Molecular genetic features of the development of restrictive cardiomyopathy in Russian children

Aim. To identify the proportion of restrictive cardiomyopathy (RCM), as well as cardiomyopathy (CMP) with a restrictive type of hemodynamics among all cases of genetic CMP and to determine the relative frequencies and spectrum of nucleotide variants in Russian children with RCM, as well as to search for phenogenotypic correlations.Material and methods. The study included 689 children with CMPs. All children underwent a molecular genetic testing of the target regions of 419 genes responsible for various cardiomyopathies and channelopathies using the method of massively parallel sequencing (MPS).Results. In 668 (97,0%) children, pathogenic, likely pathogenic nucleotide variants, as well as nucleotide variants with unknown clinical significance, were identified. Of these, 45 (6,7%) patients were selected to determine the molecular genetic characteristics of RCM, 20 of whom had clinical symptoms and morphofunctional structure of RCMP (3,0%), while the remaining 25 (3,7%) children were diagnosed with another CMP type with a restrictive type of hemodynamics. In total, these patients had 41 nucleotide variants in 15 different genes, while 19 (46,3%) variants were pathogenic, 12 (29,3%) — likely pathogenic, 10 (24,4%) — uncertain clinical significance. Pathogenic and likely pathogenic variants were identified in a total of 38 (84,4%) patients, while in 19 (42,2%) patients, the pathogenic variants described earlier were found. The most common genetic marker of RCM in Russian children was TNNI3 gene mutations. In total, they were identified in 12 (25%) children: with RCP — 8 (40%) patients; with CMP with a restrictive type of hemodynamics — 4 (16%) patients. At the same time, the most common mutation of the TNNI3 gene was the nucleotide variant c.575G>A, leading to the amino acid variant p.R192H, described earlier in patients with RCM and identified by us in three (15%) unrelated children with RCM. In addition, a significant difference was found between the averaged values of N-terminal pro-brain natriuretic peptide in patients with mutations in the MYH7 and TNNI3 genes (0,0039, p<0,05), as well as between the peak flow gradient values in children with mutations in TNNI3 and FLNC genes (0,0016, p<0,05), TNNI3 and MYH7 genes (0,039, p<0,05).Conclusion. The results of this study indicate a significant genetic heterogeneity of RCM in Russian children and the need for further research aimed at finding genotype-phenotype associations in order to predict the course of the disease and select the proper therapy.

The Restrictive Type, Infectious Complications, a Long Duration of Illness Might Predict Nadir Hematological Values Among Individuals With Anorexia Nervosa During the Refeeding Period: A Retrospective Study

BackgroundAlthough hematological abnormalities in patients with anorexia nervosa have been documented, the mechanisms involved have not been fully clarified, especially during the refeeding period, when hematological values further decrease after admission prior to improving. Here we address potential mechanisms underlying the hematological abnormalities of anorexic inpatients during the refeeding period.MethodsWe recruited patients from 101 admissions corresponding to 55 individual patients with anorexia nervosa with severe malnutrition (body mass index, 13.4 ± 3.4) from the neuropsychiatry unit in Ashikaga Red Cross Hospital during the period from October 1999 to March 2018. We analyzed three hematological cell measures (hemoglobin, white blood cells, platelets) to determine their levels at admission and their lowest levels during the refeeding period and calculated the rate of decrease in those values from admission to the nadir levels. We analyzed each measure using a general mixed model with explanatory variables, including data upon admission and a treatment-related indicator. ResultsThe initial hemoglobin value of 12.1 ± 2.7 g/dl decreased by 22.3% to 9.4 ± 2.5 g/dl; the initial white cell count was 5387 ± 3474/μl, which decreased by 33.6% to 3576 ± 1440/μl; the initial platelet count of 22.6 ± 10.1 ×104/μl decreased by 24.3% to 17.1 ± 8.0 ×104/μl. All nadir levels were observed during the refeeding period from the fifth to tenth day of hospitalization. The anorexia nervosa restrictive type was associated with a lower nadir level of hemoglobin and white blood cell count. Infectious complications were related to a lower nadir level of hemoglobin and platelet count. A longer duration of illness was associated with a lower nadir white blood cell count. ConclusionsNadir hematological cell measures of inpatients with anorexia nervosa during the refeeding period might be predicted by the restrictive type, infectious complications, and a long duration of illness. These factors might be used as indicators to guide clinical approaches for controlling hematological deficiencies during the refeeding period.

