Optimization of therapy of patients with bronchial asthma in conditions of coronavirus infection

There is suffering with bronchial asthma (BA) all over the world. This pathology is one of the most common diseases of respiratory system. In 2019, the coronavirus infection (COVID-19) pandemic spread all over the world. COVID-19 has made a big difference in the lives of the entire population. Patients with BA appeared to be especially the «weakest» cohort. At the beginning of the pandemic, it was considered that patients with asthma were most susceptible to COVID-19 infection and severe infection. Currently, it is known that BA does not affect on the COVID-19 severity. It is considering opinion that the predominance of cytokines of Th-2 immune response type and the eosinophils overproduction can somehow counteract to accumulation of pro-inflammatory cytokines, preventing development of a «cytokine storm» in COVID-19 disease, which explains the low percentage of infection in patients with BA. During the pandemic, there were 35 patients with BA under observation. As a baseline therapy, patients took a fixed combination of formoterol/budesonide (Formisonide-native) in the metered-dose powder inhaler; delivery method was carried out using “Inhaler CDM” in a single dose of 4.5/160 μg. Daily inhaled glucocorticosteroids (ICS) doses choice was corresponded to asthma severity. Medium ICS doses were taken by 17 patients (48.6%), high doses were taken by 18 patients (51.4%). Special properties of budesonide and formoterol make it possible to use their combination in the treatment of asthma both as baseline therapy and for attacks relief («therapy on demand»). Formisonide-native has advantages: the dose is strictly fixed, the patient has visual control and confidence in the delivered dose, which increases the patient’s compliance with therapy, especially in a pandemic. Also, during the period of COVID-19, patients with BA need to have followed-up regular medical care in the form of on-line consultations through modern messengers, to be trained to control the disease and implement the basic therapy dosage regimen.

Infectious-immune pericarditis: clinical assessment, diagnostics, and differentiated baseline therapy with hydroxychloroquine

Aim. To study the clinical spectrum of infectious-immune pericarditis, the potential for their invasive and non-invasive diagnosis, as well as long-term treatment with hydroxychloroquine (in comparison with other baseline therapy options).Material and methods. The study included 44 patients with infectious-immune pericarditis (28 women and 16 men aged 49,4±13,3 years). Patients with transudate and specific types of pericarditis were excluded. Levels of C-reactive protein and anticardiac antibodies were determined Multislice computed tomography of the lung (n=23) and heart (n=16), cardiac magnetic resistance tomography (n=9), scintigraphy (n=14), and if necessary — immunoelectrophoresis, DNA testing, Diaskin-test. Pericardio- and thoracentesis were performed in 3/3 patients, thoracoscopic pericardial biopsy — 1, endomyocardial biopsy — 7. The follow-up period was 14,5 [3; 39,5] months.Results. Isolated pericarditis was diagnosed in 10 patients (22,7%), myopericarditis — in 34 (77,3%). In 38 patients, pericarditis was exudative: in 24 (63,2%) with a small effusion (<10 mm), in 10 (26,3%) — with a moderate (11-20 mm), in 4 (10,5%) — with a large (>20 mm). Fibrin was detected in 18,2% of patients. Pericardial effusion was assessed as acute in 4, subacute — in 8, chronic — in 26 patients. The connection between the disease onset and infection was found in 56,8% of patents, and inflammatory blood changes — in 59,1%. In 80%, the punctate was lymphocytic; endomyocardial biopsy confirmed active/ borderline (5/2) lymphocytic myocarditis (virus-positive — in 3 patients). Anticardiac antibody titers were increased in 88,2%. Baseline therapy included NSAIDs (34,1%), colchicine (27,3%), hydroxychloroquine (43,2%), methylprednisolone (56,8%, 16 [16; 21] mg/day), azathioprine (20,5%). The treatment scheme was selected individually. In most cases, combined therapy was carried out. The results of treatment were assessed in 36 patients: an excellent effect was noted in 16 (44,4%) patients, stable effect — in 13 (36,1%), no stable effect — in 7 (19,4%). There were no cases of constrictive pericarditis, acute relapses, cardiac tamponade. Mortality of 6,8% was associated with myocardial injury.Conclusion. Criteria for the diagnosis of infectious-immune pericarditis were proposed. An increase in the titer of anticardiac antibodies was noted in all types of the disease. Prescription of corticosteroids is justified in many cases, including in combination with colchicine, cytostatics, hydroxychloroquine. Hydroxychloroquine monotherapy is effective for subacute/chronic pericarditis with moderate effusion.

