator. Patients were followed in the Cox regression models until time of outcome occurrence, end-of-EHR activity or end-of-data availability. P-values for interaction across age subgroups were adjusted to control for false discovery rates due to multiple hypothesis testing. A p-value <0.05 was considered statistically significant in all cases.Results: A total of 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971 warfarin users (time-in-therapeutic range = 47±28%) with NVAF and comorbid type 2 diabetes were included in the present study. Mean follow-up time was 2.9±1.9 years for rivaroxaban and 2.9±2.0 years for warfarin patients. There were 31,941 patients (28%) aged ≥80 years who were initiated on either rivaroxaban (n=6,606) or warfarin (n=25,335). Older patients had a higher mean CHA 2DS 2VASc (4.4±1.2 versus 3.8±1.3) and modified HASBLED (1.7±0.7 versus 1.4±0.8) score compared to younger patients. Propensity score-overlap weighted analyses found no statistically significant interaction for the relative effectiveness or safety of rivaroxaban versus warfarin across the older or younger age groups for the outcomes of stroke, systemic embolism, or vascular death (HR=0.93; 95%CI, 0.87-1.00 versus HR=0.91; 95%CI, 0.86-0.96), hospitalization for major or CRNM bleeding (HR=1.06; 95%CI, 0.96-1.18 versus HR=0.90; 95%CI, 0.84-0.96) or major adverse limb events (HR=0.79; 95%CI, 0.68-0.94 versus HR=0.76; 95%CI, 0.70-0.83) (Table). Major and intracranial bleeding were also observed significantly less frequently with rivaroxaban compared to warfarin regardless of patient age.Conclusions: The effectiveness and safety of rivaroxaban relative to warfarin remained consistent across older and younger patient subgroups, supporting rivaroxaban as an alternative for elderly NVAF patients with concomitant type 2 diabetes (NCT04509193). [Display omitted] DisclosuresColeman: Alexion Pharmaceuticals: Research Funding; Janssen Scientific Affairs LLC: Consultancy, Honoraria, Research Funding; Bayer AG: Consultancy, Honoraria, Research Funding. Vardar: Bayer AG: Current Employment. Abdelgawwad: Bayer AG: Current Employment.

Вплив реперфузійної терапії на рівні ендотеліальної синтази оксиду азоту у пацієнтів з гострим інфарктом міокарда та цукровим діабетом 2-го типу

The purpose of the study was to investigate the effect of reperfusion therapy on the levels of endothelial nitric oxide synthase in patients with acute myocardial infarction and concomitant type 2 diabetes mellitus. Materials and methods. The study involved patients with acute myocardial infarction, who were divided into groups depending on the presence of type 2 diabetes mellitus and the therapy performed for them: group 1 – 58 patients with acute myocardial infarction and diabetes mellitus who underwent percutaneous coronary intervention; group 2 – 15 patients with acute myocardial infarction and diabetes mellitus who underwent exclusively conservative treatment; group 3 – 40 patients with acute myocardial infarction without diabetes who underwent percutaneous coronary intervention; group 4 – 17 patients with acute myocardial infarction without diabetes, who underwent exclusively conservative treatment. Results and discussion. According to the obtained results, in patients with concomitant type 2 diabetes mellitus, significantly lower levels of endothelial nitric oxide synthase were revealed, compared with patients without disturbances in carbohydrate metabolism, which indicates deeper impairments of endothelial function against the background of hyperglycemia and insulin resistance. Analysis of the effect of reperfusion therapy showed a statistically significant increase in the level of endothelial nitric oxide synthase both in the group of patients with concomitant disorders of carbohydrate metabolism and without them, which indicates an improvement in the processes of endothelium-dependent dilation, regardless of the presence or absence of type 2 diabetes mellitus. The obtained results testify to the positive effect of percutaneous coronary intervention at the level of eNOS, which, in our opinion, will help to improve the vasodilating properties of vascular endothelium and prevent a complicated course of acute myocardial infarction. Conclusion. The patients with acute myocardial infarction and concomitant type 2 diabetes mellitus have significantly lower levels of endothelial nitric oxide synthase levels than patients without type 2 diabetes mellitus that indicates deep violations of endothelial function against background of metabolic changes associated with insulin resistance and hyperglycemia. Reperfusion therapy accelerates its restoration regardless of the presence or absence of type 2 diabetes mellitus

