Clinical and biological effects of different energetic surgical devices currently used for mini-invasive anatomical lung resections for the treatment of NSCLC: a prospective interventional study.

BACKGROUND: This study aims to compare three commonly used energy devices for dissection during Video-Assisted Thoracoscopic Surgery (VATS) lobectomy: monopolar hook, advanced bipolar, and ultrasonic device, in terms of duration of the surgical procedure and clinical intra- and post-operative outcomes. MATERIALS AND METHODS: In this prospective single-center study, 75 patients undergoing VATS lobectomy for non-small cell lung cancer between January 2022 and May 2023 were enrolled and divided into 3 groups based on the device used during the surgical procedure (Group 1: Ultrasonic Device, Group 2: Advanced Bipolar, Group 3: Monopolar Hook). The duration of the surgical procedure, daily pleural fluid production, post-operative pain, length of hospital stay, and occurrence of post-operative complications were compared for each group. In a subgroup of 20 patients (10 from Group 1 and 10 from Group 3), concentrations of inflammatory cytokines in pleural fluid at 3 h and 48 h post-surgery were analyzed. RESULTS: Pleural fluid production on the first and second post-operative days was significantly lower in patients treated with the Ultrasonic device compared to the other two groups (p < 0.001). The duration of the surgical procedure was significantly shorter when using the Ultrasonic device (p < 0.001). There were no significant differences in length of hospital stay (p = 0.975), pain on the first and second post-operative days (p = 0.147 and p = 0.755, respectively), and blood hemoglobin levels on the first post-operative day (p = 0.709) and at discharge (p = 0.795). No differences were observed in terms of post-operative complications, although the incidence of post-operative cardiac arrhythmias was borderline significant (p = 0.096), with no cases of arrhythmias recorded in Group 1. IL-10 levels in pleural fluid of patients in Group 3 peaked at 3 h post-surgery, with a significant reduction at 48 h (p = 0.459). DISCUSSION: The use of the ultrasonic device during VATS lobectomy may reduce pleural fluid production and shorten the duration of the surgical procedure compared to using a monopolar hook or advanced bipolar device. The choice of energy device may influence the local inflammatory response, although further studies are needed to confirm these results.

Immune checkpoint analysis of T-cell responses to pp65 and IE-1 antigens in end-stage lung diseases.

Lung transplant (LTX) patients are at high risk of cytomegalovirus (CMV) infection, which is often associated with high mortality and morbidity. Reactivation of CMV causes cell injury due to the cytopathic effect of viral replication and triggering of T cell immunity. The aim of this study was to compare expression of immune checkpoints (ICs) (PD-1, CTLA-4, LAG-3 and TIGIT) in CD4, CD8 and CD56 and activation markers CD137, CD154 and CD69 of end-stage patients awaiting lung transplant. Eighteen pre-LTX positive for anti-CMV IgG titres and 18 healthy subjects were enrolled. IC and activation markers have been evaluated through flow cytometric analysis in HC and pre-LTX patients. Reactive (QF+) and unreactive (QF-) patients were stratified according to QuantiFERON-CMV assays. ICs' and activation markers' expression were determined before and after in vitro stimulation with pp-65 and IE-1 antigens. Lower expression of PD-1 was observed in CD4 and CD8 cells of pre-LTX patients than controls, whereas CTLA4 appeared upregulated in CD56 and CD8 cells. TIGIT is increased on the surface of CD4, CD8 and NK cells after peptide stimulation in QF-negative patients and PD-1 is only downregulated after stimulation in the QF-positive patients. This study provides new evidence of immune dysregulation in patients with end-stage lung disorders, particularly in relation to immune checkpoint cell biology. The change in QF+ mostly happens on cytotoxic cells NK and CD8, while the changes in QF- were observed in adaptive immune cells, including CD4 and CD8.

Survival After Lung Transplantation for Chronic Hypersensitivity Pneumonitis: Results From a Large International Cohort Study.

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.

Cytomegalovirus Infection Is Associated with Development of Chronic Lung Allograft Dysfunction.

