Low-intensity rehabilitation in persistent post COVID-19 dyspnoea: the value of Spa health resort as appropriate setting.

Background: Post COVID-19 syndrome is a frequent disabling outcome, leading to a delay in social reintegration and return to working life. Study design: This was a prospective observational cohort study. The main objective was to explore the effectiveness of a Spa rehabilitation treatment on the improvement of post COVID-19 dyspnoea and fatigue, also analyzing the relationship between such symptoms. Additionally, it was assessed if different clinical characteristics could predispose patients in experiencing post COVID-19 symptoms or could influence the effectiveness of a Spa intervention. Methods: From July to November 2021, 187 post COVID-19 patients were enrolled in the study. All the patients complained persi-sting dyspnoea, whose impact on daily activities was assessed using the modified Medical Research Council dyspnoea scale. 144 patients (77.0%) reported also fatigue. The Spa treatment was started at least 3 months after COVID-19 acute phase. At the end of the treatment, patients were asked to rate the improvement in the dyspnoea and fatigue sensation. 118 patients also underwent the modified Borg Dyspnoea Scale for severity estimation of Exertion Dyspnoea and the Barthel index for severity estimation of Physical Limitation. Results: 165 out of 187 patients (88.2%) reported an improvement in dyspnoea, while 116 out 144 patients (80.6%) reported an improvement in both dyspnoea and fatigue. On a total of 118 subjects, a clinically significant improvement in the modified Borg Dyspnoea Scale (i.e. Delta Borg equal or more than -2.0 points) was reached by the 50.8% of patients, while a clinically significant improvement in the Barthel index (i.e. Delta Barthel equal or more than +10.0 points) was reached by the 51.7% of them. The 31.4% of patients reached a minimal clinically important improvement in both the modified Borg Dyspnoea Scale and the Barthel index. No risk factors were associated to a clinically impacting dyspnoea at entry, while a BMI>30 Kg/m2 was the main risk factor for chronic fatigue. Presence of respiratory comorbidities, obesity and severe acute COVID-19 (phenotype 4) configured risk factors for the lack of improvement of dyspnoea after the treatment, while no risk factors were associated to a lack of improvement for fatigue. Older age, obesity and comorbidities seemed to make more difficult to reach a clinically meaningful improvement in the modified Borg Dyspnoea Scale and the Barthel index after treatment. Female gender may imply more physical limitation at entry, while male patients seem to show less improvement in the Barthel index after treatment. Conclusions: Dyspnoea and fatigue were confirmed to be important post COVID-19 symptoms even in younger subjects of wor-king age and subjects with absent or modest pulmonary alterations at distance from acute COVID-19. A Spa health resort seems to be an effective "low-intensity" setting for a rehabilitation program of such patients. There is a strong relationship in terms of improvement between dyspnoea and fatigue, even if risk factors for their occurrence appear to be different. The improvement in exertion dyspnoea and physical limitation seemed to be less mutually related, probably due to a greater complexity in the asses-sment questionnaires. Some risk factors may predict a lack of improvement in symptoms after treatment.

Clinical Remission in Patients Affected by Severe Eosinophilic Asthma on Dupilumab Therapy: A Long-Term Real-Life Study.