Dose-dependent effects of rosuvastatin on circulating microRNAs-27a and 221 levels in patients with coronary artery disease with type 2 diabetes mellitus

Abstract Background Circulating microRNAs are capable of mediating cell-cell communication. MicroRNAs-27a and 221 serve an important regulatory role in both atherosclerosis and type 2 diabetes mellitus (T2DM). The lipid-lowering and pleiotropic effects of statins might be mediated by microRNAs. The purpose of the study was to investigate the dose-dependent effects of rosuvastatin on the circulating miRNAs-27a and 221 levels in patients with coronary artery disease (CAD) with T2DM. Methods The study included 22 patients with stable CAD with T2DM with rosuvastatin treatment at least 3 months (rosuvastatin 10 mg/day – 10 patients, rosuvastatin 20–40 mg/day – 12 patients), 16 patients with stable CAD with T2DM treated without statins. All patients received aspirin, beta-blockers, ACE inhibitors or sartans, metformin or its combination with sulfonylurea. The control group consisted of 16 healthy persons. MicroRNAs-27a-3p and 221-3p were determined in blood plasma by real time polymerase chain reaction. Small nuclear RNA U6 was used as endogenous control. Results expressed in relative units. Results In non-statin-treated patients with CAD with T2DM both microRNAs-27a (0,33 [0,15; 0,87]) and 221 (0,59 [0,27; 1,15]) levels were lower than in the control group ((0,90 [0,54; 2,62]), p=0,006 and (1,05 [0,57; 1,75]), p=0,043, respectively). In patients with CAD with T2DM treated with rosuvastatin 10 mg/day microRNA-27a level (0,44 [0,34; 0,69]) was decreased significantly in comparison with the control group (p=0,012) and was increased non-significantly in comparison non-statin-treated patients (p=0,439). In patients treated with rosuvastatin 20–40 mg/day microRNA-27a level (1,26 [0,31; 1,50]) was non-significantly higher than in the control group (p=0,559) and was significantly increased compared with non-statin-treated patients (p=0,038). MicroRNA-221 levels in patients treated both with rosuvastatin 10 mg/day (0,50 [0,28; 0,89]) and with rosuvastatin 20–40 mg/day (0,63 [0,40; 0,84]) were decreased in comparison with the control group (p=0,031 and p=0,042, respectively) and did not change significantly compared to patients treated without statins (p=0,928 and p=0,837, respectively). Conclusions In patients with CAD with T2DM circulating microRNAs-27a and -221 levels significantly decreased in comparison with control. Treatment with rosuvastatin in high doses (20–40 mg/day) but not in moderate dose (10 mg/day) was associated with the elevation of microRNA-27a level. Rosuvastatin at any doses did not influence on circulating microRNA-221 levels. These results revealed that rosuvastatin may serve protective roles in patients with CAD with T2DM by influencing on some microRNAs expression. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This research was funded by the Government as part of the research project to study the effects of circulating micro-ribonucleic acids in coronary artery disease with concomitant type 2 diabetes mellitus. This research did not receive any specific grant from funding.

Concomitant wild type transthyretin amyloidosis &amp; severe aortic stenosis in elderly Indian population: pilot study

