Clinical Remission Criteria and Serum Levels of Type 2 Inflammation Mediators during 24 Weeks of Treatment with the Anti-IL-5 Drug Mepolizumab in Patients with T2-High Severe Asthma.

Anti-interleukin (IL) 5 is an effective treatment modality for inhibiting eosinophilic inflammation in patients with T2-high severe asthma. The aim of this study was to determine the clinical efficacy and serum levels of type 2 inflammatory mediators during 24 weeks of mepolizumab treatment in patients with T2-high severe asthma. Eighteen patients with T2-high severe asthma were enrolled in this study. All patients received 100 mg of mepolizumab subcutaneously every 4 weeks and were retested at 4, 12, and 24 weeks. A clinical examination, asthma control test (ACT), and spirometry were performed; fractional exhaled nitric oxide (FeNO) levels were evaluated; and blood samples were drawn at every visit. Type 2 inflammation mediator levels were measured using enzyme-linked immunosorbent assay (ELISA). The blood eosinophil level significantly decreased, the ACT score and FEV1 increased after 4 weeks of mepolizumab treatment with the same tendency after 12 and 24 weeks (p < 0.05), and the FeNO level did not change (p > 0.05). A total of 27.8% of patients reached clinical remission criteria after 24 weeks of mepolizumab treatment. IL-33 and eotaxin significantly increased (p < 0.05) while IL-5, IL-13, thymic stromal lymphopoietin (TSLP), soluble IL-5 receptor subunit alpha (sIL-5Rα), and soluble high-affinity immunoglobulin E receptor (sFcεRI) decreased, with the same tendency after 12 and 24 weeks (p < 0.05). The serum levels of immunoglobulin (Ig) E and IL-4 and IL-25 levels did not change during mepolizumab treatment compared to baseline (p > 0.05). In conclusion, treatment with mepolizumab over 24 weeks improved lung function and asthma control in T2-high severe asthma patients, with nearly one-third achieving clinical remission criteria, and affected the balance of type 2 inflammatory mediators.

Systemic Manifestations of COPD and the Impact of Dual Bronchodilation with Tiotropium/Olodaterol on Cardiac Function and Autonomic Integrity.

Background: Chronic obstructive pulmonary disease (COPD) has significant systemic manifestations, including cardiovascular morbidity. The main aim of our study was to evaluate the effect of short-term COPD treatment with tiotropium/olodaterol (TIO/OLO) 5/5 µg on cardiac function and autonomic integrity. Methods: Twenty-nine patients with newly diagnosed moderate-to-severe COPD were enrolled. We performed pulmonary function tests, cardiac magnetic resonance, cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging and analysis of blood biomarkers on our study subjects. The correlations between the tests' results were evaluated at baseline. The changes in pulmonary and cardiac parameters from baseline through 12 weeks were assessed. Results: Significant associations between pulmonary function tests' results and high-sensitivity C-reactive protein (hs-CRP), as well as interleukin-22 (IL-22), were observed at baseline. Treatment with TIO/OLO significantly improved lung function as measured by spirometry and body plethysmography. Moreover, we found that the cardiac index increased from 2.89 (interquartile range (IQR) 1.09) to 3.21 L/min/m2 (IQR 0.78) (p = 0.013; N = 18) and the late heart-to-mediastinum ratio improved from 1.88 (IQR 0.37) to 2 (IQR 0.41) (p = 0.026; N = 16) after 12 weeks of treatment. Conclusions: Treatment with TIO/OLO improves lung function and positively impacts cardiac function and autonomic integrity, suggesting that dual bronchodilation might have a potential in decreasing the risk for cardiac events in COPD. Hs-CRP and IL-22 might be beneficial in determining the intensity of systemic inflammation in COPD. Further research with a larger cohort is needed to enhance the initial results of this study.

PD-L1 Expression and Tumour Microenvironment Patterns in Resected Non-Small-Cell Lung Cancer.

