Presence Of Concomitant Obesity Research Articles

Effects of Metabolic Dysfunction-Associated Steatotic Liver Disease on Bone Density and Fragility Fractures: Associations and Mechanisms.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has profound adverse effects on bone health and homeostasis. MASLD appears to be associated with changes in bone mineral density (BMD) and fracture rate. However, the data are ambiguous and conflicting. Although several studies have shown that children and adolescents with MASLD have decreased BMD, the data on the prevalence of fragility fractures among children are scarce. In adults, increasing evidence suggests that MASLD decreases BMD and increases the risk of fragility fractures, which appears to be due to deterioration of bone architecture in addition to a decrease in BMD. Effects of MASLD on bone health may also be age- and race-specific. MASLD does not seem to increase fracture risk in children and adolescents but increases the risk of fractures in elderly men, especially those of Asian origin. From a mechanistic perspective, bone remodeling is a continuous process between osteoblasts (bone-forming) and osteoclasts (bone-resorbing), with any imbalance resulting in metabolic bone disease. In individuals with MASLD, loss of anabolic insulin receptor signaling (insulin resistance) in osteoblasts and increased receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) signaling in osteoclasts (proinflammatory cytokines) swings the pendulum toward accelerated bone loss. These processes are further complicated by the concomitant presence of obesity, type 2 diabetes mellitus, or sarcopenia in individuals with MASLD. This study reviews the current literature associated with the effects of MASLD on BMD and fragility fractures in children/adolescents and adults. This review also discusses the pathomechanisms that link MASLD with changes in BMD and fragility fractures.

Features of gynecological status and concomitant morbidity in menopausal women with resistant rheumatoid arthritis and obesity

Oftentimes, women with RA experience remission during pregnancy. The beneficial effect of pregnancy on the RA course is associated with a specific hormonal status, including high levels of estriol and progesterone that have known anti-inflammatory effects. After childbirth, decreased endogenous production of steroids can trigger the onset or exacerbation of RA.Objective. Studying of the characteristics of the gynecological status and concomitant extragenital diseases in postmenopausal women with rheumatoid arthritis (RA) depending on the presence of obesity.Materials and methods. 394 postmenopausal women with RA (diagnosed according to ACR/EULAR 2010 criteria) were included. By decision of the medical commission, all patients were approved for therapy with genetically engineered biological drugs and/or JAK kinase inhibitors. Before inclusion in the study, all patients had a detailed medical history, an allergic history, registered comorbidities, and a physical and laboratory-instrumental examination. Depending on the BMI values, the study participants were divided into groups. Group A included 103 obese patients of any severity (BMI ≥ 30 kg/m2). Group B included 291 women with BMI <30 kg/m2. Patients with an inflammatory process were found to have groups of inflammation by age and duration of RA (p > 0.05).Results. In patients of group A, more often than in patients of group B, comorbidities were detected: hypertension (p < 0.0001), coronary heart disease (p = 0.03), history of “vascular accidents” (p = 0.0009), especially acute cerebrovascular accident (p = 0.004), type 2 diabetes mellitus (p = 0.0005), which manifest themselves over the age of 45, that is, during the perimenopause. When correcting the gynecological history data, he draws attention to the fact that group A patients are more likely to operate surgically and on the pelvic organs: more had the uterus removed (p = 0.002) or ovarian resection was performed (p < 0.0001), and the frequency of surgical menopause in group A was higher than in group B (p = 0.0009). The debut of RA on average chronologically coincided with the onset of menopause (p = 0.01). At the same time, in the average age of the onset of menopause, it is rare (p > 0.05). The number of women who had a history of pregnancy, childbirth, miscarriages and abortions in the groups were repeated (p > 0.05). But in group A, the average number of pregnancies (p = 0.003) and abortions (p = 0.004) per woman was higher than in group B.Conclusion. The results of the study revealed the identification of clinical manifestations of inflammation and the severity of rheumatoid arthritis, depending on the presence of concomitant obesity in postmenopausal women, as well as a rarer occurrence of osteoporosis in women with RA and concomitant obesity.

