[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

[ACTIV SARS-CoV-2 registry (Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients). Assessment of impact of combined original comorbid diseases in patients with COVID-19 on the prognosis].

AIM: Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. MATERIALS AND METHODS: The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. CLINICALTRIALS: gov ID NCT04492384. RESULTS: Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. CONCLUSION: Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2¼).

Aim      To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods  The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion      In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

[International register "Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients (ACTIV SARS-CoV-2)"].

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[Patients after acute decompensation of Heart Failure: adherence to self-monitoring and treatment depending on the mode of outpatient monitoring].

Aim      To evaluate compliance with self-monitoring and drug and non-drug treatment of patients after ADHF during the management at a specialized center for CHF treatment (CCHF) or in real-life clinical practice.Material and methods  The study included 942 CHF patients after ADHF. In two years, the entire sample of patients was retrospectively divided into 4 groups based on their compliance with the management at the CCHF: group 1, 313 patients who were managed at the CCHF continuously for two years; group 2, 383 patients who choose the management at district outpatient clinics after discharge from a hospital; group 3, 197 patients who visited the CCHF for one year but then stopped the management; and group 4, 49 patients who initially preferred the management at district clinics but then switched to constant management at the CCHF. Compliance with recommendations was analyzed by data of outpatient clinical records or by data of structured telephone calls for patients who did not visit the CCHF or did not follow the visit schedule. Statistics was performed with a Statistica 7.0 for Windows software package.Results Patients of groups 2 (72.4 %) and 3 (88.3 %) performed self-monitoring less frequently whereas patients of groups 1 (94.6 %) and 4 (87.8 %) performed self-monitoring more frequently (р1 / 3=0.01, р1 / 2<0.001, р1 / 4=0.07, р2 / 4=0.02, р2 / 3<0.001, р4 / 3=0.9). Patients of group 2 (58.1 %) performed self-monitoring of heart rate less frequently than patients of groups 1, 3, and 4 (90.7 %, 81.7 %, and 87.8 %; р1 / 3=0.003, р1 / 2<0.001, р1 / 4=0.5, р2 / 4<0.001, р2 / 3<0.001, and р4 / 3=0.3). Patients of group 2 performed body weight self-monitoring less frequently than patients of groups 1, 3, and 4 (78.6 %, 67.9 %, and 72.9 %; р1 / 3=0.008, р1 / 2<0.001, р1 / 4=0.4, р2 / 4=0.002, р2 / 3<0.001, and р4 / 3=0.5). Compliance with the diet and restriction of salt consumption was 32.3 % and 37.5 % in groups 1 and 4, and 24.9 % and 19.9 % in groups 2 and 3 (р1 / 3=0.002, р1 / 2=0.03, р1 / 4=0.5, р2 / 4=0.02, р2 / 3=0.2, and р4 / 3=0.009). Compliance with recommendations on physical rehabilitation was 44.7% in group 1, which was better than in groups 2, 3, and 4 (8.2 %, 21.6 %, and 9.1 %; р1 / 2<0.001, р1 / 3=0.0003, р1 / 4=0.002, р2 / 4=0.9, р2 / 3=0.0006, and р4 / 3=0.2). At the end of the second year of follow-up, the actual proportion of patients taking ACE inhibitors/angiotensin receptor antagonists was low in groups 2, 3, and 4 (43.2 %, 45 %, and 66.7 %) and satisfactory in group 1 (92.4 %; р1 / 2<0.001, р1 / 3<0.001, р1 / 4<0.001, р2 / 3=0.6, р2 / 4=0.05, and р3 / 4=0.05). Proportion of patients taking beta-blockers was greater in group 1 (97.2 %) than in groups 2, 3. and 4 (73.2 %, 71.1 %, and 90.5 %; р1 / 2<0.001, р1 / 3<0.001, р1 / 4=00.08, р2 / 3=0.6, р2 / 4=0.1, and р3 / 4=0.06). Patients of group 1 (96.2 %) showed good compliance with the mineralocorticoid receptor antagonist treatment compared to groups 2, 3, and 4 (58.8 %, 55.4 %, and 81.2 %; р1 / 2<0.001, р1 / 3<0.001, р1 / 4<0.001, р2 / 3=0.5, р2 / 4=0.1, and р3 / 4=0.Conclusion      Only scheduled management by a cardiologist of the specialized CCHF provided sufficient compliance with self-monitoring and drug and non-drug treatment of CHF during the long-term follow-up.