Background and Objectives: Although perioperative immunotherapy is implemented as a standard of care for resected non-small cell lung cancer (NSCLC), there is unmet need for predictive biomarkers as programmed death-ligand 1 (PD-L1) is not the perfect one. The functionality of tumour-infiltrating immune cells in the tumour microenvironment (TME) and the involvement in immune system response is one of the crucial factors that lead to pro- or anti-tumourigenic role and could predict response to PD-1 and PD-L1 inhibitors. So, the investigation of PD-L1 expression in the context of TME in early stages of resected NSCLC is urgent required. Materials and Methods: PD-L1 expression by three scoring methods: tumour proportion score (TPS), immune cell score (IC), and combined proportion score (CPS) was assessed in 72 archival tumour tissue specimens from stage I-III surgically resected NSCLC patients and associations with immune cells in TME were explored. Results: PD-L1 expression ≥1% evaluated by TPS, IC, and CPS was detected in 28%, 36%, and 39% of cases and moderate, substantial, and strong agreement between TPS and IC, TPS and CPS, CPS and IC was detected (Cohen's κ coefficient 0.556, 0.63, and 0.941, respectively). PD-L1 TPS, IC, and CPS correlated with smoking intensity defined as pack-years (r = 0.0305, p = 0.012; r = 0.305, p = 0.013, and r = 0.378, p = 0.002, respectively). Only PD-L1 TPS was associated with squamous cell carcinoma (p = 0.028). PD-L1 IC ≥1% was more often seen in tumours with high CD4+ T cells infiltration (p = 0.02), while PD-L1 CPS ≥1%-in tumours with high CD4+ and CD8+ T cells infiltration (p = 0.021 and p = 0.048, respectively). PD-L1 IC and CPS ≥10% was more often detected in tumours with greater number of tumour-infiltrating CD4+Foxp3+ T cells (p = 0.01 and p = 0.025, respectively). PD-L1 TPS ≥50% was associated with higher probability to detect greater number of tumour-infiltrating M2 macrophages (p = 0.021). No association was found between PD-L1 alone or in combination with tumour-infiltrating lymphocytes, macrophages, and disease-free or overall survival. Conclusions: This study results revealed that rates of PD-L1 expression correlated among three scoring methods (TPS, IC, and CPS). Moreover, PD-L1 expression was significantly associated with smoking intensity, squamous histology, and tumour-infiltrating immune cells.

Acquired Cardiovascular Diseases in Patients with Pulmonary Hypertension Due to Congenital Heart Disease: A Case Report.

Background: Advances in the diagnosis and treatment of congenital heart diseases (CHDs) have resulted in improved survival rates for CHD patients. Up to 90% of individuals with mild CHD and 40% with complex CHD now reach the age of 60. Previous studies have indicated an elevated risk of atherosclerotic cardiovascular disease (ASCVD) and associated risk factors, morbidity, and mortality in adults with congenital heart disease (ACHD). However, there were no comprehensive guidelines for the prevention and management of acquired cardiovascular diseases (CVDs) in ACHD populations until recently. Case presentation: A 55-year-old man with Eisenmenger syndrome and comorbidities (arterial hypertension, heart failure, dyslipidemia, hyperuricemia, and a history of pulmonary embolism (PE)) presented with progressive breathlessness. The electrocardiogram (ECG) revealed signs of right ventricle (RV) hypertrophy and overload, while echocardiography showed reduced RV function, RV overload, and severe pulmonary hypertension (PH) signs, and preserved left ventricle (LV) function. After ruling out a new PE episode, acute coronary syndrome (ACS) was diagnosed, and percutaneous intervention was performed within 24-48 h of admission. Conclusions: This case highlights the importance of increased awareness of acquired heart diseases in patients with pulmonary hypertension due to CHD.

Detailed Characterization of the Lung-Gut Microbiome Axis Reveals the Link between PD-L1 and the Microbiome in Non-Small-Cell Lung Cancer Patients.

Next-generation sequencing technologies have started a new era of respiratory tract research in recent years. Alterations in the respiratory microbiome between healthy and malignant conditions have been revealed. However, the composition of the microbiome varies among studies, even in similar medical conditions. Also, there is a lack of complete knowledge about lung-gut microbiome interactions in lung cancer patients. The aim of this study was to explore the lung-gut axis in non-small-cell lung cancer (NSCLC) patients and the associations between lung-gut axis microbiota and clinical parameters (CRP, NLR, LPS, CD8, and PD-L1). Lung tissue and fecal samples were used for bacterial 16S rRNA sequencing. The results revealed, for the first time, that the bacterial richness in lung tumor tissue gradually decreased with an increase in the level of PD-L1 expression (p < 0.05). An analysis of ß-diversity indicated a significant positive correlation between the genera Romboutsia and Alistipes in both the lung tumor biopsies and stool samples from NSCLC patients (p < 0.05). Survival analysis showed that NSCLC patients with higher bacterial richness in their stool samples had prolonged overall survival (HR: 2.06, 95% CI: 1.025-4.17, p = 0.0426).

