Venom Immunotherapy Does Not Affect Survival of Patients with Malignant Tumor in Poland.

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients' survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace's crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace's cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis.

How to Enhance the Diagnosis of Early Stages of Chronic Obstructive Pulmonary Disease (COPD)? The Role of Mobile Spirometry in COPD Screening and Diagnosis-A Systematic Review.

COPD is the third leading cause of death worldwide. Its diagnosis can be made with spirometry, which is underused due to its limited accessibility. Portable spirometry holds promise for enhancing the efficacy of COPD diagnoses. The study aimed to estimate COPD prevalence diagnosed with a portable spirometer in high-risk patients and compare it with COPD prevalence based on data from conventional, on-site spirometry. We also evaluated the strategy of a proactive approach to identify COPD in high-risk individuals. We conducted a systematic review of original studies on COPD targeted screening and diagnosis with portable and conventional spirometers selected from 8496 publications initially found in three databases: Cochrane, PubMed, and Embase. The inclusion criteria were met by 28 studies. COPD prevalence evaluated with the use of portable spirometers reached 20.27% and was lower compared to that estimated with the use of conventional spirometers (24.67%). In 11 included studies, postbronchodilator tests were performed with portable spirometers, which enabled a bedside COPD diagnosis. Portable spirometers can be successfully used in COPD targeted screening and diagnosis and thus enhance the detection of COPD at early stages.

ß-escin activates ALDH and prevents cigarette smoke-induced cell death.

BACKGROUND: The tobacco use is one of the biggest public health threats worldwide. Cigarette smoke contains over 7000 chemicals among other aldehydes, regarded as priority toxicants. ß-escin (a mixture of triterpenoid saponins extracted from the Aesculus hippocastanum. L) is a potent activator of aldehyde dehydrogenase (ALDH) - an enzyme catalyzing oxidation of aldehydes to non-toxic carboxylic acids. PURPOSE: The aim of this study was to evaluate the effect of ß-escin on ALDH activity, ALDH isoforms mRNA expression and cytotoxicity in nasal epithelial cells exposed to cigarette smoke extract (CSE). METHODS: Nasal epithelial cells from healthy non-smokers were treated with ß-escin (1 µM) and exposed to 5% CSE. After 6- or 24-hours of stimulation cell viability, DNA damage, ALDH activity and mRNA expression of ALDH isoforms were examined. RESULTS: 24 h ß-escin stimulation revised CSE induced cytotoxicity and DNA damage. Cells cultured with ß-escin or exposed to CSE responded with strong increase in ALDH activity. This effect was more pronounced in cultures treated with combination of ß-escin and CSE. The strongest stimulatory effect on ALDH isoform mRNA expression was observed in cells cultured simultaneously with ß-escin and CSE: at 6 h for ALDH1A1 and ALDH3A1, and at 24 h for ALDH1A3, ALDH3A2, ALDH3B1, and ALDH18A1. Combined ß-escin and CSE treatment prevented the CSE-induced inhibition of ALDH2 expression at 24 h. CONCLUSIONS: ß-escin is an effective ALDH stimulatory and cytoprotective agent and might be useful in the prevention or supportive treatment of tobacco smoke-related diseases.

Spoligotyping of Mycobacterium tuberculosis - Comparing in vitro and in silico approaches.

Spoligotyping is one of the molecular typing methods widely used for exploring the genetic variety of Mycobacterium tuberculosis. The aim of this study was to compare the spoligoprofiles of M. tuberculosis clinical isolates, obtained using in vitro and in silico approaches. The study included 230 M. tuberculosis isolates, recovered from Poland and Lithuania between 2018 and 2021. Spoligotyping in vitro was performed with a commercially available kit. Whole genome sequencing (WGS) was done with Illumina NovaSeq 6000 sequencer. Spoligotype International Types (SITs) were assigned according to the SITVIT2 database or using three different in silico tools, and based on WGS data, namely SpoTyping, SpolPred, and lorikeet. Upon in vitro spoligotyping, the isolates produced 65 different spoligotypes. Spoligotypes inferred from the WGS data were congruent with in vitro generated patterns in 81.7% (188/230) for lorikeet and 81.3% (187/230) for SpolPred and SpoTyping. Spacers 18 and 31 produced the highest ratio of discrepant results between in vitro and in silico approaches, with their signals discordantly assigned for 15 (6.5%) and 9 (3.9%) isolates, respectively. All three in silico approaches used were similarly efficient for M. tuberculosis spoligotype prediction. However, only SpoTyping could predict spoligotypes without a need for manual curation. Thus, we consider it as the most accurate tool. Its use is further advocated by the shortest time of analysis. A relatively high (ca. 20%) discordance between in vitro and in silico spoligotyping results was observed. While we discourage comparing conventional spoligotyping with in silico equivalents, we advise the use of the latter, as it improves the accuracy of spoligopatterns, and thus depicts the relatedness between the isolates more reliably.

