BACKGROUND AND OBJECTIVES:Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP). METHODS:A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements. RESULTS:The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502). CONCLUSIONS:Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited.

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.

The incidence of non-malignant pleural effusions far outweighs that of malignant pleural effusions and is estimated to be at least 3-fold higher. These so-called benign effusions do not follow a " benign course" in many cases, with mortality rates matching and sometimes exceeding those of malignant pleural effusions. In addition to the impact on patients, healthcare systems are also significantly affected, with recent US epidemiological data demonstrating that 75% of resource allocation for pleural effusion management is spent on non-malignant pleural effusions (excluding empyema). Despite this significant burden of disease, and by existing at the junction of multiple medical specialties, reflecting a heterogenous constellation of medical conditions, non-malignant pleural effusions are rarely the focus of research or the subject of management guidelines. With this European Respiratory Society Task Force, we assembled a multispecialty collaborative across 11 countries and three continents to provide a statement based on systematic searches of the medical literature to highlight evidence in the management of the following clinical areas: a diagnostic approach to transudative effusions, heart failure, hepatic hydrothorax, end-stage renal failure, benign asbestos-related pleural effusion, post-surgical effusion and nonspecific pleuritis.

Background: Few studies have assessed the differences of patterns of Long COVID (L-COVID) with regards to the pathogenetic SARS-CoV-2 strains. Objectives: To investigate the relationship between demographic and clinical characteristics of acute phase of infection and the persistence of L-COVID symptoms and clinical presentation across different SARS-CoV-2 strains. Methods: In this observational-multicenter study we recorded all demographic and clinical characteristics, severity of infection, presence/persistence of symptoms of fatigue, dyspnoea and altered quality of life (QoL) at baseline and after 6 months, in a sample of Italian patients from Liguria between March 2020 and March 2022. Results: 308 patients (mean age 63.2 years; 55.5% men) with previous COVID were enrolled. Obese patients were 21.2% with a significant difference in obesity prevalence across the second and third wave (p = 0.012). Treatment strategies differed between waves (p < 0.001): more patients required invasive mechanical ventilation in the first wave, more patients were treated with high-flow nasal cannula/non-invasive ventilation in the in the second and more patients were treated with oxygen-therapy in the fourth wave. At baseline, a high proportion of patients were symptomatic (dyspnoea and fatigue), with impairment in some QoL indicators. A higher prevalence of patients with pain, were seen in the first wave compared to later infections (p = 0.01). At follow-up, we observed improvement of dyspnoea, fatigue and some dimensions of QoL scale evaluation such as mobility, usual activities, pain evaluations; instead there was no improvement in remaining QoL scale indicators (usual care and anxiety-depression). Conclusions: There were no significant differences in the prevalence of the most frequent L-COVID symptoms, except for QoL pain domain that was especially associated with classical variant. Our results show substantial impact on social and professional life and usual care activities. These findings highlight the importance of multidisciplinary post COVID follow-up care including mental health support and rehabilitation program.

Background: As many as 25% patients with a histological diagnosis of NSP at a thoracoscopic biopsy are eventually diagnosed with a malignancy, mostly mesothelioma, over the following months. Aim: to evaluate the value of pleural effusion levels of soluble mesothelin-related peptides (PE-SMRP) as a diagnostic tool in patients with histological diagnosis of NSP. Methods: All patients with an exudative pleural effusion and a histological diagnosis of NSP at thoracoscopic biopsies performed between Jenuary 2008 and December 2020 were followed for 18 months. A predefined cut-off level of 20 nM PE-SMRP, based on published data, was used to distinguish high- from low- PE-SMRP patients. A binary logistic regression was used to measure the relative risk of a later diagnosis of cancer. Results: Of the 185 patients with a diagnosis of NSP, 17 (9.2%) were diagnosed with cancer during follow-up (mean 6.38 months). A malignancy was diagnosed in 9 of the 15 high-PE-SMRP patients (60%), and in 8 of the 170 low-PE-SMRP patients (4.7%) (p<0.0001). High-PE-SMRP patients had a higher risk of being diagnosed with mesothelioma at follow-up (OR 31.2, 95% IC 8.5-114.7) (table 1).). Each nM increase in PE-SMRP increased the risk of a final diagnosis of mesothelioma by 1.07-fold (p<0.001). Conclusions: Patients with high levels of PE-SMRP are at increased risk of cancer after an initial histological diagnosis of NSP and might benefit from a closer follow-up.