187 Real-world treatment patterns and clinical predictors of overall survival among anti-PD-1 exposed advanced melanoma patients with documented evidence of disease progression

BackgroundImmuno-oncology (I-O) plays a major role in the treatment of advanced melanoma (aMel); however, resistance to therapy remains an important clinical problem. This study examined treatment patterns and overall survival (OS) for aMel patients who progressed on anti-programmed death ligand 1 (anti-PD-1) therapy in a real-world clinical setting.MethodsA retrospective database study of Flatiron electronic medical records (EMR) was conducted with 304 aMel patients who progressed on first or second line anti-PD1 (baseline) therapy with pembrolizumab or nivolumab and received subsequent (index) therapy with ≥3 months of potential follow-up. Patients who discontinued treatment for reasons other than progression (primarily toxicity) were excluded. The primary outcome was OS, defined using EMR data linked to external mortality sources (e.g. Social Security Death Index). OS analysis was stratified by several factors (e.g. age, ECOG, BRAF, LDH, type of index therapy, and best overall response [BOR] to baseline anti-PD-1 therapy). BOR defined as response, stable disease, or disease progression was based on clinician assessment following radiographic imaging. Descriptive and log-rank test statistics for OS were used.ResultsAmong patients receiving index therapy (n=304), 50% received I-O (n=91/151 combination therapy), 36% received BRAFi/MEKi (n=102/109 combination therapy) and 14% received other therapies (n=34/44 chemotherapy). Median (range) age was 67 (23–85) years, with 65% male, 62% ECOG≤1, 33% elevated LDH, and 51% with BRAF mutations. Most patients received baseline anti-PD1 monotherapy (77%) as first line therapy. Median OS (95%CI) was 7.2 (6.4, 8.8) months, with a significant OS association with ECOG≤1 (p<0.001), normal LDH (p<0.001), and BRAFi/MEKi (p=0.02), with higher median OS of 9 vs 5 months, 11 vs 6 months, and 11 vs 7 and 6 months, respectively, compared to patients with ECOG≥2, elevated LDH, and treated with I-O and other therapies. For a subgroup of index therapy patients with a BOR assessment to baseline anti-PD-1 therapy (n=237), there was a significant association (p<0.01) of OS with BOR to baseline therapy, with higher median OS for those with an initial response (12 months) or stable disease (14 months) compared to a BOR of disease progression (6 months). There was also a significant OS association with BOR to baseline anti-PD-1 therapy for the subgroups receiving I-O therapy (n=119/237, p<0.01) and other therapies (n=37/237, p=0.01).ConclusionsSuboptimal OS in patients who progress on anti-PD-1 therapy in a real-world clinical setting, with predictors of enhanced survival, highlights the need for further research to inform optimal treatment strategies.AcknowledgementsThe authors would like to acknowledge the contributions of Bo Zheng, Clemens Krepler, Diana Malandrucollo, and Shelby Marx of Merck & Co, Inc.

COVID-19 Pandemic Impact on Physicians’ Decision-making: Digoxin Toxicity in View of Combination of Hydroxychloroquine and Azithromycin: A Case Report

BACKGROUND: Since the WHO declaration of COVID-19 being a global pandemic, the population in general and health-care providers, in particular, became under extraordinary pressure that remarkably impacts their decisions at multiple levels as all of us should make decisions quickly while being uncertain in many times. CASE REPORT: We are reporting a 64-year-old lady with a medical history of atrial fibrillation and mitral regurgitation that treated with digoxin and warfarin therapy, she was suspected to be a COVID-19 case and prescribed empirical hydroxychloroquine and azithromycin combination without proper adjustment of her baseline therapy, accordingly she developed adverse effect of this combination in the form of digoxin toxicity and long QT, this case highlights how this unprecedented pandemic affects the decision-making of physicians. CONCLUSION: We should be critical and vigilant in making a decision of prescription or marketing non-evidence-based therapy, and when we are obligated for this decision, we should take all precautions to minimize the adverse effects of these drugs.