A Real-World Multicenter Retrospective Observational Study on Polish Experience with Nintedanib Therapy in Patients with Idiopathic Pulmonary Fibrosis: The PolExNIB Study.

Nintedanib is a disease-modifying agent licensed for the treatment of IPF. Data on Polish experience with nintedanib in IPF are lacking. The present study aimed to describe the safety and efficacy profiles of nintedanib in a large real-world cohort of Polish patients with IPF. This was a multicenter, retrospective, observational study of IPF patients treated with nintedanib between March 2018 and October 2021. Data collection included baseline clinical characteristics, results of pulmonary function tests (PFTs), and a six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), and treatment persistence were also retrieved. A total of 501 patients (70% male) with a median age of 70.9 years (IQR 65-75.7) were included in this study. Patients were followed on treatment for a median of 15 months (7-25.5). The majority of patients (66.7%) were treated with the full recommended dose of nintedanib and 33.3% of patients were treated with a reduced dose of a drug. Intermittent dose reductions or drug interruptions were needed in 20% of patients. Over up to 3 years of follow-up, pulmonary function remained largely stable with the minority experiencing disease progression. The most frequent ADRs included diarrhea (45.3%), decreased appetite (29.9%), abdominal discomfort (29.5%), weight loss (32.1%), nausea (20.8%), fatigue (19.2%), increased liver aminotransferases (15.4%), and vomiting (8.2%). A total of 203 patients (40.5%) discontinued nintedanib treatment due to diverse reasons including ADRs (10.2%), death (11.6%), disease progression (4.6%), patient's request (6.6%), and neoplastic disease (2.2%). This real-world study of a large cohort of Polish patients with IPF demonstrates that nintedanib therapy is safe, and is associated with acceptable tolerance and disease stabilization. These data support the findings of previously conducted clinical trials and observational studies on the safety and efficacy profiles of nintedanib in IPF.

Blood and Sputum Eosinophils of COPD Patients Are Differently Polarized than in Asthma.

Different eosinophil subpopulations have been identified in asthma and other eosinophilic disorders. However, there is a paucity of data on eosinophil subpopulations in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to compare eosinophil phenotypes in blood and induced sputum in patients with COPD, asthma and controls. Stable patients with mild-to-moderate COPD (n = 15) and asthma (n = 14) with documented blood eosinophilia ≥100 cells/µL in the year prior to the study and the control group (n = 11) were included to the study. The blood and sputum eosinophil phenotypes were analyzed by flow cytometry. IL-5, IL-13, CCL5 and eotaxin-3 levels were measured in the induced sputum. The marker expression on blood eosinophils was similar among control, asthma and COPD groups. The expressions of CD125, CD193, CD14 and CD62L were higher on blood than on sputum eosinophils in all three groups. We found increased levels of CD193+ and CD66b+ sputum eosinophils from COPD patients, and an elevated level of CD11b+ sputum eosinophils in asthma compared to COPD patients. The results of our study suggest that the profile of marker expression on COPD sputum eosinophils differed from other groups, suggesting a distinct phenotype of eosinophils of COPD patients than in asthma or healthy subjects.

Phylogenetic relationships of Mycobacterium tuberculosis isolates in Poland: The emergence of Beijing genotype among multidrug-resistant cases.

