Establishment of a miRNA profile in paediatric HIV-1 patients and its potential as a biomarker for effectiveness of the combined antiretroviral therapy

AbstractmiRNAs have been extensively studied in pathological conditions, including viral infections, such as those provoked by HIV-1. Several cellular and circulating miRNAs are altered during HIV-1 infection, with either beneficial effects on host defenses or enhanced virus infectivity. Blood samples were collected in sterile EDTA tubes and plasma was separated and stored, as were PBMCs. RNA was isolated and reverse-transcribed. Finally, the miRNA gene expression profile was assessed using TaqMan Array Human microRNA Card A v2.0. A comprehensive statistical analysis was performed on the results obtained. This is the first study on miRNAs in HIV-1 paediatric patients, and a miRNA profile differentiating patients starting combination antiretroviral therapy (cART) at different times after HIV-1 diagnosis was established. Thirty-four miRNAs were observed to have different expression levels between the control group and the cART group. The data indicates the need to start cART as soon as possible after the establishment of HIV-1 infection to assure the best outcome possible. Finally, the selected 34 miRNAs may be used as biomarkers for prognosis and assessing therapy effectiveness. However, more research must be conducted to establish adequate quantitative correlations.

Influence of standard heart failure therapy on readmission rate: opportunities and limitations in modern clinical practice

This review considers the clinical and epidemiological significance of hospitalizations for decompensated heart failure, as well as using it as an indicator of therapy effectiveness. The data on the frequency of using medications that reduce the hospitalization risk in randomized clinical trials and in real practice are presented. The reasons for inadequate prescription of drugs for the treatment of heart failure with reduced ejection fraction and their use in insufficient doses, which include therapeutic inertness and physiological limitations, as well as the need to introduce drugs with alternative mechanisms of action into clinical practice, are iscussed.

Efficacy and Safety of Ergoferon in Children from 6 Months to 6 Years Old with Acute Respiratory Viral Infections in Contemporary Outpatient Practice: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial

To evaluate the efficacy and safety of Ergoferon in combination with symptomatic therapy in children from 6 months to 6 years old with acute respiratory infections (ARI) in contemporary outpatient practice, an international, multicenter, double-blind, placebo-controlled, randomized, parallel-group clinical trial was performed. Derived by technological treatment of antibodies to interferon gamma, histamine, and CD4, Ergoferon was previously proved to modulate its molecular targets promoting effective antiviral protection. The data of 282 patients with oral temperature ≥38.0°C plus mild to moderate severity of flu-like nonspecific and nasal/throat/chest symptoms were included in intention-to-treat analysis (n = 140, Ergoferon group; n = 142, placebo group). Time to alleviation of all ARI symptoms was the primary endpoint, and 8 outcome measures were estimated as the secondary endpoints. Respiratory viruses were confirmed in 57.1% (Ergoferon) and 54.9% (Placebo) of patients. Compared to placebo, Ergoferon reduced time to alleviation of all ARI symptoms (4.5 ± 1.7 versus 5.2 ± 2.2 days in placebo; p = 0.026 ) including fever (2.8 ± 1.5 vs 3.4 ± 2.0; p = 0.031 ), flu-like nonspecific (4.0 ± 1.8 vs 4.7 ± 2.2, p = 0.022 ), and nasal/throat/chest (4.3 ± 2.0 versus 5.0 ± 2.3; p = 0.024 ) symptoms. Ergoferon add-on therapy decreased the mean total symptom severity score (according to 4-point scale for each symptom), ARI severity, frequency of antipyretic use, and percentage of complication requiring antibiotics and increased the percentage of recovered patients. The incidence of adverse events (AEs) in the Ergoferon group was significantly lower compared to the placebo group (7.0% versus 18.8%; p = 0.004 ) including infectious diseases (3.5% vs 12.5%; p = 0.008 ). In the Ergoferon group, AEs were mild or moderate. In 8 (57.1%) cases, AEs were unrelated to Ergoferon, in 5 (35.7%), the relationship was uncertain, and in 1 (7.1%), it was possible (mild rash on the face). Ergoferon treatment is beneficial for infants and young children with ARI in contemporary outpatient practice. Being well-tolerated, Ergoferon increases the symptomatic therapy effectiveness and improves the patient condition and disease outcomes.

Carotid Artery Stenting in Patients with Atrial Fibrillation: Direct Oral Anticoagulants, Brief Double Antiplatelets, and Testing Strategy

Carotid endarterectomy is usually preferred over carotid artery stenting (CAS) for patients with atrial fibrillation (AF). We present our experience with short-course periprocedural triple antithrombotic therapy in 32 patients aged >18 years with nonvalvular AF undergoing CAS. There were no deaths, cardiac events, embolic strokes, hyperperfusion syndrome, intracranial hemorrhage, or stent thrombosis within 30 days. Transient intraprocedural hemodynamic instability in 15/32 (47%) and prolonged instability in 4/32 (13%) was managed conservatively. At a mean 16-month follow-up, there were no new neurological events or deterioration. Mean stenosis was reduced from 78.0% ± 9.7% to 17.3% ± 12.2%. This retrospective study included patients AF who were symptomatic (minor stroke (NIHSS ≤ 5)/TIA) with ICA stenosis >50%, or asymptomatic under DOAC therapy with carotid stenosis >80%, who underwent CAS from 6/2014–10/2020. Patients received double antiplatelets and statins. Antiplatelet therapy effectiveness was monitored. Stenting was performed when P2Y12 reaction units (PRU) were <150. DOACs were discontinued 48 h before angioplasty; one 60 mg dose of subcutaneous enoxaparin was administered in lieu. DOAC was restarted 12–24 h after intervention. Patients were discharged under DOAC and one nonaspirin antiplatelet. 32 patients on DOAC were included (26 male, mean age 71). 19 (59.4%) presented with stroke (ICA stenosis-related in 14); 13 (40.6%) were asymptomatic. Stents were deployed under filter protection following pre-angioplasty; post-angioplasty was performed at least once in 12 patients (37.5%). Our experience suggests that CAS can be safely performed in selected patients with CAS and AF requiring DOAC. The role of CAS in AF patients under DOAC warrants study in rigorous trials.