BACKGROUND: Cytomegalovirus (CMV) is the major and most common opportunistic infection complicating lung transplant (LTX). The aim of this study was to analyse the epidemiological aspects of CMV infection in lung transplant patients subject to a pre-emptive anti-CMV approach and to study the impact of this infection on lung transplant outcome, in terms of onset of chronic lung allograft dysfunction (CLAD). METHODS: This single-centre retrospective study enrolled 87 LTX patients (median age 55.81 years; 41 females, 23 single LTX, 64 bilateral LTX). All patients were managed with a pre-emptive anti-CMV approach. The incidences of the first episode of CMV infection, 1, 3, 6 and 12 months after LTX, were 12.64%, 44.26%, 50.77% and 56.14%. A median interval of 41 days elapsed between LTX and the first episode of CMV infection. The median blood load of CMV-DNA at diagnosis was 20,385 cp/ml; in 67.64% of cases, it was also the peak value. Patients who had at least one episode had shorter CLAD-free survival. Patients who had three or more episodes of CMV infection had the worst outcome. RESULTS: CMV infection was confirmed to be a common event in lung transplant patients, particularly in the first three months after transplant. It had a negative impact on transplant outcome, being a major risk factor for CLAD. The hypothesis that lower viral replication thresholds may increase the risk of CLAD is interesting and deserves further investigation.

Impact of SARS-CoV-2 outbreak on heart and lung transplant: A patient-perspective survey.

BACKGROUND: The risk of COVID-19 is expected to be higher among solid organ transplant. The aim of the present study was to evaluate the incidence of COVID-19 and the impact of the SARS-CoV-2 outbreak on the personal hygiene and expectations in heart and lung transplant recipients. METHODS: A telephone survey of heart (n = 69) and lung (n = 41) transplant patients and a group of controls (n = 41) was conducted concerning personal hygiene before and after the outbreak; the impact on subjective expectations regarding graft outcome; symptoms possibly associated with SARS-CoV-2 infection; and diagnosis of COVID-19. RESULTS: Seventy nine percent of the patients declared they increased the use of face masks and handwash. Behavior at home regarding self-isolation did not change. About half the patients said they were afraid of the virus. A higher percentage of Lung transplant (LTX) were convinced that SARS-CoV-2 could have a negative impact on the outcome of their graft. 28% declared that they were afraid to come to the hospital for routine examinations and asked to postpone. Nine LTX and five Heart transplant (HTX) patients experienced symptoms that could have been associated with SARS-CoV-2 infection, but none of them underwent a nasopharyngeal swab. Only one LTX was diagnosed with the infection. CONCLUSIONS: In our study, we observed a low incidence of COVID-19 in heart and lung transplant patients (0.9%), similar to that of the general population of our Region. Isolation measures were already observed before the pandemic and were further strengthened in most cases. Particular attention should also be paid to new psychological and physical complications indirectly linked to the COVID-19 pandemic.

The Role of Galectins in Chronic Lung Allograft Dysfunction.

BACKGROUND: Galectins are proteins that bind ß-galactosides such as N-acetyllactosamine present in N-linked and O-linked glycoproteins and that seem to be implicated in inflammatory and immune responses as well as fibrotic mechanisms. This preliminary study investigated serum galectins as clinical biomarkers in lung transplant patients with chronic lung allograft dysfunction (CLAD), phenotype bronchiolitis obliterans syndrome (BOS). MATERIALS AND METHODS: Nineteen lung transplant patients [median age (IQR), 55 (45-62) years; 53% males] were enrolled in the study. Peripheral blood concentrations of galectins-1, 3 and 9 were determined with commercial ELISA kits. RESULTS: Galectin-1 concentrations were higher in BOS than in stable LTX patients (p = 0.0394). In logistic regression analysis, testing BOS group as dependent variable with Gal-1 and 3 as independent variables, area under the receiver operating characteristics (AUROC) curve was 98.9% (NPV 90% and PPV 88.9%, p = 0.0003). With the stable LTX group as dependent variable and Gal-1, 3 and 9 as independent variables, AUROC was 92.6% (NPV 100% and PPV 90%, p = 0.0023). In stable patients were observed an inverse correlation of Gal-3 with DLCO% and KCO%, and between Gal-9 and KCO%. CONCLUSION: Galectins-1, 3 and 9 are possible clinical biomarkers in lung transplant patients with diagnostic and prognostic meaning. These molecules may be directly implicated in the pathological mechanisms of BOS. The hypothesis that they could be new therapeutic targets in BOS patients is intriguing and also worth exploring.

PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach.

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.

Age and Clinical Presentation for Primary Spontaneous Pneumothorax.

Primary spontaneous pneumothorax (PSP) is a commonly known condition due to the accumulation of air in the pleural space in otherwise healthy people, without apparent underlying lung disease. To date, the exact pathogenesis of PSP is unclear, but it still represents a public health issue. We performed a review of the literature concerning the epidemiology of PSP, examining age of onset and presentation symptoms, in order to assess the possible correlation between these characteristics and its occurrence. Data concerning age, signs, and symptoms were collected. For description purposes, information regarding aetiological and anthropomorphic data was also gathered. In total, 265 papers were evaluated. Regarding age of onset, PSP is a disease that can occur in a broad age group with a double cluster (15-30 and 40-45 yr). Regarding symptoms, pain and dyspnoea (in its various forms) are the most described in PSP. Pain was recorded in 69.25% (range, 9-100%) of the population studied, whereas dyspnoea was present in an average of 54.55% (range, 27-77.1%). Tobacco exposure seems to play an important role in the early onset of PSP. Concerning age at presentation, this review highlights that PSP can occur over a broad age range. The literature appears to be consistent in reporting PSP occurrence mostly below 45 years of age. Asymptomatic PSP is an almost unseen entity. Finally, of pollutants, cigarette smoking should be considered as the most significant exogenous risk factor in the development of PSP.

Helicobacter pylori Infection Does Not Impact on Lung Transplant Outcome.

BACKGROUND: Helicobacter pylori (HP) is a spiral, gram-negative, microaerophilic bacterium that colonises the human gastric mucosa and is associated with gastrointestinal and extragastrointestinal disorders. Since no data are yet available on HP infection in lung transplant patients, we evaluated the prevalence and impact of HP infection in a population of such patients. METHODS: Sixty-seven lung transplant patients were enrolled in the study (35 females and 32 males, age 48.4 ± 13.3 years), 54 underwent bilateral and 13 single lung transplant. Serum antibodies against HP and CagA were assayed in all subjects. RESULTS: The prevalence of HP infection in lung transplant patients was similar to that in the general population (49.25% vs. 51.4%), whereas HP-positive patients showed lower CagA positivity (9% vs. 50.2%, p < 0.0001). There was a higher prevalence of HP infection in patients who underwent lung transplant because of pulmonary fibrosis (p = 0.049), and a lower prevalence in COPD patients (p = 0.011). No correlation was found between HP infection in lung transplant patients and graft outcome. No differences in primary graft dysfunction, acute rejection or bronchiolitis obliterans syndrome-free survival were found. However, more patients who required three or more post-transplant re-hospitalisations were observed among HP-positive patients. CONCLUSIONS: The prevalence of HP infection in lung transplant patients was comparable to that of the general population and to that reported in heart and kidney transplant recipients. It did not seem to impact short-, mid- or long-term lung allograft outcome. H. pylori infection did not prove to be clinically relevant in lung transplant patients.

Mortality on the Waiting List for Lung Transplantation in Patients with Idiopathic Pulmonary Fibrosis: A Single-Centre Experience.

PURPOSE: Lung transplantation (LTX) is nowadays accepted as a treatment option for selected patients with end-stage pulmonary disease. Idiopathic pulmonary fibrosis (IPF) is characterized by the radiological and histologic appearance of usual interstitial pneumonia. It is associated with a poor prognosis, and LTX is considered an effective treatment to significantly modify the natural history of this disease. The aim of the present study was to analyse mortality during the waiting list in IPF patients at a single institution. METHODS: A retrospective analysis on IPF patients (n = 90) referred to our Lung Transplant Program in the period 2001-2014 was performed focusing on patients' characteristics and associated risk factors. RESULTS: Diagnosis of IPF was associated with high mortality on the waiting list with respect to other diagnosis (p < 0.05). No differences in demographic, clinical, radiological data and time spent on the waiting list were observed between IPF patients who underwent to LTX or lost on the waiting list. Patients who died showed significant higher levels of pCO2 and needed higher flows of O2-therapy on effort (p < 0.05). Pulmonary function tests failed to predict mortality and no other medical conditions were associated with survival. CONCLUSIONS: Patients newly diagnosed with IPF, especially in small to medium lung transplant volume centres and in Countries where a long waiting list is expected, should be immediately referred to transplantation, delay results in increased mortality. Early identification of IPF patients with a rapid progressive phenotype is strongly needed.