Introduction: The epidemiological situation of tuberculosis (TB) in Poland urges for its continuous and scrupulous monitoring. The objective of this study was to explore the genetic diversity of multidrug-resistant (MDR) and drug-susceptible (DS) Mycobacterium tuberculosis isolates from Poland with a combination of spoligotyping and high-resolution mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) analysis. The results were placed in the Northern and Eastern Europe context. Methods: The study included 89 (39 MDR and 50 DS) M. tuberculosis isolates collected from as many patients between 2018 and 2021 in Poland. The analysis was done using spoligotyping, and MIRU-VNTR typing at 24 standard loci. The data were compared to those available on Poland and neighbors and global M. tuberculosis datasets. Results: The main identified families were Beijing (28.1%) and Haarlem (16.8%) while 34.8% of isolates were in the heterogeneous L4-unclassified group. Although the Beijing family was the most prevalent (61.5%) among MDR-TB cases, it accounted for only 2% of DS isolates. Among foreign-born patients, a higher ratio of MDR isolates were observed when compared with those who Poland-born (64.3% vs. 40%). Furthermore, all patients from the Former Soviet Union (FSU) countries were infected with MDR-TB. Discussion: Whereas DS M. tuberculosis population in Poland is dominated by L4 isolates, MDR isolates are mostly of the Beijing genotype. The rise in the prevalence of the Beijing isolates in Poland, coupled with high proportion of the Beijing genotype among foreign-born TB patients may reflect an ongoing transmission of this family, imported to Poland mainly from FSU countries.

Does hiatal hernia impact gastro-oesophageal reflux-related chronic cough?

Background: Hiatal hernia may coexist with gastro-oesophageal reflux (GOR)-related chronic cough. This study aimed to evaluate whether the presence of hiatal hernia was related to chronic cough severity and the response to antireflux therapy. Methods: This was a retrospective analysis of data on adults with GOR-related chronic cough managed in our cough centre between 2017 and 2021. Patients who had undergone chest computed tomography (CT) and in whom follow-up data were available were included. The presence and size of hiatal hernia were assessed based on thorax CT scanning. Patients were treated with modification of diet and proton pump inhibitors. The response to treatment was assessed by the change in quality of life (QOL) measured by Leicester Cough Questionnaire (LCQ) and cough severity was measured by 100-mm visual analogue scale. Results: 45 adults (28 female, 17 male) were included. Hiatal hernia was demonstrated in 12 (26.6%) patients. Patients with hiatal hernia did not differ from those without hiatal hernia in clinical characteristics, cough duration and severity and cough-related QOL. We found moderate positive correlations between maximal sagittal diameter of hiatal hernia and cough severity (ρ=0.692, p=0.013) and duration (ρ=0.720, p=0.008). Patients without hiatal hernia responded better to antireflux therapy, with significant LCQ improvement. A strong negative correlation between sagittal diameter of hiatal hernia gate and increase in LCQ (ρ= -0.764, p=0.004) was demonstrated. Conclusion: The presence of hiatal hernia identified in chest CT may impact cough severity, duration and response to antireflux treatment in patients with GOR-related chronic cough. Further prospective studies are justified to confirm significance of hiatal hernia in the management of chronic cough.

Diagnostic yield of chest radiograph in management of adults with difficult-to-treat chronic cough-retrospective study.

Background: Chest radiograph (CXR) is a routine imaging test in adults with chronic cough (CC), while value of thoracic computed tomography (CT) in these patients is still a matter of discussion. The aims of the study were to assess the diagnostic yield of CXR and to evaluate the impact of thoracic CT on management of patients with difficult-to-treat CC referred to our cough clinic. Methods: The retrospective analysis of paired CXR and CT results was performed in 189 consecutive adults treated due to CC between 2015-2019 in our cough clinic. CC was defined as cough >8 weeks being the main or isolated ailment. The sensitivity, specificity, negative/positive predictive value (NPV, PPV) and diagnostic accuracy of CXR were calculated based on chest CT scan as the "gold standard". Only those CT scans which revealed abnormalities potentially related to CC and were associated with the changes in further diagnostic or therapeutic approach were construed as relevant CT findings during final analysis. Results: The median age of patients (male/female ratio 53/136) was 58 years (IQR 44-67), only 6 subjects (3.0%) were active smokers, median CC duration was 48 months (IQR 24-120). CXR revealed abnormal findings in 23/189 (12.2%) patients. Normal CXR was confirmed by CT in 141 subjects (141/166; 84.9%). In 25/166 (15.1%) patients, CT showed abnormalities that could explain the cause of CC and changed either the diagnostic protocol or therapy. In patients with abnormal CXR, CT confirmed abnormal findings in 8 cases (8/23, 34.8%). The sensitivity, specificity, PPV, NPV, diagnostic accuracy were 24.2%, 90.4%, 34.8%, 84.9% and 78.8%, respectively. Conclusions: CXR shows a limited diagnostic yield in adults with difficult-to-treat CC referred to cough clinic. Chest CT scan may add significant data impacting the diagnostic and therapeutic approach in these patients.

ERS/ESTS statement on the management of pleural infection in adults.

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice.