Novel Serum Biomarkers for Patients with Allergic Asthma Phenotype.

In distinguishing the allergic asthma (AA) phenotype, it has been identified that specific biomarkers could assist; however, none of them are considered ideal. This study aimed to analyze three groups of biologically active substances in the serum. Twenty steroid-free AA patients, sensitized to Dermatophagoides pteronyssinus, and sixteen healthy subjects (HSs) were enrolled in this study. Blood samples were collected from all patients. Additionally, all AA patients underwent a bronchial allergen challenge (BAC) with Dermatophagoides pteronyssinus, all of which were positive, and blood samples were collected again 24 h later. The concentrations of ten biologically active substances were measured in the serum samples, using enzyme-linked immunosorbent assay (ELISA) and the Luminex® 100/200™ System technology for bead-based multiplex and singleplex immunoassays. Descriptive and analytical statistical methods were used. A p-value of 0.05 or lower was considered statistically significant. The soluble interleukin 5 receptor subunit alpha (sIL-5Rα) and thioredoxin 1 (TRX1) concentrations were significantly increased, whereas those of tyrosine-protein kinase Met (MET), pentraxin 3 (PTX3), and I C-telopeptide of type I collagen (ICTP) were decreased in the AA group compared with the HS group. A significant positive correlation was noted for sIL-5Rα with fractional exhaled nitric oxide (FeNO), blood eosinophil (EOS) count, and total immunoglobulin E (IgE) levels, and a negative correlation was noted with forced expiratory volume in 1 s (FEV1). Moreover, PTX3 showed negative correlations with blood EOS count and total IgE levels, whereas ICTP exhibited a negative correlation with the blood EOS count. In conclusion, this study demonstrated that the serum concentrations of MET, PTX3, TRX1, ICTP, and particularly sIL-5Rα could potentially serve as biomarkers of the AA phenotype.

The Prognostic Value of One-Year Changes in Biventricular Mechanics for Three-Year Survival in Patients with Precapillary Pulmonary Hypertension: A Cardiovascular Magnetic Resonance Feature Tracking Study.

Background and Objectives: The management of patients with pulmonary hypertension (PH) poses a considerable challenge. While baseline cardiac magnetic resonance imaging (cMRI) indices are recognized for survival prognosis in PH, the prognostic value of one-year changes in biventricular mechanics, especially as assessed using feature tracking (FT) technology, remains underexplored. This study aims to assess the predictive value of one-year change in cMRI-derived biventricular function and mechanics parameters, along with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and six-minute walking test (6MWT) results for three-year mortality in precapillary PH patients. Materials and Methods: In this retrospective study, 36 patients diagnosed with precapillary pulmonary hypertension (mPAP 55.0 [46.3-70.5] mmHg, pulmonary capillary wedge pressure 10.0 [6.0-11.0] mmHg) were included. Baseline and one-year follow-up cMRI assessments, clinical data, and NT-proBNP levels were analyzed. FT technology was utilized to assess biventricular strain parameters. Patients were categorized into survival and non-survival groups based on three-year outcomes. Statistical analyses, including univariate logistic regression and Cox regression, were performed to identify predictive parameters. Results: The observed three-year survival rate was 83.3%. Baseline right ventricle (RV) ejection fraction (EF) was significantly higher in the survival group compared to non-survivors (41.0 [33.75-47.25]% vs. 28.0 [23.5-36.3]%, p = 0.044), and values of ≤32.5% were linked to a 20-fold increase in mortality risk. RV septum longitudinal strain (LS) and RV global LS exhibited significant improvement over a one-year period in the survival group compared to the non-survival group (-1.2 [-6.4-1.6]% vs. 4.9 [1.5-6.7]%, p = 0.038 and -3.1 [-9.1-2.6]% vs. 4.5 [-2.1-8.5]%, p = 0.048, respectively). Declines in RV septum LS by ≥2.95% and in RV GLS by ≥3.60% were associated with a 25-fold and 8-fold increase in mortality risk, respectively. Conclusions: The decrease in right ventricular septal and global longitudinal strain over a one-year period demonstrates a significant predictive value and an association with an increased three-year mortality risk in patients with precapillary PH.

