In chronic obstructive pulmonary disease (COPD), dysregulated calcium homeostasis, oxidative stress, and mucus hypersecretion converge to suppress ciliary beat frequency (CBF), thereby compromising mucociliary clearance (MCC). These mechanisms are subject to pharmacological modulation. Long-acting muscarinic antagonists (LAMAs) exert direct cilia-stimulatory effects and may counteract pathogen-induced mucin overproduction without impairing clearance. Long-acting β2-agonists (LABAs) enhance ciliary activity through the cAMP–PKA–dynein (cyclic adenosine monophosphate–protein kinase A–dynein) signalling pathway. Inhaled corticosteroids (ICSs), although largely neutral on CBF, provide indirect protection by suppressing IL-13–driven inflammation. Phosphodiesterase (PDE)-4 inhibitors sustain intracellular cAMP and promote ciliary motility, though their clinical use remains limited by adverse effects. Emerging evidence suggests that dual and triple therapies may provide additive or synergistic benefits for preserving mucociliary function. Clinically, ex vivo CBF interpretation may be influenced by ongoing pharmacotherapy and tissue sampling site. Nasal brush samples may predominantly reflect systemic rather than inhaled therapy. Moreover, differences in PDE isoform expression between nasal and bronchial epithelium further complicate direct extrapolation of results. Rigorous patient stratification by treatment regimen is therefore essential to reconcile inconsistencies reported across studies. Ultimately, preservation of MCC in COPD depends on a delicate balance between oxidative stress and pharmacological modulation of ciliary function.

Summary: Bronchoesophageal and bronchogastric fistulas are rare complications of thoracic surgery as esophagectomy, malignancy or prolonged endotracheal intubation. Although uncommon, their morbidity and mortality is substantial. Treatment of these fi stulas is challenging and often lengthy with limited success rates. Endoscopic treatment may be the treatment of choice for some types of fi stulas, but despite a variety of methods available, the success rate is relatively low with little consistent data about its eff ectiveness. At the same time, new technologies and devices have become available with a potential to address these complicated conditions. One of them are Watanabe spigots, initially used in pneumology for the treatment of persistent pneumothorax and pyothorax with bronchial fi stula. In the presented case reports Watanabe spigots are used in combination with over-the-scope clips in two of our patients with bronchoesophageal fi stulas fol lowing esophagectomy with promising results. We also present an overview of endoscopic methods of therapy in the context of and separately discuss available evidence about the possibilities of the use of Watanabeho spigots in the treatment of bronchoesophageal fi stulas. Key words: bronchoesophageal fi stula – Watanabe spigot – esophagectomy – over-the-scope clip

Power hammers are mechanised forging devices that constitute a pivotal part of steel manufacturing. Power hammer-associated injuries are a rare occurrence. We report a noteworthy case of a 52-year-old man who sustained a high-energy penetrating injury while working with a power (counterblow) hammer. The man used a sizable disc-shaped metallic object to dislodge the forging wedged in the machine by applying the force of the striking ram on it. On impact, the object ejected and struck the man in the right lateral portion of the chest. The autopsy disclosed extensive damage to the thoracic and abdominal organs. The cause of death was opined to be exsanguination due to penetrating trauma of the heart and transection of the descending aorta. The investigation confirmed a breach of safety regulations. To the best of our knowledge, this is the first power (counterblow) hammer-related fatality in medico-legal literature.