CLINICAL CONSEQUENCES IN POST COVID-19 HYPERTENSIVE PATIENTS

Objective: to evaluate the clinical consequences in hypertensive patients after 1.2 ± 0.3 years after COVID-19 recovery. Design and method: We studied 51 treated hypertensive patients, which were divided into 2 groups: 26 patients recovered from mild to moderate COVID-19 in 2020-2021 years (1st group) and 25 patients were not ill COVID-19 (2nd group). The clinical characteristics, laboratory finding, echocardiographic measurement and clinical outcomes were analyzed. Results: There were no significant differences in sex, age, duration of hypertension, frequency of family history of premature CVD and presence of concomitant obesity, DM, CAD, stroke/TIA, atrial fibrillation, heart failure, CKD, PAD and average number of antihypertensive drugs, office systolic BP between the 2 groups. Levels of office diastolic BP by 10 % (P = 0.001) and heart rate by 13 % (P = 0.01) were higher in post COVID-19 group. Low adherence was present at 81.8 % patients 1st group compared with 45 % of 2nd patients group (P = 0.03). Cognitive impairment by the MMSE scale was detected in 68.2 % of COVID-19 recovered patients and 25 % of 2nd patients group (P = 0.03). Fasting glucose by 7.5 % (P = 0.046), 24-h albuminuria in 1.8 times (P = 0.049), level of CRP by 38.5 % (P = 0.04) were higher and blood concentration of endothelial progenitor cells (CD133+CD31+CD45-/+) by 14, 9 % (P = 0.04), left ventricular ejection fraction by 10 % (P = 0.03) were lower in post COVID-19 patients than in patients of 2nd group. Conclusions: The study indicate that the changes were found in the hypertensive patients after 1.2 ± 0.3 years of recovery from COVID-19. In the future these may signal an increased risk for incidence of CV outcomes. Cognitive dysfunction and possibly as a consequence poor adherence to antihypertensive treatment contribute to negative outcomes.

Highlighting the Role of Obesity and Insulin Resistance in Type 1 Diabetes and Its Associated Cardiometabolic Complications.

This narrative review appraises research data on the potentially harmful effect of obesity and insulin resistance (IR) co-existence with type 1 diabetes mellitus (T1DM)-related cardiovascular (CVD) complications and evaluates possible therapeutic options. Obesity and IR have increasingly been emerging in patients with T1DM. Genetic, epigenetic factors,and subcutaneous insulin administration are implicated in the pathogenesis of this coexistence. Accumulating evidence implies that the concomitant presence of obesity and IR is an independent predictor of worse CVD outcomes. The prevalence of obesity and IR has increased in patients with T1DM. This increase can be partly attributed to general population trends but, additionally, to iatrogenic weight gain caused by insulin treatment. This association might be the missing link explaining the excess CVD burden observed in patients with T1DM despite optimal glycemic control. Data on newer agents for type 2 diabetes mellitus (T2DM) treatment are unraveling novel ways to challenge this aggravating coexistence.

Obesity phenotypes are, in part, associated with physical activity in diabetic hemodialysis patients

To investigate the prevalence of obesity phenotypes and their association with physical activity levels among diabetic hemodialysis patients. This is a cross-sectional study with 84 diabetic hemodialysis patients (63.5 ± 9.4years, 54.8% of men). Obesity was diagnosed as high body fat (≥ 40% for male and ≥ 30% for female). Sarcopenic obesity was considered if low skeletal muscle mass (< 20.0kg for males and < 15.0kg for females) and obesity were combined. Dynapenic obesity was defined in the presence of low handgrip strength (< 27kg for males and < 16kg for females) and obesity. Muscle failure obesity was confirmed in the concomitant presence of obesity, sarcopenia, and dynapenia. Physical activity level was assessed by the Baecke questionnaire and patients were classified as low physical activity according to the first tertile for each of and total domains. Fifty-four patients (64%) presented obesity. From these, 5 (6%), 19 (23%) and 8 (10%) were classified as sarcopenic obese, dynapenic obese, and muscle failure obese, respectively, and 22 (26%) were only obese. Patients with sarcopenic obesity and muscle failure obesity had lower leisure and locomotion physical activity scores than non-obese, whereas the total domain score did not differ across the groups. Muscle failure obesity was independently associated with low leisure physical activity (OR 10.8, 95% CI 1.3-88.1). Only sarcopenic obesity was independently associated with the locomotion and total physical activity domains (OR 15.4, 95% CI 1.4-90.2 and OR 17.0, 95% CI 1.5-95.4, respectively). Our study found a lower prevalence of sarcopenic obesity compared to dynapenic obesity and muscle failure obesity among diabetic hemodialysis patients. Moreover, sarcopenic obesity and muscle failure obesity, but not dynapenic obesity, were associated with low physical activity levels.

Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents

The mechanisms that regulate blood pressure are numerous and complex; one mechanism that plays an important role in this scenario is represented by the balance between the vasoconstrictor effect of endothelin-1 and the vasodilator effect of nitric oxide. While there is agreement on the fact that increased endothelin-1 activity and decreased nitric oxide bioavailability are present in hypertensive adults, the situation is less clear in children and adolescents. Not all studies agree on the finding of an increase in plasma endothelin-1 levels in hypertensive children and adolescents; in addition, the picture is often confused by the concomitant presence of obesity, a condition that stimulates the production of endothelin-1. Furthermore, there is recent evidence that, in younger obese and hypertensive subjects, there is an overproduction of nitric oxide, rather than a reduction. This condition may change over time, causing endothelial dysfunction due to a reduced availability of nitric oxide in hypertensive adolescents. The purpose of this review is to address the main biochemical and pathophysiological aspects of endothelin and nitric oxide involvement in hypertension and to summarize the available scientific evidence on their role in the onset and maintenance of high blood pressure in children and adolescents.

Evaluation of the obesity influence on the life quality in patients with bronchial asthma

The obese asthma is characterized by a more severe course. The feature of this comorbid condition is the reduced effectiveness of basic therapy with inhaled corticosteroids, which prevents optimal control of symptoms, requires increasing doses and increases the number of exacerbations and hospitalizations. The problem of life quality (LQ) research in patients with asthma and obesity is highly relevant today, which made it the reason for this study.&#x0D; The aim of the study was to determine the effect of obesity on LQ in patients with asthma.&#x0D; Materials and methods. We selected for participating in the study 46 patients with moderate severity asthma. Examination of the patients included: objective examination with an anthropometric evaluation, the test of the LQ with two questionnaires: general one – Medical Outcome Study SF-36 (MOS SF-36) and specialized Asthma Quality of Life Questionnaire (AQLQ).&#x0D; Results. The increase in body mass index (BMI) in patients with asthma according to the questionnaires MOS SF-36 and AQLQ is associated with significant reductions in viability (r=–0.33, p&lt;0.05), physical activity (r=–0.37, p&lt;0.01), social activity (r=–0.36, p &lt;0.01) and the degree of reduction of the patient's tolerance to adverse environmental factors (r=–0.29, p&lt;0.05)&#x0D; Conclusions. The presence of concomitant obesity in patients with asthma is associated with significant reductions in the parameters of physical and social activity, viability and with an increase in the subjective pain assessment (according to the questionnaire MOS SF-36) and characterized by significantly lower rates of activity, tolerance to adverse environmental factors and general life quality (according to the AQLQ questionnaire).

Aspects of chronic heart failure in patients with type 2 diabetes mellitus after implantation of a permanent pacemaker, depending on body weight

The course of chronic heart failure (CHF) had been analyzed in patients with type 2 diabetes mellitus (DM) who had undergone pacemaker implantation, depending on body mass index (BMI). A retrospective analysis of echocardiographic data was carried out in 203 CHF patients who underwent pacemaker implantation, among whom 102 had concomitant type 2 diabetes (main group) and 101 participants did not have this metabolic pathology (control group). Pacemaker implantation was considered effective when the left ventricular end-diastolic volume (LV EDV) increased by 15 % after 12 months after operation. Patients who did not reach the target value of LV EDV were considered non-responders; analyzed the left ventricular ejection fraction (LVEF). In the main group, 22 patients (21,57 %) did not respond to implantation of the pacemaker, in the control group 12 people (11,9 %) did not respond to implantation of the pacemaker. Among the nonresponders, obese persons of the I, II and III degrees predominated. In the cohort of persons who responded to the establishment of the pacemaker, patients with a normal and increased BMI predominated; recorded a significant (p&lt;0,001) increase in the mean values of LVEF in patients with normal BMI from (52,0±0,8) % to (61,4±0,8) %. Similar changes were noted in overweight patients: LVEF significantly (p&lt;0,05) increased from (47,7±1,4) % to (55,1±1,3) %. Patients with CHF with concomitant type 2 diabetes, requiring pacemaker, have an inherent decrease in LVEF, which progressively decreases with increasing BMI. Low LVEF values are characteristic to patients with chronic heart failure, type 2 diabetes and morbid obesity. A good response to pacemaker implantation is associated with a normal, elevated BMI; failure to achieve the target value of LV EDV and insufficient growth of LVEF is more often recorded in the presence of concomitant obesity, especially of the II and III degrees. Keywords: heart failure, pacemaker, diabetes mellitus, left ventricular ejection fraction.

Complement activation in polycystic ovary syndrome occurs in the postprandial and fasted state and is influenced by obesity and insulin sensitivity.

