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Purpose: To test the inter-reader agreement in classifying pulmonary hypertension (PH) on chest contrast-enhanced computed tomography (CECT) between a consensus of two cardio-pulmonary-devoted radiologists (CRc) and inexperienced readers (radiology residents, RRs) when using a CECT-based quick hands-on tool built upon PH imaging literature, i.e., the "Rapid Access and Practical Information Digest on Computed Tomography for PH-RAPID-CT-PH"., Material and Methods: The observational study retrospectively included 60 PH patients who underwent CECT between 2015 and 2022. Four RRs independently reviewed all CECTs and classified each case into one of the five PH groups per the 2022 ESC/ERS guidelines. While RR3 and RR4 (RAPID-CT-PH group) used RAPID-CT-PH, RR1 and RR2 (control group) did not. RAPID-CT-PH and control groups' reports were compared with CRc using unweighted Cohen's Kappa (k) statistics. RRs' report completeness and reporting time were also compared using the Wilcoxon-Mann-Whitney test., Results: The inter-reader agreement in classifying PH between the RAPID-CT-PH group and CRc was substantial (k = 0.75 for RR3 and k = 0.65 for RR4); while, it was only moderate for the control group (k = 0.57 for RR1 and k = 0.49 for RR2). Using RAPID-CT-PH resulted in significantly higher report completeness (all p < 0.0001) and significantly lower reporting time (p < 0.0001) compared to the control group., Conclusion: RRs using RAPID-CT-PH showed a substantial agreement with CRc on CECT-based PH classification. RAPID-CT-PH improved report completeness and reduced reporting time. A quick hands-on tool for classifying PH on chest CECT may help inexperienced radiologists effectively contribute to the PH multidisciplinary team., (© 2024. The Author(s).)

Introduction: Medical thoracoscopy is a minimally invasive and safe procedure mostly performed for unexplained exudative pleural effusions but may be considered for pneumothorax (PNX)., Methods: This retrospective study included participants affected by PNX who underwent medical thoracoscopy with talc poudrage at a single academic hospital from 2008 to 2021. The primary endpoint was the observation of complete radiographical lung re-expansion and absence of air supply from the chest drain within 7 days of medical thoracoscopy. The secondary endpoint was achieving no recurrence of ipsilateral PNX at 24 months post-discharge., Results: A total of 95 patients affected by primary spontaneous PNX (PSP), secondary spontaneous PNX (SSP), iatrogenic, and traumatic PNX were enrolled. An additional procedure was required by 17.89% of patients, and only one patient with SSP required subsequent surgery. Recurrence of PNX occurred on the same side within 24 months after discharge in 9.47% of patients, with a median time to recurrence of 13.5 months. The PSP group was significantly more likely to achieve the primary endpoint. Pleural morphology was significantly associated with reaching the primary endpoint, while receiving a cumulative dose of talc greater than or equal to 4 g during hospitalization was associated with a lower risk of meeting it. Receiving a cumulative dose of talc greater than or equal to 4 g led in all cases to the achievement of the secondary endpoint. Patients with iatrogenic and traumatic PNX had an excellent prognosis in both the short- and long-term evaluation., Conclusion: Medical thoracoscopy is an effective procedure for treating PNX in the acute setting in selected cases while preventing long-term relapses. Large prospective clinical studies are needed to support and better define the role of medical thoracoscopy in current clinical practice., (© 2024. The Author(s).)

