Beyond diagnosis: a narrative review of the evolving therapeutic role of medical thoracoscopy in the management of pleural diseases.

Background and Objective: Medical thoracoscopy (MT) is an endoscopic technique performed by interventional pulmonologists with a favorable safety profile and few contraindications, providing diagnostic and therapeutic intervention in a single sitting. This narrative review was designed to summarize the therapeutic role of MT based on the latest results from the available literature. Methods: Pertinent literature published in English, relative to human studies, between 2010-2022 was searched in Medline/PubMed and Cochrane databases. Publications regarded as relevant were considered for inclusion in this review; additional references were added based on the authors' knowledge and judgment. The review considered population studies, meta-analyses, case series, and case reports. Key Content and Findings: MT has mostly been described and is currently used globally in the diagnostic approach to exudative pleural effusion of undetermined origin. Carefully evaluating the literature, it is clear that there is initial evidence to support the use of MT in the therapeutic approach of malignant pleural effusion, pneumothorax, empyema, and less frequently hemothorax and foreign body retrieval. Conclusions: MT is an effective procedure for treating the clinical entities presented in this document; it must be carried out in selected patients, managed in centers with high procedural expertise. Further evidence is needed to assess the optimal indications and appropriate patients' profiles for therapeutic MT. The endpoints of length of hospital stay, surgical referral, complications and mortality will have to be considered in future studies to validate it as a therapeutic intervention to be applied globally.

Real-world impact of the introduction of chemo-immunotherapy in extended small cell lung cancer: a multicentric analysis.

Background: Recent clinical trials demonstrated longer survival in extended small cell lung cancer (SCLC) patients treated with immunotherapy in addition to chemotherapy. However, the magnitude of benefit is modest and the impact in real-world setting has to be fully established. Methods: We collected clinical data and radiological imaging of patients affected by extended or relapsing SCLC and consecutively treated according to clinical practice between 2016 and 2023. As primary end-point, we compared pre-defined outcome indicators before and after the introduction of chemo-immunotherapy (May 2020): 6-month and 12-month progression free survival (PFS) rate, 12-month and 18-month overall survival (OS). Among those who were treated after May 2020, patients who did not receive immunotherapy according to treating physician's choice were included in the analysis to minimize clinical selection bias. Results: The analysis included 214 patients: 132 (61.7%) were treated in an Academic cancer center and 82 (38.3%) in two community hospitals; 104 were treated before May 2020. Median PFS of the overall study population was 4.8 months (95% confidence interval [95% CI]: 4.4-5.4), median OS was 7.1 months (95% CI: 6.3-7.7). Estimated PFS and OS were significantly longer in patients treated after May 2020 with hazard ratio (HR) for PFS and OS of 0.61 (95% CI: 0.46-0.81, p < 0.001) and 0.70 (95% CI: 0.52-0.93, p = 0.015), respectively. 6-month PFS rate increased from 27% to 40% (p = 0.04) while 12-months PFS raised from 1% to 11% (p = 0.003). 12-month and 18-month OS rate increased from 15% to 28% (p = 0.03) and from 2.1% to 12% (p = 0.009), respectively. After May 2020 the median number of hospitalization days per patient decreased significantly and the incidence of severe AEs was similar. Among patients treated with chemo-immunotherapy, the onset of immune-related AEs was associated with improved PFS and OS (HR 0.55, 95% CI: 0.35-0.89, p = 0.012 and HR 0.47, 95%CI 0.28-0.77, p = 0.002, respectively). Conclusions: The real-world analysis shows a meaningful improvement of outcome indicators after the introduction of chemo-immunotherapy, with reduction of the duration of hospitalization, thus supporting the use of chemo-immunotherapy and the need for further biomarker research.

Immune checkpoint blockade therapy mitigates systemic inflammation and affects cellular FLIP-expressing monocytic myeloid-derived suppressor cells in non-progressor non-small cell lung cancer patients.