Background and aim:COVID-19 can be presented with various gastrointestinal symptoms. Shortly after the pandemic outbreak, several machine learning algorithms were implemented to assess new diagnostic and therapeutic methods for this disease. The aim of this study is to assess gastrointestinal and liver-related predictive factors for SARS-CoV-2 associated risk of hospitalization.Methods:Data collection was based on a questionnaire from the COVID-19 outpatient test center and from the emergency department at the University Hospital in combination with the data from internal hospital information system and from a mobile application used for telemedicine follow-up of patients. For statistical analysis SARS-CoV-2 negative patients were considered as controls in three different SARS-CoV-2 positive patient groups (divided based on severity of the disease). The data were visualized and analyzed in R version 4.0.5. The Chi-squared or Fisher test was applied to test the null hypothesis of independence between the factors followed, where appropriate, by the multiple comparisons with the Benjamini Hochberg adjustment. The null hypothesis of the equality of the population medians of a continuous variable was tested by the Kruskal Wallis test, followed by the Dunn multiple comparisons test. In order to assess predictive power of the gastrointestinal parameters and other measured variables for predicting an outcome of the patient group the Random Forest machine learning algorithm was trained on the data. The predictive ability was quantified by the ROC curve, constructed from the Out-of-Bag data. Matthews correlation coefficient was used as a one-number summary of the quality of binary classification. The importance of the predictors was measured using the Variable Importance. A 2D representation of the data was obtained by means of Principal Component Analysis for mixed type of data. Findings with the p-value below 0.05 were considered statistically significant.Results:A total of 710 patients were enrolled in the study. The presence of diarrhea and nausea was significantly higher in the emergency department group than in the COVID-19 outpatient test center. Among liver enzymes only aspartate transaminase (AST) has been significantly elevated in the hospitalized group compared to patients discharged home. Based on the Random Forest algorithm, AST has been identified as the most important predictor followed by age or diabetes mellitus. Diarrhea and bloating have also predictive importance, although much lower than AST.Conclusion:SARS-CoV-2 positivity is connected with isolated AST elevation and the level is linked with the severity of the disease. Furthermore, using the machine learning Random Forest algorithm, we have identified the elevated AST as the most important predictor for COVID-19 related hospitalizations.

Introduction Post-coronavirus disease (post-COVID) symptoms arise mostly from impaired function of respiratory tract although in many patients, the dysfunction of gastrointestinal tract and liver among other organ systems may persist. Methods Primary data collection was based on a short gastrointestinal symptom questionnaire at the initial screening. A brief telephone survey within the patient and control group was performed 5-8 months after the initial screening. R ver. 4.0.5 and imbalanced RandomForest (RF) machine-learning algorithm were used for data explorations and analyses. Results A total of 590 patients were included in the study. The general presence of gastrointestinal symptoms 208.2 days (153-230 days) after the initial acute severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection was 19% in patients with moderate-to-serious course of the disease and 7.3% in patients with mild course compared with 3.0% in SARS-CoV-2 negative controls (P < 0.001). Diarrhea and abdominal pain are the most prevalent post-COVID gastrointestinal symptoms. RF machine-learning algorithm identified acute diarrhea and antibiotics administration as the strongest predictors for gastrointestinal sequelae with area under curve of 0.68. Variable importance for acute diarrhea is 0.066 and 0.058 for antibiotics administration. Conclusion The presence of gastrointestinal sequelae 7 months after the initial SARS-CoV-2 infection is significantly higher in patients with moderate-to-severe course of the acute COVID-19 compared with asymptomatic patients or those with mild course of the disease. The most prevalent post-COVID gastrointestinal symptoms are diarrhea and abdominal pain. The strongest predictors for persistence of these symptoms are antibiotics administration and acute diarrhea during the initial infection.