Background: Postoperative pulmonary complications (PPCs) remain a challenge after esophagectomy. Despite improvement in surgical and anesthesiological management, PPCs are reported in as many as 40% of patients. The main aim of this study is to investigate whether early application of high-flow nasal cannula (HFNC) after extubation will provide benefit in terms of reduced PPC frequency compared to standard oxygen therapy., Methods: Patients aged 18-85 years undergoing esophagectomy for cancer treatment with radical intent, excluding those with American Society of Anesthesiologists (ASA) score >3 and severe systemic comorbidity (cardiac, pulmonary, renal or hepatic disease) will be randomized at the end of surgery to receive HFNC or standard oxygen therapy (Venturi mask or nasal goggles) after early extubation (within 12 hours after the end of surgery) for 48 hours. The main postoperative goals are to obtain SpO 2 ≥94% and adequate pain control. Oxygen therapy after 48 hours will be stopped unless the physician deems it necessary. In case of respiratory clinical worsening, patients will be supported with the most appropriate tool (noninvasive ventilation or invasive mechanical ventilation). Pulmonary [pneumonia, pleural effusion, pneumothorax, atelectasis, acute respiratory distress syndrome (ARDS), tracheo-bronchial injury, air leak, reintubation, and/or respiratory failure] complications will be recorded as main outcome. Secondary outcomes, including cardiovascular, surgical, renal and infective complications will also be recorded. The primary analysis will be carried out on 320 patients (160 per group) and performed on an intention-to-treat (ITT) basis, including all participants randomized into the treatment groups, regardless of protocol adherence. The primary outcome, the PPC rate, will be compared between the two treatment groups using a chi-square test for categorical data, or Fisher's exact test will be used if the assumptions for the chi-square test are not met., Discussion: Recent evidence demonstrated that early application of HFNC improved the respiratory rate oxygenation index (ROX index) after esophagectomy but did not reduce PPCs. This randomized controlled multicenter trial aims to assess the potential effect of the application of HFNC versus standard oxygen over PPCs in patients undergoing esophagectomy., Trial Registration: This study is registered at clinicaltrial.gov NCT05718284, dated 30 January 2023., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-575/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

This narrative review aims to provide an overview of medical pleurodesis techniques, and their indications and potential adverse effects. Pleurodesis is a procedure performed with the aim of obliterating the pleural space. It has indications in the management of both malignant and benign pleural effusions and pneumothorax. Various nonsurgical techniques exist to perform pleurodesis. The scope of this work is to review the different nonsurgical techniques and their indications. This narrative review was performed checking scientific databases for medical literature, focusing especially on the data derived from randomised controlled trials. Pleurodesis is an effective method to manage pleural effusions and pneumothorax, and minimally invasive techniques are now frequently used with good results. Further research is needed to assess the efficacy of new treatments and the possibility of using different techniques in association., Competing Interests: Conflict of interest: Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement) that might pose a conflict of interest in connection with the submitted article., (Copyright ©ERS 2024.)