Cancer cells favor the generation of myeloid cells with immunosuppressive and inflammatory features, including myeloid-derived suppressor cells (MDSCs), which support tumor progression. The anti-apoptotic molecule, cellular FLICE (FADD-like interleukin-1ß-converting enzyme)-inhibitory protein (c-FLIP), which acts as an important modulator of caspase-8, is required for the development and function of monocytic (M)-MDSCs. Here, we assessed the effect of immune checkpoint inhibitor (ICI) therapy on systemic immunological landscape, including FLIP-expressing MDSCs, in non-small cell lung cancer (NSCLC) patients. Longitudinal changes in peripheral immunological parameters were correlated with patients' outcome. In detail, 34 NSCLC patients were enrolled and classified as progressors (P) or non-progressors (NP), according to the RECIST evaluation. We demonstrated a reduction in pro-inflammatory cytokines such as IL-8, IL-6, and IL-1ß in only NP patients after ICI treatment. Moreover, using t-distributed stochastic neighbor embedding (t-SNE) and cluster analysis, we characterized in NP patients a significant increase in the amount of lymphocytes and a slight contraction of myeloid cells such as neutrophils and monocytes. Despite this moderate ICI-associated alteration in myeloid cells, we identified a distinctive reduction of c-FLIP expression in M-MDSCs from NP patients concurrently with the first clinical evaluation (T1), even though NP and P patients showed the same level of expression at baseline (T0). In agreement with the c-FLIP expression, monocytes isolated from both P and NP patients displayed similar immunosuppressive functions at T0; however, this pro-tumor activity was negatively influenced at T1 in the NP patient cohort exclusively. Hence, ICI therapy can mitigate systemic inflammation and impair MDSC-dependent immunosuppression.

Endobronchial ultrasound: a pictorial essay.

BACKGROUND AND AIM: endobronchial ultrasound has gained widespread popularity in the last decade, becoming the primary technique for minimally invasive evaluation of the mediastinum and staging of lung cancer. Several tertiary and quaternary care institutes use this method, performed by trained and accredited specialists. Its main indications are (I) diagnosis and staging of lung cancer, (II) mediastinal lymphadenopathy diagnosis (III) sampling peripheral pulmonary lesions. CONCLUSIONS: this manuscript aims to describe the operational potential of both convex endobronchial ultrasound probe and radial endobronchial ultrasound probe technology, focusing on lung cancer. This narrative review is complemented with by the description of peculiar clinical cases in which endobronchial ultrasound played a pivotal role in reaching the diagnosis.

Association Between Rome Classification Among Hospitalized Patients With COPD Exacerbations and Short-Term and Intermediate-Term Outcomes.

BACKGROUND: Recently, the Rome proposal updated the definition of exacerbation of COPD (ECOPD). However, such severity grade has not yet demonstrated intermediate-term clinical relevance. RESEARCH QUESTION: What is the association between the Rome severity classification and short-term and intermediate-term clinical outcomes? STUDY DESIGN AND METHODS: We retrospectively grouped hospitalized patients with ECOPD according to the Rome severity classification (ie, mild, moderate, severe). Baseline, clinical, microbiologic, gas analysis, and laboratory variables were collected. In addition, data about the length of hospital stay and mortality (in-hospital and a follow-up time line from 6 months until 3 years) were assessed. RESULTS: Of the 347 hospitalized patients, 39% were categorized as mild, 31% were categorized as moderate, and 30% were categorized as severe. Overall, patients with severe ECOPD had an extended length of hospital stay. Although in-hospital mortality was similar among groups, patients with severe ECOPD presented a worse prognosis in all follow-up time points. The Kaplan-Meier curves show the role of the severe classification in the cumulative survival at 1 and 3 years (Gehan-Breslow-Wilcoxon test, P = .032 and P = .004, respectively). The multivariable Cox regression analysis showed a higher risk of death at 1 year when patients presented a severe (hazard ratio, 1.99; 95% CI, 1.49-2.65) or moderate grade (hazard ratio, 1.47; 95% CI, 1.10-1.97) compared with a mild grade. Older patients (aged ≥ 80 years), patients requiring long-term oxygen therapy, or patients reporting previous ECOPD episodes had a higher mortality risk. A BMI between 25 and 29 kg/m2 was associated with a lower risk. INTERPRETATION: The Rome classification makes it possible to discriminate patients with a worse prognosis (severe or moderate) until a 3-year follow-up.

