Management of malignant pleural effusion in Italian clinical practice: a nationwide survey.

BACKGROUND: Pleural disease (PD), particularly malignant pleural effusion (MPE), is a common cause of hospital admission and its prevalence is rising worldwide. Recent advances in diagnostic and therapeutic options, such as Indwelling Pleural Catheters (IPCs), have simplified PD treatment, allowing an effective outpatients management. Therefore, dedicated pleural services can improve PD care, guaranteeing specialized management and optimizing time and cost. We aimed to provide an overview on MPE management in Italy, mainly focused on distribution and characteristics of pleural services and IPCs use. METHODS: A nationwide survey, endorsed by the Italian Thoracic Society, was distributed by email to members of selected subgroups in 2021. RESULTS: Ninety (23%) members replied, most of whom being pulmonologists (91%). MPE resulted the most common cause of pleural effusion and was managed with heterogenous approaches, including talc pleurodesis via slurry (43%), talc poudrage (31%), repeated thoracentesis (22%) and IPCs insertion (2%). The setting of IPC insertion was inpatient care in 48% of cases, with a predominance of draining frequency every other day. IPC management mainly relied on caregivers (42%). The presence of a pleural service was reported by 37% of respondents. CONCLUSIONS: The present study provides an extensive overview of MPE management in Italy, showing a highly heterogeneous approach, a scarce prevalence of out-patient pleural services, and a still limited adoption of IPCs, mainly due to lack of dedicated community care systems. This survey emphasizes the need of promoting a higher spreading of pleural services and an innovative healthcare delivery with more favourable cost-benefit ratio.

Endoscopic Management of Benign Airway Stenosis in Coronavirus Disease 2019 Patients.

BACKGROUND: The aims of this study were to evaluate the results of endoscopic dilation for simple benign airway stenosis in coronavirus disease 2019 (COVID-19) patients and whether COVID-19 infection was associated with higher rate of recurrence compared with a control group. METHODS: It was an observational multicenter study including consecutive patients with simple benign airway stenosis undergoing endoscopic dilatation with at least 6 months of follow-up. The outcome of patients with COVID-19 infection was compared with that of a control group in relation to patient and stenosis characteristics, and procedure type. Then, univariable and multivariable analyses identified the risk factors for recurrence. RESULTS: Seventy-nine patients were included in the study; 56 (71%) of these developed airway stenosis after COVID-19 infection. COVID-19 patients presented a higher rate of stenosis due to prolonged intubation (82 vs. 43%; p = 0.0014); no other differences were found regarding demographic data, characteristics of stenosis, and procedure type. Twenty-four (30%) patients had recurrence after first dilatation (32% for No-COVID-19 vs. 26% for COVID-19 group; p = 0.70), and in 11 (35%) of these, the stenosis recurred after repeated endoscopic treatment (65% for No-COVID-19 vs. 45% for COVID-19 group; p = 0.40). Subglottic stenosis (p = 0.013) and the use of laser (p = 0.016) were significant predictive factors for stenosis recurrence. CONCLUSION: COVID-19 infection did not affect the outcome of endoscopic treatment of simple airway stenosis, and the treatment of these subsets of patients should not differ from that of general population.

Neutrophil-to-Lymphocyte Ratio Is a Major Prognostic Factor in Non-small Cell Lung Carcinoma Patients Undergoing First Line Immunotherapy With Pembrolizumab.

BACKGROUND/AIM: Lung cancer is one of the most common malignant neoplastic diseases and by far the leading cause of cancer death worldwide. Recently, immune checkpoint inhibitors (ICIs) have received increasing attention for playing a crucial role in non-small cell lung cancer (NSCLC). Biomarkers, such as programmed cell death-ligand 1 (PD-L1) and tumor mutational burden (TMB), seemed to be helpful in selecting patients who are more likely to benefit from ICI treatment: however, their role has not yet been fully clarified. PATIENTS AND METHODS: In this retrospective study, we evaluated the relationship between pre-treatment peripheral blood neutrophil-to-lymphocyte ratio (NLR) and survival in 252 patients suffering from advanced NSCLC who had received pembrolizumab as their first-line immunotherapy. RESULTS: Compared to their NLR low counterparts who had a median overall survival (OS) of 34.8 months, patients with NLRs above 4.8 had a median OS of 7.6 months (HR=3.26, 95%Cl=2.3-4.6, p-value<0.0000001). In multivariate Cox regression analysis, alongside other variables, such as metastatic sites, age, and sex, NLR and PD-L1 predicted progression-free survival and OS; furthermore, a very high NLR - over 10 - seemed to forecast a very dismal prognosis in patients undergoing immunotherapy, with sudden deaths in the days immediately following therapy (median OS=3.8 months). CONCLUSION: NLR acts as a valuable and reliable prognostic factor in non-small cell lung carcinoma patients undergoing first line immunotherapy with pembrolizumab. Additional investigation is necessary to fully elucidate the underlying biological rationale, which can be found in myeloid derived suppressor cells, a heterogeneous population of cells with neutrophil-like immunophenotypic features.