Prevalence of concomitant aortic disease and lung cancer: an exploratory study.

Background: Lung cancer and aortic disease share multiple risk factors. The co-presence of both diseases defines a peculiar type of patient who needs a specific protocol of treatment and follow-up. The aim of our study was to evaluate the prevalence of aortic disease in a population of patients with a diagnosis of primary lung cancer. Methods: A retrospective, single center analysis of all patients admitted to the Thoracic Surgery Unit from January 2015 to January 2021. Demographic and baseline characteristics were retrieved from hospital electronic charts. All patients were screened for aortic disease, reviewing thoraco-abdominal Computed Tomography with contrast medium administration performed for oncological reasons. A cancer-free control group was obtained for comparison. Multilinear regression analysis was performed to identify the risk factors for the presence of aortic disease. Results: A total of 264 patients were preliminarily identified. After reviewing for exclusion criteria, a total of 148 patients were included in the analysis. Most of the patients were male (62.2%) with a mean age of 71±8.7 years. Cardiovascular risk factors were extensively prevalent in the population study. The incidence of aortic pathologies in the group of patients suffering from primary lung cancer was 27% (40 patients). The majority presented thoracic aortic aneurysms (11.5%). Comparison between the lung cancer group and the control group highlighted a substantial difference in terms of aortic disease prevalence (27% vs. 2.9%; P<0.0001). The regression analysis revealed that coronary artery disease [odds ratio (OR) 4.6988, P=0.001], peripheral artery disease (OR 7.7093, P=0.002), hypertension (OR 4.0152, P=0.03) and history of previous non-aortic vascular surgery procedures (OR 6.4509, P=0.003) were risk factors for aortic disease in patients with primary lung cancer. Conclusions: Patients with lung cancer have a high prevalence of aortic disease, defining a peculiar subset of patients who deserve a specific protocol of treatment and follow-up. Further studies are needed to define a dedicated standardized multidisciplinary approach.

Safety and Diagnostic Yield of Medical Pleuroscopy (MP) Performed under Balanced Analgosedation by a Pneumological Team Compared to Video-Assisted Thoracic Surgery (VATS): A Retrospective Controlled Real-Life Study (TORAPO).