Use of non-invasive respiratory supports in high-intensity internal medicine setting during the first two waves of the COVID-19 pandemic emergency in Italy: a multicenter, real-life experience.

During the first two waves of the COVID-19 emergency in Italy, internal medicine high-dependency wards (HDW) have been organized to manage patients with acute respiratory failure (ARF). There is heterogeneous evidence about the feasibility and outcomes of non-invasive respiratory supports (NIRS) in settings outside the intensive care unit (ICU), including in patients deemed not eligible for intubation (i.e., with do-not-intubate, DNI status). Few data are available about the different NIRS modalities applied to ARF patients in the newly assembled internal medicine HDW. The main aim of our study was to describe a real-life experience in this setting of cure, focusing on feasibility and outcomes. We retrospectively collected data from COVID-19 patients with ARF needing NIRS and admitted to internal medicine HDW. Patients were treated with different modalities, that is high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), or non-invasive mechanical ventilation (NIMV). Switching among different NIRS during the hospitalization and the success rate (weaning with the same NIRS) or failure (endotracheal intubation-ETI or in-hospital death) were recorded. Three hundred thirty four ARF patients (median age 74 years), of which 158 (54%) had a DNI status, were included. CPAP, NIMV, and HFNC's success rates were 54, 33, and 13%, respectively. Although DNI status was strongly associated with death (Gehan-Breslow-Wilcoxon test p < 0.001), an acceptable success rate was observed in these patients using CPAP (47%). Multivariate regression models showed older age (odds ratio-OR 4.74), chronic ischemic heart disease (OR 2.76), high respiratory rate after 24 h (OR 7.13), and suspected acute respiratory distress syndrome-ARDS (OR 21.1) as predictors of mortality risk or ETI. Our real-life experience shows that NIRS was feasible in internal medicine HDW with an acceptable success rate. Although DNI patients had a worse prognosis, the use of NIRS represented a reasonable chance of treatment.

Endoscopic Technologies for Peripheral Pulmonary Lesions: From Diagnosis to Therapy.

Peripheral pulmonary lesions (PPLs) are frequent incidental findings in subjects when performing chest radiographs or chest computed tomography (CT) scans. When a PPL is identified, it is necessary to proceed with a risk stratification based on the patient profile and the characteristics found on chest CT. In order to proceed with a diagnostic procedure, the first-line examination is often a bronchoscopy with tissue sampling. Many guidance technologies have recently been developed to facilitate PPLs sampling. Through bronchoscopy, it is currently possible to ascertain the PPL's benign or malignant nature, delaying the therapy's second phase with radical, supportive, or palliative intent. In this review, we describe all the new tools available: from the innovation of bronchoscopic instrumentation (e.g., ultrathin bronchoscopy and robotic bronchoscopy) to the advances in navigation technology (e.g., radial-probe endobronchial ultrasound, virtual navigation, electromagnetic navigation, shape-sensing navigation, cone-beam computed tomography). In addition, we summarize all the PPLs ablation techniques currently under experimentation. Interventional pulmonology may be a discipline aiming at adopting increasingly innovative and disruptive technologies.

Do Patients with Bronchiectasis Have an Increased Risk of Developing Lung Cancer? A Systematic Review.

BACKGROUND: Initial evidence supports the hypothesis that patients with non-cystic fibrosis bronchiectasis (NCFB) have a higher risk of lung cancer. We systematically reviewed the available literature to define the characteristics of lung malignancies in patients with bronchiectasis and the characteristics of patients who develop bronchiectasis-associated lung cancer. METHOD: This study was performed based on the PRISMA guidelines. The review protocol was registered in PROSPERO. RESULTS: The frequency rates of lung cancer in patients with NCFB ranged from 0.93% to 8.0%. The incidence rate was 3.96. Cancer more frequently occurred in the elderly and males. Three studies found an overall higher risk of developing lung cancer in the NCFB population compared to the non-bronchiectasis one, and adenocarcinoma was the most frequently reported histological type. The effect of the co-existence of NCFB and COPD was unclear. CONCLUSIONS: NCFB is associated with a higher risk of developing lung cancer than individuals without NCFB. This risk is higher for males, the elderly, and smokers, whereas concomitant COPD's effect is unclear.