Background. Nowadays, highly selective biological drugs offer the possibility of treating severe type 2 asthma. However, in the real-life setting, it is crucial to confirm the validity of the chosen biological treatment by evaluating the achievement of clinical remission. Study purpose. The main aims of this real-life study were to evaluate the efficacy of dupilumab in terms of clinical, functional, and inflammatory outcomes at 6, 12, 18, and 24 months of treatment and to estimate the percentage of patients achieving partial or complete clinical remission at 12 and 24 months of treatment. In addition, we attempted to identify whether baseline clinical characteristics of patients could be associated with clinical remission at 24 months of treatment. Materials and methods. In this observational prospective study, 20 outpatients with severe uncontrolled eosinophilic asthma were prescribed dupilumab and followed-up after 6, 12, 18, and 24 months of treatment. At each patient visit, the need for oral corticosteroids (OCS) and corticosteroid required dose, number of exacerbations during the previous year or from the previous visit, asthma control test (ACT) score, pre-bronchodilator forced expiratory volume in the 1st second (FEV1), fractional exhaled nitric oxide at a flow rate of 50 mL/s (FeNO50), and blood eosinophil count were assessed. Results. The number of OCS-dependent patients was reduced from 10 (50%) at baseline to 5 (25%) at one year (T12) and 2 years (T24). The average dose of OCS required by patients demonstrated a significant reduction at T12 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.015), remaining significant even at T24 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.016). The number of exacerbators showed a statistically significant decrease at T24 (10 patients, 50% vs. 3 patients, 15%, p = 0.03). The mean number of exacerbations demonstrated a statistically significant reduction at T24 (1.45 ± 1.58 vs. 0.25 ± 0.43, p = 0.02). The ACT score improved in a statistically significant manner at T12 (15.30 ± 4.16 vs. 21.40 ± 2.35, p < 0.0001), improving further at T24 (15.30 ± 4.16 vs. 22.10 ± 2.59, p < 0.0001). The improvement in pre-bronchodilator FEV1 values reached statistical significance at T24 (79.5 ± 14.4 vs. 87.7 ± 13.8, p = 0.03). The reduction in flow at the level of the small airways (FEF25-75%) also demonstrated an improvement, although it did not reach statistical significance either at T12 or T24. A total of 11 patients (55%) showed clinical remission at T12 (6 complete + 5 partial) and 12 patients (60%) reached clinical remission at T24 (9 complete + 3 partial). Only obesity was associated with a negative odds ratio (OR) for achieving clinical remission at T24 (OR: 0.03, 95% CI: 0.002-0.41, p = 0.004). No other statistically significant differences in baseline characteristics emerged between patients who reached clinical remission at T24 and the group of patients who did not achieve this outcome. Conclusion. Dupilumab appears to be an effective drug in promoting achievement of clinical remission in patients with severe uncontrolled eosinophilic asthma. The achievement of clinical remission should be continuously evaluated during treatment. Further studies are needed to clarify whether certain baseline clinical characteristics can help predict dupilumab favorable outcomes.

MiRNA and Exosomal miRNA as New Biomarkers Useful to Phenotyping Severe Asthma.

Severe asthma (SA) is a chronic inflammatory disease of the airways. Due to the extreme heterogeneity of symptoms, new biomarkers are currently needed. MiRNAs are non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In biological fluids, miRNAs are contained within exosomes, vesicles capable of giving miRNAs considerable stability and resistance to degradation by RNAses. The main function attributed to the exosomes is intercellular communication. The goal of our study was to analyze intracellular and exosomal miRNAs in order to demonstrate their potential use as non-invasive biomarkers of asthma by showing, in particular, their role in SA. We detected miRNAs by qRT-PCR in both serum and serum-derived-exosomes of asthmatic patients and healthy controls. The levels of almost all analyzed intracellular miRNAs (miR-21, miR-223, and let-7a) were greater in asthmatic patients vs. healthy control, except for miR-223. In detail, miR-21 was greater in SA, while let-7a increased in mild-to-moderate asthma. On the other hand, in exosomes, all analyzed miRNAs were higher in SA. This study identified a series of miRNAs involved in SA, highlighting their potential role in asthma development and progression. These results need validation on a larger cohort.

Switching Biological Therapies in Severe Asthma.

Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.

Thoracic ultrasound combined with low-dose computed tomography may represent useful screening strategy in highly exposed population in the industrial city of Taranto (Italy).