Polycystic ovary syndrome (PCOS) is associated with metabolic risk. Complement proteins regulate inflammation and lipid clearance but their role in PCOS-associated metabolic risk is unclear. We sought to establish whether the complement system is activated in PCOS in the fasting and postprandial state. Case-control study. Fasting complement levels were measured in 84 women with PCOS and 95 healthy controls. Complement activation post-oral fat tolerance test (OFTT) was compared in 40 additional subjects (20 PCOS, 20 controls). Activation pathway (C3, C4, C3a(desArg), factor B, factor H, properdin, Factor D) and terminal pathway (C5, C5a, terminal complement complex [TCC]) proteins were measured by commercial or in-house assays. Fasting C3, C3a(desArg) and TCC concentrations were increased in insulin-resistant (adjusted differences: C3 0.13g/L [95%CI 0-0.25]; C3a(desArg) 319.2ng/mL [19.5-619]; TCC 0.66μg/mL [0.04-1.28]) but not in insulin-sensitive women with PCOS. C3 and factor H levels increased with obesity. Post-OFTT, C3 and C4 levels increased to a similar extent in PCOS subjects and controls, whist factor H levels increased more in women with PCOS compared to controls (adjusted differences (area under the curve): 12167μgmin/mL [4942-19392]), particularly in the presence of concomitant obesity. Activation and terminal complement pathway components are elevated in patients with PCOS, especially in the presence of insulin resistance and obesity.

USE OF PLATELETS RICH PLASMA AS A FACTOR OF THE REDUCTION OF THE RISK OF EARLY POSTOPERATIVE COMPLICATIONS IN PATIENTS WITH POSTOPERATIVE VENTRAL HERNIAS

Non-tensioned allohernioplasty with a polypropylene mesh implant has several disadvantages associated with the local occurrence of non-specific long-lasting inflammatory reactions in response to a foreign body. Excessive exudation in the implantation zone leads to the formation of seromas, requiring puncture aspiration, which significantly increases the treatment time. In the long-term, chronic prolonged inflammatory process leads to the formation of coarse connective tissue, which explains the development of biomechanical complications. Growth factors, introduced by platelet rich plasma (PRP), stimulate the release of regenerative cytokines, reduce local inflammatory manifestations in the integration of homoplastic grafts and reduce the incidence of postoperative complications. Aim: through the use of plasma enriched with platelets reduce the severity of early postoperative complications in patients with postoperative ventral hernias. Materials and methods. A clinical study was performed in the surgical department of the center for reconstructive and restorative medicine (university clinic) of the Odessa National Medical University (ONMedU) in the period from 2013 to 2019: 84 patients were operated because of postoperative ventral hernia. The average age of patients was 60.1±7.6 years. The size of hernial defects was on average 8.2 cm. The average BMI was 31.8 kg/m2. According to indications, patients underwent a standard surgical extent of intervention: hernia repair, allohernioplasty of the anterior abdominal wall with a lightweight (80 g/m2) polypropylene implant. After the plastics of the main group, a prosthesis implantation zone was infiltrated with activated autologous PRP, which was prepared by double centrifugation, in a volume of 14–38 ml. There was a control group in which PRP infiltration was not performed. The cavity above the mesh implant was actively drained by Redon for 2–4 days. An ultrasound examination was performed and, if necessary, fine needle aspiration of serous fluid over the mesh was done. Results. The evaluation of the postoperative period (up to 28 days) in patients of both groups. In none of the cases were manifestations of allergic, pyrogenic, local inflammatory or infectious complications. According to the quantitative assessment of early postoperative complications as well as the assessment of the degree of pain syndrome subjectively, according to VAS, the postoperative period in the main and control study groups was almost identical. The need for puncture aspirations and the total volume of discharge was significantly less in the main study group. The dependence of the severity of the effect of the proposed technology on such factors as the size of the hernial defect, the nature of plastics, and body mass index was noted. The greatest efficacy was demonstrated in the group of patients undergoing plastic surgery with the placement of a mesh implant in direct contact with subcutaneous fatty tissue for large-sized hernias (W2+) in the presence of concomitant obesity. Conclusions: the risk of development and the severity of fluid accumulations in the area of allohernioplasty can be predicted taking into account such risk factors as the size of the hernial defect, the nature of plastics, the presence of concomitant pathology, overweight. The technique of soft tissue infiltration in contact with a polypropylene prosthesis is safe, without significantly increasing the risk of local or systemic complications. The proposed method significantly reduces the risk of development and the severity of fluid accumulations in the area of implantation of the prosthesis. The effectiveness of technology is significantly higher compared to groups of patients with a high risk of seromas formation.

