Progression Of Cardiovascular Complications Research Articles

TREATMENT OF EXTENSIVE PURULENT-NECROTIC LESIONS OF THE LEG IN PATIENTS WITH NEUROPATHIC FORM OF DIABETIC FOOT SYNDROME

Актуальность. Развитие гнойно-некротических осложнений у больных с синдромом диабетической стопы (СДС) является причиной высоких ампутаций и ранней инвалидизации, что в свою очередь приводит к развитию метаболического синдрома и прогрессированию сердечно-сосудистых осложнений. В настоящее время способы лечения гнойно-некротических процессов при СДС направлены на сохранение опорной функции конечности. Наличие обширной гнойно-некротической раны голени – фактор риска появления показаний к высокой ампутации. Цель – разработка алгоритма лечения обширных гнойно-некротических ран голени у больных с нейропатической формой СДС. Материал и методы. В областном центре «Диабетическая стопа» на базе Видновской районной клинической больницы за период с 2009 по 2013 г. были проанализированы результаты лечения 62 пациентов с нейропатической формой СДС и наличием обширных гнойно-некротических ран голени. Всем больным проводилось хирургическое вмешательство, а также комплексная консервативная терапия. Лечение разделялось на несколько этапов: очищение раны до появления грануляционной ткани – выполнение аутодермопластики – стимуляция эпителизации. Эффективность лечения оценивали по срокам очищения раны, появления грануляций, эпителизации, количеству высоких ампутаций. Результаты. Больным выполнялись радикальные хирургические операции с пересечением путей распространения в проксимальном направлении гнойной инфекции с последующим открытым ведением раны. В последующем проводились этапные некрэктомии совместно с консервативной терапией, направленной на очищение раны. Средние сроки очищения раны составили 10,6±1,2 суток. Формирование грануляционной ткани происходило через 8,4±0,8 суток после первого оперативного вмешательства. При появлении очищенной грануляционной ткани пациентам выполнялась аутодермопластика свободным расщепленным лоскутом для стимуляции процесса эпителизации. Процесс эпителизации начинался через 10,2±0,6 суток. При поступлении, на 4-е и на 10-е сутки после первого оперативного вмешательства выполнялось измерение индекса лейкоцитарной инфильтрации. Нормализация этого показателя во время лечения свидетельствует об очищении раны и удовлетворительном течении раневого процесса. В период с 2009 по 2013 г. была выполнена одна (1,6%) высокая ампутация. Заключение. Активная хирургическая тактика, заключающаяся в иссечении первичного гнойного очага, пересечении гнойных проводящих путей (сухожилия, фасции), открытом ведении раны, последующих этапных некрэктомиях, в комплексе с консервативной терапией способствует максимальному очищению раны, снижению уровня интоксикации, активации репаративного процесса. Своевременное выполнение аутодермопластики ускоряет процесс эпителизации и заживления раны.

Cardiovascular alterations do exist in children with stage-2 chronic kidney disease.

Cardiovascular disease (CVD) is an important complication of chronic kidney disease (CKD) in children. However, it is not well known when and how cardiovascular alterations start. This cross-sectional, controlled study consisted of 25 patients and 28 healthy controls. 24-h ambulatory blood pressure monitoring, aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT) and carotid distensibility (distensibility coefficient and β stiffness index), and echocardiography were assessed to evaluate CVD. Routine biochemical parameters, fibroblast growth factor-23 (FGF23) and high sensitive C- reactive protein were measured to determine cardiovascular risk factors. Hypertension was found in 12 patients (48%). Patients had higher FGF23 levels and aPWV-standard deviation score (SDS) as compared to the controls (p=0.003 and p=0.002, respectively). Aortic PWV-SDS was predicted by increased daytime systolic blood pressure load (β=0.512, p=0.009, R 2=0.262). Neither cIMT nor distensibility differed between the groups; however, older age and high level of FGF23 were independent predictors of β stiffness index in patients (β=0.507, p=0.005, R 2=0.461 and β=0.502, p=0.005, R 2=0.461, respectively). As compared to controls, patients had worse left ventricular diastolic function [lower E/A ratio p=0.006) and increased left atrial dimension (p<0.001)]. Cardiovascular deteriorations appear in children with stage-2 CKD. Good control of BP and decreasing the level of FGF23 may be useful to slow down the progression of cardiovascular complications.

DYSLIPIDEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Summury. Data about lipid disorders at different stages of chronic kidney disease (CKD), including those on dialysis are presented in the review. The possible influence of dyslipidemia on the progression of CKD, as well as the onset and progression of cardiovascular complications in patients with CKD are discussed. The questions of lipid-lowering therapy use, including statins, in patients with CKD on dialysis and predialysis, are disclosed.

The Relationship Between Neutrophil Lymphocyte Ratio With Urinary Protein Albumin Excretion in Newly Diagnosed Patients With Type 2 Diabetes

BackgroundRecent evidence suggests that neutrophil/ lymphocyte (N/L) ratio play a role in the development and progression of cardiovascular complications. Increased urinary albumin and protein excretion has been shown to be a risk factor for cardiovascular disease. Thus, this study aimed to investigate the relationship between circulating total and differential leukocyte counts including N/L ratio with urinary protein and albumin excretion in patients with newly diagnosed type 2 diabetes. MethodsAll patients underwent history taking, physical examination, blood pressure measurement, 12-lead electrocardiographic evaluation, routine urine analysis, biochemical analysis, 24-hour urine collection to measure protein and albumin excretion and creatinine clearance. Peripheral total and differential leukocyte analyses were performed using an automated cell counter. ResultsIn total, 80 patients were included. spearman correlation analysis revealed that 24-hour urinary protein excretion was correlated with neutrophil count (ρ=0.280, P=0.012), lymphocyte count (ρ=−0.365, P=0.001) and N/L ratio (ρ=0.474, P<0.0001). Spearman correlation analysis revealed that 24-hour urinary albumin excretion was correlated with neutrophil count (ρ=0.261, P=0.019), lymphocyte count (ρ=−0.278, P=0.013) and N/L ratio (ρ=0.415, P<0.0001). In stepwise linear regression analysis, 24-hour urinary protein excretion was independently associated with high-density lipoprotein cholesterol (P=0.01), blood urea (P=0.014) and N/L ratio (P=0.041). On the other hand, 24-hour urinary albumin excretion was independently associated with creatinine clearance (P=0.004), albumin (P<0.0001) and N/L ratio (P=0.011). ConclusionsThis study demonstrated that increased N/L ratio was independently related with both 24-hour urinary protein and urinary albumin excretion in newly diagnosed patients with type 2 diabetes.

The Genetic and Metabolic Determinants of Cardiovascular Complications in Type 2 Diabetes: Recent Insights from Animal Models and Clinical Investigations

Cardiovascular complications (CVC) are the most common causes of death in patients with type 2 diabetes (T2D). However the pathophysiological determinants and molecular mechanisms involved in the progression of CVC in T2D are poorly understood. We have undertaken the challenging task of identifying some of the genetic and clinical determinants of CVC through a unique multidisciplinary approach involving Canadian and Finnish investigators. We are studying novel animal models combining atherosclerosis, diet-induced obesity and T2D to understand the molecular basis of CVC in obesity-linked T2D. We are also conducting clinical studies to identify key determinants of CVC in T2D patients and to determine whether a lifestyle modification program targeting loss of visceral adipose tissue/ectopic fat could be associated with clinical benefits in these patients. Together, we strongly believe that we can fill some gaps in our understanding of the CVC pathogenesis in T2D and identify novel therapeutic targets and hope that this new knowledge may be translated into the design of effective clinical interventions to optimally reduce cardiovascular risk in T2D subjects.