Abstract Background Prevalence of both severe aortic stenosis (AS) and wild-type transthyretin cardiac amyloidosis (wtTTRCA) increases with age. Dual disease (AS+wtTTRCA) occurs in a significant proportion of patients undergoing aortic valve replacement. Prognostic significance of this dual disease is not established. Purpose TTRCA distribution has ethnic variability. This has not been studied in an Indian/Asian population before. India alone has &amp;gt;4.6 million estimated elderly individuals with severe AS. This pilot study was designed as part of a larger study to determine the prevalence of coexistence of severe AS and wtTTRCA in elderly Indian population and identify non-invasive predictors of its diagnosis. Methods Symptomatic severe AS patients aged ≥65 years undergoing surgical aortic valve replacement (SAVR) were enrolled. Detailed 2-D transthoracic echocardiogram including speckle tracking and longitudinal strain assessment was done preoperatively. TTRCA diagnosis was based on preoperative 99m-Technitium pyrophosphate scan (PYP), and intra-operatively obtained basal inter-ventricular septum (IVS) biopsy and excised native aortic valve subjected to histopathological examination (HPE). Congo red staining and immunohistochemistry using TTR monospecific antibodies were performed to identify and sub-type amyloid respectively. Serum/urine protein electrophoresis with serum immunofixation to rule out primary amyloidosis and genetic analysis to rule out mutant TTRCA were also done. Results SAVR was done in 46 severe AS patients (mean age 70±5 years, 70% men), 32 (70%) of whom also underwent PYP scan. Significant PYP uptake (Perrugini grade II or III) was seen in 3 (9%) patients (Figure 1E, F). On HPE, 33 (72%) native aortic valves had amyloid deposits, of which 19 (58%) had TTR deposition (Figure 1A, B, C, D). However, none of the IVS biopsies showed amyloid deposits. None of the patients had evidence of monoclonal protein elevation and mutation in the TTR gene. Non-invasive markers of this dual coexistence included elevated troponin-I (≥26.2 pg/mL, 35% vs 67%), combined elevated troponin-I &amp; NT-ProBNP (≥26.2 pg/mL &amp; ≥400 pg/mL, 24% vs 33%), and significantly low myocardial contraction fraction (≤30%, 72% vs 100%), deceleration time (207±80 msec vs 85±23 msec) and global longitudinal strain (−19.3±4.3% vs −13.6±3.7%). At median follow-up of 12.5 months, 1 patient each had died in TTR negative and TTR positive groups (3% vs 33%). The results are summarised in the central illustration (Figure 2). Conclusion In the Indian context, concomitant existence of severe AS and wtTTRCA is common. This pilot study suggests an absolute burden of &amp;gt;450,000 patients with dual disease of AS and wtTTRCA, in those otherwise believed to have lone severe AS. Further larger studies are thus indicated to establish the prevalence of this dual disease and to assess its prognostic implication. Funding Acknowledgement Type of funding sources: None. Figure 1. Histopathology and PYP scan resultsFigure 2. Central illustration

Type 2 diabetes mellitus promotes the proliferation, metastasis, and suppresses the apoptosis in oral squamous cell carcinoma

AbstractBackgroundOur previous study revealed that patients with oral squamous cell carcinoma and concomitant type 2 diabetes mellitus presented a lower 5‐year survival rate. Hyperglycemia has been increasingly recognized as a risk factor for more advanced disease and poorer prognosis in patients with oral squamous cell carcinoma. However, its role remains unclear.MethodsThe expressions of BRIP1, Ki67, E‐cadherin, and cleaved caspase‐3 were detected by immunohistochemistry in oral squamous cell carcinoma tissues with or without type 2 diabetes mellitus. Cell counting kit‐8 assay and wound healing assay were used to determine the proliferative and migratory ability of oral squamous cell carcinoma cells cultured with or without high glucose in vitro. Flow cytometry was applied to distinguish the role of high glucose on the cell cycle and apoptosis rates.ResultsThe expression level of Ki67 was elevated while BRIP1, E‐cadherin, and cleaved caspase‐3 were downregulated in patients with oral squamous cell carcinoma coexisting with diabetes. The cell proliferation and migration in oral squamous cell carcinoma cell lines were significantly enhanced by high glucose. Flow cytometric analysis suggested that high glucose predisposed cancer cells to stay at S/G2 phase and to exhibit lower apoptosis rates.ConclusionOur results implicated that type 2 diabetes mellitus may play a crucial role in the development and progression of oral squamous cell carcinoma through hyperglycemia, affecting cancer cell proliferation, migration, and apoptosis. This finding might provide a new direction for the prevention and treatment of oral squamous cell carcinoma.

Immune response and phagocytosis of children with streptococcal tonsillitis and infected with the herpes virus type 6.