To evaluate the possible prognostic significance of the development of peripheral consolidations at chest x-ray in COVID-19 pneumonia, we retrospectively studied 92 patients with severe respiratory failure (PaO2/FiO2 ratio < 200 mmHg) that underwent at least two chest x-ray examinations (baseline and within 10 days of admission). Patients were divided in two groups based on the evolution of chest x-ray toward the appearance of peripheral consolidations or toward a greater extension of the lung abnormalities but without peripheral consolidations. Patients who developed lung abnormalities without peripheral consolidations as well as patients who developed peripheral consolidations showed, at follow-up, a significant worsening of the PaO2/FiO2 ratio but a significantly lower mortality and intubation rate was observed in patients with peripheral consolidations at chest x-ray. The progression of chest x-ray toward peripheral consolidations is an independent prognostic factor associated with lower intubation rate and mortality.

A 50-year-old man, a current smoker with a history of alcohol abuse, presented to the emergency room with fever, breathlessness, palpitations, and occasional cough with hemoptysis. He was found with respiratory failure; atrial fibrillation, with a high mean ventricular response, elevated white blood cell count, and high inflammatory indices. Chest radiography revealed abundant right hydropneumothorax, and ultrasonography was suggestive of pyopneumothorax. Therapy with oxygen supplement, beta-blocker, calcium channel blocker, anticoagulant, antibiotic, and antipyretic was needed. After the initial medical treatment, a large-bore (24-French [Fr]) chest tube was placed. Abundant creamy and foul-smelling pus flowed out from the pleural space, together with many air bubbles. Colonies of methicillin-resistant Staphylococcus aureus (MRSA) grew in the pleural fluid cultures. Despite clinical improvement, chest computed tomography (CT) showed incomplete expansion of the right lung, with persistence of pneumothorax and a small amount of pleural effusion. It also documented irregular excavated lung hyperdensity resulting from necrotizing pneumonia, with peripheral bronchopleural fistula (BPF). Medical thoracoscopy revealed pleural thickening and tenacious adhesions between the lung and the pleura, which could not be removed. The histology of parietal pleural biopsies showed negative results for malignancy. The patient finally underwent thoracotomy with lysis of adhesions, suture of BPF, and decortication for lung re-expansion. This chapter deals with the diagnosis and management of BPF caused by necrotizing pneumonia. It also discusses the ultrasound appearance of empyema and choosing the ideal chest drain insertion site.

Background: LUS is used to define the severity and prognosis of Covid-19 patients. Over the last 12 months, anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively used to treat COVID-19. Aim: To evaluate if LUS may predict hospitalization in COVID-19 patients treated with mAbs. Methods: We enrolled consecutive outpatients with mild/moderate Covid-19 who received an intravenous infusion of mAbs between August and November 2021. Before the infusion the patients underwent complete LUS, 14 areas/patient were scanned and a LUS score from 0 (best) to 42 (worst) was assigned according to the Soldati score. The scores for patients hospitalized and non-hospitalized within 21 days of mAbs infusion were compared; sensitivity and specificity for different cut-off values were calculated by means of ROC curve analysis. Results:38 consecutive patients (53% male; median age 66 years) were included. There was a significant difference between LUS score in non-hospitalized and hospitalized patients (1 [3] vs. 13 [5] respectively, median [IQR], p<0,001), Fig.1. ROC curve analysis showed that a cut off value of 8 had a sensitivity and specificity of 100% in predicting hospitalization. Conclusions: Our data show a significant association between LUS score at the time of mAbs administration and subsequent hospitalization demonstrating that LUS effectively predicts the need for hospitalization.

For a long time, Medical Thoracoscopy (MT) has played a marginal role in the management of pleural infection but in recent years his role has become more established. Pleural empyema defined as pus in the pleural cavity has been subdivided on the basis of ultrasonography and endoscopic appearance into 3 stages: free-flowing effusion (stage 1), multiloculated with a tendency toward loculations (stage 2) and chronic fibrous thickening involving also visceral pleural (stage 3). (Fig.1) Aim: The aim of this study was to evaluate efficacy and safety of medical thoracoscopy in patients with all stages of infectious pleural effusion Methods: We performed a retrospective study of patients referred for empyema and treated by medical thoracoscopy at Brescia and Sarzana pleural disease departments from December 2016 to December 2019. All patients underwent ultrasonography to localize and to stage pleural fluid collection and received MT with rigid thoracoscope to identify and break down fibrous pleural adhesions. Results: A total of 83 patients with empyema were treated by medical thoracoscopy; empyema was stage 1 in 6 patients ( 7,2%), stage 2 in 44 patients (53 %), and stage 3 in 33 patients ( 39,8%). MT was successful without further intervention in 79 patients (95,2%): all patients with stage 1 and 2 and 29 patients with stage 3 organizing effusion. Only 4 (12%) of the 33 patients with stage 3 required surgical intervention. Conclusion: pleural empyema, as stratified by ultrasonography, can safely and successfully be treated by MT in particular if performed in early stages of infection.