Inflammatory Cytokine Profiles During Exercise in Obese, Diabetic, and Healthy Children

Objective: Modulation of inflammatory status is considered a key component of the overall health effects of exercise. This may be especially relevant in children with obesity (Ob) or type 1 diabetes (T1DM), in which an imbalance between pro- and anti-inflammatory mediators could accelerate onset and progression of cardiovascular complications. To date, exercise-induced alterations in immuno-modulatory mediators in Ob and T1DM children remain largely unknown. Methods: In this study, we monitored the kinetic profiles of 8 pro-and anti-inflammatory cytokines (TNF-a, IL-6, IL-2, IL-8, IL-5, IL-13, IL-10, IL-4) during a standardized exercise challenge (ten 2-min cycling bouts at 80% VO2max, separated by 1-min intervals) in 23 Ob (12 females, 11 males), 23 T1DM (10 females and 13 males) patients and 20 healthy (CL, 10 females and 10 males) children. Blood glucose of T1DM patients was kept in the 4.4-6.1 mM range for at least 90 minute prior to and during exercise. Blood samples were drawn at rest and after every other exercise bout.Results: In Ob, TNF-a and IL-2 were significantly greater (p<0.0167) as compared to T1DM and CL, both at baseline and throughout exercise. All other variables, while not significant, were quantitatively elevated in Ob vs. CL. In T1DM, IL-4 and IL-8 levels were similar to Ob, IL-2 and TNF-a similar to CL, and IL-6, IL-5, IL-13, IL-4 levels were intermediate between the Ob and CL groups. Conclusions: During exercise, therefore, both Ob and T1DM children displayed exaggerated pro-inflammatory responses, although with clearly different magnitude and involved mediators. Our data support the necessity to identify specific exercise formats through which each at-risk pediatric population can draw maximal beneficial health effects.Conflict of interest:None declared.

Endothelial cells from humans and mice with polycystic kidney disease are characterized by polyploidy and chromosome segregation defects through survivin down-regulation

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common hereditary and systemic disorder associated with various cardiovascular complications. It has been implicated with dysfunction in primary cilia. We and others have shown that the immediate function of endothelial cilia is to sense extracellular signal. The long-term function of cilia is hypothesized to regulate cell cycle. Here, we show that ciliary function (polycystins) and structure (polaris) are required for proper cellular division. Cilia mutant cells undergo abnormal cell division with apparent defects in mitotic spindle formation, cellular spindle assembly checkpoint and centrosome amplification. Down-regulation of the chromosomal passenger survivin contributes to these abnormalities, which further result in cell polyploidy. Re-expression of survivin restores a competent spindle assembly checkpoint and reduces polyploidy. Aged animals show a more severe phenotype in cellular division, consistent with progression of cardiovascular complications seen in older ADPKD patients. For the first time, we show that structure and function of mechanosensory cilia are crucial in maintaining proper cellular proliferation. Furthermore, developmental aging plays a crucial role in the progression of these abnormal cellular phenotypes. We propose that abnormal function or structure of primary cilia not only causes failure to transmit extracellular signals, but also is associated with cytokinesis defects in both mice and humans with polycystic kidney disease.

Refractory Progression of Coronary Aneurysms, a Case of Delayed Onset Kawasaki Disease as Depicted by Cardiac Computed Tomography Angiography

Kawasaki disease (KD) is an immune-mediated vasculitis of unknown etiology with self-limited clinical course that was first described in 1967 by Dr. Tomisaku Kawasaki. It is a disease of early childhood and rare past late adulthood but one that can have detrimental consequences when there is a delay in diagnosis and treatment. Cardiovascular complications causing increased morbidity and mortality may include coronary artery aneurysms, myocardial infarction, heart failure, arrhythmias, and peripheral artery occlusion. Here, we present an atypical case of delayed onset KD in a young teenager. DS had visited three different emergency departments during the course of 2 weeks for unrelenting fevers. Despite multiple treatment protocols including immunoglobulin, steroids, and tumor necrosis factor-alpha antagonists, he continued to have progression of cardiovascular complications. While echocardiographic findings were suspicious for cardiac complications, a cardiac computed tomography (CT) angiography was able to clearly distinguish giant coronary aneurysms. Without prompt therapy, fever and manifestations of acute inflammation can last for several weeks to months with increased risk toward complications. The incidence of coronary artery aneurysms has been noted to be 25% in untreated patients with a mortality rate of up to 2%. Using low-dose protocols along with high spatial and temporal resolution of cardiac CT angiography may provide a useful and complimentary imaging modality in accurate diagnosis and follow-up of patients with KD.