The aim of the work is to study the indicators of cellular and humoral immune response and FAN of patients with tonsillitis in children infected with HHV-6 type.&#x0D; Materials and methods of research. In 72 children aged 3–15 years (mean age 8.42±1.44 years), patients with streptococcal tonsillitis of moderate severity, the levels of the main subpopulations of blood lymphocytes were determined using monoclonal antibodies by solid-phase enzyme-linked immunosorbent assay, phagocytic activity of neutrophils (FAN) using the nitrosine tetrazolium reduction test (HCT test) and serum IgA, IgM, IgG levels by radial immunodiffusion. The studies were carried out in the acute period and in the period of convalescence. Mathematical and statistical processing of the data obtained was carried out using Microsoft Excel 2003 and Statistica 6.0 programs. The significance of differences between the mean values was determined using the Student's test (t).&#x0D; Results. Different mechanisms of formation of pathological process at streptococcal tonsillitis at children depending on the concomitant HHV-6 type infection are revealed. In patients with mixed infection in the acute period of tonsillitis determine the signs of deficiency of the cellular immune system with the maximum deviation of CD-lymphocytes (t=3.13 vs. t=2.16 in mono-infection), the tension in the humoral link of the immune response Ig deviation (t=1.63 against t=0.91 in mono-infection) on the background of phagocytosis violation in terms of FAN deviation (t=3.22 against t=2.01 in mono-infection). By the period of convalescence, the restoration of the imbalance of specific and non-specific protection factors does not occur. Increased IgG content in the acute period is one of the features of streptococcal tonsillitis in children on the background of HHV-6t infection.&#x0D; Conclusions. Concomitant VGL-6 type infection in children with streptococcal tonsillitis affects the mechanisms of formation of the inflammatory process and the reactivity of patients, forming the preconditions for adverse outcomes of the disease. The obtained results can be the basis for early detection of herpes virus infection in patients with tonsillitis, will help to optimize the management of patients in different periods of the disease.

Сhanges in the quality of life of patients undergoing coronary stenting and with concomitant pathology

Goal — was to assess the quality of life of patients with coronary heart disease, concomitant type II diabetes mellitus and arterial hypertension at 2 years after coronary stenting. Material and methods. The study included 103 patients aged 44 to 67 years. Clinical and laboratory results were assessed after stenting of the coronary arteries, 2 years later in an outpatient setting. The patients were divided into two groups: the 1st group included 54 patients with ischemic heart disease, angina pectoris III–IV f.c. in combination with arterial hypertension; in the 2nd group — 49 patients with ischemic heart disease, angina pectoris III–IV f.k. in combination with arterial hypertension and type II diabetes mellitus. The study was carried out in accordance with Good Clinical Practice and Declaration of Helsinki principles. The study protocol was approved by the Ethics Committees of all participating clinical centers. Written informed consent was obtained from all participants prior to enrollment.Results. In our study, 103 patients with ischemic heart disease and angina pectoris III–IV f.c. Within 2 years after coronary artery stenting, 33 cases of myocardial infarction (32.0%) were registered. The quality of life improved to stable exertional angina pectoris I–II f.k. 34 patients (33.0%). At the same time, 39.8% did not change their quality of life. Myocardial infarction in the group with angina pectoris III–IV f.k. and arterial hypertension, developed in 12 (22.2%) patients, and in the group with angina pectoris III–IV f.c. and arterial hypertension + type II diabetes mellitus were registered in 21 (42.8%) patients, which is almost twice as high as in group 1, the same for improving the quality of life. That is, despite the stenting of the coronary arteries, the high incidence of complications in the form of myocardial infarction can be explained by a combination of concomitant diseases, in the form of arterial hypertension + type II diabetes mellitus. We are confident that type II diabetes mellitus has a greater impact on the quality of life and complications in patients who have undergone coronary stenting. At the same time, the risk of complications decreases with adequate control of arterial hypertension and type II diabetes mellitus — the transition of angina pectoris III–IV to I–II f.c. characterized by a significant improvement at p-0.0034; odds ratio 0.50; the confidence interval is 0.31–0.80. Conclusion. The improvement in the quality of life in patients with coronary heart disease and arterial hypertension after stenting of the coronary arteries in the long-term period is twice as good as in patients with coronary heart disease and arterial hypertension + type II diabetes mellitus. Arterial hypertension is a serious but manageable risk factor for the development of macrovascular and microvascular complications. The study demonstrated the effectiveness of correcting only arterial hypertension in terms of preventing cardiovascular and microvascular complications than the combination of arterial hypertension and type II diabetes mellitus, which significantly worsen the prognosis of the disease in patients with coronary artery disease after coronary artery stenting. This is reflected in the recommendations for stratification of the risk of arterial hypertension and type II diabetes mellitus.

