Effects of inhaled beclometasone dipropionate/formoterol fumarate/glycopyrronium vs. beclometasone dipropionate/formoterol fumarate and placebo on lung hyperinflation and exercise endurance in chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: The single-inhaler triple combination of beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G) is available for maintenance therapy of chronic obstructive pulmonary disease (COPD). Cardinal features of COPD are lung hyperinflation and reduced exercise capacity. TRIFORCE aimed to evaluate the effect of BDP/FF/G on lung hyperinflation and exercise capacity in patients with COPD. METHODS: This double-blind, randomised, active- and placebo-controlled, crossover study recruited adults with COPD aged ≥ 40 years, who were hyperinflated and symptomatic, and were receiving mono- or dual inhaled maintenance COPD therapy. In the three treatment periods, patients were randomised to receive BDP/FF/G, BDP/FF, or placebo, each for 3 weeks, with a 7-10-day washout between treatment periods. Assessments included slow inspiratory spirometry (for resting inspiratory capacity [IC]) and constant work-rate cycle ergometry (for dynamic IC and exercise endurance time). The primary objective was to compare BDP/FF/G and BDP/FF vs. placebo for resting IC at Week 3. Key secondary objectives were to compare BDP/FF/G and BDP/FF vs. placebo for dynamic IC and exercise endurance time during constant work rate cycle ergometry at Week 3. RESULTS: Of 106 patients randomised, 95 completed the study. Resting IC adjusted mean differences vs. placebo were 315 and 223 mL for BDP/FF/G and BDP/FF, respectively (p < 0.001 for both). Adjusted mean differences vs. placebo for the key secondary endpoints were: 245 mL for dynamic IC (p < 0.001) and 69.2 s for exercise endurance time (nominal p < 0.001) with BDP/FF/G, and 96 mL (p = 0.053) and 70.1 s (nominal p < 0.001) with BDP/FF. Differences between BDP/FF/G and BDP/FF for resting and dynamic IC were 92 and 149 mL (p < 0.01 for both). All three treatments were generally well tolerated, with 27.3%, 25.3% and 19.0% of patients reporting adverse events with BDP/FF/G, BDP/FF and placebo, respectively, all mild or moderate. CONCLUSIONS: In patients with COPD, BDP/FF/G provided significant and clinically relevant improvements vs. placebo and BDP/FF in static and dynamic hyperinflation, with an improvement vs. placebo in exercise endurance. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05097014), registered 27th October 2021.

Baseline characteristics from a 3-year longitudinal study to phenotype subjects with COPD: the FOOTPRINTS study.

BACKGROUND: FOOTPRINTS® is a prospective, longitudinal, 3-year study assessing the association between biomarkers of inflammation/lung tissue destruction and chronic obstructive pulmonary disease (COPD) severity and progression in ex-smokers with mild-to-severe COPD. Here, we present baseline characteristics and select biomarkers of study subjects. METHODS: The methodology of FOOTPRINTS® has been published previously. The study population included ex-smokers with a range of COPD severities (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages 1-3), ex-smokers with COPD and alpha-1-antitrypsin deficiency (A1ATD) and a control group of ex-smokers without airflow limitation (EwAL). At study entry, data were collected for: demographics, disease characteristics, history of comorbidities and COPD exacerbations, symptoms, lung function and volume, exercise capacity, soluble biomarkers, and quantitative and qualitative computed tomography. Baseline data are presented with descriptive statistical comparisons for soluble biomarkers in the individual GOLD and A1ATD groups versus EwAL. RESULTS: In total, 463 subjects were enrolled. The per-protocol set comprised 456 subjects, mostly male (64.5%). The mean (standard deviation) age was 60.7 (6.9) years. At baseline, increasing pulmonary symptoms, worse lung function, increased residual volume, reduced diffusing capacity of the lung for carbon monoxide (DLco) and greater prevalence of centrilobular emphysema were observed with increasing disease severity amongst GOLD 1-3 subjects. Subjects with A1ATD (n = 19) had similar lung function parameters to GOLD 2-3 subjects, a high residual volume comparable to GOLD 3 subjects, and similar air trapping to GOLD 2 subjects. Compared with EwAL (n = 61), subjects with A1ATD had worse lung function, increased residual volume, reduced DLco, and a greater prevalence of confluent or advanced destructive emphysema. The soluble inflammatory biomarkers white blood cell count, fibrinogen, high-sensitivity C-reactive protein and plasma surfactant protein were higher in GOLD 1-3 groups than in the EwAL group. Interleukin-6 was expressed less often in EwAL subjects compared with subjects in the GOLD and A1ATD groups. Soluble receptor for advanced glycation end product was lowest in GOLD 3 subjects, indicative of more severe emphysema. CONCLUSIONS: These findings provide context for upcoming results from FOOTPRINTS®, which aims to establish correlations between biomarkers and disease progression in a representative COPD population. TRIAL REGISTRATION NUMBER: NCT02719184, study start date 13/04/2016.