On the Free Vibrations of Non-Classically Damped Locally Resonant Metamaterial Plates.

In this paper, the focus is on the free vibrations of locally resonant metamaterial plates with viscously damped resonators. Upon formulating a dynamic-stiffness model where the resonators are represented via pertinent reaction forces depending on the deflections of the attachment points, the complex eigenvalues are calculated by a contour-integral algorithm introduced in the literature for general nonlinear eigenvalue problems. The interest in the proposed approach is twofold. The dynamic-stiffness model involves a limited number of generalised coordinates compared to the nodal degrees of freedom of a standard finite-element model, and the contour-integral algorithm proves successful in evaluating all complex eigenvalues, without missing any one, with remarkable computational efficiency. Numerical results are presented for Lévy plates, but are readily extendible to other plate theories. Finally, an ad hoc dynamic-stiffness approach is formulated to calculate the frequency response of the plate under arbitrarily placed loads, which is of particular interest to investigate its elastic wave attenuation properties.

Bronchoscopy during COVID-19 pandemic, ventilatory strategies and procedure measures.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has changed bronchoscopy practices worldwide. Bronchoscopy is a high-risk aerosol-generating procedure with a potential for direct SARS-CoV-2 exposure and hospital-acquired infection. Current guidelines about personal protective equipment and environment considerations represent key competencies to minimize droplets dispersion and reduce the risk of transmission. Different measures should be put in field based on setting, patient's clinical characteristics, urgency and indications of bronchoscopy. The use of this technique in SARS-CoV-2 patients is reported primarily for removal of airway plugs and for obtaining microbiological culture samples. In mechanically ventilated patients with SARS-CoV-2, bronchoscopy is commonly used to manage complications such as hemoptysis, atelectasis or lung collapse when prone positioning, physiotherapy or recruitment maneuvers have failed. Further indications are represented by assistance during percutaneous tracheostomy. Continuous positive airway pressure, non-invasive ventilation support and high flow nasal cannula oxygen are frequently used in patient affected by Coronavirus disease 2019 (COVID-19): management of patients' airways and ventilation strategies differs from bronchoscopy indications, patient's clinical status and in course or required ventilatory support. Sedation is usually administered by the pulmonologist (performing the bronchoscopy) or by the anesthetist depending on the complexity of the procedure and the level of sedation required. Lastly, elective bronchoscopy for diagnostic indications during COVID-19 pandemic should be carried on respecting rigid standards which allow to minimize potential viral transmission, independently from patient's COVID-19 status. This narrative review aims to evaluate the indications, procedural measures and ventilatory strategies of bronchoscopy performed in different settings during COVID-19 pandemic.

A case of haemoptysis and bilateral areas of lung consolidation sparing the right lower lobe.

Multiple primary lung cancers (MPLC) are often neglected. Obtaining pre-operative specimens through bronchoscopy could play a role. It is important to distinguish aerogenous metastasis from MPLC in the adenocarcinoma spectrum due to the different prognosis. https://bit.ly/3zbdVrw.

Advanced materials modelling via fractional calculus: challenges and perspectives.

Fractional calculus is now a well-established tool in engineering science, with very promising applications in materials modelling. Indeed, several studies have shown that fractional operators can successfully describe complex long-memory and multiscale phenomena in materials, which can hardly be captured by standard mathematical approaches as, for instance, classical differential calculus. Furthermore, fractional calculus has recently proved to be an excellent framework for modelling non-conventional fractal and non-local media, opening valuable prospects on future engineered materials. The theme issue gathers cutting-edge theoretical, computational and experimental studies on advanced materials modelling via fractional calculus, with a focus on complex phenomena and non-conventional media. This article is part of the theme issue 'Advanced materials modelling via fractional calculus: challenges and perspectives'.

Prognostic value of two geriatric screening tools in a cohort of older patients with early stage Non-Small Cell Lung Cancer treated with hypofractionated stereotactic radiotherapy.