Treatment strategies and survival of patients with connective tissue disease and pulmonary arterial hypertension: a COMPERA analysis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. METHODS: We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes. RESULTS: This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n = 390) were 85%, 59% and 42%; for SLE-PAH (n = 34) they were 97%, 77% and 61%; for MCTD-PAH (n = 33) they were 97%, 70% and 59%; for UCTD-PAH (n = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P = 0.001). In these patients, the survival estimates were significantly better with initial ERA-PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P = 0.016 and P = 0.012, respectively). CONCLUSIONS: Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA-PDE5i combination therapy compared with initial monotherapy.

Effect of Short-Term Treatment with Continuous Positive Airway Pressure on Cardiopulmonary Exercise Tolerance, Pulmonary and Cardiac Function in Patients with Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) is a condition with a high prevalence, linked to an increased risk of cardiovascular disease as well as increased morbidity and death. CPAP is currently considered the "gold standard" treatment for OSA, but more thorough research and testing are required to assess its efficacy on cardiopulmonary function. Objectives: To evaluate pulmonary function of OSA patients, cardiopulmonary exercise tolerance test (CPET) performance, cardiac magnetic resonance imaging (MRI) parameters, and polysomnographic changes before and after 3 months of CPAP therapy. Materials and methods: A total of 34 patients diagnosed with moderate or severe OSA, as well as 17 patients as a control group for the evaluation of the cardiac MRI, were included in this study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Lung function tests, CPETs, cardiac MRIs, and polysomnography were performed at the time of the study's enrolment before the initiation of the CPAP therapy and after 3 months of the CPAP treatment. Results: The patients' VO2max during the CPAP treatment tended to increase, but no statistical significance was found (before treatment it was 17.52 ± 3.79 mL/kg/min and after 3 months of treatment, it was 18.6 ± 3,4 mL/kg/min; p = 0.255). The CPAP treatment had positive effects on pulmonary ventilation at the anaerobic threshold (VEAT): 44.51 L/min (43.21%) during the baseline visit and 38.60 L/min (37.86%) after the 3-month treatment period (p = 0.028). The ventilator equivalent for the carbon dioxide slope (VE/VCO2) at peak exercise decreased from 23.47 to 20.63 (p = 0.042). The patients' pulmonary function tests were without abnormalities and did not change after treatment. When assessing cardiac the MRIs, the RV ejection fraction was lower in the OSA group compared to that of the control subjects (53.69 ± 8.91 and 61.35 ± 9.08, p = 0.016). Both LA and RA global longitudinal strains (GLS) improved after 3 months of treatment with CPAP (20.45 ± 7.25 and 26.05 ± 14.00, p = 0.043; 21.04 ± 7.14 and 26.18 ± 7.17, p = 0.049, respectively). Additionally, it was found that CPAP therapy led to statistical improvements in RV end-diastolic volume (164.82 ± 32.57 and 180.16 ± 39.09, p = 0.042). The AHI and oxygen desaturation index (ODI) significantly changed after 3 months of the initiation of the CPAP treatment (p = 0.049 and p = 0.001, respectively). The REM sleep duration decreased, while the duration of non-REM sleep increased after treatment initiation with CPAP (p = 0.016 and p = 0.017, respectively). Conclusions: Short-term CPAP treatment improves pulmonary ventilation, sleep efficiency, and sleep architecture. Significant alterations in both atrias' GLS and RV end-diastolic volume were observed after 3 months of treatment. Longer-term follow-up and a larger patient sample are needed to confirm the reproducibility of our results.

Blood Inflammatory-like and Lung Resident-like Eosinophils Affect Migration of Airway Smooth Muscle Cells and Their ECM-Related Proliferation in Asthma.