The Role of Chitinases in Chronic Airway Inflammation Associated with Tobacco Smoke Exposure.

Chitinases and chitinase-like proteins are thought to play a role in innate inflammatory responses. Our study aimed to assess whether chitinase concentration and activity in induced sputum (IS) of patients exposed to tobacco smoke are related to the level of airway inflammation including the level and activity of chitinases and chitinase-like proteins. The study included 22 patients with chronic obstructive pulmonary disease (COPD), 12 non-COPD smokers, and nine nonsmoking subjects. Sputum CHIT1 and YKL-40 levels and chitinolytic activity were compared with sputum IL-6, IL-8, IL-18, and MMP-9 levels. A hierarchical cluster analysis was also performed. Sputum YKL-40 was higher in COPD patients than in the control groups. Sputum CHIT1 and YKL-40 levels correlated with IS inflammatory cell count as well as with MMP-9 and IL-8 levels. Two main clusters were revealed: Cluster 1 had lower chitinase levels and activity, lower IS macrophage and neutrophil count, and lower IS IL-8, IL-18, and MMP-9 than Cluster 2. Comparison of COPD patients from both clusters revealed significant differences in the IS inflammatory profile despite comparable clinical and functional data. Our findings seem to confirm the involvement of chitinases in smoking-associated chronic airway inflammation and show that airway chitinases may be a potential novel marker in COPD phenotyping.

Pharmacological Inhibition of Chitotriosidase (CHIT1) as a Novel Therapeutic Approach for Sarcoidosis.

Introduction: Sarcoidosis is a systemic disease of unknown etiology characterized by granuloma formation in the affected tissues. The pathologically activated macrophages are causatively implicated in disease pathogenesis and play important role in granuloma formation. Chitotriosidase (CHIT1), macrophage-derived protein, is upregulated in sarcoidosis and its levels correlate with disease severity implicating CHIT1 in pathology. Methods: CHIT1 was evaluated in serum and bronchial mucosa and mediastinal lymph nodes specimens from sarcoidosis patients. The therapeutic efficacy of OATD-01 was assessed ex vivo on human bronchoalveolar lavage fluid (BALF) macrophages and in vivo in the murine models of granulomatous inflammation. Results: CHIT1 activity was significantly upregulated in serum from sarcoidosis patients. CHIT1 expression was restricted to granulomas and localized in macrophages. Ex vivo OATD-01 inhibited pro-inflammatory mediators' production (CCL4, IL-15) by lung macrophages. In the acute model of granulomatous inflammation in mice, OATD-01 showed anti-inflammatory effects reducing the percentage of neutrophils and CCL4 concentration in BALF. In the chronic model, inhibition of CHIT1 led to a decrease in the number of organized lung granulomas and the expression of sarcoidosis-associated genes. Conclusion: In summary, CHIT1 activity was increased in sarcoidosis patients and OATD-01, a first-in-class CHIT1 inhibitor, demonstrated efficacy in murine models of granulomatous inflammation providing a proof-of-concept for its clinical evaluation in sarcoidosis.

Evaluation of patients' satisfaction with bronchoscopy procedure.

BACKGROUND: The bronchoscopy (BS) experience provokes anxiety amongst some patients. It can have a negative impact on the course of the procedure and on the willingness of patients to undergo the next BS in the future. OBJECTIVE: We aimed to identify factors influencing patients' satisfaction with BS. METHODS: The prospective study had been conducted between January and June 2019. It included patients hospitalized in our Department, who underwent elective BS. Patients assessed their anxiety and satisfaction level before and after BS using the Visual Analogue Scale (VAS). Data concerning the course of the bronchoscopy was collected. RESULTS: The median level of anxiety prior to the procedure was moderate, higher in women (p<0.0001). The majority of patients (116/125, 93%) were satisfied with appropriate information before the procedure. Almost one-third of the interviewees (39/125, 31%) declared complete satisfaction (VAS = 0) with their procedure, 17 patients (14%) were dissatisfied (VAS >5/10). Overall 113 (90%) patients declared unconditional consent for future bronchoscopy. Multivariate linear regression analysis revealed two factors affecting patients' satisfaction with bronchoscopy: anxiety prior to BS (standardized regression coefficient ß = 0.264, p = 0.003) and discomfort (ß = 0.205, p = 0.018). Neither age, degree of amnesia, duration of the procedure nor its type added any significant value as factors affecting patient satisfaction. The most common factors inducing patients' discomfort during BS were local anesthesia of the throat (56/125, 45%) and cough (47/125, 38%). CONCLUSIONS: Low anxiety level before bronchoscopy and reduced discomfort during the procedure are associated with better patient satisfaction. Thus, it is important to reduce patient anxiety and discomfort during the procedure.

