Probiotics have been used to prevent antibiotic-associated diarrhea (AAD), but practical guidelines are sparse. This trial evaluated the efficacy and safety of a high-dose, multi-strain probiotic mix (Sinquanon^®), specially designed for prevention of AAD in adults. A Phase IV, multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted over 5 months. Participants receiving broad-spectrum antibiotics were administered the specialized probiotic mix or placebo from the first dose of antibiotics until 14 days after the last antibiotic dose. The primary outcome measure was the incidence of AAD. In total, 564 participants were randomized (probiotic mix: 285; placebo: 279), of which 9 participants discontinued the trial early (probiotic mix: 3; placebo:6), had no efficacy data, and were excluded from the efficacy analysis. The 555 remaining participants completed the trial and were included in the efficacy analysis (probiotic mix: 282; placebo: 273). AAD occurred less frequently in the studied probiotic mix versus placebo group (9.2% versus 25.3%, p<0.001), resulting in an absolute risk reduction of 16% and a number needed to treat of 6 (95% CI: 4.55-10.49). A significant improvement in the average gastrointestinal quality of life in the studied probiotic mix versus placebo group was also observed. There were no clinically relevant differences in the incidence of adverse events between the studied probiotic mix and the placebo group. The specially designed high-dose, multi-strain probiotic mix (Sinquanon^®) demonstrated to be beneficial compared with placebo in the prevention of AAD in adults who received broad-spectrum antibiotics. NCT05607056.

Background: The presence of abnormal heart rate recovery (HRR) and chronotropic incompetence (CI) suggests autonomic dysfunction (AD) and is associated with diminished physical activity and increased cardio-vascular (CV) risk. Aim: Our aim is to analyse the correlation between AD and airflow obstruction - forced expiratory volume in 1 s (FEV1), dynamic hyperinflation (DH) and disease prognosis - the BODE – index (BMI; Obstruction – FEV1;Dyspnea – mMRC;E – exercise capacity) in non-severe COPD patients without overt CV comorbidities. Methods: We used cardio-pulmonary exercise testing (CPET) with 67 subjects. Inspiratory capacity (IC) manouevres were performed for DH assessment. Echocardiography was executed before CPET and 1−2 min after peak exercise. Stress left ventricular diastolic dysfunction (LVDD) was assumed if stress E/e’ > 15.Wilkoff method calculated the metabolic-chronotropic relationship (MCR). Chronotropic incompetence (CI) and abnormal HR recovery (HRR) were determined. Main results: CI was detected in 44% of the mild and 65% of the moderate COPD patients. Abnormal HRR was present in 75% of the mild and 78% of the moderate COPD subjects. Multivariate regression analysis showed no association between FEV1, CPET parameters, BODE index, stress LVDD and AD. DH was the only independent predictor for both abnormal HRR and CI. Conclusion: Evaluation of AD during incremental CPET unravels lung hyperinflation as a potential mechanism of attenuated HR response and diminished physical activity in non-severe COPD free of overt CV comorbidities. This multifaceted approach to dyspnea may facilitate the discrimination of its pathogenesis and improve its proper clinical management.

Background:Bronchial asthma is a heterogeneous disease that includes various subtypes. They may share similar clinical characteristics, but probably have different pathological mechanisms.Aim:To identify phenotypes using cluster analysis in moderate to severe bronchial asthma and to compare differences in clinical, physiological, immunological and inflammatory data between the clusters.Patients and methods:Forty adult patients with moderate to severe bronchial asthma out of exacerbation were included. All underwent clinical assessment, anthropometric measurements, skin prick testing, standard spirometry and measurement fraction of exhaled nitric oxide. Blood eosinophilic count, serum total IgE and periostin levels were determined. Two-step cluster approach, hierarchical clustering method and k-mean analysis were used for identification of the clusters.Results:We have identified four clusters. Cluster 1 (n=14) - late-onset, non-atopic asthma with impaired lung function, Cluster 2 (n=13) - late-onset, atopic asthma, Cluster 3 (n=6) - late-onset, aspirin sensitivity, eosinophilic asthma, and Cluster 4 (n=7) - early-onset, atopic asthma.Conclusions:Our study is the first in Bulgaria in which cluster analysis is applied to asthmatic patients. We identified four clusters. The variables with greatest force for differentiation in our study were: age of asthma onset, duration of diseases, atopy, smoking, blood eosinophils, nonsteroidal anti-inflammatory drugs hypersensitivity, baseline FEV1/FVC and symptoms severity. Our results support the concept of heterogeneity of bronchial asthma and demonstrate that cluster analysis can be an useful tool for phenotyping of disease and personalized approach to the treatment of patients.