Airway remodeling is a hallmark feature of asthma, and one of its key structural changes is increased airway smooth muscle (ASM) mass and disturbed extracellular matrix (ECM) homeostasis. Eosinophil functions in asthma are broadly defined; however, we lack knowledge about eosinophil subtypes' interaction with lung structural cells and their effect on the airway's local microenvironment. Therefore, we investigated the effect of blood inflammatory-like eosinophils (iEOS-like) and lung resident-like eosinophils (rEOS-like) on ASM cells via impact on their migration and ECM-related proliferation in asthma. A total of 17 non-severe steroid-free allergic asthma (AA), 15 severe eosinophilic asthma (SEA) patients, and 12 healthy control subjects (HS) were involved in this study. Peripheral blood eosinophils were enriched using Ficoll gradient centrifugation and magnetic separation, subtyped by using magnetic separation against CD62L. ASM cell proliferation was assessed by AlamarBlue assay, migration by wound healing assay, and gene expression by qRT-PCR analysis. We found that blood iEOS-like and rEOS-like cells from AA and SEA patients' upregulated genes expression of contractile apparatus proteins, COL1A1, FN, TGF-ß1 in ASM cells (p < 0.05), and SEA eosinophil subtypes demonstrated the highest effect on sm-MHC, SM22, and COL1A1 gene expression. Moreover, AA and SEA patients' blood eosinophil subtypes promoted migration of ASM cells and their ECM-related proliferation, compared with HS (p < 0.05) with the higher effect of rEOS-like cells. In conclusion, blood eosinophil subtypes may contribute to airway remodeling by upregulating contractile apparatus and ECM component production in ASM cells, further promoting their migration and ECM-related proliferation, with a stronger effect of rEOS-like cells and in SEA.

Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis.

BACKGROUND: A diagnosis of idiopathic pulmonary arterial hypertension (IPAH) is frequently made in elderly patients who present with comorbidities, especially hypertension, coronary heart disease, diabetes mellitus, and obesity. It is unknown to what extent the presence of these comorbidities affects the response to PAH therapies and whether risk stratification predicts outcome in patients with comorbidities. METHODS: We assessed the database of COMPERA, a European pulmonary hypertension registry, to determine changes after initiation of PAH therapy in WHO functional class (FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-pro-BNP), and mortality risk assessed by a 4-strata model in patients with IPAH and no comorbidities, 1-2 comorbidities and 3-4 comorbidities. RESULTS: The analysis was based on 1,120 IPAH patients (n = 208 [19%] without comorbidities, n = 641 [57%] with 1-2 comorbidities, and n = 271 [24%] with 3-4 comorbidities). Improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk from baseline to first follow-up were significantly larger in patients with no comorbidities than in patients with comorbidities, while they were not significantly different in patients with 1-2 and 3-4 comorbidities. The 4-strata risk tool predicted survival in patients without comorbidities as well as in patients with 1-2 or 3-4 comorbidities. CONCLUSIONS: Our data suggest that patients with IPAH and comorbidities benefit from PAH medication with improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk, albeit to a lesser extent than patients without comorbidities. The 4-strata risk tool predicted outcome in patients with IPAH irrespective of the presence of comorbidities.

IL-5 and GM-CSF, but Not IL-3, Promote the Proliferative Properties of Inflammatory-like and Lung Resident-like Eosinophils in the Blood of Asthma Patients.

Blood eosinophils can be described as inflammatory-like (iEOS-like) and lung-resident-like (rEOS-like) eosinophils. This study is based on the hypothesis that eosinophilopoetins such as interleukin (IL)-3 and IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) alter the proliferative properties of eosinophil subtypes and may be associated with the expression of their receptors on eosinophils. We investigated 8 individuals with severe nonallergic eosinophilic asthma (SNEA), 17 nonsevere allergic asthma (AA), and 11 healthy subjects (HS). For AA patients, a bronchial allergen challenge with Dermatophagoides pteronyssinus was performed. Eosinophils were isolated from peripheral blood using high-density centrifugation and magnetic separation methods. The subtyping of eosinophils was based on magnetic bead-conjugated antibodies against L-selectin. Preactivation by eosinophilopoetins was performed by incubating eosinophil subtypes with IL-3, IL-5, and GM-CSF, and individual combined cell cultures were prepared with airway smooth muscle (ASM) cells. ASM cell proliferation was assessed using an Alamar blue assay. The gene expression of eosinophilopoetin receptors was analyzed with a qPCR. IL-5 and GM-CSF significantly enhanced the proliferative properties of iEOS-like and rEOS-like cells on ASM cells in both SNEA and AA groups compared with eosinophils not activated by cytokines (p < 0.05). Moreover, rEOS-like cells demonstrated a higher gene expression of the IL-3 and IL-5 receptors compared with iEOS-like cells in the SNEA and AA groups (p < 0.05). In conclusion: IL-5 and GM-CSF promote the proliferative properties of iEOS-like and rEOS-like eosinophils; however, the effect of only IL-5 may be related to the expression of its receptors in asthma patients.