Immunotherapy in patients with non-small cell lung cancer with ECOG PS 2.

Immunotherapy is a new and very promising method of anti-cancer treatment. Unfortunately, not every patient can benefit from this treatment. The Polish drug program determines the selection of patients based on PD-L1 expression and the performance status assessed with the use of Eastern Cooperative Oncology Group Performance Status (ECOG PS) score. Patients with ECOG PS 2 represent a significant proportion of the cancer population, one which is overlooked in most clinical trials of immunotherapy. Often, a reduced performance status is the only factor that excludes the patient from treatment with immunotherapy. Choosing the optimal method of treatment in patients with a worse general condition and with multiple diseases may be a significant problem for the doctor. Assessment of performance status may be a particular problem because not every patient has a worse PS score for the same reasons. In this study, we analyse the results of treatment of patients with a poorer performance status to date, and we present tools that improve the precise assessment of the degree of the performance status, which may enable more patients to access novel lung cancer treatments.

Noninvasive Ventilation-Facilitated Bronchofiberoscopy in Patients with Respiratory Failure.

Respiratory failure is one of the most important risk factors for diagnostic bronchofiberoscopy (BF), whereas therapeutic bronchoscopies are typically performed in intubated patients. Only a few published studies analyzed the outcomes of noninvasive mechanical ventilation (NIV)-facilitated BF. In this case series, we present our experiences with NIV-facilitated diagnostic and therapeutic BF performed in patients with respiratory failure that was associated with acute interstitial pulmonary disease, chronic obstructive pulmonary disease, cystic fibrosis exacerbation, foreign body aspiration, tracheal stenosis, pneumonia, and in a patient with a neuromuscular disease. All of the patients were initially hypoxic and some had PaO2/FiO2 < 200, which corresponded to moderate-to-acute respiratory distress syndrome (ARDS). NIV-facilitated BF were performed for the diagnostic or therapeutic purposes. The former consisted of bronchoalveolar lavage and bacterial sampling in a patient with impaired cough reflex, airway assessment in otherwise unexplained respiratory failure and hemoptysis, and the latter of mucous plugs resolution, foreign body removal, and assistance in weaning from mechanical ventilation. All procedures were carried out using NIV in the spontaneous timed (ST) or average volume assured pressure support (AVAPS) mode with oxygen supplementation. There were no procedure-related complications noticed during NIV-facilitated BF. We conclude that NIV is a useful and safe tool that facilitates the performance of BF in severe pulmonary diseases. Prospective studies are required to set the recommendations for the procedure and to define the optimum ventilatory modes to be used.

Estimates of Medication Expenditure for Ischemic Heart Disease Accompanying Chronic Obstructive Pulmonary Disease.

Ischemic heart disease (IHD) is a frequent accompaniment of chronic obstructive pulmonary disease (COPD). Co-occurrence of these two diseases is associated with many risk factors, difficulties in implementing appropriate therapies, numerous complications, and high spending for treatment. All these elements significantly reduce the quality of life of patients. The aim of this study was to estimate the expenditure for medications involved with IHD pharmacotherapy in the course of COPD. This retrospective study was based on the review of medical files of 57 patients, 27 women and 30 men, diagnosed with IHD, according to the severity classification, in the course of COPD which was staged according to the GOLD criteria. We found a considerable increase in per capita per year retail spending for drugs. The spending increased with the severity class of IHD; from 27.41 EUR in Class I to 142.30 EUR in Class IV. This spending did not include the treatment cost for the basic disease, i.e., COPD. A high individual cost burden was decreased by a discounting intervention of the National Health Fund. Despite a relatively high drug expenditure, we consider the treatment being cost-effective since we noticed a reduction in the classical risk factors for IHD, related to metabolic disturbances and lifestyle features, as soon as 2 months after treatment initiation. This study confirms that heart disease accompanying COPD is a frequent occurrence, generating high costs of treatment, which relates to the severity of this comorbidity.