Background: Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated., Research Question: Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis?, Study Design and Methods: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥ 500 mL were assigned at a 1:1 ratio to wall suction or gravity drainage. Wall suction was performed with a suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100 cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 min. Secondary outcomes included measures of postprocedure chest discomfort, breathlessness, procedure time, volume of fluid drained, and complication rates., Results: Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (P = .08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 min. No differences in rate of pneumothorax or reexpansion pulmonary edema were noted between the two groups., Interpretation: Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement., Clinical Trial Registry: ClinicalTrials.gov; No.: NCT05131945; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Medical thoracoscopy (MT) is an endoscopic technique performed by interventional pulmonologists with a favorable safety profile and few contraindications, providing diagnostic and therapeutic intervention in a single sitting. This narrative review was designed to summarize the therapeutic role of MT based on the latest results from the available literature., Methods: Pertinent literature published in English, relative to human studies, between 2010-2022 was searched in Medline/PubMed and Cochrane databases. Publications regarded as relevant were considered for inclusion in this review; additional references were added based on the authors' knowledge and judgment. The review considered population studies, meta-analyses, case series, and case reports., Key Content and Findings: MT has mostly been described and is currently used globally in the diagnostic approach to exudative pleural effusion of undetermined origin. Carefully evaluating the literature, it is clear that there is initial evidence to support the use of MT in the therapeutic approach of malignant pleural effusion, pneumothorax, empyema, and less frequently hemothorax and foreign body retrieval., Conclusions: MT is an effective procedure for treating the clinical entities presented in this document; it must be carried out in selected patients, managed in centers with high procedural expertise. Further evidence is needed to assess the optimal indications and appropriate patients' profiles for therapeutic MT. The endpoints of length of hospital stay, surgical referral, complications and mortality will have to be considered in future studies to validate it as a therapeutic intervention to be applied globally., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1745/coif). The series “Malignant and Benign Pleural Effusions” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Postoperative pulmonary complications after esophagectomy still represent a matter of concern. High flow nasal cannula (HFNC) early after major abdominal and thoracic surgery has demonstrated some advantages over conventional oxygen therapy. Data about respiratory effect of HFNC after esophagectomy is scarce. The primary aim of this study is to investigate if the early use of HFNC after esophagectomy could enhance patients' postoperative respiratory oxygenation (ROX) index and, ultimately, reduce postoperative pneumonia., Methods: In this single center retrospective study all patients undergoing to esophagectomy for cancer from May 2020 to November 2022 were evaluated. Historical cohort (HC) received postoperative oxygen supplementation with Venturi mask or nasal goggles, and a cohort was put under HFNC (HFNC cohort). ROX index, blood gas analysis, radiological atelectasis score (RAS), post-operative complications' data and information on hospital stay have been collected and analyzed., Results: Seventy-one patients were included for the final statistical analysis, 31 in the HFNC and 40 in the HC cohort. Mean age was 64±10 years and body mass index (BMI) was 26 [24-29] kg/m 2 . ROX index was higher in the HFNC patients than in the HC, 20.8 [16.7-25.9] vs. 14.9 [10.8-18.2] (P<0.0001). In the HFNC cohort patients, pH was higher, 7.42 [7.40-7.44] vs. 7.39 [7.37-7.43] than HC, while PaCO 2 was lower in HFNC cohort compared with HC, 39 [36-41] vs. 42 [39-45] mmHg, respectively (P=0.01). RAS was similar between the two cohorts of patients, 1.5±0.98 vs. 1.4±1.04 in the HFNC and the HC cohort, respectively (P=0.611). Lower acute respiratory failure (ARF) rate was recorded among HFNC than HC cohort, 0% vs. 13% respectively, P=0.06. No difference in pneumonia frequency between two cohorts was shown., Conclusions: HFNC improved the ROX index after esophagectomy through significant respiratory rate reduction. This tool should be considered for early respiratory support after extubation in this category of patients, not only as a rescue therapy for ARF, but also to optimize early postoperative respiratory function. Whether this will improve patients' outcomes requires further large randomized controlled trials., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1176/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication., Methods: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death., Results: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001)., Conclusions: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality., Trial Registration: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

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

Background: Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting., Methods: COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded., Results: In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls ( p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO 2 /FiO 2 ( p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO 2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001)., Conclusions: COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

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

Objective: To test the inter-reader agreement in assessing lung disease extent, HRCT signs, and Radiological Society of North America (RSNA) categorization between a chest-devoted radiologist (CR) and two HRCT-naïve radiology residents (RR1 and RR2) after the latter attended a COVID-19-based chest high-resolution computed tomography (HRCT) "crash course"., Methods: The course was built by retrospective inclusion of 150 patients who underwent HRCT for COVID-19 pneumonia between November 2020 and January 2021. During a first 10-days-long "training phase", RR1 and RR2 read a pool of 100/150 HRCTs, receiving day-by-day access to CR reports as feedback. In the subsequent 2-days-long "test phase", they were asked to report 50/150 HRCTs with no feedback. Test phase reports of RR1/RR2 were then compared with CR using unweighted or linearly-weighted Cohen's kappa (k) statistic and intraclass correlation coefficient (ICC)., Results: We observed almost perfect agreement in assessing disease extent between RR1-CR (k = 0.83, p < 0.001) and RR2-CR (k = 0.88, p < 0.001). The agreement between RR1-CR and RR2-CR on consolidation, crazy paving pattern, organizing pneumonia (OP) pattern, and pulmonary artery (PA) diameter was substantial (k = 0.65 and k = 0.68), moderate (k = 0.42 and k = 0.51), slight (k = 0.10 and k = 0.20), and good-to-excellent (ICC = 0.87 and ICC = 0.91), respectively. The agreement in providing RSNA categorization was moderate for R1 versus CR (k = 0.56) and substantial for R2 versus CR (k = 0.67)., Conclusion: HRCT-naïve readers showed an acceptable overall agreement with CR, supporting the hypothesis that a crash course can be a tool to readily make non-subspecialty radiologists available to cooperate in reading high burden of HRCT examinations during a pandemic/epidemic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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