Objectives: We validated a screening protocol in which thoracic ultrasound (TUS) acts as a first-line complementary imaging technique in selecting patients which may deserve a second-line low-dose high resolution computed tomography (HRCT) scan among a population of asymptomatic high-risk subjects for interstitial lung abnormalities (ILA) and lung cancer. Due to heavy environmental pollution burden, the district Tamburi of Taranto has been chosen as "case study" for this purpose. Methods: From July 2018 to October 2020, 677 patients aged between 45 and 65 year and who had been living in the Tamburi district of Taranto for at least 10 years were included in the study. After demographic, clinical and risk factor exposition data were collected, each participant underwent a complete TUS examination. These subjects were then asked to know if they agreed to perform a second-level examination by low-dose HRCT scan. Results: On a total of 167 subjects (24.7%) who agreed to undergo a second-level HRCT, 85 patients (50.9%) actually showed pleuro-pulmonary abnormalities. Interstitial abnormalities were detected in a total of 36 patients on HRCT scan. In particular, 34 participants presented subpleural ILAs, that were classified in the fibrotic subtype in 7 cases. The remaining 2 patients showed non-subpleural interstitial abnormalities. Subpleural nodules were observed in 46 patients. TUS showed an overall diagnostic accuracy of 88.6% in detecting pleuro-pulmonary abnormalities in comparison with HRCT scan, with a sensitivity of 95.3%, a specificity of 81.7%, a positive predictive value of 84.4% and a negative predictive value of 94.4%. The matched evaluation of specific pulmonary abnormalities on HRTC scan (i.e., interstitial abnormalities or pulmonary nodules) with determinate sonographic findings revealed a reduction in both TUS sensibility and specificity. Focusing TUS evaluation on the assessment of interstitial abnormalities, a thickened pleural line showed a sensitivity of 63.9% and a specificity of 69.5%, hypoechoic striae showed a sensitivity of 38.9% and a specificity of 90.1% and subpleural nodules showed a sensitivity of 58.3% and a specificity of 77.1%. Regarding to the assessment of subpleural nodules, TUS showed a sensitivity of 60.9% and a specificity of 81.0%. However, the combined employment of TUS examination and HRCT scans allowed to identify 34 patients with early subpleural ILA and to detect three suspicious pulmonary nodules (of which two were intraparenchymal and one was a large subpleural mass), which revealed to be lung cancers on further investigations. Conclusion: A first-line TUS examination might aid the identification of subjects highly exposed to environmental pollution, who could benefit of a second-line low-dose HRCT scan to find early interstitial lung diseases as well as lung cancer. Protocol registration code: PLEURO-SCREENING-V1.0_15 Feb, 17.

[Inclusion of vaccination into clinical pathways for COPD and asthma: current challenges and future perspectives in Italy]. / La vaccinazione dei pazienti con BPCO e Asma nei PDTA in Italia: gap da colmare e prospettive future.

OBJECTIVES: to describe the importance given to vaccination as a preventive measure in the clinical pathways (CPWs) of patients affected by chronic obstructive pulmonary disease (COPD) and asthma in the Italian regional healthcare services. DESIGN: a comparative analysis was conducted to assess the presence/absence of vaccination recommendations among the available regional CPWs for the management of COPD and asthma. SETTING AND PARTICIPANTS: all the regional CPWs for COPD and asthma available in the "Fondazione ReS" database between 2008 and 2019 have been analysed. MAIN OUTCOME MEASURES: the role attributed to vaccination was assessed in terms of type of recommended vaccinations, management step indicated for administration, vaccination schedules, healthcare professionals involved in the vaccination pathway, potential contraindications, use of indicators for the monitoring of the offer. RESULTS: thirteen CPWs for COPD and only 3 for asthma were published between 2008 and 2019. Twelve of the CPWs for COPD included recommendation for influenza vaccination, 11 of which including also pneumococcal vaccination. The most recent CPW also contained recommendations for measles-mumps-rubella, varicella, Herpes Zoster, and tetanus-diphtheria-acellular pertussis vaccinations. Two of the CPWs related to asthma in adults recommended influenza vaccination. All CPWs provided for the vaccination recommendations during the patient follow-up step. CONCLUSIONS: Italian CPWs still pay little attention to the topic of vaccinations in patients with COPD and asthma. CPWs are required to be updated in the future being compliant with the national immunization schedule recommendations.

A Review on Biological Effects of Ultrasounds: Key Messages for Clinicians.