Association between Sympathetic Nervous System Activation, Obesity and Insulin Resistance

The review discusses the problem of overweight, obesity and metabolic syndrome and their activating effect on the sympathetic nervous system and the increase in blood pressure. Current epidemiological data on the prevalence of obesity and metabolic syndrome and trends in their occurrence in recent decades are presented, indicating the high significance of these disorders in modern health care and their important role in development of the overall disease burden. In accordance with the clinical guidelines, types of obesity are described with a special focus on its abdominal type, as a factor that increases cardiovascular risk. The mechanisms of sympathetic overactivity in obesity, including insulin resistance, hyperleptinemia, the effect of nonesterified fatty acids, obstructive sleep apnea and baroreflex impairment are considered in detail. In the second part of the paper experimental and clinical findings are presented indicating worsening of the hypertension mediated target-organ damage in the presence of concomitant obesity that emphases on the crucial role of amplified adrenergic stimuli in the formation of these disorders. The promoting effect of obesity and concomitant sympathetic nervous system overactivation on the development of left ventricular hypertrophy, endothelial dysfunction and vascular damage, renal dysfunction and cognitive decline are considered. Finally, body of evidence of high antihypertensive efficacy as well as prominent target organ protective features of the highly selective β 1 -blocker bisoprpolol are presented especially when it prescribed in patients with arterial hypertension and concomitant obesity and metabolic syndrome.

Quality of life associated with handgrip strength and sarcopenia: EpiFloripa Aging Study

BackgroundQuality of life (QoL) is an important measure, and it can be defined as the presence of control, autonomy, self-realization and pleasure. This study aims to verify the association between handgrip strength (HGS), sarcopenia and sarcopenic obesity with quality of life (QoL) among community-dwelling older adults in southern Brazil. MethodsCross-sectional analyses data of the “EpiFloripa Aging” cohort study were carried out. The participants were community-dwelling older adults (60 years and over). QoL was evaluated by CASP-16 Brazil instrument, with a score of zero, representing no QoL, to 48, total satisfaction. The TAKEI hand dynamometer verified the HGS. Sarcopenia was defined as appendicular skeletal muscle mass/body weight <2 standard deviations below gender-specific means for young adults. Sarcopenic obesity was identified as the concomitant presence of obesity and sarcopenia. Multiple linear regression was performed to estimate the associations. ResultsThe analytical sample consisted of 584 older adults (652% females). In the adjusted analysis, at each increase of one kgf in HGS there was a 0.24 and 0.18 increase in the QoL score, for females and males, respectively. Sarcopenia was negatively associated with QoL in males, and sarcopenic obesity wasn’t associated with QoL. ConclusionQoL was positively associated with HGS for both sexes, and negatively associated with sarcopenia for males. Low HGS, as well as sarcopenia, lead to critical health losses. Interventions that minimize phenotypes related to these conditions are fundamental, but mainly, conditions as severe as these need to be early identified to reduce the impact on QoL.

The role of system inflammation in bronchial asthma and obesity

The prevalence of bronchial asthma and obesity has grown in the recent decades worldwide. The urgency of this problem due to its medical and social significance for the society in connection with a reduction of patients ‘ quality of life and considerable economic damage to the health system. The relationship of these diseases, there are gender-related, age-related characteristics no doubt. Growing clinical-epidemiological evidence indicates that obesity might be an independent risk factor for bronchial asthma. On the other hand, the clinical data of bronchial asthma is a consequence of obesity remain indicative. The presence of concomitant obesity, bronchial asthma is considered as a state, significantly worsens its course. Etiology the causal relationship between obesity and asthma, despite the proposed mechanical, immunological, genetic and hormonal concepts still remains unclear. The underlying mechanism for this association is still unclear although several theories have been postulated in an attempt to describe it. Many studies demonstrate that bronchial asthma and obesity have some common mechanisms, including chronic systemic inflammation. In the review, we outline the current understanding of the role of systemic inflammation linked to obesity in the pathophysiology of bronchial asthma. An important role in the pathophysiology of systemic inflammation is given to changing levels of key adipose tissue hormones - leptin and adiponectin, respectively, having proinflammatory and anti-inflammatory activity. '/'his review article will focus on the leptin and adiponectin. Understanding the mechanisms of correlation between the metabolic activity of adipose tissue and the functional status of the respiratory tract with the development of systemic inflammation with comorbid asthma and obesity will review a number of existing provisions for the diagnosis and treatment of associated course of these diseases, to expand understanding the phenotypes of asthma and to develop new treatment strategies.