An evaluation of family-based treatment for restrictive-type eating disorders, delivered as standard care in a public mental health service

Background Family-based treatment (FBT) has demonstrated efficacy for anorexia nervosa (AN) in youth in randomized, controlled trials. It is important to assess if it shows a similar effectiveness when implemented in standard care. Aim To evaluate outcomes of FBT for restrictive-type eating disorders, delivered as standard care in a public mental health service. Outcomes are remission, frequency of hospital admissions and day-patient treatment, and frequency of other adaptations within 12 months from commencement of treatment. Second, to compare the collaborative clinical decisions of successful treatment in standard care made by family therapist at the end of treatment, with more objective definitions of recovery. Methods The design is a prospective, uncontrolled study of a consecutive series of patients with restrictive-type eating disorders, treated with FBT in a specialty unit at the Child and Adolescent Mental Health Centre in the Capital Region of Denmark. Results FBT was successfully completed within 12 months by 57% of participants, and 47% completed with 20 sessions or fewer. Weight restoration was achieved by 75% within 12 months, and 46% achieved both normalisation of body weight and behavioural symptoms of AN within 12 months. A total of 20% needed intensified treatment. All aspects of remission were often not present simultaneously, and the collaborative clinical decisions of successful treatment only partly aligned with other parameters of remission. Conclusion FBT showed good results when implemented as standard care, and it can be adapted to the specifics of local service organisation without compromising effectiveness.

Сharacteristics of nutrition and content of certain microelements in blood in adolescents with signs of metabolic syndrome

Purpose — to study the nature of nutrition and blood zinc and magnesium levels in adolescents with signs of metabolic syndrome (MS). Materials and methods. The 200 patients with obesity (aged 14–18: 100 boys and 100 girls) were examined at the clinic of the Institute of Children and Adolescent Health Care of the National Academy of Medical Sciences of Ukraine. All patients underwent a comprehensive clinical and laboratory examination. The study of eating behavior (EB) was conducted by questionnaire using the Dutch questionnaire (DEBQ, The Dutch Eating Behavior Questionnaire). The control group consisted of 30 healthy children of the same age category. The criteria for the diagnosis of MS in children, proposed by the International Diabetes Federation [IDF, 2007], were used, which allowed to divide patients into two groups: 1 — with signs of MS (50.0%) and 2 — without signs of MS (50.0%), each of which included 100 patients. Results and discussion. According to the anamnesis, adolescents had an unbalanced and irrational diet, as evidenced by complaints of pain and dyspepsia. Analysis of DEBQ data showed that in most adolescents there was a restrictive type of EB — (73.9±3.2%), also quite common variants were external (in 43.8±3.1%) and emotional type of EB (32.3±3.1%). The results showed significant zinc and magnesium deficiency in obese adolescents, in contrast to the surveyed control group (ϕ<0.05), in particular, the most pronounced (ϕ<0.05) deficiency of these trace elements was observed in the surveyed group with restrictive type of EB. Conclusions. Thus, an unbalanced diet naturally leads to disorders of both the digestive system and the formation of comorbid pathology, including obesity and MS. Analysis of the results of the DEBQ survey showed that patients with signs of MS were twice as likely to have EB disorders (71.8±3.7%) than patients without them (39.4±4.1%, ϕ<0.05). Among the violations of EB, the most common was the restrictive type (73.9%). Adolescents have a significant deficiency of zinc and magnesium in the blood (ϕ<0.05), in particular the most pronounced (ϕ<0.05) in the group of subjects with a restrictive type of EB. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: adolescents, microelements, nutrition, insulin resistance, metabolic syndrome.

Features of eating behavior in children with different forms of non-alcoholic fatty liver disease

Aim – to study the features of the eating behavior (EB) in children with different forms of nonalcoholic fatty liver disease (NAFLD) - simple steatosis (SS) and nonalcoholic steatohepatitis (NASH), to compare the obtained data with the eating behavior of children without liver steatosis. 120 patients aged 7 to 16 years were examined, the average age of the patients was (12.00 ± 2.56) years. The presence and degree of liver steatosis was determined by transient elastography using a FibroScan®502Touch with an assessment of CAP (controlled attenuation parameter). According to the CAP, gender-specific alanine aminotransferase levels and body mass index, patients were divided into 4 groups: 1 group consisted of 26 patients with NASH, 2 group – of 44 patients with SS, 3 group – of 35 patients with obesity without liver steatosis, 4 group (control) – of 15 patients with normal weight without metabolic disorders. The groups were homogeneous in age. Assessment of EB was carried out using the pediatric modification of the Dutch eating behavior questionnaire (DEBQ-C). It was found that most patients with SS (75,0%) and NASH (87,5%) demonstrated an emotional type of EB. The restrictive type of EB was predominant in obese children without hepatic steatosis (73,7%). The total score of the restrictive type of EB in children of the 3 group was significantly higher compared with the data of the 4 group (p<0,05). The external type of EB occurred in 25% of children with SS and was not observed in children with NASH. Thus, children with NAFLD and obesity are characterized by an increased incidence of various types of unhealthy eating behavior compared to children with normal weight, which requires appropriate correction and involvement of psychologists in a team of specialists involved in the health care of the obese children.

