N-Chromosome Royal Jelly, Propolis and Bee Pollen Supplementation Improve the Clinical Conditions of COVID-19 Patients: A Randomized Controlled Trial

Royal jelly, propolis, and bee pollen are used for different purposes all around the world according to their anti-inflammatory, antioxidant, and antimicrobial activities. Given that Coronavirus 2019 (COVID-19) is a viral condition accompanied by a dysregulated inflammatory response in the body, we intend to evaluate the effects of natural supplementations on the disease course. A randomized, open-label, controlled trial was conducted among 50 definitive cases of COVID-19. These patients were randomly assigned into control and intervention groups. Royal Jelly, propolis, and bee pollen were prescribed to patients in the intervention group (n = 24) in addition to conventional treatment; while the control group only received the standard treatment (n = 26). At the end of the study, functional class improved in both groups, but this change was more pronounced in the intervention group (p < 0.05). Moreover, total symptoms duration and the time to return to work were significantly reduced in the intervention group (p < 0.05). Although royal jelly, propolis, and bee pollen are not definitive treatments in COVID-19 patients, they can be used as an adjuvant treatment to limit disease symptoms and virus propagation.

Macitentan and Tadalafil (Opsynvi)

CADTH recommends that Opsynvi should be reimbursed by public drug plans for the long-term treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to reduce morbidity in patients in WHO functional class (FC) II or III whose PAH is idiopathic, heritable, or associated with connective tissue disease or congenital heart disease if certain conditions are met. Opsynvi should only be covered for patients who are currently treated simultaneously with stable doses of macitentan 10 mg and tadalafil 40 mg as separate tablets. Opsynvi should only be reimbursed if prescribed by a specialist with expertise in managing and treating patients with PAH and if the price of Opsynvi is negotiated to ensure cost savings in comparison with separate macitentan and tadalafil tablets.

Resolving Missing Protein Problems Using Functional Class Scoring

Despite technological advances in proteomics, incomplete coverage and inconsistency issues persist, resulting in “data holes”. These data holes cause the missing protein problem (MPP), where relevant proteins are persistently unobserved, or sporadically observed across samples. This hinders biomarker and drug discovery from proteomics data. Network-based approaches are powerful: The Functional Class Scoring (FCS) method using protein complexes was able to easily recover missed proteins with weak or partial support. However, there are limitations: The verification approach (in determining missing protein recovery) is potentially biased as the test data was based on relatively outdated Data-Dependent Acquisition (DDA) proteomics and FCS does not provide a scoring scheme for individual protein components (in significant complexes). To address these issues: First, we devised a more rigorous evaluation of FCS based on same-sample technical replicates. And second, we evaluate using data from more recent Data-Independent Acquisition (DIA) technologies (viz. SWATH).Although cross-replicate examination reveals some inconsistencies amongst same-class samples, tissue-differentiating signal is nonetheless strongly conserved. This confirms FCS as a viable method that selects biologically meaningful networks. We also report that predicted missing proteins are statistically significant based on FCS p-values. Although cross-replicate verification rates are not spectacular, the predicted missing proteins as a whole, have higher peptide support than non-predicted proteins. FCS also has the capacity to predict missing proteins that are often lost due to weak specific peptide support. As a yet unresolved limitation, we find that FCS cannot assign meaningful probabilities to individual protein components (no relationship between actual probability of verification and FCS-assigned probability) as it only provides a p-value at the level of complexes.

Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis

Aim. The goal of the study was to analyze the differential expression of lipid metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis.Material and Methods. The study was performed on the specimens of atherosclerotic plaques in 45–65-year-old patients with coronary atherosclerosis with stable exertional angina functional class II-IV without acute coronary syndrome. Coronary atherosclerosis was verified by coronary angiography. Atherosclerotic plaque tissue was sampled intraoperatively when indicated. Whole-genome sequencing of ribonucleic acid (RNA) was performed using the TruSeq RNA Sample Preparation Kit (Illumina, USA).Results. We analyzed the differences in the expression of 12 genes including LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, ABCA1, APOA1, APOE, LPL, SCARB1, and SREBF2 depending on the type of atherosclerotic plaques. The expression level of APOE gene was eight times higher in unstable atherosclerotic plaques of dystrophic-necrotic type (p < 0.0001). The expression levels of LDLR and APOB genes were eight times higher in stable atherosclerotic plaques (p < 0.0001). We did not find differences in the expression levels of the ABCG5, ABCG8, APOC3, CETP, CLPS, CYP7A1, and PNPLA5 genes.Conclusion. The study showed the differences in the activity of individual metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis. Obtained data may become the basis for the development of test systems aimed at predicting the development of atherosclerotic process and its complications.