INTRODUCTION: Medical pleuroscopy (MP) is an invasive technique that provides access to the pleural space with a rigid or semi-rigid work instrument, allowing for visualization and the obtaining of bioptic pleural samples. Using pulmonologist-based analgosedation to perform pleuroscopy is still debated for safety reasons. The aim of this real-life study is to demonstrate the safety and diagnostic yield of MP performed under balanced analgosedation by a pulmonologist team with expertise in the management of critically ill patients in the respiratory intensive care unit (RICU) and interventional pulmonology unit as compared to video-assisted thoracic surgery (VATS) performed by a thoracic surgeon team under anesthesiologist-based analgosedation. METHODS: In this multicentric retrospective controlled study, the inclusion criteria were patients older than 18 years old with pleural effusion of unknown diagnosis consecutively admitted in the years 2017-2022 to the pulmonology unit and RICU of San Donato Hospital in Arezzo (Italy, Tuscany) and to the thoracic surgery unit of Santa Maria Le Scotte in Siena (Italy, Tuscany) to undergo, respectively, MP under balanced propofol-based analgosedation on spontaneous breathing with local anesthesia provided by a pulmonologist team (Group A), and VATS provided by a surgeon team under propofol-based analgosedation managed by an anesthesiologist using invasive mechanical ventilation (IMV) via endotracheal intubation (ETI) (Group B). The primary endpoints were (1) a comparison between the two groups in terms of the diagnostic yield of pleural effusion, and (2) major and minor complications of pleuroscopic procedures. The secondary endpoints were (1) the length of the pleuroscopic procedure; (2) the duration of hospitalization; (3) propofol doses; and (4) the patient's comfort after the procedure assessed using the Visual Analogue Scale (VAS). RESULTS: We enrolled 91 patients in Group A and 116 patients in Group B. A conclusive diagnosis was obtained in 97.8% of Group A vs. 100% of Group B (p = 0.374). Malignant effusion was diagnosed in 59.3% of Group A and in 55.1% of Group B; p = 0.547. No intraoperative or postoperative mortality events or major complications were observed in Group A. The major complications observed in Group B were three major bleeding events (p = 0.079) and one exitus (p = 0.315) not related to the interventional procedure. No significant difference emerged between the two groups in terms of minor complications. The duration of the intervention was significantly lower in Group A (40.0 min ± 12.6 versus 51.5 ± 31.0; p = 0.001). Pain control and, therefore, patient comfort were better in Group A, with an average VAS of 0.34 ± 0.65 versus 2.58 ± 1.26, p < 0.001. The duration of hospitalization was lower in Group B (5.1 ± 2.6 vs. 15.5 ± 8.0, p < 0.001). The average overall dose of propofol administered was significantly lower in Group A (65.6 ± 35.8 mg versus 280 ± 20.0 mg; p < 0.001). CONCLUSIONS: This real-life study shows that the MP performed under propofol-based analgosedation by an independent pneumologist team is a safe and well-tolerated procedure with a diagnostic yield and complication rates similar to those obtained with VATS.

Lung Resection for Non-Small Cell Lung Cancer following Bronchoscopic Lung Volume Reduction for Heterogenous Emphysema.

Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment for emphysema. Lung cancer may be associated with emphysema due to common risk factors. Thus, a growing number of patients undergoing BLVR may develop lung cancer. Herein, we evaluated the effects of lung resection for non-small cell lung cancer in patients undergoing BLVR. The clinical data of patients undergoing BLVR followed by lung resection for NSCLC were retrospectively reviewed. For each patient, surgical and oncological outcomes were recorded to define the effects of this strategy. Eight patients were included in our series. In all cases but one, emphysema was localized within upper lobes; the tumor was detected during routine follow-up following BLVR and it did not involve the treated lobe. The comparison of pre- and post-BLVR data showed a significant improvement in FEV1 (29.7 ± 4.9 vs. 33.7 ± 6.7, p = 0.01); in FVC (28.5 ± 6.6 vs. 32.4 ± 6.1, p = 0.01); in DLCO (31.5 ± 4.9 vs. 38.7 ± 5.7, p = 0.02); in 6MWT (237 ± 14 m vs. 271 ± 15 m, p = 0.01); and a reduction in RV (198 ± 11 vs. 143 ± 9.8, p = 0.01). Surgical resection of lung cancer included wedge resection (n = 6); lobectomy (n = 1); and segmentectomy (n = 1). No major complications were observed and the comparison of pre- and post-operative data showed no significant reduction in FEV1% (33.7 ± 6.7 vs. 31.5 ± 5.3; p = 0.15) and in DLCO (38.7 ± 5.7 vs. 36.1 ± 5.4; p = 0.15). Median survival was 35 months and no cancer relapses were observed. The improved lung function obtained with BLVR allowed nonsurgical candidates to undergo lung resection for lung cancer.

A Strange Case of Traumatic Pleural Effusion: Pleural Empyema Due to Actinomyces meyeri, a Case Report.