Predictors of community-acquired pneumonia in patients with acute decompensated heart failure: the results of the analysis of the hospital sample EPOHA-D-CHF.

AIM: Identify the most significant predictors of community-acquired pneumonia and their im-pact on the risk of this disease in patients with ADHF. MATERIALS AND METHODS: The analysis of the hospital sample of patients (n=852) with ADHF. In 16.5% of hospitalizations, community-acquired pneumonia was found. RESULTS: The presence of symmetrical rales in the lungs, hepatomegaly, left ventricular failure signs, dilated cardiomyopathy, hypotension are increasing the risk of pneumonia in 3.7 (p<0.001), 1.6 (p=0.02), 1.86 (p=0.005), 1.72 (p=0.002), 2.7 (p=0.003) times. CONCLUSION: Based on results of a single and multivariate regression analysis, the risk of pneumonia is statistically significant increase in patients with acute left ventricular failure, dilated cardiomyopathy, hypotension, with signs of stagnation in the small and large circulatory circles. Different combinations of these predictors were found in 80% of patients with ADHF, among which in 20% of cases there was a combination of 3-5 factors.

[Evaluation of the impact of community-acquired pneumonia on short-term and long-term prognosis in a patient with chronic decompensated heart failure]. / Otsenka vliyaniya vnebol'nichnoi pnevmonii na kratkosrochnyi i dolgosrochnyi prognoz u bol'nogo s dekompensatsiei khronicheskoi serdechnoi nedostatochnosti.

AIM: To evaluate the impact of community-acquired pneumonia (CAP) on short-term and long-term prognosis in patients hospitalized with signs of chronic decompensated heart failure (CDHF). SUBJECTS AND METHODS: A total of 852 cases were admitted to therapy/cardiology hospital with signs of CDHF during a year. RESULTS: Among the patients hospitalized with signs of CDHF, the prevalence of CAP was 16.5%. This indicator did not depend on the age of hospitalized patients. Among the multisystem disorders, hypertension, different forms of coronary heart disease, diabetes mellitus, and chronic obstructive pulmonary disease were more common in the patients with CAP. The presence of the latter in a patient with CDHF statistically significantly increased the length of hospital stay (13.1 versus 11.9 days; p = 0.009) and also the probability of rehospitalization during a year (odds ratio (OR) 1.9; p = 0.02). The presence of CAP in a patient with CDHF resulted in an increase in mortality rates (OR 13.5; p < 0.001); moreover, the highest risk of a fatal outcome was noted on day 1 of hospitalization (12.7%). During one-year follow-up, the risk of death in patients hospitalized with CDHF and concomitant pneumonia proved to be higher (OR 4.8; p < 0.001) than in those without pneumonia.

A new 5-alkylresorcinol glucoside derivative from Cybianthus magnus.

One new 5-alkylresorcinol glucoside (1) was isolated from leaves of Cybianthus magnus, along with 12 known compounds (2-13), isolated from four plants belonging to Myrsinaceae family. Their structures were determined on the basis of spectroscopic analysis and by comparison of their spectral data with those reported in the literature. Among the tested molecules, only compound 2 displayed a strong cytotoxic activity with IC50 values ranging between 22 and 100 µM for all cell lines tested. One new 5-alkylresorcinol glucoside (1) was isolated from leaves of Cybianthus magnus, along with 12 known compounds, isolated from four plants belonging to Myrsinaceae family (2, 3 isolated from C. magnus; 4-7, 10 and 11 isolated from Myrsine latifolia; 4, 8 and 9 isolated from Myrsine sessiflora; 6, 7, 10, 12 and 13 isolated from Myrsine congesta). Their structures were determined on the basis of spectroscopic analysis and by comparison of their spectral data with those reported in the literature. So far, only nine 5-alkylresorcinol glucosides were isolated from leaves of Grevillea robusta. Since resorcinols are known to exhibit strong cytotoxic activity, compounds 1 and 2 were tested against cell lines 3T3, H460, DU145 and MCF-7 for cytotoxicity in vitro and compounds 3-13 were tested for their antileishmanial activity. Compound 2 displayed a strong cytotoxic activity with IC50 values ranging between 22 and 100 µM for all tested cell lines. Compounds 3-13 were not active against Leishmania amazonensis amastigotes.

