Depression, cognitive dysfunction and other factors associated with 5-year overall mortality in type 2 diabetes mellitus: a pilot prospective observational study

BACKGROUND: Psychological predictors of overall mortality in the Russian population of Type 2 diabetic patients and their impact compared to biological risk factors have not been studied.AIM. To identify clinical, laboratory and psychological factors independently associated with the 5-year overall mortality in Type 2 diabetic patients in the Moscow region.MATERIALS AND METHODS: This open label observational prospective study included 178 consecutive type 2 diabetic patients (women 145, men 33, age range 37 to 82 years, duration of diabetes 0,5 to 30 years). At baseline, in addition to the standard clinical, laboratory and instrumental work-up, all patients were assessed for depression, cognitive dysfunction and diabetes-related quality of life. No study-related intervention was performed; all patients were followed up and treated by their local physicians. After 5 years, we assessed the patients’ vital status (alive or dead). Multiple logistic regression was used to identify baseline patients’ characteristics, which were significantly and independently associated with 5-year overall mortality. Taking into account the exploratory type of multiple regression, the results were considered significant at α<0.1.RESULTS: At 5 years, 150 (84%) patients were alive and 15 (8,4%) were dead; no information could be obtained for the rest 13 (7,3%) patients. The analysis of 165 patients with the verified outcome, independent and significant associations with the death outcome were found for male gender (odds ratio [OR] 6,36 [95%CI 0,91–44.40]; p=0.06), age (OR 2.06 [1.30–3.27]; p<0.002), chronic heart failure (CHF) (OR 2.78 [1.25–6.2]; р=0.012), Hamilton depression scale score (OR 1,18 [1.03–1.34]; р=0.016), cognitive dysfunction score (Roschina scale) (OR 1.20 [1.05–1.35]; р=0.006), and age — body mass index interaction (OR 0,98 [0,97–0,997]; р = 0,013). The predicted probability of death within the next 5 years in men and women was 22,9% and 6,7%, respectively. The highest score of cognitive dysfunction was associated with a 25% predicted probability of death and the lowest, with a 2% probability of death; predicted probabilities of death for the highest and lowest depression scores were 26% and 2%, respectively. The 5-year predicted probability of death in the patients without CHF was 6,7%, with CHF I NYHA functional class, 9,8%, II functional class 13,6%, III functional class 18,2%, and IV functional class 23,5%. All other baseline clinical, laboratory, demographic, psychological and socioeconomic variables were not significantly associated with the 5-year survival rate. The model was not verified on an external cohort.CONCLUSION: Cognitive dysfunction and depression have a significant negative impact on the 5-year mortality rate at much higher degree, than glycemic control, any diabetes-related complications and cardiovascular disorders, excluding CHF. The results obtained highlight the importance of the diagnosis and treatment of depression and cognitive dysfunction in type 2 diabetes mellitus

IMMUNE PREDICTORS OF FIBROGENESIS AND THEIR APPLICATION FOR NON-INVASIVE DIAGNOSTICS OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC VIRAL HEPATITIS

The study was devoted to development of non-invasive methods for diagnosis of liver fibrosis in patients with chronic viral hepatitis (CVH). The stepwise logistic multivariate regression analysis of biochemical (PTI, glucose, albumin, AST, LDH) and immunological parameters (the functional activity of neutrophils and monocytes, the relative content of CD8+ T- and CD19+B-cells) was used for the establishment of diagnostic model. Based on the multiple regression analysis we derived a 2 novel Integral Indexes of Liver Fibrosis (IILF-biochem and IILF-immun, respectively). It is shown that IILF-biochem allows, without resorting to liver biopsy to predict the appropriate stage of fibrosis in CHV patients with diagnostic accuracy of 86—87 %, and in combination with IILF — at 97.7 %

INTRANASAL INHALATIONS OF BIOACTIVE FACTORS PRODUCED BY M2 MACROPHAGES IN THE TREATMENT OF PATIENTS WITH ORGANIC BRAIN SYNDROME