EVALUATION OF THE TREATMENT COSTS OF ASTHMA EXACERBATIONS IN OUTPATIENTS.

The aim of this study was to assess the correlation between the costs of controlled and uncontrolled asthma therapy in outpatients care. To determine the efficacy of the medicinal care there was performed a retrospective study on a group of 150 patients. Thirty eight patients have been enrolled to study group. Drug costs were estimated on the basis of documentation of patients. The assessment takes into account the cost of the retail price of drugs, the cost of diagnostic tests and outpatient care. Evaluation of the costs of treatment of patients was performed from a societal perspective. In the study there was calculated the value of the daily, monthly and annual treatment of the patient depending on the degree of asthma control. There was analyzed the frequency of reception of certain preparations in the study group. It was compared the annual cost of therapy for the given preparation in both examined groups. The total annual costs of therapy in patients with controlled and uncontrolled asthma were compared. Properly controlled asthma is potential source of savings. Treatment of asthma in an outpatient setting allow to avoid exacerbation of the disease, reducing and limiting direct and indirect costs of disease and improving the quality of patient's life.

[Influence of inhaler and fine particle on efficacy of inhalation therapy in COPD]. / Wplyw doboru inhalatora i czastki na skutecznosc terapii wziewnej w POChP.

Orally inhaled products delivered via inhalation exert their effect directly to the target organ. This allows to administer a very low dose of a drug compared with an oral route with similar clinical effect and significantly reduced toxicity. However inhalation therapy is also limited by several factors. Delivery of the desired dose of the drug to the airways depends on a type of the inhaler - pressurised metered-dose inhaler (pMDI) or dry powder inhaler (DPI), inhaler characteristics (low or high internal resistance, diameter of particles and distribution of the generated aerosol fine particles), thermal conditions of air, and ability of patient to generate sufficient inspiratory flow (for DPI) or to coordinate actuation with inhalation (for pMDI). Unlike pMDIs, DPIs are breath- -actuated, hence avoiding the need for the patient to coordinate actuation with inspiration. Furthermore, DPIs are propellant-free and do not produce the cold sensation on inhalation. Currently available DPIs vary widely in design, operating characteristics and performance. And poor inhalation technique may compromise treatment efficacy. Hence, there is a clear need for a careful selection of DPIs for different patient groups, including children, elderly patients and those with severe airway obstruction.

First insight about the ability of specific glycerophospholipids to discriminate non-small cell lung cancer subtypes.

Introduction: Discrimination between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) subtypes in non-small cell lung cancer (NSCLC) patients is a significant challenge in oncology. Lipidomics analysis provides a promising approach for this differentiation. Methods: In an accompanying paper, we explored oxPCs levels in a cohort of 200 NSCLC patients. In this research, we utilized liquid chromatography coupled with mass spectrometry (LC-MS) to analyze the lipidomics profile of matching tissue and plasma samples from 25 NSCLC patients, comprising 11 ADC and 14 SCC cases. This study builds upon our previous findings, which highlighted the elevation of oxidised phosphatidylcholines (oxPCs) in NSCLC patients. Results: We identified eight lipid biomarkers that effectively differentiate between ADC and SCC subtypes using an untargeted approach. Notably, we observed a significant increase in plasma LPA 20:4, LPA 18:1, and LPA 18:2 levels in the ADC group compared to the SCC group. Conversely, tumour PC 16:0/18:2, PC 16:0/4:0; CHO, and plasma PC 16:0/18:2; OH, PC 18:0/20:4; OH, PC 16:0/20:4; OOH levels were significantly higher in the ADC group. Discussion: Our study is the first to report that plasma LPA levels can distinguish between ADC and SCC patients in NSCLC, suggesting a potential role for LPAs in NSCLC subtyping. This finding warrants further investigation into the mechanisms underlying these differences and their clinical implications.

AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD.

Background: Accumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of COPD. In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile. Methods: The study designs of AERIFY-1 and AERIFY-2 are described in this article. Discussion: The primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomised, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimab versus placebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40-85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥ 1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack-year smoking history, and ≥6 months since smoking cessation for former smokers. The primary end-point is the annualised rate of moderate or severe acute exacerbation of COPD. Secondary end-points include change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 s, and annualised frequency of severe exacerbations. Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses.