Ultrasound (US) is acoustic energy that interacts with human tissues, thus, producing bioeffects that may be hazardous, especially in sensitive organs (i.e., brain, eye, heart, lung, and digestive tract) and embryos/fetuses. Two basic mechanisms of US interaction with biological systems have been identified: thermal and non-thermal. As a result, thermal and mechanical indexes have been developed to provide a means of assessing the potential for biological effects from exposure to diagnostic US. The main aims of this paper were to describe the models and assumptions used to estimate the "safety" of acoustic outputs and indices and to summarize the current state of knowledge about US-induced effects on living systems deriving from in vitro models and in vivo experiments on animals. This review work has made it possible to highlight the limits associated with the use of the estimated safety values of thermal and mechanical indices relating above all to the use of new US technologies, such as contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) shear wave elastography (SWE). US for diagnostic and research purposes has been officially declared safe, and no harmful biological effects in humans have yet been demonstrated with new imaging modalities; however, physicians should be adequately informed on the potential risks of biological effects. US exposure, according to the ALARA (As Low As Reasonably Achievable) principle, should be as low as reasonably possible.

Contrast-Enhanced Ultrasound in Distinguishing between Malignant and Benign Peripheral Pulmonary Consolidations: The Debated Utility of the Contrast Enhancement Arrival Time.

Background. Limited studies and observations conducted on a too small number of patients prevent determining the actual clinical utility of pulmonary contrast-enhanced ultrasound (CEUS). The aim of the present study was to examine the efficacy of contrast enhancement (CE) arrival time (AT) and other dynamic CEUS findings for differentiating between malignant and benign peripheral lung lesions. Methods. 317 inpatients and outpatients (215 men, 102 women; mean age: 52 years) with peripheral pulmonary lesions were included in the study and underwent pulmonary CEUS. Patients were examined in a sitting position after receiving an intravenous injection of 4.8 mL of sulfur hexafluoride microbubbles stabilized by a phospholipid shell as ultrasound contrast agent (SonoVue-Bracco; Milan, Italy). Each lesion was observed for at least 5 min in real-time and the following temporal characteristics of enhancement were detected: the arrival time (AT) of microbubbles in the target lesion; the enhancement pattern; the wash-out time (WOT) of microbubbles. Results were then compared in light of the definitive diagnosis of community acquired pneumonia (CAP) or malignancies, which was not known at the time of CEUS examination. All malignant cases were diagnosed by histological results, while pneumonia was diagnosed on the basis of clinical and radiological follow-up, laboratory findings and, in some cases, histology. Results. CE AT has not been shown to differ between benign and malignant peripheral pulmonary lesions. The overall diagnostic accuracy and sensibility of a CE AT cut-off value < 10 s in discriminating benign lesions were low (diagnostic accuracy: 47.6%; sensibility: 5.3%). Poor results were also obtained in the sub-analysis of small (mean diameter < 3 cm) and large (mean diameter > 3 cm) lesions. No differences were recorded in the type of CE pattern showed between benign and malignant peripheral pulmonary lesions. In benign lesions we observed a higher frequency of delayed CE wash-out time (WOT) > 300 s. Anyhow, a CE WOT cut-off value > 300 s showed low diagnostic accuracy (53.6%) and sensibility (16.5%) in discriminating between pneumonias and malignancies. Similar results were also obtained in the sub-analysis by lesion size. Squamous cell carcinomas showed a more delayed CE AT compared to other histopathology subtypes. However, such a difference was statistically significant with undifferentiated lung carcinomas. Conclusions. Due to an overlap of CEUS timings and patterns, dynamic CEUS parameters cannot effectively differentiate between benign and malignant peripheral pulmonary lesions. Chest CT remains the gold standard for lesion characterization and the eventual identification of other pneumonic non-subpleural localizations. Furthermore, in the case of malignancy, a chest CT is always needed for staging purposes.

Economic impact of implementing prescription of single-inhaler triple therapies versus current multiple-inhaler triple therapies for COPD in the Apulia Region.