Overweight and Obesity: Is there a Relationship with Eating Behaviour?

Obesity is a non-infectious epidemic of the XXI century. The social significance of the problem of obesity is determined by the threat of disability of young patients and the reduction of overall life expectancy due to the frequent development of severe diseases. Eating behaviour disorders are the leading factors in the development of overweight and obesity. The purpose of the work was to determine the relationship between overweight and obesity with eating behaviour, taking into account the gender and age characteristics of patients. Material and methods. A survey of 272 people (136 men and 136 women) was conducted. The examined patients were divided into two clinical groups: I group included 90 people (45 women and 45 men) with excess weight (BMI = 27.7±1.31 kg / m2); Group II had 92 people (46 women and 46 men) with obesity of 1 degree (BMI = 31.74±1.03 kg / m2). Evaluation of eating disorders was carried out using the DEBQ questionnaire (Netherlands) adapted to the purpose of the study. Results and discussion. Eating behaviour disorders are one of the leading factors in the development of overweight and obesity: in overweight patients a healthy type of eating behaviour was recorded 4.86 times less often than in normal weight (D = 13.56, p = 2.35 e-14 <0.05), and in obese patients it was 7.14 times less often than in normal weight individuals (D = 21.04, p = 2.2e-16 <0.05). Overweight and obesity are most often associated with a restrictive type of eating behaviour: in overweight people they were met 4 times more often (D = 0.16, p-value = 4.637e-06 <0.05), and in obese patients disorders of the restrictive type of eating behaviour were 4.24 times more often compared to the control group (D = 0.15, p-value = 6.148e-07 <0.05). The type of eating behaviour in all clinical groups, except for body mass index, was influenced by gender and age of the subjects. Thus, in overweight men after the age of 45 a healthy type of eating behaviour occurred 8.09 times more often than in men under the age of 45 (D = 0.11, p-value = 0.03 <0.05) and in overweight women (D = 0.11, p-value = 0.03 <0.05). The relationship between the type of eating behaviour and gender and age characteristics of patients was found and confirmed by correlation analysis in all clinical groups. Conclusions. Healthy eating behaviour disorders are one of the leading factors in the development of overweight and obesity. Correction of eating disorders in obese people must be carried out taking into account the gender and age characteristics of the patient, to obtain positive results for a shorter course of treatment. Medical advice for women and young people, taking into account the prevalence of restrictive eating behaviour disorders, should be aimed at combating strict diets and periods of prolonged starvation; men and people over 45, taking into account the prevalence of external eating behaviour disorders, should follow a balanced diet. The duration of corrective treatment in obese women should be increased through psychotherapy

Is Serum BDNF Altered in Acute, Short- and Long-Term Recovered Restrictive Type Anorexia Nervosa?

Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the regulation of food intake and body weight, has been implicated in the development and maintenance of Anorexia nervosa (AN). The majority of previous studies reported lower BDNF levels in acutely underweight AN patients (acAN) and increasing levels after weight rehabilitation. Here, we investigated serum BDNF concentrations in the largest known AN sample to date, both before and after weight restoration therapy. Serum BDNF was measured in 259 female volunteers: 77 in-patient acAN participants of the restrictive type (47 reassessed after short-term weight rehabilitation), 62 individuals long-term recovered from AN, and 120 healthy controls. We validated our findings in a post-hoc mega-analysis in which we reanalyzed combined data from the current sample and those from our previous study on BDNF in AN (combined sample: 389 participants). All analyses carefully accounted for known determinants of BDNF (age, sex, storage time of blood samples). We further assessed relationships with relevant clinical variables (body-mass-index, physical activity, symptoms). Contrary to our hypotheses, we found zero significant differences in either cross-sectional or longitudinal comparisons and no significant relationships with clinical variables. Together, our study suggests that BDNF may not be a reliable state- or trait-marker in AN after all.