Respimat as the new standard for inhalation therapy devices

The effectiveness of inhalation therapy can be significantly reduced by a number of problems. For example, inhalation technique errors can reduce the dose delivered by 22-95% compared to the optimal value in patients with technical errors in the use of the inhaler. Sub-optimal inspiratory flow rates in a number of patients with chronic obstructive pulmonary disease and asthma are often the cause of technical errors during inhalation. Patient education does not produce the expected results, as the underlying cause of reduced flow is high hyperinflation and weakening of the respiratory musculature. The use of technologically outdated inhalers is another significant cause of reduced therapy effectiveness. Patient education and even conversion to a different inhaler do not always increase the effectiveness of therapy. Respimat, a brand new delivery agent introduced in 2004, allows 39% to 67% of the nominal dose to be delivered to the airways, while the degree of pulmonary deposit is independent of inspiratory flow and pulmonary drug deposit does not decrease with increasing obstruction. Compared to powder inhalers, Respimat creates less resistance to airflow on inhalation. In addition, Respimat is an active device that requires no effort on the part of the patient to move the aerosol particles. These features make Respimat the new standard for inhalation therapy. This review aims to familiarise readers with the main features of the Respimat and the latest research findings

Algorithmic Music for Therapy: Effectiveness and Perspectives

This study assessed the short-term effects of conventional (i.e., human-composed) and algorithmic music on the relaxation level. It also investigated whether algorithmic compositions are perceived as music and are distinguishable from human-composed music. Three hundred twenty healthy volunteers were recruited and randomly allocated to two groups where they listened to either their preferred music or algorithmic music. Another 179 healthy subjects were allocated to four listening groups that respectively listened to: music composed and performed by a human, music composed by a human and performed by a machine; music composed by a machine and performed by a human, music composed and performed by a machine. In the first experiment, participants underwent one of the two music listening conditions—preferred or algorithmic music—in a comfortable state. In the second one, participants were asked to evaluate, through an online questionnaire, the musical excerpts they listened to. The Visual Analogue Scale was used to evaluate their relaxation levels before and after the music listening experience. Other outcomes were evaluated through the responses to the questionnaire. The relaxation level obtained with the music created by the algorithms is comparable to the one achieved with preferred music. Statistical analysis shows that the relaxation level is not affected by the composer, the performer, or the existence of musical training. On the other hand, the perceived effect is related to the performer. Finally, music composed by an algorithm and performed by a human is not distinguishable from that composed by a human.

Molecular genetics and phenotypic features of congenital isolated hypogonadotropic hypogonadism

Congenital isolated hypogonadotropic hypogonadism includes a group of diseases related to the defects of secretion and action of gonadotropin-releasing hormone (GNRH) and gonadotropins. In a half of cases congenital hypogonadism is associated with an impaired sense of smell. It’s named Kallmann syndrome. Now 40 genes are known to be associated with function of hypothalamus pituitary gland and gonads. Phenotypic features of hypogonadism and therapy effectiveness are related to different molecular defects. However clinical signs may vary even within the same family with the same molecular genetic defect. Genotype phenotype correlation in patients with congenital malformations prioritizes the search for mutations in candidate genes. There are data of significant contribution of oligogenicity into the phenotype of the disease are presented in the review. Moreover, an issue of current isolated hypogonadotropic hypogonadism definition and classification revision is raised in the review due to hypogonadotropic hypogonadism development while there are mutations in genes not associated with GNRH neurons secretion and function.

Quercetin effectiveness in patients with COVID-19 associated pneumonia

The aim of this work was to evaluate the effectiveness of quercetin addition to the treatment regimen for patients with COVID-19 associated pneumonia. Materials and methods. The effectiveness of two dosage forms of quercetin was studied in 200 patients, who were divided equally into the main and control groups. The main group patients received quercetin in addition to the basic therapy: intravenous drip of Quercetin/Polyvinylirolidone during the first 10 days followed by oral administration of Quercetin/Pectin over the next 10 days. Patients from the control group received only the basic therapy drugs. The study evaluated the dynamics of the disease symptoms (saturation level, respiratory rate, body temperature, cough, general weakness), as well as laboratory markers (C-reactive protein (CRP), ferritin, D-dimer). Results. Two dosage forms of quercetin consistently used in addition to the basic therapy improve pulmonary gas exchange and accelerate the lung function recovery. This is evidenced by a statistically significant majority of patients with positive dynamics in the symptoms of “Saturation level” and “Cough” as well as the meeting a complex indicator of the therapy effectiveness 2 days earlier than in the control group. The treatment regimen applied also helps to stabilize the level of D-dimer in the blood of the main group patients. Conclusions. The use of two dosage forms of quercetin in addition to the basic therapy accelerates the recovery of patients with coronavirus disease associated pneumonia and can help to prevent the progression of COVID-19 associated coagulopathy.