Problems of the differential diagnosis of MODY3 in obesity

MODY3 is one of the most common subtypes of MODY. Obesity in MODY3 patients modifies the disease course and complicates diagnostics at the clinical stage.&#x0D; A proband was diagnosed with type 2 diabetes mellitus (T2DM) at the age of 12 years; metformin therapy was used. A family history of DM involves three generations: the mother, aunt, and maternal grandfather have suffered from insulin-dependent DM since the age of 23, 22, and 40 years, respectively. The patient was examined at the age of 14 years. Obesity was present (SDS BMI 2.3). The insulin and C-peptide levels were 4.4 μU/mL and 1.5 ng/mL, respectively. The HbA1c level was 7.3%. Under glucose load, glycemia reached diabetic values; hyperinsulinemia and insulin resistance were not detected. Specific pancreatic antibodies were absent. Metformin was discontinued, and a sulfonylurea (SU) drug was prescribed, which had a positive effect. The heterozygous mutation p.P291fs was identified in the HNF1A gene. Therefore, MODY3 was verified.&#x0D; The presence of concomitant obesity in the patient significantly complicates the differential diagnosis, and only a careful comprehensive analysis of clinical and laboratory parameters and a family history makes it possible to suspect the diagnosis of MODY3 (requiring subsequent molecular genetic verification) and prescribe pathogenetic therapy.

The relationship between metabolic disorders and small for gestational age with idiopathic premature adrenarche

Abstract Background There is still controversy on the relationship between idiopathic premature adrenarche (IPA) and a history of small for gestational age, as well as the concomitant presence of obesity and other metabolic disturbances. An attempt is made to study these potential associations in a cohort of girls with IPA from our hospital. Patients and methods A descriptive cross-sectional study was conducted that included girls with a diagnosis of IPA from the Paediatric Department of the Fundacion Jimenez Diaz (Madrid, Spain) between January 2007 and May 2015. A record was made of family and personal history with perinatal data, as well as anthropometric data and biochemical values at the time of diagnosis. Results Out of a total of 76 girls with IPA, 2.7% had a history of small for gestational age. When body mass index was analysed according to modified criteria of WHO 2007/Cole 2000, 11.8% were overweight, and 11.8% were obese at diagnosis. Using the criteria set by the Spanish Ministry of Health, 6.6% were overweight and 18.4% obese, with 21.2% of the girls being insulin resistance, and 13.95% having dyslipidaemia. None of them had hypertension. From a comparative analysis between normal and overweight and obesity IPA girls, the latter had significantly higher levels of triglycerides and insulin, a higher HOMA index, and lower levels of HDL cholesterol. Conclusions IPA girls included in the study do not have a higher prevalence of small for gestational age compared to the general population. Prevalence of overweight and obesity in girls with IPA is not higher than the prevalence in the normal population.

Hypercoagulability in patients with atrial fibrillation and associated obesity: a way to hemorrhage or thromboembolia?

Despite the increased hypercoagulability of the blood plasma in patients with AF, the study of the processes of plasma hemostasis has still received insufficient attention, especially in patients with comorbid obesity or with excessive body weight. Purpose of the study. To establish the specific features of the effect of concomitant obesity on the indices of plasma hemostasis in patients with AF, on the basis of which to identify prognostically significant risk factors for adverse arrhythmia. Materials and methods. 75 patients with permanent AF were examined. For deducing prognostically significant risk factors, we conducted a retrospective analysis of the case histories of 421 inpatients. Results. The presence of concomitant obesity in patients with AF is accompanied by an acceleration of the prothrombinase-forming stage both in the internal and external hemocoagulation pathways. At the same time, the increase in procoagulant properties of blood is associated with a significant increase in fibrinogen and soluble fibrin-monomer complexes against the background of depletion of fibrinolytic and anticoagulant blood activity, which is a reflection of changes at the level of all links of hemocoagulation. Most diagnostically significant coagulation factors in the risk of thrombotic complications in patients with atrial fibrillation and concomitant obesity can be considered a measure of INR 30 minutes. Prognostically significant risk factors for small bleeding in patients with AF and associated obesity when taking warfarin are a BMI> 40kg/m 2 , level of AT III ≥40 % and ≥130 %, and in patients with AF and normal body weight, the amount of small bleeding increases if variability of INR beyond 2.0–3.0 and levels of AT III ≥130 %, as well as in the spring period of the year. Conclusions. Patients with AF are characterized by a moderate increase in the thrombogenic potential of the blood, which is accompanied by a significant inhibition of anticoagulant activity, while an increase in BMI leads to further deterioration of hemostasis equilibrium with an increase in procoagulant properties, depletion of fibrinolytic and anticoagulant blood activity.