THE ROLE OF BETA-BLOCKERS IN VETIANGINAL THERAPY IN THE CORRECTION OF VIOLATIONS OF THE AMINO ACID SPECTRUM IN PATIENTS WITH UNSTABLE ANGINA WITH CONCOMITANT DIABETES MELLITUS

The purpose of the study: to study the effect of bisoprolol and nebivolol on the spectrum of essential blood plasma AK in patients with concomitant diabetes mellitus (DM) type 2 in order to optimize drug treatment of this pathology in the future.Material and methods. The study involved 70 patients with NA with concomitant DM type 2, which was divided into two groups: group I (37 patients) as part of basic antianginal therapy received bisoprolol, group II (33 patients) received nebivolol. The control group (CG) consisted of 18 healthy individuals. All patients were tested for irreplaceable blood plasma AA by ion exchange liquid chromatography on an automatic analyzer AK T-339 produced by «Microtechna» (Czech Republic, Prague) at the Institute of Biochemistry named after OV Palladin NAMS of Ukraine. The following essential AAs were identified: arginine, valine, histidine, isoleucine, leucine, lysine, methionine, threonine, phenylalanine. Examination of patients was performed at the beginning of treatment and after 20 days. Results. It was determined that in patients with NA with concomitant DM type 2 under the influence of antianginal therapy in both groups significantly decreased the total amount of irreplaceable AA compared with control group, indicating an increase in intracellular metabolism as a compensatory response in coronary circulation. It should be noted that in patients of group II, in contrast to patients of group I, under the influence of treatment the level of histidine remained normal. The level of threonine significantly decreased compared to CG and the rate of patients in group I, the level of valine significantly increased compared to pre-treatment, the level of isoleucine significantly decreased compared with CG and with the rate of patients of group I. Importantly, ammonia levels returned to normal under the influence of basic therapy, which included nebivolol.Conclusion. The dynamics of changes in the levels of individual irreplaceable AA blood plasma, due to the mechanisms of their metabolic transformations in patients with NA with concomitant DM type 2 indicates greater effectiveness of nebivolol and the feasibility of its prescription іn complex of a basic antianginal therapy.

Diabetes concomitant to aortic stenosis is associated with increased expression of NF-\u03baB and more pronounced valve calcification

Aims/hypothesisType 2 diabetes has been demonstrated to predispose to aortic valve calcification. We investigated whether type 2 diabetes concomitant to aortic stenosis (AS) enhances valvular inflammation and coagulation activation via upregulated expression of NF-κB, with subsequent increased expression of bone morphogenetic protein 2 (BMP-2).MethodsIn this case–control study, 50 individuals with severe isolated AS and concomitant type 2 diabetes were compared with a control group of 100 individuals without diabetes. The median (IQR) duration of diabetes since diagnosis was 11 (7–18) years, and 36 (72%) individuals had HbA1c ≥48 mmol/mol (≥6.5%). Stenotic aortic valves obtained during valve replacement surgery served for in loco NF-κB, BMP-2, prothrombin (FII) and active factor X (FXa) immunostaining. In vitro cultures of valve interstitial cells (VICs), isolated from obtained valves were used for mechanistic experiments and PCR investigations.ResultsDiabetic compared with non-diabetic individuals displayed enhanced valvular expression of NF-κB, BMP-2, FII and FXa (all p ≤ 0.001). Moreover, the expression of NF-κB and BMP-2 positively correlated with amounts of valvular FII and FXa. Only in diabetic participants, valvular NF-κB expression was strongly associated with serum levels of HbA1c, and moderately with fructosamine. Of importance, in diabetic participants, valvular expression of NF-κB correlated with aortic valve area (AVA) and maximal transvalvular pressure gradient. In vitro experiments conducted using VIC cultures revealed that glucose (11 mmol/l) upregulated expression of both NF-κB and BMP-2 (p < 0.001). In VIC cultures treated with glucose in combination with reactive oxygen species (ROS) inhibitor (N-acetyl-l-cysteine), the expression of NF-κB and BMP-2 was significantly suppressed. A comparable effect was observed for VICs cultured with glucose in combination with NF-κB inhibitor (BAY 11–7082), suggesting that high doses of glucose activate oxidative stress leading to proinflammatory actions in VICs. Analysis of mRNA expression in VICs confirmed these findings; glucose caused a 6.9-fold increase in expression of RELA (NF-κB p65 subunit), with the ROS and NF-κB inhibitor reducing the raised expression of RELA by 1.8- and 3.2-fold, respectively.Conclusions/interpretationType 2 diabetes enhances in loco inflammation and coagulation activation within stenotic valve leaflets. Increased valvular expression of NF-κB in diabetic individuals is associated not only with serum HbA1c and fructosamine levels but also with AVA and transvalvular gradient, indicating that strict long-term glycaemic control is needed in AS patients with concomitant type 2 diabetes. This study suggests that maintaining these variables within the normal range may slow the rate of AS progression.Graphical abstract