BACKGROUND: The most impacting direct costs associated to COPD for the National Health Systems (NHS) are those related to accesses to the emergency room and hospital admissions, due to the onset of one or more COPD exacerbations. At the same time, severe COPD treatment, that often require a combination of medicaments, represents a substantial economic burden for the National Health Systems (NHS). This study aimed to evaluate the potential saving deriving from the implementation in the prescription of the two currently available single-inhaler triple therapies (SITTs) versus the currently used multiple-inhaler triple therapies (MITTs) in an eligible COPD population residing in the Apulia Region. METHODS: A budget impact model was developed hypothesizing the progressive replacement of the different MITTs on the reference market (Scenario A) with the pre-established SITTs, assuming a degree of penetration of 30%, 50% and 100% (Scenario B). Drug costs were based on prices published on the Official Gazette and therapy durations were based on prescribing information over the year 2019 (IQVIA™ prescription dataset). RESULTS: Our analysis showed that the extemporaneous MITT with the highest prevalence on the reference market was the inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) combination plus a long-acting muscarinic antagonists (LAMA). This association of medicaments was paradoxically also the one associated to the highest expense value. The expanded use of a pre-established ICS/LAMA/LABA SITT was associated to a significant economic saving, ranging from a minimum of -€ 1,108,814 (SITT use: 30%) to a maximum of -€ 3,658,950 (SITT use: 100%). The cheapest pre-established SITT contained the fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) combination. CONCLUSION: A pre-fixed ICS/LAMA/LABA SITT is cost-saving, compared to the different currently used extemporaneous MITTs. Clinicians should consider the potential benefits of finding less expensive regimens while maintaining adequate efficacy in the prescriptive decision making process of COPD patients.

EVs-miRNA: The New Molecular Markers for Chronic Respiratory Diseases.

Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be increasing every year. Extracellular vesicles (EVs) are small-sized vesicles released by every cell in the body. They are present in most body fluids and contain various biomolecules including proteins, lipids, mRNA and non-coding RNA (micro-RNA). The EVs can release their cargo, specifically micro-RNAs (miRNAs), to both neighboring and/or distal cells, playing a fundamental role in cell-cell communication. Recent studies have shown their possible role in the pathogenesis of various chronic respiratory diseases. The expression of miRNAs and, in particular, of miRNAs contained within the extracellular vesicles seems to be a good starting point in order to identify new potential biomarkers of disease, allowing a non-invasive clinical diagnosis. In this review we summarize some studies, present in the literature, about the functions of extracellular vesicles and miRNAs contained in extracellular vesicles in chronic respiratory diseases and we discuss the potential clinical applications of EVs and EVs-miRNAs for their possible use such as future biomarkers.

Adaptive immunity in different CT patterns of active tuberculosis and possible variability according to patients' geographic provenience.

Background: It is still unclear if low lymphocyte levels are directly related to immunological modifications induced by the TB infection or if they depend on the general pre-existing health impairment of affected patients. Our aim was to detect eventual differences in the immunological status of patients with pulmonary TB compared to an age and sex-matched group of hospitalized patients with other bacterial community-acquired pneumonia (CAP). In addition, we tried to assess an association between alterations in the peripheral lymphocyte subsets and the development of different CT patterns of active TB and to discover differences in the immunological status and in the radiological patterns of TB presentation between patients of different geographic proveniences. Methods: This observational study included 48 patients with TB and 48 sex- and age-matched patients affected by other bacterial CAP. The presence of HIV/AIDS, other immunocompromising conditions, and confounding chronic pulmonary comorbidities was excluded. Flow cytometry was performed on all the enrolled subjects at admission, before starting the appropriate antibiotic therapy. Patients with TB also underwent a computed tomography (CT) scan. Results: Patients with TB showed a decrease in the absolute count of all the lymphocyte subsets compared to the CAP group. Only the reduction in the percentage of CD4+ T-lymphocytes was significant, while the percentage of CD8+ T-lymphocytes was significantly increased. Patients presenting exudative forms with atypical locations of TB showed a significant reduction in the absolute count and percentage of CD19+ B-lymphocytes compared to those affected by productive TB forms with the typical location. Despite being younger, our black Sub-Saharan Africans showed a significant reduction in the CD4+ T-lymphocytes compartment and a higher prevalence of atypical and exudative forms of TB compared with white Europeans. Conclusion: Tuberculosis itself may alter peripheral blood lymphocyte subsets compared to other CAP. An impaired CD19+ B-lymphocyte compartment may result in an abnormal exudative response in atypical locations and a suboptimal bacterial control. Other constitutive or environmental causes may influence immunological differences found in patients with TB, particularly in case of different geographic origins. Anyhow, flow cytometry may be of great value in evaluating the immune function of these patients.

