Łukasz Minarowski

Primary cultures and organoids from lung cancer patients preserve tumor heterogeneity and enable patient-specific functional testing. Their generation has relied largely on surgical resection, which most patients never undergo because their disease is diagnosed too late. This review examines whether minimally invasive sources, namely cryobiopsy, endobronchial ultrasound-guided transbronchial needle aspiration, bronchoscopic biopsy, computed tomography (CT)-guided transthoracic needle biopsy, and malignant pleural effusion, can serve as alternatives. To compare outcomes across studies, we distinguish four endpoints: tissue adequacy, initial formation, long-term validated establishment, and molecular fidelity to the source tumor. Reported establishment rates from these sources range from 10% to over 80%, and some matched or exceeded surgical tissue within the same study. Yet these figures depend on how success is defined. In one cohort, organoids formed from 41% of specimens, but only 17% yielded verified tumor organoids. In another, cancer-associated fibroblasts dominated 46 of 51 cultures. Anatomical site, medium composition, and overgrowth by stromal or normal airway cells therefore explain outcomes better than acquisition route alone. Ex vivo drug responses have been linked to clinical outcomes, but prospective validation is lacking. Standardized multi-endpoint reporting and routine confirmation of molecular fidelity are needed before these models can guide therapy.

Introduction: Deventilation syndrome (DVS), defined as increased dyspnoea after cessation of prolonged non-invasive ventilation (NIV), remains a diagnostic and therapeutic challenge. Knowledge of its pathophysiology, prevalence and treatment is limited. This study aimed to characterise patients receiving home NIV, determine DVS prevalence and explore associated factors. Material and methods: This nationwide questionnaire-based observational study included patients treated within a home NIV programme and their attending physicians. DVS was defined using criteria based on the modified Borg scale/visual analogue scale and oxygen saturation changes after mask removal. Clinical and ventilatory variables were compared between patients with and without DVS. Results: Sixty-five patients were included. DVS was identified in 21 patients (32.3%). Patients with DVS had greater dyspnoea intensity after NIV discontinuation and more often reported dyspnoea lasting more than one hour, immediate discomfort after mask removal and dyspnoea-related limitation of daily functioning. Achieved pressure support was higher in the DVS group than in patients without DVS (15.26 ± 4.78 vs 12.31 ± 3.68 cmH₂O; p=0.020). In exploratory logistic regression, higher achieved pressure support was associated with increased odds of DVS (OR 1.20 per 1 cmH₂O; 95% CI 1.02–1.41; p=0.031). BMI, Mallampati score, frailty, underlying diagnosis, NIV treatment duration and respiratory rate were not significantly associated with DVS. Conclusions: DVS affected approximately one-third of patients receiving home NIV and was associated with substantial post-ventilation symptoms. Higher achieved pressure support emerged as the main ventilatory correlate of DVS and requires further investigation.

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Survival outcomes are strongly stage-dependent. Many patients are diagnosed at advanced stages due to pre-clinical and diagnostic delays. While advances in imaging, bronchoscopic techniques, molecular diagnostics, and systemic therapies have improved individualized treatment, system-level delays continue to limit their impact. Aim of the study: The aim of this narrative review is a synthesis with an implementation-oriented framework proposal. Part I synthesizes the peer-reviewed literature, Part II presents an operational framework integrating a Fast Trac Clinic (FTC) and a network of Lung Cancer Units (LCUs) including proposed turnaround-time (TAT) goals. Methods: A narrative review of the literature of selected European policy documents addressing diagnostic delays, rapid-access lung cancer pathways, and coordinated care models was conducted. Results: European models demonstrate that structured referral criteria, centralized coordination, and predefined interval targets can achieve the first specialist assessment within 7–10 days and the completion of diagnostics within 21–28 days in optimized settings. Key determinants of timeliness include: direct primary care referral, parallel diagnostic processes, prioritized pathology and molecular testing, and multidisciplinary team (MDT) assessment. We propose operational TAT targets for chest CT, PET-CT, histopathology, NGS, PFTs, and MDT decision-making. Conclusions: Reducing avoidable diagnostic and therapeutic delays in LC requires a coordinated, system-level approach. A standardized FTC-LCU pathway with explicit TAT benchmarks, multidisciplinary governance, and digital support infrastructure may improve diagnostic efficiency, increase the proportion of patients treated at earlier stages, and enhance patient experience. Prospective evaluation of implementation impact on stage distribution and survival is advised.

Background: Persistent pulmonary hypertension of the newborn (PPHN) remains a life-threatening condition resulting from failure of postnatal circulatory adaptation. Inhaled nitric oxide (iNO) is the standard first-line therapy; however, limited access or inadequate response highlight the need for alternative treatments. Milrinone, a selective phosphodiesterase-3 inhibitor with nitric oxide-independent vasodilatory and inotropic properties, has been proposed as one such option. Methods: In this study we present a case series of three neonates with PPHN—term (41 weeks), late preterm (35 weeks), and extremely preterm (23 weeks)—treated with intravenous milrinone in a neonatal unit without immediate access to iNO. A narrative literature review was also conducted, focusing on clinical outcomes, safety, and therapeutic applicability. Results: Milrinone was initiated within the first 24 h of life. In the term and late-preterm infants, oxygenation and echocardiographic parameters improved within 48 h, with normalization of shunt direction and successful extubation by days 4–10. Transient systemic hypotension occurred in both cases and required dose adjustment or vasoactive support. In the extremely preterm neonate, only temporary hemodynamic improvement was achieved, followed by severe intraventricular hemorrhage and coagulopathy, possibly exacerbated by vasodilatory and antiplatelet effects of milrinone. Conclusions: Milrinone may serve as a feasible adjunct or bridging therapy for PPHN when iNO is unavailable. However, its use requires careful hemodynamic and neurological monitoring, particularly in very preterm infants. Further studies are needed to confirm safety and define optimal dosing across gestational ages.