Efficacy and safety of aclidinium bromide compared with placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease: results from a 6-week, randomized, controlled Phase IIIb study.

BACKGROUND: This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). METHODS: Patients received aclidinium 400 µg twice daily (morning and evening), tiotropium 18 µg once daily (morning), or placebo for 6 weeks. The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6. Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety. RESULTS: Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]). Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (∆ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (∆ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6. Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo. Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05). Adverse-event (AE) incidence (28%) was similar between treatments. Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group. CONCLUSIONS: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks. Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium. Aclidinium was generally well tolerated.

Non-Invasive Cardiac Output Measurement Using Inert Gas Rebreathing Method during Cardiopulmonary Exercise Testing-A Systematic Review.

BACKGROUND: The use of inert gas rebreathing for the non-invasive cardiac output measurement has produced measurements comparable to those obtained by various other methods. However, there are no guidelines for the inert gas rebreathing method during a cardiopulmonary exercise test (CPET). In addition, there is also a lack of specific standards for assessing the non-invasive measurement of cardiac output during CPET, both for healthy patients and those suffering from diseases and conditions. AIM: This systematic review aims to describe the use of IGR for a non-invasive assessment of cardiac output during cardiopulmonary exercise testing and, based on the information extracted, to identify a proposed CPET report that includes an assessment of the cardiac output using the IGR method. METHODS: This systematic review was conducted by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines. PubMed, Web of Science, Scopus, and Cochrane Library databases were searched from inception until 29 December 2022. The primary search returned 261 articles, of which 47 studies met the inclusion criteria for this review. RESULTS AND CONCLUSIONS: This systematic review provides a comprehensive description of protocols, indications, technical details, and proposed reporting standards for a non-invasive cardiac output assessment using IGR during CPET. It highlights the need for standardized approaches to CPET and identifies gaps in the literature. The review critically analyzes the strengths and limitations of the studies included and offers recommendations for future research by proposing a combined report from CPET-IGR along with its clinical application.

Genome-engineering technologies for modeling and treatment of cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease caused by defects in the CF transmembrane conductance regulator (CFTR) protein. Due to the genetic nature of the disease, interventions in the genome can target any underlying alterations and potentially provide permanent disease resolution. The current development of gene-editing tools, such as designer nuclease technology capable of genome correction, holds great promise for both CF and other genetic diseases. In recent years, Cas9-based technologies have enabled the generation of genetically defined human stem cell and disease models based on induced pluripotent stem cells (iPSC). In this article, we outline the potential and possibilities of using CRISPR/Cas9-based gene-editing technology in CF modeling.

Impact of COVID-19 in Patients with Lung Cancer: A Descriptive Analysis.

The COVID-19 pandemic poses a challenge to health systems worldwide. Limiting healthcare availability may delay early diagnosis and worsen the treatment effects of various diseases, including oncological diseases. We analyzed patients presenting to the 2nd Department of Lung Diseases and Tuberculosis in Bialystok, Poland, with suspicion of lung cancer 12 months prior to the COVID-19 pandemic (pre-COVID-19) and, similarly, 12 months after the outbreak of the pandemic (mid-COVID). In total, 320 patients were analyzed-132 prior to and 188 after the COVID-19 outbreak. During the COVID-19 period, there was a lower percentage of patients presenting with ECOG performance status 0-1, with a noticeably increased percentage of patients with ECOG PS ≥2. The disease's clinical stage (CS) was higher on admission during COVID-19. We observed more use of immunotherapy and more deaths before the start of treatment during the COVID-19 period. These results provide insight into the early effects of the COVID-19 pandemic on lung cancer patients and underscore the importance of conducting further studies to assess the long-term effects of the COVID-19 pandemic on this population.

Management of nicotine dependence in patients with psychiatric disorders - recommendations of the Polish Psychiatric Association - part I. / Postepowanie w uzaleznieniu od nikotyny u pacjentów z zaburzeniami psychicznymi ­ zalecenia Polskiego Towarzystwa Psychiatrycznego ­ czesc I.