Changes in Left Heart Geometry, Function, and Blood Serum Biomarkers in Patients with Obstructive Sleep Apnea after Treatment with Continuous Positive Airway Pressure.

Background: Cardiovascular remodeling is essential in patients with obstructive sleep apnea (OSA), and continuous positive airway pressure (CPAP) therapy could improve these processes. Two-dimensional (2D) speckle-tracking (ST) echocardiography is a useful method for subclinical biventricular dysfunction diagnosis and thus might help as an earlier treatment for OSA patients. It is still not clear which blood serum biomarkers could be used to assess CPAP treatment efficacy. Objectives: To evaluate left heart geometry, function, deformation parameters, and blood serum biomarker (galectin-3, sST2, endothelin-1) levels in patients with OSA, as well as to assess changes after short-term CPAP treatment. Materials and Methods: Thirty-four patients diagnosed with moderate or severe OSA, as well as thirteen patients as a control group, were included in the study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Transthoracic 2D ST echocardiography was performed before and after 3 months of treatment with CPAP; for the control group, at baseline only. Peripheral blood samples for the testing of biomarkers were collected at the time of study enrolment before the initiation of CPAP therapy and after 3 months of CPAP treatment (blood samples were taken just for OSA group patients). Results: The left ventricle (LV) end-diastolic diameter and volume, as well as LV ejection fraction (EF), did not differ between groups, but an increased LV end-systolic volume and a reduced LV global longitudinal strain (GLS) were found in the OSA group patients (p = 0.015 and p = 0.035, respectively). Indexed by height, higher LV MMi in OSA patients (p = 0.007) and a higher prevalence of LV diastolic dysfunction (p = 0.023) were found in this group of patients. Although left atrium (LA) volume did not differ between groups, OSA group patients had significantly lower LA reservoir strain (p < 0.001). Conventional RV longitudinal and global function parameters (S', fractional area change (FAC)) did not differ between groups; however, RV GLS was reduced in OSA patients (p = 0.026). OSA patients had a significantly higher right atrium (RA) diameter and mean pulmonary artery pressure (PAP) (p < 0.05). Galectin-3 and sST2 concentrations significantly decreased after 3 months of CPAP treatment. Conclusions: OSA is associated with the left heart remodeling process­increased LV myocardial mass index, LV diastolic dysfunction, reduced LV and RV longitudinal strain, and reduced LA reservoir function. A short-term, 3-months CPAP treatment improves LV global longitudinal strain and LA reservoir function and positively affects blood serum biomarkers. This new indexing system for LV myocardial mass by height helps to identify myocardial structural changes in obese patients with OSA.

The Treatment Strategy for the Atrial Septal Defect in the Presence of Severe Pulmonary Hypertension.

Atrial septal defect is one of the most common congenital heart diseases in adults. The defect often leads to volume overload in the right heart coupled with the potential risk of right heart failure and pulmonary arterial hypertension. These conditions lead to worsening in quality of life, decrease in physical capacity, and even to fatal outcomes. The main strategy for treatment of atrial septal defect is a transcatheter or surgical closure of the defect, but in patients with severe pulmonary arterial hypertension, it is recommended to manage pulmonary arterial hypertension and after that treat the defect invasively. This strategy is called "treat and repair" strategy. We present an illustrative case report of management and treatment of atrial septal defect, complicated with severe pulmonary arterial hypertension. In this case, surgical closure of the defect was contraindicated because of the high pulmonary vascular resistance. Therefore, the "treat and repair" strategy was approached. After specific medical treatment of pulmonary arterial hypertension, surgical closure of the defect was chosen and proven successful.