OBJECTIVES: To investigate whether assessment with two geriatric screening tools shows a correlation with clinical outcomes of patients aged 65 years or more, with early-stage Non-Small Cell Lung Cancer (es-NSCLC) treated with hypofractionated stereotactic radiotherapy. METHODS: From March 2014 to June 2018 we retrospectively evaluated 42 patients with stage I and II lung tumors. Patients were assessed with Charlson Comorbidity Index (CCI) and G8 screening tool. Median age was 74 years (range, 65-91). Stereotactic radiotherapy was performed with Helical Tomotherapy delivering 50-70 Gray (Gy) in 8-10 fractions. Toxicity was evaluated using Common Terminology Criteria for Adverse Events v4.0 criteria. RESULTS: Median CCI and G8 scores were 6 (4-11) and 14 (12-17), respectively. With a median follow-up of 14 months (3-37), we observed: 3 cases of acute Grade 2 (G2) radiation pneumonitis, 1 late G2 non-cardiac chest pain, 1 late G2 dysphagia and 1 case of late G2 radiation pneumonitis. At statistical analysis, G8 scores ≤14 were significantly associated with late toxicity rates (p = .0073). Local failure was predictive of disease free survival and Overall Survival (p < .001 and p = .001). Death occurred in 12 patients, 6 for non-cancer related causes, with 1- and 2-yrs cancer specific survival rates of 94.8% and 90%, 1- and 2-yrs OS rates of 93% and 80%, respectively. CONCLUSIONS: Our experience shows a correlation between G8 scores and late toxicity in older patients treated with stereotactic radiotherapy for lung cancer, suggesting the need for prospective studies evaluating its use for the identification of patients at higher risk of adverse events.

Complications related to endoscopic lung volume reduction for emphysema with endobronchial valves: results of a multicenter study.

BACKGROUND: Despite bronchoscopic lung volume reduction (BLVR) with valves is a minimally invasive treatment for emphysema, it can associate with some complications. We aimed at evaluating the rate and type of complications related to valve treatment and their impact on clinical outcomes. METHODS: It is a retrospective multicenter study including all consecutive patients with severe heterogeneous emphysema undergoing BLVR with endobronchial valve treatment and developed any complications related to this procedure. The type of complication, the time of onset, the treatment required and the out-come were evaluated. Response to treatment was assessed according to the minimal clinically important difference (MCID) as follows: an improvement of ≥15% in forced expiratory volume in one second (FEV1); of -8% in residual volume (RV); of ≥26 m in 6-minnute walking distance (6MWD); and of ≥4 points on the St. George's Respiratory Questionnaire (SGRQ). Target lobe volume reduction (TLVR) ≥350 mL was considered significant. RESULTS: One hundred and seven out of 423 (25.3%) treated patients had complications related to valve treatment including pneumothorax (17.3%); pneumonia (1.7%), chronic obstructive pulmonary disease (COPD) exacerbation (0.9%), respiratory failure (1.4%), valve migration (2.1%), and hemoptysis (1.9%). In all cases complications resolved with appropriate treatment including removal of valves in 21/107 cases (19.6%). Patients with TLVR ≥350 mL (n=64) vs. those <350 mL (n=43) had a statistically significant higher improvement in FEV1 (19.0%±3.9% vs. 3.0%±0.9%; P=0.0003); in RV (-10.0%±4.8% vs. -4.0%±2.9%; P=0.002); in 6MWD (33.0±19.0 vs. 12.0±6.3 metres; P=0.001); and in SGRQ (-15.0±2.9 vs. -8.0±3.5 points; P=0.01). Only patients with TLVR ≥350 mL met or exceeded the MCID cut-off criteria for FEV1 (19.0%±3.9%), RV (-10.0%±4.8%), 6MWT (33.0±19.0 metres), and SGQR (-15.0±2.9 points). Five patients (1.2%) died during follow-up for causes not related to valves treatment neither to any of the complications described. CONCLUSIONS: Valve treatment is a safe and reversible procedure. The presence of complications seems not to have a significant impact on clinical outcome in patients with lobar atelectasis. Due to poor clinical conditions and possible complications, BLVR should be performed in high volume centers with a multidisciplinary approach.

Unidirectional endobronchial valves for management of persistent air-leaks: results of a multicenter study.