For centuries, macroalgae, or seaweeds, have been a significant part of East Asian diets. In Europe, seaweeds are not considered traditional foods, even though they are increasingly popular in Western diets in human food applications. In this study, a biological processing method based on semi-solid fermentation was optimized for the treatment of the seaweed Gracilaria gracilis . For the first time, selected lactic acid bacteria and non-conventional coagulase-negative staphylococci were used as starter preparations for driving a bio-processing and bio-stabilization of raw macroalga material to obtain new seaweed-based food prototypes for human consumption. Definite food safety and process hygiene criteria were identified and successfully applied. The obtained fermented products did not show any presence of pathogenic or spoilage microorganisms, thereby indicating safety and good shelf life. Lactobacillus acidophilus -treated seaweeds revealed higher α-amylase, protease, lipase, endo-cellulase, and endo-xylanase activity than in the untreated sample. This fermented sample showed a balanced n-6/n-3 fatty acid ratio. SBM-11 ( Lactobacillus sakei , Staphylococcus carnosus and Staphylococcus xylosus ) and PROMIX 1 ( Staphylococcus xylosus ) treated samples showed fatty acid compositions that were considered of good nutritional quality and contained relevant amounts of isoprenoids (vitamin E and A). All the starters improved the nutritional value of the seaweeds by significantly reducing the insoluble indigestible fractions. Preliminary data were obtained on the cytocompatibility of G. gracilis fermented products by in vitro tests. This approach served as a valid strategy for the easy bio-stabilization of this valuable but perishable food resource and could boost its employment for newly designed seaweed-based food products.