Impact of Hepatopulmonary Syndrome in Liver Transplantation Candidates and the Role of Angiogenesis

Hepatopulmonary syndrome affects 10–30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation.The Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar-arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography, and absence of lung disease.We included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median [interquartile range] 15 [12, 19] versus 14 [10, 17], p=0.006). Hepatopulmonary syndrome patients had significantly lower six minute walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin-2, Tie2, tenascin-C, c-kit, VCAM-1, and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80 [1.03–3.16], p=0.04) which persisted despite adjustment for covariates (hazard ratio 1.79 [1.02–3.15], p=0.04). This association did not vary based on levels of oxygenation reflecting the severity of hepatopulmonary syndrome.Hepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.

The Efficacy of a Commercial Physical Activity Monitor in Longitudinal Tracking of Pulmonary Hypertension Patients

Patients with pulmonary arterial hypertension (PAH) have quality of life (QoL) limitations, decreased exercise capacity, and poor prognosis if left untreated. Standard exercise testing is routinely performed for the evaluation of patients with PAH but may be limited in its ability to monitor activity levels in daily living. We evaluated the validity of the commercial Fitbit Charge HR as a tool to assess real time exercise capacity as compared to standard exercise testing in patients with PAH. Ambulatory pediatric and adult PAH patients were enrolled and given a Fitbit with instructions to continuously wear during waking hours. Subjects underwent a 6-minute walk test (6MWT), cardiopulmonary exercise test (CPET) and an SF-36 QoL survey on the day of enrollment and follow-up. Twenty-seven ambulatory subjects with PH were enrolled and 21 had sufficient data for analyses (median age 25, range 13-59, 14 F) were enrolled. Daily steps measured by the Fitbit had a positive correlation with 6MWT distance (r = 0.72, p = 0.03) and an inverse correlation with WHO functional class. On the QoL survey, 77% reported improvement in energy/fatigue (p = 0.055). At follow up there was a strong correlation between Fitbit steps and role limitations due to physical problems (r = 0.88, p = 0.020) and weaker correlations with less related QoL markers. These findings suggest activity monitors may have potential as a simple/novel method of assessing longitudinal exercise capacity and activity levels in PAH patients. Further study in larger cohorts of patients is warranted to determine the best accelerometric correlates with outcomes.

Immediate clinical results of the new biological support ring for correction of mitral insufficiency

Aim. To make the first clinical experience evaluation of the new biological closed support ring for mitral valve.Methods. 26 patients (16 men, 10 women, mean age 55 [49; 62] years) with dysplastic mitral insufficiency were implanted “NEORING” biological ring for the first time from March 2020 to June 2021. The etiological factor of the defect formation in all cases was the connective tissue dysplasia. The mean functional class of heart failure before surgery was 2 [2; 3] according to NYHA, the effective regurgitant orifice (ERO) was 0.4 [0.3; 0.5], vena contracta was 0.7 [0.6; 0.8]. Ten patients received rings of 28 mm diameter, ten patients – 30 mm, six patients – 32 mm.Results. No significant adverse events such as death from any causes, strokes, myocardial infarction, cardiac complications, bleeding, and return of regurgitation or failure of plastic surgery requiring reoperation, infective endocarditis after the intervention were observed. In two cases a permanent pacemaker was implanted due to sinus node dysfunction. At discharge all patients had no regurgitation (ERO 0), medium transvalvular gradient was 4.0 [3.0; 5.3] mm Hg. All the patients were assigned to NYHA functional class I heart failure after the surgery.Conclusion. New biological support ring “NEORING” (“NeoKor”, Kemerovo) use in the middle age group of patients showed high hemodynamic efficiency, the absence of specific complications in the early stages after the surgery. It is planned to expand the clinical material on the use of the biological ring, as well as to evaluate the long-term results in the format of a prospective, randomized trial and compare the new device with the existing ones.