Smoking and nicotine dependence are still one of the main reasons for a number of serious and life-shortening somatic diseases. At the same time, they are more prevalent in mentally ill individuals than in the general population. This work, which constitutes the first part of recommendations of the Polish Psychiatric Association, presents the scale of the phenomenon in the general population and among people with psychiatric disorders, diagnostic criteria of nicotine dependence and nicotine withdrawal. It discusses the impact of smoking and exposure to cigarette smoke on the development and course of psychiatric disorders as well as on the treatment of psychiatric disorders, including interactions between nicotine and psychotropic medications. Many psychiatric patients can reduce smoking or achieve complete abstinence if they are offered adequate motivation and therapeutic support. Contrary to popular belief, smoking cessation and nicotine dependence treatment do not negatively affect the symptoms of psychiatric disorders; patients' mental conditions can improve following smoking cessation therapy. The best results in terms of maintaining abstinence are achieved with a treatment approach that combines pharmacotherapy with psychotherapeutic intervention integrated into routine psychiatric care.

Management of nicotine dependence in patients with psychiatric disorders - recommendations of the Polish Psychiatric Association - part II. / Postepowanie w uzaleznieniu od nikotyny u pacjentów z zaburzeniami psychicznymi ­ zalecenia Polskiego Towarzystwa Psychiatrycznego ­ czesc II.

The development of treatment methods for nicotine dependence has progressed slowly because people with psychiatric disorders are usually excluded from participating in clinical trials. There are several therapeutic options to support smoking cessation, including psychological and pharmacological interventions, which should be offered to smokers with mental disorders. The first step in helping tobacco smokers and nicotine-dependent individuals is the assessment of smoking intensity and confirmation of nicotine dependence. Currently, we have several methods of treating nicotine dependence - starting from education and psychotherapy, through pharmacotherapy and replacement therapy, and ending up with obtaining gradual progress with the application of harm reduction. Pharmacological treatment options include nicotine replacement therapy, varenicline or bupropion. The effectiveness of such interventions can be improved by providing anti-smoking therapy under psychiatric treatment and promoting harm reduction as an acceptable initial therapeutic goal. The harm reduction strategy is an approach that should be taken into account individually, particularly in the case of individuals unable to stop smoking, patients with limited insight into their illness, patients experiencing an exacerbation of their illness and persistently uncooperative patients. In this paper, recommendations of the Polish Psychiatric Association on the diagnostics and different treatment methods for nicotine dependence in patients with psychiatric disorders are presented.

Ceragenins exhibit bactericidal properties that are independent of the ionic strength in the environment mimicking cystic fibrosis sputum.

The purpose of the work was to investigate the impact of sodium chloride (NaCl) on the antimicrobial efficacy of ceragenins (CSAs) and antimicrobial peptides (AMPs) against bacterial and fungal pathogens associated with cystic fibrosis (CF) lung infections. CF-associated bacterial (Pseudomonas aeruginosa, Ochrobactrum spp., and Staphylococcus aureus), and fungal pathogens (Candida albicans, and Candida tropicalis) were used as target organisms for ceragenins (CSA-13 and CSA-131) and AMPs (LL-37 and omiganan). Susceptibility to the tested compounds was assessed using minimal inhibitory concentrations (MICs) and bactericidal concentrations (MBCs), as well as by colony counting assays in CF sputum samples supplemented with various concentrations of NaCl. Our results demonstrated that ceragenins exhibit potent antimicrobial activity in CF sputum regardless of the NaCl concentration when compared to LL-37 and omiganan. Given the broad-spectrum antimicrobial activity of ceragenins in the microenvironments mimicking the airways of CF patients, ceragenins might be promising agents in managing CF disease.

Serum Insights: Leveraging the Power of miRNA Profiling as an Early Diagnostic Tool for Non-Small Cell Lung Cancer.

Non-small cell lung cancer is the predominant form of lung cancer and is associated with a poor prognosis. MiRNAs implicated in cancer initiation and progression can be easily detected in liquid biopsy samples and have the potential to serve as non-invasive biomarkers. In this study, we employed next-generation sequencing to globally profile miRNAs in serum samples from 71 early-stage NSCLC patients and 47 non-cancerous pulmonary condition patients. Preliminary analysis of differentially expressed miRNAs revealed 28 upregulated miRNAs in NSCLC compared to the control group. Functional enrichment analyses unveiled their involvement in NSCLC signaling pathways. Subsequently, we developed a gradient-boosting decision tree classifier based on 2588 miRNAs, which demonstrated high accuracy (0.837), sensitivity (0.806), and specificity (0.859) in effectively distinguishing NSCLC from non-cancerous individuals. Shapley Additive exPlanations analysis improved the model metrics by identifying the top 15 miRNAs with the strongest discriminatory value, yielding an AUC of 0.96 ± 0.04, accuracy of 0.896, sensitivity of 0.884, and specificity of 0.903. Our study establishes the potential utility of a non-invasive serum miRNA signature as a supportive tool for early detection of NSCLC while also shedding light on dysregulated miRNAs in NSCLC biology. For enhanced credibility and understanding, further validation in an independent cohort of patients is warranted.