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. METHODS: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. RESULTS: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). CONCLUSION: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population.

Urinary extracellular vesicle mRNA analysis of sodium chloride cotransporter in hypertensive patients under different conditions.

Urinary extracellular vesicles (UEV) mainly derive from cells of the urogenital tract and their cargo (proteins, nucleic acids, lipids, etc.) reflects their cells of origin. Na chloride cotransporter (NCC) is expressed at the kidney level in the distal convoluted tubule, is involved in salt reabsorption, and is the target of the diuretic thiazides. NCC protein has been recognized and quantified in UEV in previous studies; however, UEV NCC mRNA has never been studied. This study aimed to identify and analyze NCC mRNA levels in primary aldosteronism (PA). The rationale for this investigation stems from previous observations regarding NCC (protein) as a possible biomarker for the diagnosis of PA. To evaluate modulations in the expression of NCC, we analyzed NCC mRNA levels in UEV in PA and essential hypertensive (EH) patients under different conditions, that is, before and after saline infusion, anti-aldosterone pharmacological treatment, and adrenal surgery. NCC mRNA was measured by RT-qPCR in all the samples and was regulated by volume expansion. Its response to mineralocorticoid receptor antagonist was correlated with renin, and it was increased in PA patients after adrenalectomy. NCC mRNA is evaluable in UEV and it can provide insights into the pathophysiology of distal convolute tubule in different clinical conditions including PA.

Selection Criteria and Treatment Outcome for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Unfit for Platinum-Based First-Line Therapy: Results of the MOON-OSS Observational Trial.

Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFR/ALK negative and PD-L1 < 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy. Two-hundred and twenty-one patients were included. Median age was 79 (range 56−92) years, M/F 165(74.6%)/56(25.4%), ECOG performance status (PS) 0/1/ ≥ 2 23(10.9%)/94(42.5%)/103(46.6%), with a median of two serious comorbidities. A median of 25% (range 10%-30%) of newly diagnosed NSCLC did not receive a first-line platinum combination. Clinical criteria according to which decision was made were older age (76.5%), comorbidities (72%), poor PS (55.2%) and familiar or social issues (10%). Single-agent treatment consisted of oral metronomic vinorelbine (MetV 78.6%), gemcitabine (Gem 10%), oral standard vinorelbine (Vin 8.2%) and other (O 3.2%). Median progression-free survival (PFS) and overall survival (OS) of single agent treatments ranged from 4.5 to 5 months and from 9 to 10.5 months, respectively. All grade toxicities did not differ among single agents, while grade 3−4 toxicities were less frequent with MetV. Up to 30% of newly diagnosed advanced EGFR/ALK negative and PD-L1 < 50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (>70 years), comorbidities and poor PS. An oral treatment was frequently proposed with MetV being the most frequent choice according to its safety profile.

High Plasma Levels of Activated Factor VII-Antithrombin Complex Point to Increased Tissue Factor Expression in Patients with SARS-CoV-2 Pneumonia: A Potential Link with COVID-19 Prothrombotic Diathesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19), in which coagulation abnormalities and endothelial dysfunction play a key pathogenic role. Tissue factor (TF) expression is triggered by endothelial dysfunction. Activated factor VII-antithrombin (FVIIa-AT) complex reflects indirectly FVIIa-TF interaction and has been proposed as a potential biomarker of prothrombotic diathesis. FVIIa-AT plasma concentration was measured in 40 patients (30 males and 10 females; 64.8 ± 12.3 years) admitted with SARS-CoV-2 pneumonia during the first pandemic wave in Italy. Two sex- and age-matched cohorts without COVID-19, with or without signs of systemic inflammation, were used to compare FVIIa-AT data. The FVIIa-AT plasma levels in COVID-19 patients were higher than those in non-COVID-19 subjects, either with or without inflammation, while no difference was observed among non-COVID-19 subjects. The association between COVID-19 and FVIIa-AT levels remained significant after adjustment for sex, age, C-reactive protein, renal function, fibrinogen, prothrombin time and activated partial thromboplastin time. Our results indicate that SARS-CoV-2 infection, at least during the first pandemic wave, was characterized by high FVIIa-AT levels, which may suggest an enhanced FVIIa-TF interaction in COVID-19, potentially consistent with SARS-CoV-2-induced endotheliopathy.