Introduction The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report provides guidance on effective management of chronic obstructive pulmonary disease (COPD) according to local healthcare systems. However, COPD is a heterogenous disease and certain aspects, including prevalence, disease-time course and phenotype distribution, can differ between countries. Moreover, features of clinical practice and healthcare systems for patients with COPD can vary widely, even in geographically close and economically similar countries. Areas covered Based on an initial workshop of respiratory physicians from eleven countries across Central and Eastern Europe (CEE) in December 2018 and subsequent discussions, this article offers region-specific insights from clinical practice and healthcare systems in CEE. Taking recommendations from the GOLD 2022 report into account, we suggest approaches to adapt these into national clinical guidelines for COPD management in CEE. Expert opinion Several factors should be considered when optimizing management of COPD in CEE compared with other regions, including differences in smoking status, vaccination uptake, prevalence of tuberculosis and nontuberculous mycobacteria, and variations in healthcare systems. We provide guidance and algorithms for pharmacologic and non-pharmacologic management of COPD for the following scenarios: initial and follow-up treatment, treatment of patients with frequent exacerbations, and withdrawal of inhaled corticosteroids where appropriate. PLAIN LANGUAGE SUMMARY Chronic obstructive pulmonary disease (COPD) is a common disease of the lungs. It causes symptoms such as breathlessness, cough, and production of phlegm. In people with COPD, these symptoms often reduce the quality of their lives. From time to time, symptoms may get worse in people with the disease. This worsening is known as 'exacerbation'. Exacerbations of COPD can be so bad that they lead to hospital admissions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) regularly gives advice to doctors around the world. This can help them to provide their patients with the best possible treatment for COPD. However, people with the disease and healthcare systems vary from country to country. This means that the guidance may need to be adjusted to the needs and available resources of different regions. This review looks at how COPD is treated in Central and Eastern Europe. We suggest how to adapt the GOLD recommendations to best suit the Central and Eastern European region.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an appropriate function of the immune system is important for a rapid clearance of the virus, progression to the severe and critical phases of the disease is related to an exaggerated immune response associated with a cytokine storm. We analyzed differences and longitudinal changes in selected immune parameters in 823 adult COVID-19 patients hospitalized in the Martin University Hospital, Martin, Slovakia. Examined parameters included the differential blood cell counts, various parameters of cellular and humoral immunity (serum concentration of immunoglobulins, C4 and C3), lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, NK cells, CD4+CD45RO+), expression of activation (HLA-DR, CD38) and inhibition markers (CD159/NKG2A). Besides already known changes in the differential blood cell counts and basic lymphocyte subsets, we found significantly higher proportion of CD8+CD38+ cells and significantly lower proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission in non-survivors, compared to survivors; recovery in survivors was associated with a significant increase in the expression of HLA-DR and with a significant decrease of the proportion of CD8+CD38+cells. Furthermore, patients with fatal outcome had significantly lower concentrations of C3 and IgM on admission. However, none of the examined parameters had sufficient sensitivity or specificity to be considered a biomarker of fatal outcome. Understanding the dynamic changes in immune profile of COVID-19 patients may help us to better understand the pathophysiology of the disease, potentially improve management of hospitalized patients and enable proper timing and selection of immunomodulator drugs.

The global pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having a tremendous impact on the global economy, health care systems and the lives of almost all people in the world. The Central European country of Slovakia reached one of the highest daily mortality rates per 100,000 inhabitants in the first 3 months of 2021, despite implementing strong prophylactic measures, lockdowns and repeated nationwide antigen testing. The present study reports a comparison of the performance of the Standard Q COVID-19 antigen test (SD Biosensor) with three commercial RT-qPCR kits (vDetect COVID-19-MultiplexDX, gb SARS-CoV-2 Multiplex-GENERI BIOTECH Ltd. and Genvinset COVID-19 [E]-BDR Diagnostics) in the detection of infected individuals among employees of the Martin University Hospital in Slovakia. Health care providers, such as doctors and nurses, are classified as "critical infrastructure", and there is no doubt about the huge impact that incorrect results could have on patients. Out of 1231 samples, 14 were evaluated as positive for SARS-CoV-2 antigen presence, and all of them were confirmed by RT-qPCR kit 1 and kit 2. As another 26 samples had a signal in the E gene, these 40 samples were re-isolated and subsequently re-analysed using the three kits, which detected the virus in 22, 23 and 12 cases, respectively. The results point to a divergence not only between antigen and RT-qPCR tests, but also within the "gold standard" RT-qPCR testing. Performance analysis of the diagnostic antigen test showed the positive predictive value (PPV) to be 100% and negative predictive value (NPV) to be 98.10%, indicating that 1.90% of individuals with a negative result were, in fact, positive. If these data are extrapolated to the national level, where the mean daily number of antigen tests was 250,000 in April 2021, it points to over 4700 people per day being misinterpreted and posing a risk of virus shedding. While mean Ct values of the samples that were both antigen and RT-qPCR positive were about 20 (kit 1: 20.47 and 20.16 for Sarbeco E and RdRP, kit 2: 19.37 and 19.99 for Sarbeco E and RdRP and kit 3: 17.47 for ORF1b/RdRP), mean Ct values of the samples that were antigen-negative but RT-qPCR-positive were about 30 (kit 1: 30.67 and 30.00 for Sarbeco E and RdRP, kit 2: 29.86 and 31.01 for Sarbeco E and RdRP and kit 3: 27.47 for ORF1b/RdRP). It confirms the advantage of antigen test in detecting the most infectious individuals with a higher viral load. However, the reporting of Ct values is still a matter of ongoing debates and should not be conducted without normalisation to standardised controls of known concentration.