Short-Term Continuous Positive Air Pressure Treatment: Effects on Quality of Life and Sleep in Patients with Obstructive Sleep Apnea.

Background and Objectives: The aim of this study was to evaluate short-term continuous positive air pressure (CPAP) treatment for health-related quality of life (HRQL) in patients with obstructive sleep apnea. Materials and Methods: Our subjects were 18−65 years old, diagnosed with moderate-to-severe obstructive sleep apnea and treated with CPAP between January 2020 and June 2021 in Hospital of Lithuanian University of Health Sciences Kaunas clinics. All the patients completed the Epworth Sleepiness Scale (ESS), the 36-Item Short Form Health Survey (SF-36), the and Pittsburgh Sleep Quality Index (PSQI) before and after 3 months of treatment. Polysomnography was also repeated. Statistical analyses were performed using SPSS 27.0 software. The value of p < 0.05 was considered as statistically significant. Results: The active-treatment group comprised 17 subjects with a mean age of 51.9 ± 8.9 years. The total SF-36 questionnaire score improved from 499.8 ± 122.3 to 589.6 ± 124.7 (p = 0.012). The SF-36 role limitations due to emotional problems (p = 0.021), energy (fatigue) (p = 0.035), and general health (p = 0.042) domains score significantly improved after CPAP treatment for 3 months. The PSQI mean score at baseline was 12.6 ± 2.9 and in the post-treatment group, it was −5.5 ± 2.3 (p = 0.001). The ESS also changed significantly from a pretreatment mean score of 10.9 ± 5.7 to −5.3 ± 3.2 (p = 0.002) after 3 months. Conclusions: Improvement in HRQL is seen even after a short treatment period with CPAP. Questionnaires are a good tool to evaluate CPAP treatment efficacy.

Diagnostic Yield of Transbronchial Cryobiopsy Guided by Radial Endobronchial Ultrasound and Fluoroscopy in the Radiologically Suspected Lung Cancer: A Single Institution Prospective Study.

Transbronchial cryobiopsy (TBCB) is being studied in the diagnosis of peripheral lung lesions; however, there are only a few clinical studies around the world. The aim of our study was to evaluate the diagnostic values and safety of transbronchial cryobiopsy for radiologically suspected peripheral lung cancer. The prospective clinical study was executed from September 2019 to September 2021 at a tertiary clinical centre in Lithuania. A total of 48 patients out of 102 underwent combined procedures of transbronchial forceps biopsy (TBFB) and TBCB. Diagnostic values and safety outcomes of TBFB and TBCB were analysed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 72.9%, 100%, 100%, 7.7%, and 88.0% for TBFB, 85.1%, 100%, 100%, 12.5%, and 93% for TBCB, as well as 91.5%, 100%, 100%, 20.0% and 96.7% for the combined procedures, respectively, with a significantly higher accuracy for cryobiopsies compared to forceps biopsies (p < 0.05). The diagnostic values for transbronchial cryobiopsies were similar, irrespective of the radial mini probe endobronchial ultrasound (RP-EBUS) position, lesion size or bronchus sign, however, the sensitivity of the combined procedures in cases with RP-EBUS adjacent to the target was significantly higher compared to TBFB (86.2% vs. 64.3%, p = 0.016). Samples of cryobiopsies were significantly larger than forceps biopsies (34.62 mm2 vs. 4.4 mm2, p = 0.001). The cumulative diagnostic yield of transbronchial cryobiopsy was 80.0% after the second biopsy and reached a plateau of 84.1% after four biopsies. No severe bleeding, pneumothorax, respiratory failure or death was registered in our study. TBCB is a potentially safe procedure, which increases diagnostic values in diagnosing peripheral lung lesions compared to TBFB.

Fatal pulmonary tumour thrombotic microangiopathy in patient with ovarian adenocarcinoma: review and a case report.