EATING BEHAVIOUR AND OBESITY: GENDER-AGE FEATURES

The aim: Identify the types of eating behaviour in overweight and obesity depending on gender and age. Materials and methods: A survey of 210 people (men -105, women -105) was conducted. The age of women ranged from 19 to 60 years, the average age was 41.5 ± 11.2 years. The age of men ranged from 22 to 60 years, the average age was 42.3 ± 12.3 years. The examined patients were divided into two clinical groups: group I – 70 people (women – 35, men – 35) with overweight. BMI of persons of the I group from 25.8 kg / m2 to 29,3 kg / m2 (BMTmid. = 27,5 ± 1,31 kg / m2); Group II – 72 people with 1st degree obesity (women -36, men – 36). Evaluation of eating disorders was carried out using the DEBQ questionnaire (Nederland) adapted to the purpose of the study. Results: In patients of groups I and II healthy type of eating behaviour was recorded less often than in control groups, 5.38 times (D = 13.561, p = 0.002 <0.05) and 10.45 times (D = 21.043, p = 0.022 <0.05), respectively. In group I, the restrictive type of EB among women occurred 1.7 times more often than in men (D = 0.852, p = 0.001). In group II, the restrictive type of EB among women was observed 1.3 times more often than in men (D = 0.382, p = 0.005). Conclusions: Restrictive eating behaviour disorders are one of the leading factors in the development of overweight and obesity. Correction of eating disorders in obese people must be carried out taking into account the gender and age characteristics of the patient, to obtain positive results for a shorter course of treatment.

Effect of perioperative infusion therapy on the functional state of the hemostatic system in patients with concomitant coronary heart disease

Background. The choice of the infusion therapy regimen in the perioperative period remains a complex and controversial issue of modern anesthesiology. This is especially true for elderly patients with concomitant cardiovascular diseases, primarily coronary heart disease (CHD). Excessive fluid restriction in the perioperative period during the intervention can contribute to the development of arterial hypotension and hypoperfusion of vital organs. At the same time, excessive fluid intake in these patients is dangerous in terms of developing complications such as decompensation of heart activity, ischemic myocardial damage. There are many factors of the perioperative period that affect the processes of fluid metabolism in the body, the state of hemodynamics and other vital functions. Among them, the most significant factors are operational stress, features of the underlying disease and surgical intervention, the influence of anesthetics, the functional state of the cardiovascular system, kidneys, etc. One of the insufficiently considered factors that may influence the choice of infusion therapy, in our opinion, is the functional state of the hemostatic system in the preoperative period. Objective. To investigate the effect of perioperative infusion therapy on the functional state of the hemostatic system in patients with concomitant CHD. Materials and methods. A total of 92 patients who underwent abdominal surgery under combined general anesthesia with a ventilator were examined. The average age of patients was 61±12 years; risk on the ASA scale – II-III; risk of cardiac complications on the RCRI – 1-3; risk of thrombosis on the Caprini scale – 6.5±0.1. The functional state of platelets was assessed using the platelet aggregation analyzer AR 2110 (Belarus); the state of plasma hemostasis was assessed using standard coagulogram indicators. Results and discussion. When studying platelet aggregation in the initial state, significant fluctuations in the studied parameters were found from significant hypoaggregation to significant platelet hyperaggregation. For further analysis and differential correction, patients were divided into three groups depending on the degree of platelet aggregation. Group 1 included 22 patients with established hypoaggregation, 2nd group – 38 patients with established normal platelet aggregation, and 3rd group – 32 patients with platelet hyperaggregation. The coagulogram in the majority of patients in the initial state characterized normocoagulation or a tendency to hypercoagulation. Correction of changes in primary hemostasis was performed using infusion therapy, depending on the initial data of platelet aggregation. In the group with greegreece platelets was conducted infusion therapy with the liberal type – 5-10 ml/kg/h for intraoperative stage and 20-25 ml/kg/day after surgery; in the group with hoareau for restrictive type an average of 3-5 ml/kg/h for intraoperative stage and 20-25 ml/kg/day after surgery; in the group with normoergic the relatively restrictive type that was 5-7 ml/kg/h intraoperatively; 25 ml/kg/day after surgery. For specific correction of platelet-vascular hemostasis, etamzilate 12.5 % 4.0 ml was used in group 1 patients before surgery and later 4.0 ml three times a day; in group 3 patients, pentoxifylline 2 % 5.0 ml twice a day. Thromboprophylaxis with low-molecular-weight heparins in the perioperative period was performed in all patients according to current recommendations. As a result of this approach to the correction of established disorders of platelet-vascular hemostasis, a clear trend towards normalization of the studied parameters was established already at the intraoperative stage, this trend persisted a day after the operation. Thus, the indicators of platelet aggregation in group 1 patients at the intraoperative and early postoperative stages were 68.2 (59.5; 78.1) and 63.6 (60; 72.6); in group 3 patients – 79.7 (75.3; 94.2) and 74.6 (59.2; 83.4), respectively. Conclusions. Individualized infusion and pharmacological therapy allows correction of disorders of platelet-vascular hemostasis in patients with concomitant CHD, which may be useful for reducing the risk of thrombotic complications.