The term "connective tissue diseases" (CTDs) refers to a heterogeneous group of autoimmune disorders, including systemic sclerosis, rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, polymyositis, dermatomyositis, antisynthetase syndrome, and mixed connective tissue disease. Chest high-resolution computed tomography (HRCT) is the imaging method of choice for evaluating patients with known or suspected CTD-related interstitial lung disease (CTD-ILD), a complication accounting for substantial morbidity and mortality. While specific HRCT patterns and signs of CTD-ILD have been extensively described (hence the designation "the usual suspects"), the knowledge of various, less frequent conditions involving the lungs in patients with CTD would help the radiologist produce a clinically valuable report, thus potentially influencing patient management. This paper aims to provide an up-to-date review of various unusual pulmonary CTD-related conditions the radiologist should be aware of; namely, acute exacerbation of CTD-ILD, CTD-related interstitial lung abnormalities, lung amyloidosis, MALT lymphoma, antisynthetase syndrome, pleuroparenchymal fibroelastosis-like lesion, drug-induced ILD, combined pulmonary fibrosis and emphysema, and pulmonary hypertension. For each condition, the chest HRCT appearance and the key histopathological and clinical features are resumed, helping the radiologist participate actively in the multidisciplinary discussion of complex clinical cases., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Pulmonary embolism (PE) without overt deep vein thrombosis (DVT) was common in hospitalized coronavirus-induced disease (COVID)-19 patients and represented a diagnostic, prognostic, and therapeutic challenge. The aim of this study was to analyze the prognostic role of PE on mortality and the preventive effect of heparin on PE and mortality in unvaccinated COVID-19 patients without overt DVT., Methods: Data from 401 unvaccinated patients (age 68 ± 13 years, 33% females) consecutively admitted to the intensive care unit or the medical ward were included in a retrospective longitudinal study. PE was documented by computed tomography scan and DVT by compressive venous ultrasound. The effect of PE diagnosis and any heparin use on in-hospital death (primary outcome) was analyzed by a classical survival model. The preventive effect of heparin on either PE diagnosis or in-hospital death (secondary outcome) was analyzed by a multi-state model after having reclassified patients who started heparin after PE diagnosis as not treated., Results: Median follow-up time was 8 days (range 1-40 days). PE cumulative incidence and in-hospital mortality were 27% and 20%, respectively. PE was predicted by increased D-dimer levels and COVID-19 severity. Independent predictors of in-hospital death were age (hazards ratio (HR) 1.05, 95% confidence interval (CI) 1.03-1.08, p < 0.001), body mass index (HR 0.93, 95% CI 0.89-0.98, p = 0.004), COVID-19 severity (severe versus mild/moderate HR 3.67, 95% CI 1.30-10.4, p = 0.014, critical versus mild/moderate HR 12.1, 95% CI 4.57-32.2, p < 0.001), active neoplasia (HR 2.58, 95% CI 1.48-4.50, p < 0.001), chronic obstructive pulmonary disease (HR 2.47; 95% CI 1.15-5.27, p = 0.020), respiratory rate (HR 1.06, 95% CI 1.02-1.11, p = 0.008), heart rate (HR 1.03, 95% CI 1.01-1.04, p < 0.001), and any heparin treatment (HR 0.35, 95% CI 0.18-0.67, p = 0.001). In the multi-state model, preventive heparin at prophylactic or intermediate/therapeutic dose, compared with no treatment, reduced PE risk and in-hospital death, but it did not influence mortality of patients with a PE diagnosis., Conclusions: PE was common during the first waves pandemic in unvaccinated patients, but it was not a negative prognostic factor for in-hospital death. Heparin treatment at any dose prevented mortality independently of PE diagnosis, D-dimer levels, and disease severity., (© 2022. The Author(s).)

Background and Aim: Pleural effusions (PE) can complicate the course of hematologic disorders (HD) and may arise in the form of malignant PE or as a consequence of non-neoplastic complications. While a certain amount of data has been published regarding infectious and iatrogenic HD-associated PE (HPE), no comprehensive review regarding the other types of HPE has ever been conducted. To address this issue, we performed a systematic review of the literature regarding HPE, focusing on the clinical and chemical characteristics of PE, therapeutic approaches and ì outcomes at the one-year follow-up., Methods: We conducted our review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Overall, 283 manuscripts and 1216 cases were included. In summary, PE frequently signals an underlying HD, especially Hodgkin's lymphoma and IgG4-related disease; it mainly consists of exudate, although chylothorax is diagnosed in some cases. Although cytological examination has a discrete diagnostic yield, it is generally insufficient to render a definitive diagnosis; pleural biopsy remains an important diagnostic means in such cases. Invasive diagnostic procedures are not frequently performed because of an increased risk of haemorrhagic complications. The majority of PE are resolved by means of systemic therapy. When local treatments are attempted, the most frequently adopted procedures are evacuative thoracentesis and indwelling chest tube placement Conclusions: This review highlights the need for well-designed prospective studies comparing diagnostic means and therapeutic interventions for HPE to increase the quality of available data.  (www.actabiomedica.it).

A 52-year-old man was re-admitted two weeks after recovering from severe COVD-19 following a 3-days history of cough and worsening shortness of breath. The chest radiograph showed a large right-sided pneumothorax. The first attempt at drainage, performed through a large bored tube, failed. Due to the large dimension of the pneumothorax, and the lung condition (extensive consolidation and diffuse bullous dystrophies), the only thoracic surgical approach prospected was a pneumonectomy. Willing to preserve the lung, the pulmonology team attempted a multi-phase medical-oriented strategy based on medical thoracoscopy. Therefore, the patient underwent 5 chest tube insertions, 2 talc pleurodesis, and an intrapleural blood patch. Air leakage resolution was progressively achieved, and the patient became asymptomatic.