BACKGROUND: Actinomycosis by Actinomyces meyeri is rare and scarcely reported in the literature. The lung is the main organ involved. Penicillin and amoxicillin are the first-choice treatments. Surgery is indicated when empyema and abscesses are resistant to medical treatment. CASE PRESENTATION: We report an underdiagnosed case of pleural empyema due to A. meyeri in a patient with closed chest trauma. The patient, a male, 47 years old, presented with a dry cough, thoracic pain, and dyspnea a month after the trauma. A chest X-ray showed a left lower lobe pleural effusion, so he was subjected to a thoracentesis, leading to a partial re-expansion of the left lung. The patient also complained about gum discomfort; thus, a dental x-ray scan was taken, which showed the presence of vertical bone resorption in a periodontal pocket. The patient was treated with levofloxacin 500 mg orally once a day, which was continued for 15 days after discharge. Two months after the accident, he presented again with intermittent fever, a worsening cough, and dyspnea. A CT scan showed thickening of the left pleura and a loculated pleural effusion with partial collapse of the left lower lobe. A decision was made to refer the patient to the Thoracic Unit to undergo surgery via a left thoracoscopic uniportal approach. The lung was thoroughly decorticated, and the purulent fluid was aspirated. The postoperative course was uneventful. Cultures showed the growth of Actinomyces meyeri, which is sensitive to imipenem and amoxicillin. The patient started a proper antibiotic regimen and, whenever possible, was discharged. At 12 months follow-up, a chest X-ray showed a complete resolution of the left pleural effusion with complete re-expansion of the left lung. CONCLUSIONS: Although rare, Actinomycetes infections must be considered especially in front of non-solving empyema or severe pneumonia of unknown cause because in the majority of cases, with the proper treatment, the restitutio ad integrum is possible.

A multicentric evaluation of pediatric lung transplantation in Italy.

BACKGROUND: Pediatric lung transplantation is performed in highly experienced centers due to the peculiar population characteristics. The literature is limited and not representative of individual countries' differences. The purpose of this study was to analyze the Italian experience. METHODS: A multicentric retrospective analysis was performed on 110 pediatric patients (<18 years old) who underwent lung transplantation from 1992 to 2019 at 9 Italian centers. Heart-lung transplantations and lung retransplantations were excluded. RESULTS: The population was composed of 44 male and 66 female patients, with a median age of 15 years. The most frequent indication was cystic fibrosis (83%). One quarter of patients were transplanted in an emergency setting. Median donors' Oto score and age were 1 and 15 years, respectively, with 43% of adult donors. In 17% of patients a graft reduction was performed. Postoperatively, the median duration of mechanical ventilation, intensive care unit, and in-hospital stay were 48 hours, 11 and 35 days, respectively. Thirty-day mortality was 6%, and 1-, 5-, and 10-year survival was 72%, 52%, and 33%, respectively. Risk factors for mortality were Oto score and recipients' body mass index. CONCLUSIONS: The outcomes of pediatric lung transplantation in Italy are comparable with current literature. Particular attention should be paid to the Oto score and recipient body mass index. Conversely, adult donors and graft reductions can be safely used to expand the donor pool.

Clinical score for colorectal cancer patients with lung-limited metastases undergoing surgical resection: Meta-Lung Score.

BACKGROUND: Radical resection of isolated lung metastases (LM) from colorectal cancer (CRC) is debated. Like Fong's criteria in liver metastases, our study was meant to assign a clinical prognostic score in patients with LM from CRC, aiming for better surgery selection. METHODS: We retrospectively analyzed data from 260 CRC patients who underwent curative LM resection from December 2002 to January 2022, verifying the impact of different clinicopathological features on the overall survival (OS). RESULTS: At the univariate analysis: higher baseline CEA levels (p = 0.0001), disease-free survival less than or equal to 12 months (m) (p = 0.0043), LM size larger than 2 cm (p = 0.0187), multiple resectable nodules (p = 0.0083), and positive nodal status of the primary tumor (p = 0.0011) were associated with worse prognosis. In a Cox regression model, these characteristics retained their independent role for OS (p < 0.0001) and were chosen as criteria to be assigned one point each for clinical risk score. The 5-year survival rate in patients with 0 points was 88%, while no patients with a 5-point score survived at 2 years. Based on the 0-1 vs. 2-5 score range, we obtained a significant difference in median OS: not reached vs. 40.8 months (95 %CI 36 to 87.5), respectively (p < 0.0001) stratifying patients into good and poor prognosis. The prognostic role of the score was also confirmed in terms of median RFS: not reached in 0-1 scored patients vs. 30.5 months (95 %CI 19.4 to 42) in patients with 2-5 scores (p = 0.0006). CONCLUSIONS: When LM from CRC is resectable, the Meta-Lung Score provides valuable prognostic information. Indeed, while upfront surgery should be considered in patients with scores of 0 to 1, it should be cautiously suggested in patients with scores of 2 to 5, for whom a prognosis comparison between preventive surgery and other treatments should be investigated in prospective randomized clinical trials.