Evaluating the results of surgical treatment and quality of life in patients with postoperative ventral hernia and concomitant obesity after different types of hernioplasty

Background. The problem of improving the quality of life of patients after surgical treatment of ventral hernias is very relevant, which is explained by the growing number of persons with this pathology, a high rate of relapses and complications when performing reconstructive surgical interventions (4.3–46 %) in this category of patients. The purpose of the research was to study the long-term results of surgical treatment of patients with cicatricial hernia of the anterior abdominal wall in obesity (late postoperative complications and quality of life), to perform a comparative evaluation of results in groups of patients operated by traditional methods using polypropylene mesh and allohernioplasty in combination with dermatolipectomy. Materials and methods. 108 patients were operated for postoperative ventral hernia. The first group consisted of patients who, according to their personal beliefs, refused to use the mesh, therefore, they underwent surgical procedures in traditional ways, the second group of patients underwent only allohernioplasty. In the third group of patients, allohernioplasty was supplemented by the simultaneous dermatolipectomy. We studied late postoperative complications (recurrences of hernias in a period of up to 3 years) and the quality of life of patients. Results. According to the received data, it can be asserted that the incidence of late postoperative complications in patients who underwent surgery for postoperative ventral hernia with the use of prosthetic plasty, especially in combination with dermatolipectomy, is significantly lower than the indices of the group operated by traditional methods. A decrease in body weight was noted in the majority of patients who underwent prosthetic hernioplasty. The analysis of the received data on the basic criteria of the quality of life assessment has shown that in the majority of patients with hernioplasty concerning primary ventral and cicatricial hernias by traditional classical ways it was low. Conclusions. The quality of life in most patients after prosthetic hernioplasty was high. The analysis of the incidence of late postoperative complications makes it possible to distinguish the advantages of performing prosthetic hernioplasty in comparison with traditional autoplastic methods. We consider this technique as an operation of choice in patients with postoperative ventral hernia in the presence of concomitant obesity.

Abstract 5919: Identification of a novel molecular interaction, targeted by Metformin, between breast cancer and white adipose tissue progenitors

Abstract The white adipose tissue (WAT) contains a resident population of progenitors with mesenchymal- or endothelial-like phenotype, able to promote breast cancer (BC) progression (Orecchioni et al., 2013). We recently characterized a novel molecular axis underneath the interaction between BC and WAT progenitors, possibly explaining the acquisition of a cancer-associated phenotype by WAT progenitor cells and the establishment of a permissive tumor microenvironment. GM-CSF balance was identified to be the principal regulator of the transcriptional alteration occurring in WAT progenitors exposed to BC: GM-CSF, produced by BC cells, dramatically changed the secretion profile of progenitors, enhancing its own production through a positive regulatory loop and inducing the expression of several factors involved in inflammation (IL-1β), ECM remodeling and angiogenesis (MMP9). IL-1β was strongly down-regulated by GM-CSF neutralization in WAT progenitors in vitro and in preclinical models. Induction of IL-1β by GM-CSF was able, in turn, to up-regulate MMP9 in the same cells. The markedly increased expression of MMP9 was already observed in BC-associated WAT progenitors, being addressed to increased local and metastatic tumor growth in obese mice. GM-CSF production was significalntly enhanced in the presence of concomitant obesity in preclinical models of BC, both in orthotopic models (MMTV-neu/ErbB2; 4T1) and in spontaneous tumor-bearing mice (MMTV-PyMT). GM-CSF neutralization in several obese syngeneic models of BC significantly reduced immunosuppressive cells in tumors and in the surrounding WAT, including T-regs (CD4+CD25brightCD127low), Granulocytic myeloid-derived suppressor cells (G-MDSCs, CD11b+Ly6C-Ly6G+), tumor-associated macrophages (TAMs, F4/80+CD206+MCHIIlow) and tumor infiltrating lymphocytes (TILs, CD8+PD1+). Different BC types produce distinct amounts of GM-CSF: triple negative BC (TNBC) expressed higher levels compared to hormone receptors positive cells, correlating GM-CSF expression to higher tumor grade. In the context of targeting WAT-BC interaction, Metformin was able to impair tumor growth, metastasis and angiogenesis in preclinical models (Orecchioni et al., 2015) and affecting immune cells, including T-regs, TAMs and MDSCs. From our data, GM-CSF was identified to be a new target of Metformin in both BC and WAT progenitors, suggesting a novel inhibitory mechanism mediated by the drug. Metformin displayed the same efficacy in reducing BC growth, metastatic spread and immune system regulation, when compared to GM-CSF specific neutralization in obese syngeneic models. Taken together, these results indicate GM-CSF as a new molecular target of Metformin and support the role of this novel mechanism in BC progression. Ongoing studies also suggest that this pathway might be induced in WAT progenitors by other solid tumors, including non-Hodgkin’s B-lymphoma. Citation Format: Francesca Reggiani, Valentina Labanca, Patrizia Mancuso, Andrea Manconi, Francesco Bertolini. Identification of a novel molecular interaction, targeted by Metformin, between breast cancer and white adipose tissue progenitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5919. doi:10.1158/1538-7445.AM2017-5919