Could transthoracic ultrasound be useful to suggest a small airways disease in severe uncontrolled asthma?

BACKGROUND: Transthoracic ultrasound (TUS) is an accepted complementary tool in the diagnostic process of several pleuro-pulmonary diseases. However, to the best of our knowledge, TUS findings in patients with severe asthma have never been systematically described. OBJECTIVE: To explore if TUS examination is a useful imaging method in suggesting the presence of a "small airways disease" in patients with severe uncontrolled asthma. METHODS: Seventy-two consecutive subjects with a diagnosis of severe uncontrolled asthma were enrolled. The presence of a "small airways disease" was assessed through the execution of pulmonary function tests. All the patients underwent a complete TUS examination and a chest high resolution computed tomography (HRCT), which was regarded as the reference standard for comparison with TUS findings. RESULTS: Pulmonary function tests results have confirmed a reduction in expiratory flows relative to the small airways and a condition of hyperinflation in 78% and 82% of our patients, respectively. The main signs observed in the TUS examination were a thickened and/or irregular pleural line and the lack or reduction of the "gliding sign." TUS showed high sensitivity and specificity in suggesting the presence of hyperinflation and distal airways inflammation according to the HRCT scan. K Cohen's coefficients showed substantial agreement between the 2 diagnostic tests. CONCLUSION: TUS in patients with severe uncontrolled asthma can provide useful information on the state of the peripheral lung, suggesting the execution of a second-line HRCT scan for better assessment of eventual alterations that may represent the underlying causes of nonresponse to treatment.

Effectiveness and Safety of Real-Time Transthoracic Ultrasound-Guided Thoracentesis.

PURPOSE: The purpose of the present study was to specifically evaluate the effectiveness and safety of real-time ultrasound-guided thoracentesis in a case series of pleural effusion. PATIENTS AND METHODS: An observational prospective study was conducted. From February 2018 to December 2019, a total of 361 consecutive real-time transthoracic ultrasound (TUS)-guided thoracentesis were performed in the Unit of Diagnostic and Interventional Ultrasound of the Research Hospital "Fondazione Casa Sollievo della Sofferenza" of San Giovanni Rotondo, Foggia, Italy. The primary indication for thoracentesis was therapeutic in all the cases (i.e., evacuation of persistent small/moderate pleural effusions to avoid super-infection; drainage of symptomatic moderate/massive effusions). For completeness, further diagnostic investigations (including chemical, microbiological, and cytological analysis) were conducted. All the procedures were performed by two internists with more than 30 years of experience in interventional ultrasound using a multifrequency convex probe (3-8 MHz). For pleural effusions with a depth of 2-3 cm measured at the level of the costo-phrenic sinus was employed a dedicated holed convex-array probe (5 MHz). RESULTS: In all the cases, the attempts at thoracentesis were successful, allowing the achievement of the therapeutic purpose of the procedure (i.e., the complete drying of the pleural space or the withdrawal of fluid till a "safe" quantity [a mean of 1.5 L, max 2 L] producing relief from symptoms) regardless of the initial extent of the pleural effusion. There were only 3 cases of pneumothorax, for a prevalence rate of complications in this population of 0.83%. No statistical difference was recorded in the rate of pneumothorax according to the initial amount of pleural fluid in the effusion (p = 0.12). All the pleural effusions classified as transudates showed an anechoic TUS appearance. Only the exudative effusions showed a complex nonseptated or a hyperechoic TUS appearance. However, an anechoic TUS pattern was not unequivocally associated with transudates. Some chronic transudates have been classified as exudates by Light's criteria, showing also a complex nonseptated TUS appearance. The cytological examination of the drained fluid allowed the detection of neoplastic cells in 15.89% cases. On the other hand, the microbiological examination of effusions yielded negative results in all the cases. CONCLUSIONS: Real-time TUS-guided thoracentesis is a therapeutically effective and safe procedure, despite the diagnostic yield of the cytological or microbiological examinations on the collected liquid being very low. Future blinded randomized studies are required to definitely clarify the actual benefit of the real-time TUS-guided procedure over percussion-guided and other ultrasound-based procedures.

CT-Guided Transthoracic Biopsy of Pulmonary Lesions: Diagnostic versus Nondiagnostic Results.