Lung cancer and interstitial lung diseases: the lack of prognostic impact of lung cancer in IPF.

Lung Cancer (LC) is the first cause of death worldwide. Recently increased interest in interstitial lung diseases (ILD) has highlighted an association with lung cancer, offering interesting insights into the pathogenesis of the latter. Describe the association between lung cancer and ILD and evaluate the impact of LC on survival in these populations. We collected clinical, radiological, histologic data of 53 cases of advanced pulmonary fibrosis with lung cancer: 17 with UIP pattern (usual interstitial pneumonia, UIP/IPF-LC) and 36 with non-UIP pattern (ILD-LC). Adenocarcinoma was the most frequent histological subtype of lung cancer in all three groups and in UIP/IPF-LC developed in the lung periphery and in an advanced fibrosis context. Patients with DLCO% < 38% showed survival < 10 months, irrespective of group and development of carcinoma in UIP/IPF does not necessarily affect survival, unlike in SR-ILD. Our results confirm that the oncogenic mechanism is closely linked to fibrotic and inflammatory processes and that the development of carcinoma affects survival in SR-ILD but not in IPF.

Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective.

Bronchiolitis obliterans syndrome (BOS) is the most common form of CLAD and is characterized by airflow limitation and an obstructive spirometric pattern without high-resolution computed tomography (HRCT) evidence of parenchymal opacities. Computed tomography and microCT analysis show abundant small airway obstruction, starting from the fifth generation of airway branching and affecting up to 40-70% of airways. The pathogenesis of BOS remains unclear. It is a multifactorial syndrome that leads to pathological tissue changes and clinical manifestations. Because BOS is associated with the worst long-term survival in LTx patients, many studies are focused on the early identification of BOS. Markers may be useful for diagnosis and for understanding the molecular and immunological mechanisms involved in the onset of BOS. Diagnostic and predictive markers of BOS have also been investigated in various biological materials, such as blood, BAL, lung tissue and extracellular vesicles. The aim of this review was to evaluate the scientific literature on markers of BOS after lung transplant. We performed a systematic review to find all available data on potential prognostic and diagnostic markers of BOS.

Characterization of NKG2-A/-C, Kir and CD57 on NK Cells Stimulated with pp65 and IE-1 Antigens in Patients Awaiting Lung Transplant.

INTRODUCTION: Cytomegalovirus (CMV) is the leading opportunistic infection in lung transplant (LTx) recipients. CMV is associated with graft failure and decreased survival. Recently, new antiviral therapies have been proposed. The present study aimed to investigate NK and T cell subsets of patients awaiting LTx. We analyzed the cellular populations between reactive and non-reactive QuantiFERON (QF) CMV patients for the prediction of immunological response to infection. METHODS: Seventeen pre-LTx patients and 15 healthy controls (HC) have been enrolled. QF and IFN-γ ELISA assay detections were applied. NK cell subsets and T cell and proliferation assay were detected before and after stimulation with pp-65 and IE-1 CMV antigens after stratification as QF+ and QF-. Furthermore, we quantified the serum concentrations of NK- and T-related cytokines by bead-based multiplex analysis. RESULTS: CD56brCD16lowNKG2A+KIR+ resulted in the best discriminatory cellular subsets between pre-LTx and HC. Discrepancies emerged between serology and QF assay. Better proliferative capability emerged from patients who were QF+, in particular in CD8 and CD25-activated cells. CD56brCD16low, adaptive/memory-like NK and CD8Teff were highly increased only in QF+ patients. CONCLUSIONS: QF more than serology is useful in the detection of patients able to respond to viral infection. This study provides new insights in terms of immunological responses to CMV in pre-LTX patients, particularly in NK and T cells biology.

Air leak and intraoperative bleeding in thoracic surgery: a Delphi consensus among the members of Italian society of thoracic surgery.

Background: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. Methods: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.