Estudio de la asociación de adrenarquia prematura idiopática con la presencia de alteraciones metabólicas y con antecedente de pequeño para edad gestacional

BackgroundThere is still controversy on the relationship between idiopathic premature adrenarche (IPA) and a history of small for gestational age, as well as the concomitant presence of obesity and other metabolic disturbances. An attempt is made to study these potential associations in a cohort of girls with IPA from our hospital. Patients and methodsA descriptive cross-sectional study was conducted that included girls with a diagnosis of IPA from the Paediatric Department of the Fundación Jiménez Díaz (Madrid, Spain) between January 2007 and May 2015. A record was made of family and personal history with perinatal data, as well as anthropometric data and biochemical values at the time of diagnosis. ResultsOut of a total of 76 girls with IPA, 2.7% had a history of small for gestational age. When body mass index was analysed according to modified criteria of WHO 2007/Cole 2000, 11.8% were overweight, and 11.8% were obese at diagnosis. Using the criteria set by the Spanish Ministry of Health, 6.6% were overweight and 18.4% obese, with 21.2% of the girls being insulin resistance, and 13.95% having dyslipidaemia. None of them had hypertension. From a comparative analysis between normal and overweight and obesity IPA girls, the latter had significantly higher levels of triglycerides and insulin, a higher HOMA index, and lower levels of HDL cholesterol. ConclusionsIPA girls included in the study do not have a higher prevalence of small for gestational age compared to the general population. Prevalence of overweight and obesity in girls with IPA is not higher than the prevalence in the normal population.

Metabolic Syndrome Reduces the Survival Benefit of the Obesity Paradox after Infrainguinal Bypass

Metabolic syndrome, having risen to epidemic proportions in the United States, is associated with future cardiovascular disease and mortality and increased postoperative complication rates. However, the impact of metabolic syndrome on outcomes after infrainguinal bypass surgery remains poorly defined. Using the American College of Surgeons-National Surgical Quality Improvement Program database from 2005-2011, patients undergoing infrainguinal bypass were identified. Data on preoperative risk factors, operative details, and 30-day outcomes were collected. Metabolic syndrome was defined as the concomitant presence of obesity (body mass index: >30 kg/m(2)), hypertension, and diabetes mellitus. A total of 19,604 patients underwent an infrainguinal bypass, 16% of whom suffered from metabolic syndrome. Patients with metabolic syndrome were younger (P < 0.001), more obese (P < 0.001), and suffered from more comorbidities overall. On univariate analysis, metabolic syndrome was associated with an increased risk of developing any complication (odds ratio [OR]: 1.67; P < 0.001), including superficial surgical site infection (SSI), deep SSI, wound dehiscence, bleeding, cardiac arrest, myocardial infarction, renal insufficiency, sepsis, and returning to the operating room. However, metabolic syndrome was protective of 30-day mortality (OR: 0.71; P = 0.02). On multivariate regression, metabolic syndrome remained associated with the development of any complication (OR: 1.55; P < 0.001), any wound complication (OR: 1.84; P < 0.001), and renal insufficiency (OR: 1.75; P < 0.03). There was a trend for metabolic syndrome to be protective of 30-day mortality (OR: 0.74; P = 0.09). When compared to obese patients without metabolic syndrome, those with metabolic syndrome had a higher rate of any postoperative complication (22.5% vs. 16.6%) and death (1.82% vs. 1.42%). Patients with metabolic syndrome are at an increased risk of postoperative complications after infrainguinal bypass. Despite increased morbidity, metabolic syndrome was not associated with inferior 30-day mortality, but did diminish the survival benefit of the obesity paradox.