BACKGROUND: To evaluate the efficacy of Endo-Bronchial Valves in the management of persistent air-leaks (PALs) and the procedural cost. METHODS: It was a retrospective multicenter study including consecutive patients with PALs for alveolar pleural fistula (APF) undergoing valve treatment. We assessed the efficacy and the cost of the procedure. RESULTS: Seventy-four patients with persistent air leaks due to various etiologies were included in the analysis. In all cases the air leaks were severe and refractory to standard treatments. Sixty-seven (91%) patients underwent valve treatment obtaining a complete resolution of air-leaks in 59 (88%) patients; a reduction of air-leaks in 6 (9%); and no benefits in 2 (3%). The comparison of data before and after valve treatment showed a significant reduction of air-leak duration (16.2±8.8 versus 5.0±1.7 days; P<0.0001); chest tube removal (16.2±8.8 versus 7.3±2.7 days; P<0.0001); and length of hospital stay (LOS) (16.2±8.8 versus 9.7±2.8 days; P=0.004). Seven patients not undergoing valve treatment underwent pneumo-peritoneum with pleurodesis (n=6) or only pleurodesis (n=1). In only 1 (14%) patient, the chest drainage was removed 23 days later while the remaining 6 (86%) were discharged with a domiciliary chest drainage removed after 157±41 days. No significant difference was found in health cost before and after endobronchial valve (EBV) implant (P=0.3). CONCLUSIONS: Valve treatment for persistent air leaks is an effective procedure. The reduction of hospitalization costs related to early resolution of air-leaks could overcome the procedural cost.

How Effective and Safe Is Bronchial Thermoplasty in "Real Life" Asthmatics Compared to Those Enrolled in Randomized Clinical Trials?

There is limited information on the efficacy and safety of bronchial thermoplasty (BT) in real life. We evaluated the outcomes of the randomized clinical trials for BT in severe asthmatics, in whom the exclusion criteria were not strictly controlled. A case series of seven asthmatics (M/F: 4/3; age: 54.6 ± 2.9 years) is reported. Subjects had a statistically significant improvement in AQLQ (from a mean of 3.96 ± 1.1 to 4.5 ± 1.2 and 5.5 ± 0.6 after 6 and 12 months of treatment; p = 0.0007) and in the ACQ score (from 2.77 ± 0.8 to 1.83 ± 1.2 and 1.5 ± 0.8 after 6 and 12 months; p < 0.001). In the year after BT, severe exacerbations, salbutamol use, and OCS use were significantly lower compared with the 1-yr pretreatment period (p < 0.001). No ED visits and hospitalization occurred in the year after BT. No changes in functional parameters were recorded. Our investigation confirms the safety and efficacy of BT in severe asthmatics in real life settings.

Sequential Bilateral Bronchoscopic Lung Volume Reduction With One-Way Valves for Heterogeneous Emphysema.

BACKGROUND: Clinical benefits of bronchoscopic lung volume reduction with one-way endobronchial valves have been reported for heterogeneous emphysema after unilateral treatment. We assessed the potential role of contralateral treatment to prolong the benefits obtained with the first procedure. METHODS: This was a retrospective multicenter study including consecutive patients with heterogeneous emphysema undergoing bronchoscopic valves deployment during the last 4 years. Patients were split into two groups depending on the procedure (unilateral versus bilateral). The intergroup differences were evaluated to assess the viability, effectiveness, and safety of the bilateral procedure. RESULTS: Forty-nine patients were enrolled. Of these, 14 (28%) had a sequential bilateral procedure mainly due to loss of the clinical benefits obtained with the first treatment. A significant improvement of forced expiratory volume in 1 second (p < 0.05), forced vital capacity (p < 0.05), residual volume (p < 0.05), 6-minute walking test (p < 0.05), and St. George respiratory questionnaire (p < 0.02) was achieved after the second procedure. These results were maintained during follow-up. There was no significant difference regarding the changes of forced expiratory volume in 1 second (p = 0.4), forced vital capacity (p = 0.08), residual volume (p = 0.9), 6-minute walking test (p = 0.3), and St. George respiratory questionnaire (p = 0.1) between the bilateral and unilateral groups. CONCLUSIONS: A sequential bilateral approach seems to be a valid strategy to improve respiratory function in patients with bilateral heterogeneous emphysema who have lost the benefits obtained with the first procedure.

Seismic analysis of offshore wind turbines on bottom-fixed support structures.

This study investigates the seismic response of a horizontal axis wind turbine on two bottom-fixed support structures for transitional water depths (30-60 m), a tripod and a jacket, both resting on pile foundations. Fully coupled, nonlinear time-domain simulations on full system models are carried out under combined wind-wave-earthquake loadings, for different load cases, considering fixed and flexible foundation models. It is shown that earthquake loading may cause a significant increase of stress resultant demands, even for moderate peak ground accelerations, and that fully coupled nonlinear time-domain simulations on full system models are essential to capture relevant information on the moment demand in the rotor blades, which cannot be predicted by analyses on simplified models allowed by existing standards. A comparison with some typical design load cases substantiates the need for an accurate seismic assessment in sites at risk from earthquakes.