Background: COVID-19 has caused considerable morbidity and mortality worldwide and cardiac involvement has been reported during infection. The short-term cardiac outcome in survivors of COVID-19 is not known., Objective: To examine the heart of patients who survived COVID-19 and to compare the cardiac outcome between patients who recovered from mild-to-moderate or severe illness., Methods: With use of ECG and echocardiography, we examined the heart of 105 patients who had been hospitalized with COVID-19 and were consecutively recruited after hospital discharge while attending follow-up visits. Survivors of COVID-19 were compared with 105 matched controls. We also compared the cardiac outcome and lung ultrasound scan between COVID-19 patients who had mild-to-moderate or severe illness., Results: Cardiac data were collected a median of 41 days from the first detection of COVID-19. Symptoms were present in a low percentage of patients. In comparison with matched controls, no considerable structural or functional differences were observed in the heart of survivors of COVID-19. Lung ultrasound scan detected significantly greater residual pulmonary involvement in COVID-19 patients who had recovered from severe than mild-to-moderate illness. No significant differences were detected in ECG tracings nor were found in the left and right ventricular function of patients who had recovered from mild-to-moderate or severe illness., Conclusions: In a short-term follow-up, no abnormalities were identified in the heart of survivors of COVID-19, nor cardiac differences were detected between patients who had different severity of illness. With the limitations of a cross-sectional study, these findings suggest that patients who recover from COVID-19 do not have considerable cardiac sequelae.

Objective: To report clinical and electroneuromyographic (ENMG) characteristics of patients affected by severe COVID-19 infection, evaluated for muscular weakness., Materials and Methods: ENMGs performed for evaluation of diffuse weakness in patients who could not be discharged from semi-intensive care COVID unit because of difficulties in ventilation weaning were reviewed. Patients with severe COVID-19 infection who had undergone endotracheal intubation and able to co-operate were considered. ENMG protocol was focused on neurophysiological items that excluded or confirmed critical illness polyneuropathy (CIP), myopathy (CIM), or polyneuromyopathy (CIPM). Standardized clinical evaluation was performed using Medical Research Council (MRC) sum score., Results: Eight patients were included in the study. All presented known risk factors for intensive care unit-acquired weakness (ICU-AW), and none of them had history of underlying neuromuscular disorders. ENMG findings were normal in two patients, while only two patients had an altered MRC sum score (< 48). Neuromuscular involvement was diagnosed in 6/8 patients (75%): 2 had CIP, 1 had possible CIM, 1 had CIPM, while 1 patient, with clinically evident weakness but equivocal ENMG findings, was classified as ICU-AW. Finally, 1 patient was diagnosed with acute demyelinating neuropathy. Patients with neuromuscular involvement were those with longer intubation duration and higher levels of IL-6 at admission., Conclusion: Neuromuscular complications are frequent in severe COVID-19 and cannot be excluded by MRC sum scores above 48. Standardized ENMG is helpful in guiding diagnosis when clinical evaluation is not reliable or possible. Elevated IL-6 at admission may be a predictor biomarker of ICU-AW in COVID-19.

Background: The best policy to follow when nursing homes are massively hit by SARS-CoV2 is unclear., Aim: To describe COVID-19 containment in a nursing home transformed into a caring center., Methods: Physicians and nurses were recruited. The facility was reorganized and connected with the laboratory of the reference hospital. Ultrasound was used to diagnose pneumonia. Patients needing intensive care were transferred to the reference hospital. Hydroxychloroquine/azithromycin/enoxaparin were used initially, while amiodarone/enoxaparin were used at a later phase. Under both regimens, methylprednisolone was added for severe cases. Prophylaxis was done with hydroxychloroquine initially and then with amiodarone., Period Covered: March 22-July 31, 2020., Results: The facility was reorganized in two days. Ninety-two guests of the 121 (76%) and 25 personnel of 118 (21.1%) became swab test positive. Seven swab test negative patients who developed symptoms were considered to have COVID-19. Twenty-seven patients died, 23 swab test positive, 5 of whom after full recovery. Four patients needing intensive care were transferred (3 died). Mortality, peaking in April 2020, was correlated with symptoms, comorbidities, dyspnea, fatigue, stupor/coma, high neutrophil to lymphocyte ratio, C-reactive protein, interleukin-6, pro-calcitonin, and high oxygen need (p ≤ 0.001 for all). Among swab-positive staff, 3 had pneumonia and recovered. Although no comparison could be made between different treatment and prophylaxis strategies, potentially useful suggestions emerged. Mortality compared well with that of nursing homes of the same area not transformed into care centers., Conclusion: Nursing homes massively hit by SARS-CoV-2 can become caring centers for patients not needing intensive care.