Applied Molecular-Based Quality Control of Biobanked Samples for Multi-Omics Approach.

Biobanks are vital for high-throughput translational research, but the rapid development of novel molecular techniques, especially in omics assays, poses challenges to traditional practices and recommendations. In our study, we used biospecimens from oncological patients in Polish clinics and collaborated with the Indivumed Group. For serum/plasma samples, we monitored hemolysis, controlled RNA extraction, assessed cDNA library quality and quantity, and verified NGS raw data. Tissue samples underwent pathologic evaluation to confirm histology and determine tumor content. Molecular quality control measures included evaluating the RNA integrity number, assessing cDNA library quality and quantity, and analyzing NGS raw data. Our study yielded the creation of distinct workflows for conducting preanalytical quality control of serum/plasma and fresh-frozen tissue samples. These workflows offer customization options to suit the capabilities of different biobanking entities. In order to ensure the appropriateness of biospecimens for advanced research applications, we introduced molecular-based quality control methods that align with the demands of high-throughput assays. The novelty of proposed workflows, rooted in innovative molecular techniques, lies in the integration of these QC methods into a comprehensive schema specifically designed for high-throughput research applications.

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin.

BACKGROUND Atezolizumab is an immune checkpoint inhibitor used as first-line treatment with carboplatin and etoposide chemotherapy for advanced small cell lung cancer. Immunochemotherapy treatment decisions can be affected by patients' physical ability. Because of the exclusion of patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2 from clinical trials, treatment outcome evidence in this group is limited. CASE REPORT We present the case of a 75-year-old woman with an ECOG PS of 2 admitted with respiratory symptoms and diagnosed with advanced small-cell lung cancer. After managing exacerbation of COPD and decompensated heart failure, atezolizumab with carboplatin and etoposide was administered. After 2 cycles of immunochemotherapy, deterioration of health was observed, including anemia and thrombocytopenia. Because of the good response in imaging tests and restored balance of the patient condition, immunochemotherapy was continued. After 4 cycles of combined treatment, complete regression was achieved. No another adverse effects were observed. The patient was qualified for maintenance therapy with atezolizumab. In follow-up CT scan after 2 cycles of atezolizumab, progression was observed and patient was qualified for second-line treatment. CONCLUSIONS This report presents the case of an older patient with advanced small cell lung cancer and an ECOG status of 2 who responded to combined immunochemotherapy with atezolizumab, etoposide, and carboplatin. Adverse effects observed during immunotherapy were not a reason for discontinuation of the therapy. The assessment of the effectiveness of immunotherapy in patients with ECOG PS ³2 is difficult owing to the insufficient representation of this group in clinical trials.

Case Report: Case report: Non-invasive mechanical ventilation in combination with bronchoscopy in the treatment of respiratory failure of lung cancer patient.

Background: Respiratory failure (RF) is a common medical problem among cancer patients. Particularly active or ex-smokers diagnosed with chronic obstructive pulmonary disease (COPD) or lung cancer may develop severe hypoxemic and hypercapnic respiratory failure. Moreover, pneumonitis as a complication of the currently widely used immunotherapy of various cancers, may cause respiratory disorders requiring ventilation support. Non-invasive ventilation (NIV) is recommended as the first-line treatment for this type of respiratory failure and reduces the need for endotracheal intubation. Case presentation: We present a case report of lung cancer patient, who received NIV in the treatment of RF due to an infectious exacerbation of COPD. In addition, NIV enabled assisted flexible bronchoscopy (NIV-FB) to be performed. During the procedure tumor samples were collected for further molecular diagnosis of lung cancer. Improvement of the patient general condition and quality of life was also achieved. Conclusions: NIV can be used at any stage of oncological management in patients with lung cancer. It can also be implemented during endoscopic procedures of the respiratory system, as well as support in palliative care of patients with lung cancer at the end of life. Further studies should evaluate the use of NIV in conjunction with various oncological treatments and identify the exact contradictions for BF with NIV support in advanced cancer patients with RF.