BACKGROUND: Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease in which tumour cells embolize to the pulmonary vasculature leading to pulmonary hypertension and right heart failure. Early diagnosis is essential for timely treatment which can reduce intimal pulmonary vascular proliferation and prolong survival, improve the symptoms. Due to rare occurrences and no clear diagnostic guidelines the disorder usually is found post-mortem. We present a review of this rare disease and a case of post-mortem diagnosed pulmonary tumour thrombotic microangiopathy in a young female. CASE PRESENTATION: 51 years old woman presented with progressively worsening dyspnea, right ventricular failure signs and symptoms. Computerized tomography denied pulmonary embolism. 2D transthoracic echocardiography demonstrated right ventricle dilatation and dysfunction, severely increased systolic pulmonary pressure. Right heart catheterization revealed pre-capillary pulmonary hypertension with mean pulmonary artery pressure of 78 mmHg, pulmonary wedge pressure of 15 mmHg, reduced cardiac output to 1.78 L/min with a calculated pulmonary vascular resistance of 35 Wood units, and extremely low oxygen saturation (26%) in pulmonary artery. Because of worsening ascites, pelvic magnetic resonance imaging was performed, tumours in both ovaries were diagnosed. Due to the high operative risk, detailed tumour diagnosis surgically was not established. The patient developed progressive cardiorespiratory failure, unresponsive to optimal heart failure drug treatment. A postmortem morphology analyses revealed tumorous masses in pre-capillary lung vessels, right ventricle hypertrophy, ovary adenocarcinoma. CONCLUSIONS: An early diagnosis of PTTM is essential. Most cases are lethal due to respiratory failure progressing rapidly. Patients with a history of malignancy, symptoms and signs implying of PH should be considered of having PTTM. If detected early enough, combination of chemotherapy with specific PH therapy is believed to be beneficial in reducing intimal proliferation and prolonging survival, along with improving the symptoms.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 µg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 µg/ml by BMD and 0.25 µg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 µg/ml and 0.5 µg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

Different Causes of Functional Tricuspid Valve Regurgitation Are Linked to Differences in Tricuspid Valve and Right-Sided Heart Geometry and Function: 3D Echocardiography Study.

Background and Objectives: The aim of this study was to clarify the tricuspid valve (TV) and right ventricular (RV) geometry and function characteristics using 3D echocardiography-based analysis and to identify echocardiographic predictors for severe tricuspid regurgitation (TR) in different etiologies of functional TR (fTR). Methods and Results: The prospective study included 128 patients (median age 64 years, 57% females): 109 patients with moderate or severe fTR (69-caused by dominant left-sided valvular pathology (LSVP), 40 due to precapillary pulmonary hypertension (PH)), and 19 healthy controls. The 2D and 3D-transthoracic echocardiography analysis included TV, right atrium, RV geometry, and functional parameters. All the RV geometry parameters as well as 3D TV parameters were increased in both fTR groups when compared to controls. Higher RV diameters, length, areas, volumes, and more impaired RV function were in PH group compared to LSVP group. PH was associated with larger leaflet tenting height, volume, and more increased indices of septal-lateral and major axis tricuspid annulus (TA) diameters. LVSP etiology was associated with higher anterior-posterior TA diameter and sphericity index. Univariate and multivariate logistic regression and ROC analyses revealed that different fTR etiologies were associated with various 2D and 3D echocardiographic parameters to predict severe TR: major axis TA diameter and TA perimeter, the leaflet tenting volume had the highest predictive value in PH group, septal-lateral systolic TA diameter-in LSVP group. The 3D TA analysis provided more reliable prediction for severe fTR. Conclusions: TV and RV geometry vary in different etiologies of functional TR. Precapillary PH is related to more severe RV remodeling and dysfunction and changes of TV geometry, when compared to LSVP group. The 3D echocardiography helps to determine echocardiographic predictors of severe TR in different fTR etiologies.

Effective Initial Treatment of Diffuse Pulmonary Lymphangiomatosis with Sirolimus and Propranolol: A Case Report.

Diffuse pulmonary lymphangiomatosis (DPL), an exceptionally rare disease, mainly occurs in children and young adults of both sexes. Even though DPL is considered to be a benign disease, its prognosis is relatively poor. Because of its rarity, little guidance on diagnosis and treatment is available, which makes working with patients with DPL challenging for clinicians. We present here a case of a young man with DPL in whom treatment with sirolimus and propranolol rapidly achieved positive radiological and clinical effects.