Background: Post-COVID-19 syndrome (PCS) is defined as the persistence of symptoms 3 months after acute SARS-CoV-2 infection. The long-term prevalence and clinical progression of PCS has not been established. Our aim was to investigate the symptoms in PCS patients, explore the degree of physical activity, according to the fatigue severity score, and analyze its association with basic cardio-pulmonary exercise testing (CPET) parameters. Methods: A total of 192 subjects with history of SARSCoV-2 infection were included. They filled in the Chronic Fatigue Syndrome Questionnaire (CFSQ) and were divided into symptomatic and asymptomatic groups. Forty-seven had persistent post-COVID complaints—reduced physical capacity, fatigue, dyspnea, sleep disturbances, muscle pain. CPET was performed and the pathophysiological parameters in the different fatigue severity groups were compared. Results: Subjects with persistent long-term PCS were divided into two groups—mild (20) and moderate–severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. The average period between the acute illness and the study was 1028 ± 214 days. Subjects with moderate–severe PCS had more symptoms during CPET (73.6% vs. 24.8% vs. 17.4%), as compared to mild/asymptomatic. The rate of perceived effort was subjective and did not correspond to the workload, heart, or breathing rate in the symptomatic group. These subjects were unable to reach the anaerobic threshold, compared to mild/asymptomatic subjects (51.8% vs. 25%, vs. 12.5%). Patients with moderate–severe PCS showed lower peak VO₂ (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to mild/asymptomatic subjects. Conclusions: Long-term PCS is still present in up to 24% of the general population, more than thirty months after the acute episode. It is characterized by increased perception of symptom burden and diminished aerobic metabolism. A third of the long-term PCS exhibit lower cardio-respiratory fitness, independently from the severity of the symptoms.

Purpose: Post-COVID-19 syndrome (PCS) is characterized by low cardio-respiratory fitness (CRF). Recent research focuses on the role of autonomic nervous system dysfunction (AD) as a potential contributor to the diminished exercise performance. The aim is to determine the prevalence of AD—chronotropic insufficiency (CI) and abnormal heart rate recovery (HRR) in long-term PCS subjects and to analyse their association with exercise capacity. Patients and Methods: A total of 192 subjects with a history of SARS-CoV-2 infection were included. Chronic Fatigue Syndrome Questionnaire (CFSQ) was applied, and two symptomatic and asymptomatic emerged. Forty-seven had post-COVID complaints, persisting up to thirty months post-acute episode. CI and HRR were determined during the cardio-pulmonary exercise test (CPET). Results: Symptomatic subjects were divided into mild (20) and moderate-severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. Subjects with moderate-severe PCS showed lower peak VO2 (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to the mild/asymptomatic subjects. Diminished physical activity was established in 10 (37%) of the moderate-severe, 7 (35%) of the mildly symptomatic and 14 (29%) of the asymptomatic groups. The occurrence of AD in the mild/moderate-severe and control groups were, respectively, CI 35% vs. 81.5% vs. 12.5%. Abnormal HRR was, respectively, 20% vs. 33% vs. 8%. None of the subjects had depleted breathing reserve, dynamic hyperinflation, exercise bronchospasm or desaturation. Neither CI nor abnormal HRR correlated to peak O2. Conclusions: AD is present among long-term PCS subjects and may limit the cardio-respiratory response to exercise but is not independently associated with it. Assuming the multiorgan ANS innervation, it is highly probable that AD has diverse pathological pathways in the various PCS phenotypes and contributes differently by cerebral, cardiovascular, respiratory, peripheral or mixed pathways to the diminished neuro-cognitive and physical performance.