Laboratory Dynamics in Children With Mild Persistent Bronchial Asthma

Study Objective: to track the laboratory dynamics in children with mild persistent bronchial asthma (BA) at various stages of disease with or without baseline therapy. Study Design: prospective cohort study. Materials and Methods. The study included 42 patients with mild persistent BA aged 5 to 16 years. Each child was followed up for 3 years. At initiation of the study and during each visit, all patients had their blood eosinophils, nasal discharge (ND) and induced sputum (IS), as well as serum eosinophil cation protein (ECP) tested; and their respiratory function was assessed. All children were prescribed baseline therapy with low doses of inhalative glucocorticosteroids (GCS); 18 children also received allergen-specific immunotherapy (ASIT). Study Results. Inhalative GCS for BA exacerbations facilitated normalisation of sputum, ND and blood eosinophils. During periods of BA remission, ND and IS eosinophil levels increased, but patients did not have rhinitis and BA symptoms. Eosinophil levels in IS were higher vs. BA control (р = 0.05) and lower vs. disease exacerbations (р < 0.05). We did not find any differences in laboratory results in children with or without ASIT who were treated with low doses of inhalative and nasal GCS. Conclusion. Eosinophile inflammatory phenotype in patients did not charge depending on disease duration and control therapies. According to the study data, eosinophile levels in IS, when BA exacerbation was recorded, were 8.0% [3.0–16.0%]. This value can be used as an additional predictor for the need in increased therapy (a step forward). Irrespective of the disease stage and therapy, there was correlation between blood eosinophile level and IS eosinophile level and between IS eosinophile level and blood ECP concentration. Keywords: bronchial asthma, children, eosinophiles, induced sputum, inflammatory phenotype.

The use of a polyvalent bacterial lysate in a complex therapy of chronic urticaria

The aim of the study was to study trigger factors in chronic urticaria, peculiarities in the expression of Toll-like receptors, clinical and immunological efficacy of microbial antigens in patients with chronic urticaria.Materials and methods. Patients with chronic urticaria (134 patients). A study of the expression of TLR2, TLR3, TLR4, TLR9 on blood cells using flow cytometry. 62 patients received polyvalent bacterial lysate against baseline therapy per os, 72 patients received monotherapy with basic drugs.Results. In patients with bacterial infection, high levels of TLR2, TLR4 expression were detected. In the presence of viral infections, high TLR3 expression values were observed. The use of PBL contributed to an increase in the number of patients with clinical remission, decreased urticaria activity, led to a correction in TLR2 and TLR4, and decreased the level of total IgE.Conclusion. Inclusion in the complex of therapeutic and prophylactic measures in patients with urticaria of a chronic drug based on microbial antigens (polyvalent bacterial lysate) contributes to the increase of clinical effectiveness and activation of the links of innate immunity.

Immunogenetic Indicators as Markers of Aggressive Flow and Efficiency of Basic Therapy in Rheumatoid Arthritis in Children

The immunological and immunogenetic features of juvenile rheumatoid arthritis in the Kyrgyz population are studied for the first time. The study was conducted in 30 healthy children and 67 patients aged 3 to 16 years. The method of rosette formation was used. Associative links were established in the systemic form of juvenile rheumatoid arthritis with histocompatibility antigens in the HLA Cw5, B12 system, and the B15, A2, A9 antigens with high activity of the process, early development of bone and cartilage destruction and functional impairments. In the first 6 months of disease, it recommended the appointment of an aggressive baseline therapy.