Tissue factor/its pathway inhibitor system and kynurenines in chronic kidney disease patients on conservative treatment

The abnormalities of tissue factor (TF) and its inhibitor (TFPI) system could potentially contribute to high incidence of thrombotic complications and atherosclerosis in patients with chronic kidney disease (CKD). Recently, the role of the kynurenine (KYN) pathway of tryptophan (TRP) degradation has been postulated in the progression of cardiovascular complications. We compared the plasma TF, TFPI and the metabolites of TRP degradation: KYN and 3-hydroxykynurenine (3-HKYN) levels in 55 CKD patients on conservative treatment and 19 healthy controls; and we tried to establish whether or not there is an association between TF/TFPI system and above-mentioned metabolites in these patients. Compared with the controls, the patients with CKD showed a significant increase in plasma concentrations of TF (P < 0.01), KYN, 3-HKYN (both P < 0.0001), KYN-to-TRP (kyn/trp) ratio (P < 0.001) and 3-HKYN-to-KYN (3-hkyn/kyn) ratio (P < 0.05). In contrast, TRP concentrations were significantly decreased in the CKD group compared with controls (P < 0.001). The difference in TFPI levels between CKD patients and controls was not statistically significant. TF/TFPI system was inversely correlated with TRP, whereas it was positively related to the 3-HKYN, kyn/trp and 3-hkyn/kyn ratios. Moreover, both the TF/TFPI system and KYNs were associated with the markers of kidney function. These data suggested for the first time a significant relationship between TF/TFPI system and KYN pathway in CKD patients on conservative treatment.

Kidney Transplantation with and without Prior Dialysis Therapy in Diabetic Patients with End-Stage Renal Failure

Cardiovascular disease is the main cause of death in diabetic patients. Uraemia seems to increase progression of cardiovascular morbidity. Therefore early transplantation even without pretransplant dialysis could be a way of slowing progression of cardiovascular complications in patients with endstage renal failure due to diabetic nephropathy. The risk for impaired graft survival and operation-induced complications have been considered contraindications for kidney transplantation without previous dialysis. To examine whether dialysis before transplantation influences the outcome of diabetic patients after kidney transplantation data from 125 diabetic patients receiving a kidney graft during 1973-1982 was retrospectively analyzed. Twenty-four of them were transplanted without previous dialysis. One-year patient survival was somewhat higher in patients transplanted without previous dialysis than in dialyzed patients (82 and 65%) but similar 7 years after transplantation (45% and 41%). Graft survival was also similar in both groups. Although the nondialyzed patients had had more myocardial infarctions before transplantation, prevalence of mortality in cardiovascular complications after transplantation were not increased compared with dialyzed patients. Previous dialysis did not influence surgery-related complications.

A model of psychosocial hypertension showing reversibility and progression of cardiovascular complications.

The sequence of pathophysiological changes that can result from the stimulating effects of a sustained disturbance of the social environment was studied in ten colonies of socially deprived mice. Sixteen formerly isolated males were placed with 16 normal females in population cages consisting of seven intercommunicating boxes. Six of these socially disturbed 32-member colonies were terminated after periods of interaction ranging from 2 days to 9 months. The remaining four were terminated a month or more after the males had been returned to individual isolation. Indirect blood pressure measurements, body and heart weights, and sections of hearts and aortas were studied in the males. Following the shorter exposures, blood pressure reverted to normal in a few days. Exposure of 6 months or more were associated with unchanged body weights and sustained increases in heart weight and blood pressure readings. In addition, there was a significant development of aortic arteriosclerosis and myocardial fibrosis. These changes persisted despite prolonged return to isolation.