Therapeutic decisions in a cohort of patients with idiopathic pulmonary fibrosis: a multicenter, prospective survey from Poland.

Background: Pirfenidone and nintedanib are considered as the standard of care in idiopathic pulmonary fibrosis (IPF), but there is no consensus as to which of these two agents should be regarded as first-line treatment. Objective: To provide real-world data on therapeutic decisions of pulmonary specialists, particularly the choice of the antifibrotic drug in patients with IPF. Methods: This was a multicenter, prospective survey collecting clinical data of patients with IPF considered as candidates for antifibrotic treatment between September 2019 and December 2020. Clinical characteristics and information on the therapeutic approach were retrieved. Statistical evaluation included multiple logistic regression analysis with stepwise model selection. Results: Data on 188 patients [74.5% male, median age 73 (interquartile range, 68-78) years] considered for antifibrotic therapy were collected. Treatment was initiated in 138 patients, while 50 patients did not receive an antifibrotic, mainly due to the lack of consent for treatment and IPF severity. Seventy-two patients received pirfenidone and 66 received nintedanib. Dosing protocol (p < 0.01) and patient preference (p = 0.049) were more frequently associated with the choice of nintedanib, while comorbidity profile (p = 0.0003) and concomitant medication use (p = 0.03) were more frequently associated with the choice of pirfenidone. Age (p = 0.002), lung transfer factor for carbon monoxide (TLCO) (p = 0.001), and gastrointestinal bleeding (p = 0.03) were significantly associated with the qualification for the antifibrotic treatment. Conclusion: This real-world prospective study showed that dose protocol and patient preference were more frequently associated with the choice of nintedanib, while the comorbidity profile and concomitant medication use were more frequently associated with the choice of pirfenidone. Age, TLCO, and history of gastrointestinal bleeding were significant factors influencing the decision to initiate antifibrotic therapy.

RNA-Seq Analysis of UPM-Exposed Epithelium Co-Cultivated with Macrophages and Dendritic Cells in Obstructive Lung Diseases.

BACKGROUND: Elevated concentrations of airborne pollutants are correlated with an enlarged rate of obstructive lung disease morbidity as well as acute disease exacerbations. This study aimed to analyze the epithelium mRNA profile in response to airborne particulate matter in the control, asthma, and COPD groups. RESULTS: A triple co-culture of nasal epithelium, monocyte-derived macrophages, and monocyte-derived dendritic cells obtained from the controls, asthma, and COPD were exposed to urban particulate matter (UPM) for 24 h. RNA-Seq analysis found differences in seven (CYP1B1, CYP1B1-AS1, NCF1, ME1, LINC02029, BPIFA2, EEF1A2), five (CYP1B1, ARC, ENPEP, RASD1, CYP1B1-AS1), and six (CYP1B1, CYP1B1-AS1, IRF4, ATP1B2, TIPARP, CCL22) differentially expressed genes between UPM exposed and unexposed triple co-cultured epithelium in the control, asthma, and COPD groups, respectively. PCR analysis showed that mRNA expression of BPIFA2 and ENPEP was upregulated in both asthma and COPD, while the expression of CYP1B1-AS1 and TIPARP was increased in the epithelium from COPD patients only. Biological processes changed in UPM exposed triple co-cultured epithelium were associated with epidermis development and epidermal cell differentiation in asthma and with response to toxic substances in COPD. CONCLUSIONS: The biochemical processes associated with pathophysiology of asthma and COPD impairs the airway epithelial response to UPM.

The impact of spontaneous cough on pleural pressure changes during therapeutic thoracentesis.