The velocity of the COVID-19 pandemic spread and the variable severity of the disease course has forced scientists to search for potential predictors of the disease outcome. We examined various immune parameters including the markers of immune cells exhaustion and activation in 21 patients with COVID-19 disease hospitalised in our hospital during the first wave of the COVID-19 pandemic in Slovakia. The results showed significant progressive lymphopenia and depletion of lymphocyte subsets (CD3+, CD4+, CD8+ and CD19+) in correlation to the disease severity. Clinical recovery was associated with significant increase in CD3+ and CD3+CD4+ T-cells. Most of our patients had eosinopenia on admission, although no significant differences were seen among groups with different disease severity. Non-survivors, when compared to survivors, had significantly increased expression of PD-1 on CD4+ and CD8+ cells, but no significant difference in Tim-3 expression was observed, what suggests possible reversibility of immune paralysis in the most severe group of patients. During recovery, the expression of Tim-3 on both CD3+CD4+ and CD3+CD8+ cells significantly decreased. Moreover, patients with fatal outcome had significantly higher proportion of CD38+CD8+ cells and lower proportion of CD38+HLA-DR+CD8+ cells on admission. Clinical recovery was associated with significant decrease of proportion of CD38+CD8+ cells. The highest AUC values within univariate and multivariate logistic regression were achieved for expression of CD38 on CD8+ cells and expression of PD1 on CD4+ cells alone or combined, what suggests, that these parameters could be used as potential biomarkers of poor outcome. The assessment of immune markers could help in predicting outcome and disease severity in COVID-19 patients. Our observations suggest, that apart from the degree of depletion of total lymphocytes and lymphocytes subsets, increased expression of CD38 on CD3+CD8+ cells alone or combined with increased expression of PD-1 on CD3+CD4+ cells, should be regarded as a risk factor of an unfavourable outcome in COVID-19 patients. Increased expression of PD-1 in the absence of an increased expression of Tim-3 on CD3+CD4+ and CD3+CD8+ cells suggests potential reversibility of ongoing immune paralysis in patients with the most severe course of COVID-19.

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subserve pruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Ad nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subservepruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Adelta nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

Introduction. Sarcoidosis is a multisystem granulomatous disease of unknown aetiology, commonly involving the lungs. Cough is a frequent and troublesome symptom of sarcoidosis that reduces patients’ quality of life. Aim. Retrospective analysis of different factors—smoking history, Scadding stage, results of lung function testing, calcium metabolism, endobronchial finding, CD4+/CD8+ T-cell ratio in bronchoalveolar lavage fluid (BALF), and other sarcoidosis symptoms in relationship to presence/absence of cough in sarcoidosis patients. Methods. We retrospectively studied sarcoidosis patients diagnosed at the Clinic of Pneumology and Phthisiology of Martin University Hospital between 1998 and 2018. Patients with a history of cough-relevant comorbidities were excluded from the study. GraphPad Prism 7.0 software was used to perform statistical analysis. Results. 101 sarcoidosis patients were included to the study: 65 patients reporting from cough and 36 without cough. The cough was slightly more frequent in nonsmokers (p=0.166) and in women (p=0.688). Cough was associated with dyspnoea (p=0.0007), fever (p=0.0324), and chest pain (p=0.0206) and did not associate with arthralgia (p=0.317) and erythema nodosum (p=0.505). Patients with cough had significantly a lower average value of calciuria (p=0.0014) and lower MEF25 (p=0.0304), MEF50 (p=0.0061), FEV1 (p=0.0025), and FVC (p=0.0025) in % of predicted values, and more often positive endobronchial finding (p=0.0206), compared to patients without cough. Calcemia, FEV1/FVC, DLCO, and CD4+/CD8+ T-cell ratio in BALF and occurrence of cough did not differ between different stages of the disease. Conclusions. We found significant differences between sarcoidosis patients with/without cough regarding symptoms, results of lung function tests, endobronchial finding, and calcium metabolism. Further research is needed to understand the etiopathogenesis of cough in sarcoidosis patients.