[Assessment of Impact of Acute Kidney Injury on Prognosis of a Hospitalized Patients With Acute Decompensated Heart Failure].

OBJECTIVE: to assess prevalence of acute kidney injury (AKI) among patients with acute decompensated heart failure (ADHF) and its impact on prognosis in a hospitalized patient. MATERIAL AND METHODS: a sample of patients hospitalized with signs of ADHF. RESULTS: Prevalence of AKI in this sample was 23.1%. There was no significant difference between patients with and without AKI by age, gender, and hemodynamic parameters. Portion of subjects with systolic blood pressure below 125 mm Hg among patients with AKI did not exceed one third. Development of AKI was associated with 3-fold elevation of risk of injury of the liver. Hospital mortality in patients with AKI was 7 times higher than in patients without AKI. CONCLUSION: These results resemble those obtained in foreign studies on AKI prevalence among patients with ADHF except hospital mortality which turned out to be twice higher. Acute liver injury highly prevalent among patients with AKI worsened their prognosis. Risk of lethal outcome in patients with ADHF and AKI was inversely related to diastolic blood pressure and directly depended on maximal concentrations of creatinine and aspartate aminotransferase. Management of patients with ADHF should include measures of correction of renal and hepatic dysfunction and as well as use of drugs improving prognosis during hospital stay and in remote period.

Spirolactone iridoids might be responsible for the antileishmanial activity of a Peruvian traditional remedy made with Himatanthus sucuuba (Apocynaceae).

Extracts of seven medicinal plants used specifically against cutaneous leishmaniasis in the Madre de Dios region of Peru were evaluated in vitro against promastigote and axenic amastigote forms of Leishmania amazonensis. One of them showed interesting leishmanicidal activities (IC(50)=5 microg/ml in amastigotes). Bio-guided isolation of the stem bark's ethanol extract of Himatanthus sucuuba (Spruce ex Müll. Arg.) Woodson (Apocynaceae) afforded the spirolactone iridoids isoplumericin and plumericin. The latter showed a reduction of macrophage infection similar to that of the reference drug Amphotericin B (IC(50)=0.9 and 1 microM, respectively). These findings validate the traditional use of Himatanthus sucuuba in the treatment of cutaneous leishmaniasis (Uta) in Peru.

Immune response to measles vaccine in Peruvian children.

OBJECTIVE: To evaluate the immune response in Peruvian children following measles vaccination. METHODS: Fifty-five Peruvian children received Schwarz measles vaccine (about 10(3) plaque forming units) at about 9 months of age. Blood samples were taken before vaccination, then twice after vaccination: one sample at between 1 and 4 weeks after vaccination and the final sample 3 months post vaccination for evaluation of immune cell phenotype and lymphoproliferative responses to measles and non-measles antigens. Measles-specific antibodies were measured by plaque reduction neutralization. FINDINGS: The humoral response developed rapidly after vaccination; only 4 of the 55 children (7%) had plaque reduction neutralization titres <200 mlU/ml 3 months after vaccination. However, only 8 out of 35 children tested (23%) had lymphoproliferative responses to measles antigens 3-4 weeks after vaccination. Children with poor lymphoproliferative responses to measles antigens had readily detectable lymphoproliferative responses to other antigens. Flow cytometric analysis of peripheral blood mononuclear cells revealed diffuse immune system activation at the time of vaccination in most children. The capacity to mount a lymphoproliferative response to measles antigens was associated with expression of CD45RO on CD4+ T-cells. CONCLUSION: The 55 Peruvian children had excellent antibody responses after measles vaccination, but only 23% (8 out of 35) generated detectable lymphoproliferative responses to measles antigens (compared with 55-67% in children in the industrialized world). This difference may contribute to the less than uniform success of measles vaccination programmes in the developing world.

A bioactive spirolactone iridoid and triterpenoids from Himatanthus sucuuba.

Himatanthus sucuuba is an Amazonian tree with abundant, yet conflicting ethnobotanical information. Investigation of the polar and non-polar constituents led to the isolation of plumericin, a bioactive spirolactone iridoid, and four known pentacylic triterpenes: lupeol acetate, lupeol cinnamate, lupeol beta-phenyl propionate, and alpha-amyrin cinnamate.