Critical care transfers and COVID-19: Managing capacity challenges through critical care networks.

The intensive care units in North West London are part of one of the oldest critical care networks in the UK, forming a mature and established strategic alliance to share resources, experience and knowledge for the benefit of its patients. North West London saw an early surge in COVID-19 admissions, which urgently threatened the capacity of some of its intensive care units even before the UK government announced lockdown. The pre-existing relationships and culture within the network allowed its members to unite and work rapidly to develop agile and innovative solutions, protecting any individual unit from becoming overwhelmed, and ultimately protecting its patients. Within a short 50-day period 223 patients were transferred within the network to distribute pressures. This unprecedented number of critical care transfers, combined with the creation of extra capacity and new pathways, allowed the region to continue to offer timely and unrationed access to critical care for all patients who would benefit from admission. This extraordinary response is a testament to the power and benefits of a regionally networked approach to critical care, and the lessons learned may benefit other healthcare providers, managers and policy makers, especially in regions currently facing new outbreaks of COVID-19.

Removal of a Tracheal Mesh Stent: How I Do It.

We illustrate how to remove a stent from the tracheal lumen 12 years after its deployment. Maintaining the stent in situ for a long time degrades the stent materials, making it fragile and very difficult to manipulate. A rigid bronchoscopy approach was chosen for the treatment of this case. We describe the preparation of the intervention and its execution step by step.

A narrative review on tumor microenvironment in oligometastatic and oligoprogressive non-small cell lung cancer: a lot remains to be done.

OBJECTIVE: In this review, we aim to collect and discuss available data about the role and composition of tumor microenvironment (TME) in oligometastatic (OMD) and oligoprogressive (OPD) non-small cell lung cancer (NSCLC). Furthermore, we aim to summarize the ongoing clinical trials evaluating as exploratory objective the TME composition, through tissue and/or blood samples, in order to clarify whether TME and its components could explain, at least partially, the oligometastatic/oligoprogressive process and could unravel the existence of predictive and/or prognostic factors for local ablative therapy (LAT). BACKGROUND: OMD/OPD NSCLC represent a heterogeneous group of diseases. Several data have shown that TME plays an important role in tumor progression and therefore in treatment response. The crucial role of several types of cells and molecules such as immune cells, cytokines, integrins, protease and adhesion molecules, tumor-associated macrophages (TAMs) and mesenchymal stem cells (MSCs) has been widely established. Due to the peculiar activation of specific pathways and expression of adhesion molecules, metastatic cells seem to show a tropism for specific anatomic sites (the so-called "seed and soil" hypothesis). Based on this theory, metastases appear as a biologically driven process rather than a random release of cancer cells. Although the role and the function of TME at the time of progression in patients with NSCLC treated with tyrosine-kinase inhibitors and immune checkpoint inhibitors (ICIs) have been investigated, limited data about the role and the biological meaning of TME are available in the specific OMD/OPD setting. METHODS: Through a comprehensive PubMed and ClinicalTrials.gov search, we identified available and ongoing studies exploring the role of TME in oligometastatic/oligoprogressive NSCLC. CONCLUSIONS: Deepening the knowledge on TME composition and function in OMD/OPD may provide innovative implications in terms of both prognosis and prediction of outcome in particular from local treatments, paving the way for future investigations of personalized approaches in both advanced and early disease settings.