(1) Background: Despite the high accuracy of CT-guided transthoracic biopsy for diagnosis of pulmonary lesions, in a certain amount of cases biopsy results may indicate the presence of nonspecific findings or insufficient material. We aimed to investigate the effectiveness of CT-guided transthoracic biopsy of pulmonary lesions in providing a specific diagnosis and to analyze the variables affecting biopsy results. (2) Methods: In this retrospective study, a total of 170 patients undergoing 183 CT-guided transthoracic biopsies of pulmonary lesions were included. The clinical, radiological and pathological data were reviewed to classify biopsy results as diagnostic or nondiagnostic and to identify which variables were associated with the two groups. (3) Results: The biopsy results were diagnostic in 150 cases (82.0%), of which 131 (87.3%) positive for malignancy and 19 (12.7%) with specific benign lesions, and nondiagnostic in 33 cases (18.0%). Twenty-two of the thirty-three (66.7%) nondiagnostic cases were finally determined as malignancies and eleven (33.3%) as benign lesions. In the diagnostic group, all the 131 biopsies positive for malignancy were confirmed to be malignant at final diagnosis (87.3%); of 19 biopsies with specific benign lesions, 13 cases were confirmed to be benign (8.7%), whereas six cases had a final diagnosis of malignancy (4%). Multivariate analysis showed increased risk of nondiagnostic biopsy for lesions ≤ 20 mm (p = 0.006) and lesions with final diagnosis of benignity (p = 0.001). (4) Conclusions: CT-guided transthoracic lung biopsy is an effective technique for the specific diagnosis of pulmonary lesions, with a relatively acceptable proportion of nondiagnostic cases. Small lesion size and final benign diagnosis are risk factors for nondiagnostic biopsy results.

Dysphagia in non-intubated patients affected by COVID-19 infection.

PURPOSE: Patients affected by COVID-19 are assumed to be at high risk of developing swallowing disorders. However, to our best knowledge, data on the characteristics and incidence of dysphagia associated with COVID-19 are lacking, especially in non-intubated patients. Therefore, we investigated the onset of swallowing disorders in patients with laboratory-confirmed COVID-19 infection who have not been treated with invasive ventilation, in order to evaluate how the virus affected swallowing function regardless of orotracheal intubation. METHODS: We evaluated 41 patients admitted to the COVID department of our Hospital when they had already passed the acute phase of the disease and were therefore asymptomatic but still positive for SARS-CoV-2 RNA by RT-PCR. We examined patients' clinical history and performed the Volume-Viscosity Swallow Test (VVST). Each patient also answered the Swallowing Disturbance Questionnaire (SDQ). After 6 months, we performed a follow-up in patients with swallowing disorders. RESULTS: Eight of 41 patients (20%) presented with dysphagia symptoms during hospitalization and 2 of them (25%) still presented a SDQ high score and swallowing disorders with liquid consistency after 6 months. CONCLUSION: Non-intubated patients can experience various grades of swallowing impairment that probably directly related to pulmonary respiratory function alterations and viral direct neuronal lesive activity. Although these symptoms show natural tendency to spontaneous resolution, their impact on a general physical impaired situation should not be underestimated, since it can adversely affect patients' recovery from COVID-19 worsening health outcomes.

Transthoracic ultrasound shear wave elastography for the study of subpleural lung lesions.

PURPOSE: The aim of this study was to assess whether new-generation shear wave elastography (SWE) is suitable for the characterization of lung subpleural lesions. METHODS: In total, 190 consecutive patients with subpleural lung lesions received ultrasonography and SWE. Patients with suspected malignancy underwent ultrasound-guided transthoracic needle biopsy. Final diagnoses were made on the basis of patients' clinical course, microbiological studies, and histological results. SWE was also performed in 25 healthy volunteers. RESULTS: We found no statistically significant differences in stiffness between lung carcinomas, lung metastases, and pneumonia (P=0.296) or between different histological types of lung cancer (P=0.393). Necrosis was associated with reduced stiffness in pneumonia. Excluding necrotic lesions, pneumonia showed higher stiffness than lung carcinomas (2.95±0.68 m/s vs. 2.60±0.54 m/s, P=0.006). Chronic pneumonia showed increased stiffness (3.03±0.63 m/s), probably due to the presence of fibrotic tissue on histology. Pleural effusion was associated with a statistically significant reduction in stiffness, both in lung carcinomas (P=0.004) and lung metastases (P=0.002). The presence of air in healthy lung tissue may lead to incorrect speed estimates due to shear wave reflection (very high values, 14.64±2.19 m/s). CONCLUSION: Transthoracic SWE could not distinguish lung malignancy from pneumonia, or between different histological types of lung carcinomas. In particular, SWE seems unable to resolve the clinical dilemma of chronic subpleural consolidations.