Background: Bariatric surgery is a well-established intervention for severe obesity, resulting in substantial weight loss and cardiometabolic benefits. However, the physiological mechanisms driving changes in functional capacity postoperatively remain incompletely characterized. Methods: Fourteen patients scheduled for bariatric surgery underwent serial assessments preoperatively and at 3 and 6 months postoperatively. Evaluations included body composition analysis, cardiopulmonary exercise testing (CPET), and non-invasive measurement of cardiac output (CO) and arteriovenous oxygen difference (AVDiff) using the inert gas rebreathing (IGR) method. Patients were stratified into four hemodynamic response profiles (Q1–Q4) based on directional changes in CO and AVDiff. Repeated measures changes were analyzed using Friedman and Wilcoxon signed-rank tests; correlations were assessed using Spearman’s rank method. Results: Following surgery, patients exhibited significant reductions in BMI, body fat percentage, and CO at both rest and peak exercise (all p < 0.05). VO₂ peak was preserved or modestly improved. Notably, the majority of patients exhibited a response pattern of reduced CO accompanied by increased AVDiff (Q1), both at rest and during exertion. At three months, VO₂ rest correlated positively with both CO rest and AVDiff rest, while VO₂ peak correlated with AVDiff peak. At six months, VO₂ rest and VO₂ peak both correlated positively with CO peak. Conclusions: Aerobic performance following bariatric surgery is not solely determined by peak oxygen uptake but also depends on the interaction between cardiac output and oxygen extraction, as reflected by AVDiff. These findings align with the Fick principle (VO₂ = CO × AVDiff) and emphasize the importance of comprehensive physiological profiling—beyond VO₂ peak alone—in understanding adaptation after bariatric surgery.

Introduction: Pulmonary involvement in Systemic Sclerosis (SSc) significantly contributes to disease-related morbidity and mortality. Impaired exercise capacity serves as a prognostic indicator for mortality in SSc. Assessments commonly used to evaluate physical fitness include the six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET). Objectives: To compare physical fitness and indirect markers of pulmonary circulation dysfunction in SSc patients with pulmonary involvement to healthy controls during maximal CPET and 6MWT a portable CPET unit. Results: During both tests, patients performed maximal effort (CPET RER=1.17 vs. 6MWT RER=1.08). SSc patients demonstrated impaired exercise tolerance: low peakVO2 values during both maximal CPET (mean peak VO2=1027 mL/min; 66% of predicted value) and 6MWT (mean peak VO2 937 mL/min; 64.5 % of predicted value), along with exercise-induced desaturation (−26% in CPET vs. -19% 6MWT) and decreasing PETCO2 values (mean CPET rest PETCO2= 31.5 mmHg, mean CPET max PETCO2=30 mmHg vs. mean 6MWT rest PETCO2=29 mmHg, mean 6MWT max PETCO2=31 mmHg). Only maximal CPET revealed abnormalities in ventilation-perfusion ratio, expressed as an elevated VE/VCO2 slope (mean CPET VE/VCO2 slope=43.2, vs. mean 6MWT VE/VCO2 slope=33.95), and ventilation abnormalities, manifested as reduced breathing reserve (mean CPET BR=12.6%, vs. mean 6MWT BR=63.4%). The research is currently ongoing. Conclusions: Maximal CPET on a cycle ergometer appears to be a superior tool for assessing exercise capacity and reasons for its limitation in individuals with SSc, aiding in disease progression monitoring and treatment compared to the 6MWT.

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.

The coronavirus disease 2019 pandemic created a significant crisis in global health. The aim of the study was to compare the impact of the COVID-19 pandemic on self-rated health status and smoking and alcohol habits. The Bialystok PLUS cohort study was conducted in 2018–2022. A total of 1222 randomly selected city residents were examined and divided into two groups: before and during the COVID-19 pandemic. The participants’ lifestyle habits and medical history were collected from self-reported questionnaires. The Alcohol Use Disorders Identification Test (AUDIT) and the Fagerström Test for Nicotine Dependence (FTND) were used to assess the degree of alcohol and nicotine dependence. The survey revealed a reduced frequency of reported allergies vs. an increased frequency of reported sinusitis and asthma; increased incidence of declared hypercholesterolemia and visual impairment; a reduced number of cigarettes smoked per day, lower FTND score, and a greater desire to quit smoking in the next six months; and an increase in hs-CRP and FeNO levels in the population during the pandemic compared to the pre-pandemic population. The COVID-19 pandemic had a measurable impact on the general population’s prevalence of certain medical conditions and lifestyle habits. Further research should continue to examine the long-term health implications of the pandemic.