(+)-epi-Alpha-bisabolol [correction of bisbolol] is the wound-healing principle of Peperomia galioides: investigation of the in vivo wound-healing activity of related terpenoids.

Bioassay-guided investigation of the ethanol extract of Peperomia galioides using a tensile strength method in mice as a monitor led to the isolation of epi-alpha-bisabolol (1) (ED(50) 155 microg/mL). An in vivo healing study of selected commercially available monoterpenoids yielded two bioactive compounds, alpha-bisabolol (2) and alpha-terpineol (3) (ED(50) of 228 and 240 microg/g mouse[corrected], respectively).

Cytotoxic triterpene acids from the Peruvian medicinal plant Polylepis racemosa.

Cytotoxicity-guided fractionation of the bark and stem extract of Polylepis racemosa led to the identification of ursolic acid, pomolic acid, 3-O-acetylpomolic acid, and 2-oxopomolic acid. Pomolic acid was the most cytotoxic component, and was specific for M-14 melanoma and ME180 cervical carcinoma, with GI50 values of 6.9 and 8.3 micrograms/mL respectively.

Bioactive indole alkaloids from the bark of Uncaria guianensis.

Bioassay-guided fractionation of the EtOH extract of the bark of Uncaria guianensis (Aubl.) Gmel (Rubiaceae) using a yeast-based assay for DNA-damaging agents has furnished the two weakly but selectively active indole alkaloids uncarine C (1) and uncarine E (2) as the major bioactive constituents in this assay.

A survey of traditional medicinal plants from the Callejón de Huaylas, Department of Ancash, Perú.

The medicinal uses of local flora from the Callejón de Huaylas, Department of Ancash, northeastern Perú, are reported. This geographical area has an old tradition of herbal healing. A total of 33 species have been documented through interactions with village elders, traditional doctors and herbalists. Of the 33 medicinal plant species surveyed in the Callejón de Huaylas, six have not been previously reported, seven have received only minor phytochemical coverage in the literature, and the medicinal uses of seven other plants have not been corroborated with traditional medicinal reports from around the world. The traditional medicinal uses of six medicinal plants have been corroborated with previously published reports but their biological activities have yet to be confirmed in the laboratory. The medicinal uses of four other plants have been corroborated with previously published reports and their biological activities have been confirmed in the laboratory. The purported medicinal use of three plant species could not be confirmed in the laboratory.

Evaluation of the wound-healing activity of selected traditional medicinal plants from Perú.

Folk medicine practitioners in Perú employ plant preparations as wound-healing agents on superficial and internal wounds (gastric ulcers). The results of a scientific evaluation of the wound-healing activity of nine plants found in the Amazon jungle near Iquitos and in the Andes mountains is presented. The species studied were: Peperomia galioides, Mentzelia cordifolia, Mutisia acuminata, Himatanthus sucuuba, Spondias mombin, Eleutherine bulbosa, Muehlenbeckia tamnifolia, Anredera diffusa and Jatropha curcas. These plants have also been examined for their toxicological properties, their effect on blood pressure, smooth muscle and capillary permeability. Significant wound-healing activity was detected in Peperomia galioides, Anredera diffusa and Jatropha curcas. Extracts from Peperomia galioides and Anredera diffusa had no effect on cell proliferation and did not exhibit mutagenic activity.

Sublingual buprenorphine compared to morphine delivered by a patient-controlled analgesia system as postoperative analgesia after prostatectomy.

After open prostatectomy, 52 patients were randomly allocated to two treatment groups. Group A (26 patients) received buprenorphine sublingually, and in group B (26 patients) the analgesia was induced using a patient-controlled analgesia system with morphine. The total dose of morphine given during the first 24 h was 72 +/- 8 mg compared to 1.6 +/- 0.45 mg of buprenorphine. The total dose of buprenorphine on days 2 and 3 was significantly lower than the total dose of morphine (p < 0.01). There were no significant differences in visual pain scores, side effects, mean arterial blood pressure, pulse rate and respiration rate between the two groups. Sublingual application of buprenorphine offers an effective and easy alternative to the parenteral route of morphine for the management of postoperative pain.