Anaesthesia-Specifi c Oxygen Transport Assessment in Robot-Assisted Pelvic Surgery: a Clinical Trial

Background. Robot-assisted pelvic surgery rapidly becomes a choice in surgeries for gynaecological oncology and urology. These interventions require special settings (pneumoperitonaeum and Trendelenburg position), which inevitably and systemically impact oxygen transport. Low oxygen delivery during surgery associates with manifold adverse outcomes. A single universal oxygen delivery threshold is impractical, as oxygen consumption must be taken into account. This study examines the effects of pneumoperitonaeum and Trendelenburg position on oxygen transport in patients of ASA functional class I–III (as per American Society of Anaesthesiologists).Materials and methods. Delivery, consumption, oxygen extraction, perioperative adverse events and type of general anaesthesia were prospectively studied in 126 adult patients.Results and discussion. Mean oxygen consumption was 242 mL/min/m2 , mean oxygen delivery — 612 mL/min/m2 . Oxygen delivery was below median 529 mL/min/m2 in 54 (43 %) patients. Perioperative adverse events developed in 36 (29 %) patients. A strong correlation (r > 0.500; p<0.001) between oxygen delivery and consumption was observed in 54 patients. Blood lactate level of 2.7 mmol/L at surgery end was indicative of inadequate oxygen delivery.Conclusion. No relationship was revealed between oxygen delivery and adverse perioperative events, and neither — between oxygen delivery and consumption relative to a particular anaesthetic.

Can Severity of Pulmonary Hypertension Affect Success Rate of Balloon Mitral Commissurotomy?

Introduction: Rheumatic heart disease is responsible for the most prevalent pathological causes of mitral stenosis and is closely coupled with pulmonary hypertension. Balloon mitral commissurotomy as an alternative method for mitral valve replacement leads to a reduction in pulmonary pressure. All grades of pulmonary hypertension usually regress after mitral commissurotomy; however, the insignificant changes of pulmonary artery hypertension following balloon mitral valvuloplasty are not uncommon. Methods: This retrospective observational study was carried out on 160 patients with significant symptomatic mitral stenosis (mitral valve area [MVA] <1.5 cm ) who underwent successful percutaneous transvenous mitral commissurotomy (PTMC) within 2016-2020 at Shaheed Rajaie Cardiovascular, Medical and Research Center, Tehran, Iran. Results: In this study, 89.4% of the patients were female, and the mean age of the participants was 47.2±12.4 years. Most (74%) patients presented with dyspnea on exertion functional class II. The mean basic MVA was 1±0.20 cm that increased to 1.43±0.23 cm , and the mean basic systolic pulmonary artery pressure (PAP) was 43.84±11.93 mmHg that decreased to 35.13±7.7 mmHg. Persistent PAP after successful PTMC was observed in 34% of the patients. This group of patients showed smaller MVA gain and PAP reduction after the procedure. Pulmonary vascular resistance (PVR) > 2 Wood units was correlated to 91.7% of the post-procedural success rate. Conclusion: The PTMC plays an important role in the reduction of PAP; nevertheless, the chronicity and severity of PAP can lead to persistent pulmonary hypertension. The assessment of initial PAP and basic PVR can help select patients with more likely intended results.

Functional activity of platelets in aged patients with chronic heart failure with hyperbaric oxygenation

105 patients with chronic heart failure (CHF) with ischemic etiology of functional class were examined, among them 70 men (67%) and 35 women (33%), average age 78,67±13,80 years. A five-day course of hyperbaric oxygen treatment in the BLKS-303MK pressure chamber (Russia) in the 1.2 ATA with a 30-45 minutes session was accompanied by a study of the func-tional activity of platelets. It was found that after hyperbaric oxygenation treatment ADP-induced aggregation significantly decreased in women, spontaneous aggregation in men. How-ever, the nature of the response of platelet functional activity to hyperbaric oxygenation is af-fected by the initial state of the platelet hemostasis. Key words: platelets, hyperbaric oxygenation, platelet aggregation, heart failure, hemo-stasis.