Оцінка фільтраційно-екскреторної функції єдиної нирки у пацієнтів із сечокам’яною хворобою на тлі цукрового діабету 2-го типу

Мета дослідження. Вивчення внутрішньониркової гемодинаміки та фільтраційно-екскреторної функції з використанням динамічної реносцинтиграфії у хворих із сечокам’яною хворобою (СКХ) єдиної нирки на тлі цукрового діабету (ЦД) 2-го типу. Матеріали та методи. Обстежено 62 пацієнти з єдиною ниркою, що залишилась після нефректомії, які були розподілені на 3 групи: перша група — 21 пацієнт з нефролітіазом єдиної нирки та супутнім ЦД 2-го типу; друга група — 23 пацієнти з нефролітіазом єдиної нирки; третя група — 18 пацієнтів зі «здоровою» єдиною ниркою, що залишилась після нефректомії. Пацієнтам проводили біохімічні дослідження крові (рівень креатиніну, сечовини) та динамічну реносцинтиграфію. Результати. У хворих з єдиною ниркою при виникненні СКХ діагностується нирково-венна гіпертензія, збільшується внутрішньоклубочковий тиск, формується гіперфільтрація та гіперсекреція. За наявності ЦД і його ускладнень поступово підвищується периферичний судинний опір у нирці зі зниженням фільтраційно-екскреторної функції. Висновки. При умовній компенсації ниркової функції за біохімічними показниками крові у хворих на нефролітіаз єдиної нирки при динамічній нефросцинтиграфії виявляються значні негативні зміни внутрішньониркового кровотоку та фільтраційно-екскреторної функції нирки, особливо у пацієнтів із ЦД 2-го типу.

Патоморфоз метаболічного фенотипу остеоартрозу: роль ожиріння, цукрового діабету та гіпотиреозу (вікові та гендерні аспекти)

Актуальність. Остеоартроз (ОА) — одне із найпоширеніших захворювань опорно-рухового апарату, якому притаманний високий рівень коморбідності. Серед коморбідних явищ заслуговують на увагу зростаюча частота ожиріння, цукрового діабету (ЦД) та гіпотиреозу як складових частин метаболічного фенотипу ОА. Мета дослідження: дослідити вікові та гендерні особливості патоморфозу метаболічного фенотипу ОА з коморбідними явищами ожиріння, ЦД 2-го типу та гіпотиреозу. Матеріали та методи. Обстеженням охоплено 312 хворих на первинний ОА віком від 37 до 76 років. Методи дослідження: клінічні, рентгенологічні, ультрасонографічні, біохімічні, радіоімунологічні, статистичні. Результати. Серед обраної вибірки хворих метаболічний фенотип ОА був домінуючим (62,9 %), основною його складовою було ожиріння, але у 19 % випадків цього фенотипу згодом нашаровувався ЦД 2-го типу, а у 18 % інших випадків виявляли гіпотиреоз (субклінічна форма становить 13,78 %), переважно у жінок. Відзначається суттєва різниця у вікових періодах виникнення ожиріння, ЦД та гіпотиреозу. Верифіковані ендокринні недуги вагомо погіршували прояви, перебіг, ступінь дисліпідемії та результати лікування ОА й коморбідних захворювань серцево-судинної і травної систем. За клінічних, прогностичних і лікувально-профілактичних особливостей із метаболічного фенотипу ОА пропонується виділення підтипу А — ожиріння та цукровий діабет та підтипу Б — ожиріння та гіпотиреоз. Висновки. Метаболічний фенотип ОА є домінуючим в його структурі, а виділення підтипів А (ОА, ожиріння та ЦД) і Б (ОА, ожиріння та гіпотиреоз) сприятиме обґрунтованим вдосконаленням в лікувально-профілактичній стратегії в аспекті персоніфікованого лікування.