INTRODUCTIONClinical practice guidelines need rigorous and transparent methods for summarizing the evidence, rate its certainty and moving from evidence to recommendations. We describe an intervention to support local efforts to provide optimal and safer care bridging the gap between researchers and local busy clinicians.METHODSA group of methodologists provided a wide range of research services to the medical community of a local non-teaching general hospital in Italy. Methodological support encompassed synthesis of evidence, rating of uncertainty and moving from evidence to recommendations. Local professionals were asked to judge GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology and its impact on patients' safety, professional liability, and guideline reliability. The research team then reflected on the barriers of implementing GRADE in local settings.RESULTSSeven clinical recommendations about frequent complex medical conditions were produced. Few local clinicians completed the project. All clinicians found the GRADE methodology a guarantee for defending excellent standards of care. However, we identified a diffuse sense of inability to improve clinical behaviours as negative effects of general poor working conditions, in particular the strained health care workforce.DISCUSSIONCurrent financial constraints may be impeding the ability of clinicians in improving their clinical practice through adaptation and use of evidence. A successful integration of evidence-based guidelines cannot be separated from an activate promotion by the institutional management.

Uomo di 61 anni, ex fumatore da 10 anni (pack-year 20), avvocato. All’anamnesi patologica pregresso ictusischemico nel 2010 senza esiti funzionali; diabete mellito in terapia con ipoglicemizzanti orali; cardiopatia ischemicacronica e pregressa angioplastica con posizionamento di stent su coronaria destra e marginale nel 2017; insufficienzarenale cronica secondaria a glomerulonefrite non precisata (non eseguita biopsia) evoluta fino allo stadiodi “end stage renal disease” e in trattamento emodialitico dal 2016, ora in fase di valutazione per trapianto renale. (...)

Background: TTP is one of the most effective pleurodesis methods in MPE but its optimal timing is not well-defined. While some groups perform thoracoscopic pleurodesis on the basis of endoscopic malignancy appearance during diagnostic medical thoracoscopy (MT), others wait for a definitive histological diagnosis. Aim: to evaluate if the presence of thoracoscopic features of neoplastic pleural involvement predicts the final diagnosis of malignancy and if TTP decreases PE recurrence in these cases. Methods: We included consecutive patients, among those referred for MT to two pleural units (1, Brescia and 2, Sarzana), with unilateral PE and an endoscopic appearance of malignant pleural involvement (nodules, masses, thickenings or mixed lesions). During MT all patients received pleural biopsies but only the patients referred to unit 1 received TTP. All cases with recurrent symptomatic PE that required drainage in the following 3 months were deemed as failures. Results: 62 patients (59 malignancies) were included (32/group). The positive predictive value of endoscopic appearance was 100% for nodules, masses and mixed lesions, 82.4% for thickenings. In group 1, the recurrence of PE was significantly lower than in group 2 (6.7% vs 56.7%, p<0.001; chi-square). The median time to recurrence of PE in the failure cases was 15 days. Conclusion: The accuracy of endoscopic appearance of malignancy was high, particularly in the presence of nodules, masses and mixed lesions. In the presence of these lesions, TTP might be warranted prior to final histological diagnosis to reduce recurrence of PE and the ensuing necessity for reintervention. Caution is necessary when thickening is the only feature.

Diseases of the pleura and pleural space are common and present a significant contribution to the workload of respiratory physicians, with most cases resulting from congestive heart failure, pneumonia, and cancer. Although the radiographic and ultrasonographic detection of pleural abnormalities may be obvious, the determination of a specific diagnosis can often represent a challenge. Invasive procedures such as pleural drainage, ultrasound/CT-guided pleural biopsy or medical thoracoscopy can be useful in determining specific diagnosis of pleural diseases. Management of primary and secondary spontaneous pneumothorax is mandatory in an interventional pulmonology training program, while the medical or surgical treatment of the recurrence is still a matter of discussion. Pleural drainage is a diagnostic and therapeutic procedure used in the treatment of pneumothorax and pleural effusions of different etiologies and even in palliation of symptomatic in malignant pleural effusion. Medical thoracoscopy (MT) is a minimally invasive procedure aimed at inspecting the pleural space. It could be a diagnostic procedure in pleural effusions (suspected malignant pleural effusion, infective pleural disease such as empyema or tuberculosis) or therapeutic procedure (chemical pleurodesis or opening of loculation in empyema). Diagnostic yield is 95% in patients with pleural malignancies and higher in pleural tuberculosis. In parapneumonic complex effusion, MT obviates the need for surgery in most cases. Thoracoscopy training should be considered being as important as bronchoscopy training for interventional pulmonology, although prior acquisition of ultrasonography and chest tube insertion skills is essential.