Chest Imaging in the Diagnosis and Management of Pulmonary Tuberculosis: The Complementary Role of Thoraci Ultrasound.

Tuberculosis (TB) is a severe infectious disease that still represents a major cause of mortality and morbidity worldwide. For these reasons, clinicians and radiologists should use all the available diagnostic tools in the assessment of the disease in order to provide precise indications about starting an anti-tubercular treatment and reduce risk of TB transmission and complications especially in developing countries where the disease is still endemic. As TB mycobacteria are mainly transmitted through respiratory droplets, the pulmonary parenchyma is usually the first site of infection. As a result, chest imaging plays a central role in the diagnostic process. Thoracic ultrasound (TUS) is a portable, non-invasive, radiation-free, and cost-contained technology which could be easily available in resource-limited settings. This perspective article focuses on the potential role of TUS in the diagnosis and management of patients with pulmonary TB. Unfortunately, there are still insufficient evidence and too contrasting data to judge TUS as an appropriate diagnostic method for the screening of the disease. Despite this, TUS may have a useful role in identifying pleural and anterior pericardial effusions or in the identification of abscesses of the anterior chest wall and paraspinal collections in low- and middle-income settings. In addition, TUS seems to have a milestone role in guiding minimally invasive interventional procedures, such as placement of chest tubes, drainage of loculated collections, thoracentesis and pericardiocentesis, and percutaneous biopsy of subpleural pulmonary consolidations or pleural plaques.

Effectiveness and Safety of Transthoracic Ultrasound in Guiding Percutaneous Needle Biopsy in the Lung and Comparison vs. CT Scan in Assessing Morphology of Subpleural Consolidations.

(1) Background: The aim of this study was to conduct a prospective analysis on the diagnostic accuracy of transthoracic ultrasound-guided percutaneous needle biopsy (TUS-PNB) for the histological assessment of peripheral lung lesions and to assess the performance of transthoracic ultrasound (TUS) examination vs. chest CT (gold standard) in the differentiation between malignant and benign peripheral lung lesions. (2) Methods: A total of 961 consecutive patients with subpleural pulmonary lesions were enrolled. All the patients received a CT scan with contrast; 762 patients underwent TUS-PTNB for suspicion of malignancy, and the remaining 199 enrolled patients underwent only TUS examination as a part of routine follow-up for known non-malignant subpleural consolidations. (3) Results: Among the 762 TUS-guided biopsies, there were 627 (82.28%) malignant lesions, 82 (10.76%) benign lesions, and 53 (6.96%) indeterminate lesions. The overall diagnostic accuracy was 93.04%. The rates of pneumothorax not requiring chest-tube insertion and self-limited hemoptysis were 0.79 and 0.26%, respectively. Patients were divided into two groups based on the benign or malignant nature of the subpleural consolidations. On TUS, both malignant and benign lesions showed mostly irregular margins and a hypoechoic pattern, but no differences were assessed in terms of sonographic margins and pattern between the two groups. There was poor agreement between TUS and chest CT in assessing air bronchograms and necrotic areas. The only finding in the detection of which TUS showed superiority compared to chest-CT was pleural effusion. (4) Conclusions: TUS-PNB was confirmed to be an effective and safe diagnostic method for peripheral pulmonary consolidation, but their sonographic pattern did not allow to rule out a malignant nature. A pre-operative evaluation on CT images, combined with the possibility of performing additional immunohistochemical and cytological investigations and the experience of the medical staff, may improve the diagnostic yield of TUS-guided biopsies.