Особливості змін згортальної та фібринолітичної активності у пацієнтів з ішемічною хворобою серця із супутнім цукровим діабетом 2-го типу залежно від наявності діабетичних судинних ускладнень

Мета. Вивчення маркерів ендогенної коагуляції/фібринолізу у пацієнтів з ішемічною хворобою серця (ІХС) із супутнім цукровим діабетом (ЦД) 2-го типу та порівняння цих показників стосовно мікросудинних ускладнень. Матеріали та методи. Обстежено 54 пацієнти з ІХС і супутнім ЦД 2-го типу (розподілено на дві групи: з ускладненнями та без них), яких було госпіталізовано в кардіологічне та ендокринологічне відділення Київської клінічної лікарні на залізничному транспорті. Результати. При оцінюванні показників у двох групах (ІХС + ЦД 2-го типу та ІХС + ЦД 2-го типу + діабетичні ускладнення) у згортальній системі було виявлено подовжений протромбіновий час (на 7,64 % у пацієнтів без мікросудинних ускладнень і на 7,49 % — з ускладненнями) та значне підвищення вмісту фібриногену (на 36 та 42 % відповідно), але вірогідних змін між групами не було. Під час дослідження показників антикоагулянтної системи крові встановлено, що активність антитромбіну ІІІ і протеїну С у групі пацієнтів з ІХС і супутнім ЦД 2-го типу та діабетичними ускладненнями була нижчою (на 26 та 19,4 % відповідно) від значень контрольної групи. З боку фібринолітичної системи було виявлено значне пригнічення фібринолітичної активності плазми крові. Висновки. Отримані дані вказують на пригнічення фібринолітичної та антикоагулянтної активності плазми крові, що найбільше проявлялося у пацієнтів з ІХС і супутнім ЦД 2-го типу та мікросудинними ускладненнями. Зв’язок між фібринолізом і судинними захворюваннями залежить від стану судинного русла, що є значним збільшенням ризику розвитку макро- та мікросудинних уражень у пацієнтів з ІХС і супутнім ЦД 2-го типу.

INFLUENCE OF FIBRINOLYTIC THERAPY ON THE APPEARANCE OF COMPLICATIONS IN ACUTE PHASE OF MYOCARDIAL INFARCTION IN PATIENTS WITH CONCOMITANT DIABETES MELLITUS TYPE 2

It was examined 15 patients with acute myocardial infarction and were divided on groups depending on the presence or absence of concomitant diabetes mellitus type 2 and selected tactics of treatment (fibrinolytic or standart antiplatelet therapy). It was estimated requency of the complications development in acute period of myocardial infarction. It was found that patients with concomitant diabetes mellitus the most frequently had complicated course of acute phase of myocardial infarction in comparison with patients without previous fibrinolytic therapy. Using of fibrinolytic therapy has leveled the negative influence of diabetes mellitus on short-term prognosis of these patients. It’s confirmed the necessity of its carrying out in patients with co morbid pathology.

28463 Aprelimast and psoriasis: Significant hemoglobin A1c reduction and improved insulin resistance independent of changes in body mass index

A 46-year-old male with a 25-year history of plaque psoriasis and psoriatic arthritis presented for follow up with uncontrolled disease despite six months of adalimumab. The patient’s past medical history was notable for decompensated cirrhosis due to nonalcoholic steatohepatitis, splenomegaly, esophageal varices, thrombocytopenia, obstructive sleep apnea, obesity, and type 2 diabetes. Given his medical comorbidities, the patient was started on apremilast, reaching goal dose of 30 mg twice daily by four weeks. He achieved total clearance of his psoriasis at four month follow-up. Interestingly, patient’s glucose metabolism and glycemic control had dramatically improved since starting apremilast: hemoglobin A1c dropped from 10.9% at the initiation of therapy to 7.9% at three months and then to 6.6% by six months. His insulin requirement went from 250 units daily to zero by three months. Patient’s BMI, diet, and exercise activity all remained unchanged during this timeframe. No other medication changes were noted except for the addition of low dose propranolol for his history of esophageal varices. The patient continues to remain clear on apremilast after six months with sustained glycemic benefits. This case suggests that apremilast acts as a metabolic modulator of glucose metabolism irrespective of its ability to induce weight loss or reduce BMI. Further studies should investigate the link between proinflammatory chronic conditions, such as psoriasis, and type 2 diabetes. Better understanding of the pathophysiology may help influence therapeutic recommendations, as apremilast could be considered a preferred agent in patients that have psoriasis and concomitant type 2 diabetes or metabolic syndrome.

Frequency of Detection of the Main Risk Factors for Cardiovascular Events Among Servicemen

Frequency of Detection of the Main Risk Factors for Cardiovascular Events Among Servicemen