The aim of present study was to evaluate safety and clinical efficacy of inhalatory immunotherapy based on intranasal delivery of bioactive factors produced by M2 macrophages applied for treatment of patients with organic brain syndrome (OBS).Materials and methods. The study under the NCT02957123 protocol (www.ClinicalTrails.gov) included thirty patients with OBS of various genesis (10 men and 20 women aged 18 to 81; Me, 62.5 years). Neurological assessment and the levels of 32 cytokines in the blood serum of patients were evaluated before and 2-3 days after completion of inhalation immunotherapy.Intranasal inhalations of cell-free culture medium of M2 macrophages (2 mL, once a day for 28-30 days) were safe and well tolerated. None of 30 treated patients had severe adverse events and serious treatmentrelated side reactions. One month after starting the inhalations, a positive dynamics in neurological status was noted in all the patients. A marked clinical response was documented in twenty out of thirty patients (67%), which manifested as improvement, according to all scales and questionnaires. The neurological improvement was not reversed over 6 months of follow-up period. In other ten patients (33%), a moderate clinical response was shown as improvement of individual scores. The positive changes were as follows: 1) a 43% decrease in anxiety and depression scores (according to HADS scale, pU = 0.0008); 2) an increase of total motor activity (stability and gait) by 25%, pU = 0.0001); 3) correction of cognitive functions (MoCa test, pU = 0.007); 4) reduced number and intensity of the disease symptoms by 52% (pU = 0.0001). This marked clinical response to immunotherapy is shown to be associated with correction/normalization of serum hepatocyte growth factor (HGF) level.Conclusion. Inhalation immunotherapy based on intranasal delivery of bioactive factors produced by M2 macrophages can improve neurological and functional recovery in patients with organic brain syndrome

Prevalence and correlates of depressive disorders in people with Type 2 diabetes: results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET‐DD) study, a collaborative study carried out in 14 countries

Aims To assess the prevalence and management of depressive disorders in people with Type 2 diabetes in different countries. Methods People with diabetes aged 18–65 years and treated in outpatient settings were recruited in 14 countries and underwent a psychiatric interview. Participants completed the Patient Health Questionnaire and the Problem Areas in Diabetes scale. Demographic and medical record data were collected. Results A total of 2783 people with Type 2 diabetes (45.3% men, mean duration of diabetes 8.8 years) participated. Overall, 10.6% were diagnosed with current major depressive disorder and 17.0% reported moderate to severe levels of depressive symptomatology (Patient Health Questionnaire scores >9). Multivariable analyses showed that, after controlling for country, current major depressive disorder was significantly associated with gender (women) (PPPPP<0.0001). The proportion of those with either current major depressive disorder or moderate to severe levels of depressive symptomatology who had a diagnosis or any treatment for their depression recorded in their medical records was extremely low and non-existent in many countries (0–29.6%). Conclusions Our international study, the largest of this type ever undertaken, shows that people with diabetes frequently have depressive disorders and also significant levels of depressive symptoms. Our findings indicate that the identification and appropriate care for psychological and psychiatric problems is not the norm and suggest a lack of the comprehensive approach to diabetes management that is needed to improve clinical outcomes

SPONTANEOUS AND LPS-INDUCED PRODUCTION OF 26 CYTOKINES SECRETED BY BLOOD CELLS OF PATIENTS WITH LIVER CIRRHOSIS DURING OF CELL THERAPY