Cough during therapeutic thoracentesis (TT) is considered an adverse effect. The study was aimed to evaluate the relationship between cough during TT and pleural pressure (Ppl) changes (∆P). Instantaneous Ppl was measured after withdrawal of predetermined volumes of pleural fluid. Fluid withdrawal (FW) and Ppl measurement (PplM) periods were analyzed separately using the two sample Kolmogorov-Smirnov test and the nonparametric skew to assess differences between ∆P distributions in periods with and without cough. The study involved 59 patients, median age 66 years, median withdrawn fluid volume 1800 mL (1330 ÷ 2400 mL). In total, 1265 cough episodes were recorded in 52 patients, in 24% of FW and 19% of PplM periods, respectively. Cough was associated with significant changes in ∆P distribution (p < 0.001), decreasing the left tail of ∆P distribution for FW periods (the skew = - 0.033 vs. - 0.182) and increasing the right tail for PplM periods (the skew = 0.182 vs. 0.088). Although cough was more frequent in 46 patients with normal pleural elastance (p < 0.0001), it was associated with significantly higher ∆P in patients with elevated elastance (median Ppl increase 2.9 vs. 0.2 cmH2O, respectively). Cough during TT is associated with small but beneficial trend in Ppl changes, particularly in patients with elevated pleural elastance, and should not be considered solely as an adverse event.

Should Thorax Thin-Section Computed Tomography Be a Standard Diagnostic Procedure in the Evaluation of Potential Kidney Transplant Recipients? Lessons Learned From the COVID-19 Pandemic.

BACKGROUND: Kidney transplant is the preferred treatment for most patients with end-stage renal disease. Because dialyzed patients often have significant comorbidities or multimorbidities, they should be carefully evaluated before being waitlisted for transplant. The COVID-19 pandemic presents a major challenge for surgery, including transplant surgery. Owing to a fear of COVID-19 symptoms occurring in lungs, thin-section computed tomography (TSCT) became a standard evaluation technique in potential kidney transplant recipients before surgery. METHODS: The aim of the study was to evaluate the rationale and usefulness of TSCT in deceased donor kidney transplant during the COVID-19 pandemic. All adult patients who underwent deceased donor kidney transplant between May 1, 2020, and December 15, 2021, were included in the study. Potential kidney transplant recipients who were admitted to the Department of General, Vascular, and Transplant Surgery at the Medical University of Warsaw in Warsaw, Poland, were tested for COVID-19 (CovGenX rapid test); blood chemistries were performed; dialysis was performed (if needed); and, on a negative reverse transcriptase polymerase chain reaction test, HRCT was performed. RESULTS: From May 2020 until the end of December 2021, 54 patients were transplanted; however, 7 patients were disqualified after TSCT and consulted with a pulmonary specialist. Disqualification from kidney transplant accounted for 13% of the potential kidney allograft recipients. CONCLUSIONS: Despite the possibility of overdiagnosis by TSCT, TSCT should be considered a standard evaluation technique in potential kidney transplant recipients. Potential kidney transplant recipients must be periodically reassessed given the prolonged wait time for a donor kidney and the significant number of comorbid conditions in this patient population. However, more data with longer follow-ups are needed to prove or disprove the rationale to use TSCT in transplant surgery.

Impact of Factors Secreted by Tumor Cells on Response of Pleural Mesothelial Cells to Different Sclerosing Agents in an In Vitro Model.

BACKGROUND Chemical pleurodesis is one of the major therapeutic options for patients with recurrent malignant pleural effusion. Mesothelial cells are considered to play a pivotal role in the response to different chemical compounds (sclerosants) used for pleurodesis. Malignant cells might have an impact on the mesothelial response to applied sclerosing agents and, in consequence, on the efficacy of pleurodesis. We aimed to evaluate the impact of cancer cell paracrine on mesothelial cell response to different sclerosing agents. MATERIAL AND METHODS The study used mesothelial cell (MeT-5A) cultures stimulated with sclerosing agents (talc, doxycycline, iodopovidone, and TGF-ß for 24 h) in the presence or absence of supernatants from adenocarcinoma cultures (HCC827). The mesothelial mRNA expression and protein levels of IL-6, IL-8, and TGF-ß was assessed. Further, lung fibroblasts were cultured with and without cell supernatants from previously established cell cultures for 24 h. Then, concentration of soluble collagen was evaluated in culture supernatants. RESULTS The exposure of mesothelial cells to sclerosants decreased the concentration of IL-6 and IL-8 protein. The addition of mediators secreted by adenocarcinoma altered the inflammatory response of the mesothelial cells to sclerosing agents. IL-8 concentration in cultures stimulated with talc and adenocarcinoma supernatant was higher compared to cultures stimulated with talc only. The exposure of lung fibroblasts to supernatant from mesothelial cell (with or without adenocarcinoma) did not affect collagen secretion. CONCLUSIONS An addition of soluble factors produced by adenocarcinoma altered the inflammatory response of the pleural mesothelial cells after stimulation with sclerosing agents. Our observations suggest that the tumor paracrine effect affects biological pathways of pleurodesis.