New perspectives in offshore wind energy.

The design of offshore wind turbines is one of the most fascinating challenges in renewable energy. Meeting the objective of increasing power production with reduced installation and maintenance costs requires a multi-disciplinary approach, bringing together expertise in different fields of engineering. The purpose of this theme issue is to offer a broad perspective on some crucial aspects of offshore wind turbines design, discussing the state of the art and presenting recent theoretical and experimental studies.

The mechanically based non-local elasticity: an overview of main results and future challenges.

The mechanically based non-local elasticity has been used, recently, in wider and wider engineering applications involving small-size devices and/or materials with marked microstructures. The key feature of the model involves the presence of non-local effects as additional body forces acting on material masses and depending on their relative displacements. An overview of the main results of the theory is reported in this paper.

A phase II study of carboplatin and paclitaxel as first line chemotherapy in elderly patients with advanced non-small cell lung cancer (NSCLC).

INTRODUCTION: Lung cancer is the leading cause of tumour-related deaths in the elderly population but the optimal management of advanced NSCLC in older patients has not been defined to date. The present phase II study was planned to evaluate the efficacy and toxicity of the combination of carboplatin and paclitaxel in elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients (>70 years old) who had pathologically been proven to have a NSCLC and measurable lesions were treated with paclitaxel (175 mg/m2 for 3h) and carboplatin [area under the concentration-time curve (AUC=5)] on day 1 every 3 weeks. RESULTS: Forty patients were enrolled into the study. The median age was 74 years (range, 70-78 years). Approximately 85% of the patients had stage IV and 80% had a performance status (PS) of 0-1. Nine of the 40 (22.5%; 90% CI 17.6-28.1) included patients had a partial response; one patient (2.5%; 90% CI 1.7-3.2) achieved a complete response. The overall response rate was 25% (90% CI 15.3-38.6). In addition stable disease was observed in 13 patients (32.5%; 90% CI 24.3-40.7). The median survival was 7.8 months (95% confidence interval, 5.1-11.8 months). The actual 1-year survival was 18% (95% confidence interval, 12-29%). The median time to disease progression was 4.1 months (95% CI 2.8-8.5). Overall, 37.5% of patients experienced grade 3-4 neutropenia of any duration with only two patients (5%) developing neutropenic fever. Grade 3 or 4 non-haematological toxicity was uncommon apart alopecia. CONCLUSIONS: In the present phase II study the combination of paclitaxel and carboplatin has demonstrated to be active and safe in an age-selected population.

Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study.

INTRODUCTION: The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-treated patients, limited therapeutic option is available and the results of availability therapies reported in literature are disappointing. The present phase II study was designed to assess the efficacy and safety of temozolomide (TMZ) as palliative treatment for brain metastases (BrM) in NSCLC patients pre-treated with WBRT and at least one line of chemotherapy for metastatic brain disease. MATERIAL AND METHODS: Temozolomide was administered orally at 150 mg/mq/day for five consecutive days for the first cycle, doses were increased to 200 mg/mq/day for 5 days every 28 days for subsequent cycles if no grade 3/4 haematological toxicity was observed. Eligibility criteria included cytological or histological confirmed NSCLC; BrM, recurrent or progressing after WBRT and at least one line of chemotherapy. A total of 30 consecutive patients entered the study and received the allocated treatment. RESULTS: Three patients (10%) achieved an objective response (OR) of BrM with two complete remission. Stable disease and progressive disease were achieved in 3 (10%) and 24 patients (80%), respectively. A correlation between response to TMZ and sensitivity to the previous first line chemotherapy was reported. Time to progression and overall survival were examined both for responder patients and for all included patients. For long-term survivors, we considered the patients who survived >12 months after the start of TMZ. According to this definition, three patients resulted long-term survivors: 2 with OR and 1 with stable brain disease. No grades 3 or 4 toxicity occurred. The total of treatment-related adverse events were mild or moderate (G1-2) in intensity. No patients discontinued TMZ as a result of treatment-related toxicity. DISCUSSION: The results of the present trial clearly demonstrates that TMZ is active and safe in BrM NSCLC patients previously treated with WBRT and at least one line of chemotherapy.