The objective of the present study was to assess the level of 26 cytokines secreted by peripheral blood cells of the patients with liver cirrhosis (LC; n = 20) during the cell therapy (CT). All the patients were administered with intravenously injected autologous bone marrow-derived mononuclear cells (MNCs) in a dose of 1.3±0.3 × 109 (Ме 1.0 × 109 ) followed by 14 days later intravenous injection of ex vivo generated mesenchymal stromal cells (MSCs) in a dose of 22.3±5.0 × 106 (Ме 16.0 × 106 ). The patients were examined before the CT, 2-3 days after the administration of MNCs and, then, 2-3 days after the introduction of MSCs. Cytokine-secretory function of peripheral blood cells was evaluated in a 24-hour whole blood cultures both in the absence of any stimulation and in response to lipopolysaccharide (LPS). The control group consisted of 10 healthy donors. The administration of patients’ bone marrow cells (both MNCs and MSC) was safe and well tolerated and caused no any adverse (toxic or allergic) events. Compared with donors, LC patients (especially, with class B+C by Child-Pugh) differed by an initially increased production of several cytokines and chemokines. Actually, there was a statistically significant increase of the spontaneous production of IL-9, MIP-1β, and IP-10, as well as a distinct trend to an increase in TNFα, IL-1ra, IL-4, IL-5, IL-6, IL-13, of MCP-1, MIP-1α, RANTES and Eotaxin. Moreover, the blood cells of LC patients were susceptible to the stimulatory effect of LPS, and the LPS-induced production of 11 out of 26 cytokines (IL-1ra, IL-6, IL-9, IL-15, IL-17, IL-7, IL-8, IP-10, MIP-1α, MIP-1β, Eotaxin) significantly exceeded the normative values. Transplantation of bone marrow MNCs had minimal impact on cytokine production. Meanwhile, the MSCs introduction resulted in a significant decrease in spontaneous and LPS-induced production of, respectively, 20 and 18 analytes including pro-/anti-inflammatory and immunoregulatory cytokines, chemokines and growth factors. The normalization of cytokine-secretory function following transplantation of MSCs revealed in the patients with LC indicates the weakening of an inflammatory activity of circulating blood cells and the decrease in their reactivity to endotoxin. MSC suppressive effect on cytokine production was dose-dependent, and most pronounced in patients with decompensated LC (class B+C by Child-Pugh) of viral etiology

Measurement of J/ψ→γηcJ/\psi\to\gamma\eta_{\rm c} decay rate and ηc\eta_{\rm c} parameters at KEDR

Using the inclusive photon spectrum based on a data sample collected at the $J/\psi$ peak with the KEDR detector at the VEPP-4M $e^+e^-$ collider, we measured the rate of the radiative decay $J/\psi\to\gamma\eta_{\rm c}$ as well as $\eta_{\rm c}$ mass and width. Taking into account an asymmetric photon lineshape we obtained $\Gamma^0_{\gamma\eta_{\rm c}}=2.98\pm0.18 \phantom{|}^{+0.15}_{-0.33}$ keV, $M_{\eta_{\rm c}} = 2983.5 \pm 1.4 \phantom{|}^{+1.6}_{-3.6}$ MeV/$c^2$, $\Gamma_{\eta_{\rm c}} = 27.2 \pm 3.1 \phantom{|}^{+5.4}_{-2.6}$ MeV.Comment: 6 pages, 3 figure

Measurement of J/psi to eta_c gamma at KEDR

We present a study of the inclusive photon spectra from 5.9 million J/psi decays collected with the KEDR detector at the VEPP-4M e+e- collider. We measure the branching fraction of radiative decay J/psi to eta_c gamma, eta_c width and mass. Our preliminary results are: M(eta_c) = 2979.4+-1.5+-1.9 MeV, G(eta_c) = 27.8+-5.1+-3.3 MeV, B(J/psi to eta_c gamma) = (2.34+-0.15+-0.40)%.Comment: To be published in Proceedings of the PhiPsi09, Oct. 13-16, 2009, Beijing, Chin

Precise measurement of RudsR_{\text{uds}} and RR between 1.84 and 3.72 GeV at the KEDR detector

The present work continues a series of the KEDR measurements of the $R$ value that started in 2010 at the VEPP-4M $e^+e^-$ collider. By combining new data with our previous results in this energy range we measured the values of $R_{\text{uds}}$ and $R$ at nine center-of-mass energies between 3.08 and 3.72 GeV. The total accuracy is about or better than $2.6\%$ at most of energy points with a systematic uncertainty of about $1.9\%$. Together with the previous precise $R$ measurement at KEDR in the energy range 1.84-3.05 GeV, it constitutes the most detailed high-precision $R$ measurement near the charmonium production threshold.Comment: arXiv admin note: text overlap with arXiv:1610.02827 and substantial text overlap with arXiv:1510.0266