Evidence showed, that free radical species and nitric oxide (NO) or its derrivates are the key dominators in carcinogenesis. The aim of our study was to determine the alteration of NO derivates- nitrites, nitrates and 3-nitrotyrosine, as markers of oxidative/nitrosative stress in blood samples of lung cancer (LC) patients and to asses the importance of exhaled nitric oxide measurement (FeNO) in LC patients and and their relationship to type of cancer and smoking status. 54 newly diagnosed patients with LC and 43 healthy controls (HC) were studied. FeNO levels were measured by analyzer NIOX. Concentrations of NO2-/NO3– were assesed using the modified cadmium-reduction method based. 3-nitrotyrosine was assesed using specific antibody. Our results have shown that plasma nitrites concentrations in patiens with LC were significantly higher (4,41+/-2,24 µM) when compared with HC (2,53+/-1,39 µM). There was not difference between male and female, smokers and nonsmokers and LC types. There was not stastisticaly significant difference in level of nitrates in patients with LC (6,71+/-6,04 µM) and in HC (8,53+/-2,36 µM) regardless of gender, smoking status and type of cancer. Levels of 3-nitrotyrosin in patients with LC (0,22+/-0,17ng/ml) were significantly higher than in HC (-2,85 +/-0,34 ng/ml) regardless of type of cancer and smoking status. Patients with LC had significantly higher levels of FeNO (13ppb, IQR 8) than HC (10,1ppb, IQR 3,05) not depending on cancer type and smoking status. The prognosis of lung cancer is still poor because of the absence of valid approaches to its early detection. Exhaled breath analysis and measurements of NO derivates may provide useful assays in this field.

Long term exposure of cells to high nitric oxide (NO) concentrations during chronic inflammation coud have a role in cancer formation. The aim of our study was to asses the importance of exhaled nitric oxide (FeNO) measurement in lung lancer patients and its relationship to type of cancer, smoking status and use of inhaled corticosteroids (ICS) in indication of chronic obstructive pulmonary disease (COPD) treatment. 33 newly diagnosed patients with lung cancer and 43 healthy individuals took part in the study. FeNO was measured by analyzer NIOX. Patients with lung cancer had significantly (p=0,004) higher levels of FeNO (13ppb, IQR 8) than controls (10,1ppb, IQR 3,05). Patients with non-small cell lung cancer (NSCLC) had significantly (p=0,005) higher levels of FeNO (15ppb, IQR 11) than controls, as well as small cell lung cancer (SCLC) patients (12,5ppb, IQR 6,25) (p=0,043). FeNO levels in 8 non-smokers with lung cancer (16,5ppb, IQR 5 ppb) were significantly higher (p=0,001) than in healthy non-smokers as well as FeNO levels in 24 smokers with lung cancer (12,5ppb, IQR 7,5) (p=0,022). FeNO in 17 patients with lung cancer, current smokers with COPD without ICS tratment (13ppb, IQR 8) was significantly higher (p=0,024) than in healthy subjects. When lung cancer smokers with COPD were treated with ICS, the FeNO levels (11ppb, IQR 4) did not differ from FeNO levels in controls. In lung cancer patients the production of NO is increased regardless of type of cancer and smoking status. FeNO levels in lung cancer smoking patients treated with ICS are similar as in healthy controls. Support: VEGA 1/0062/13, VEGA 1/0110/12, Projectu code: 26110230067.