Background: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality., Methods: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels., Results: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 ( P  = .07) and 14 vs 26 ( P  = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8; P  = .001). Study treatment was associated with rapid improvement in PaO 2 :FiO 2 and CRP levels. The complication rate was similar for the 2 groups ( P  = .84)., Conclusion: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration.  ClinicalTrials.gov NCT04323592., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Treatment with positive airway pressure devices improved signs and symptoms of obstructive sleep apnea syndrome (OSA); however, auto-adjusting positive pressure (APAP) device was not as effective as continuous positive airway pressure (CPAP) in reducing arterial blood pressure and insulin resistance. The role played by autonomic cardiac regulation remains to be clarified. We aimed to test the effects of CPAP and APAP on autonomic regulation and cardiorespiratory coupling during sleep., Methods: We retrospectively analyzed full-night polysomnographic studies. 19 patients newly diagnosed with severe OSA (AHI>30) and 7 obese subjects without OSA (CON) were enrolled. Each OSA subject was assigned to CPAP or APAP treatment and underwent a sleep study after 1 week of treatment. Spectral and cross-spectral analyses of heart rate variability (HRV) and respiration were performed to assess autonomic profile and coherence (K2) between respiration and HF oscillation during sleep in CPAP, APAP and CON groups., Results: In CPAP and CON, LFnu and LF/HF, markers of sympathetic modulation, decreased from N2 to N3 and increased during REM sleep (p<0.001), while in APAP group, sympathetic modulation was significantly higher compared with those of CPAP and CON during all sleep stages. K2 values were lower in APAP compared with those in CPAP and CON., Conclusion: APAP treatment was characterized by a greater sympathetic activation and it was associated with a lower cardio-respiratory coupling compared with CPAP. This might account for the different effects on cardiovascular risk factors induced by the two treatments., (Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to estimate the prevalence and nature of sleep breathing disorders in Myotonic dystrophy type 1 (DM1). We wanted to determine whether there is a relationship between sleep breathing disorders and clinical parameters such as pulmonary function, degree of neuromuscular impairment, daytime sleepiness, and fatigue. This will help assess the prevalence of DM1 patients requiring nocturnal ventilatory treatments. We studied a random sample of 40 unrelated patients and found that 22/40 patients had obstructive sleep apnoea. Of these 22 patients, five showed also periodic breathing and four showed sleep hypoventilation. Nine patients were put on nocturnal ventilation following clinical and instrumental evaluations. Our study reveals that obstructive sleep apnoea is very common in these patients, but cannot be predicted on the basis of clinical-neurological features and diurnal functional respiratory tests. Our data emphasize that a periodical evaluation by polysomnography should be mandatory to ascertain, and treat if necessary, the presence of obstructive sleep apnoea, periodic breathing or nocturnal hypoventilation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Time-frequency analysis of the heart rate variability during arousal from sleep, with and without EMG activation, coming from five obese healthy subjects was performed. Additionally, a comparative analysis of three time-frequency distributions, smooth pseudo Wigner-Ville (SPWVD), Choi-Williams (CWD) and Born-Jordan distribution (BJD) is presented in this study. SPWVD showed higher capacity for eliminating the cross terms independently of the signal. After applying Hilbert transformation to real signals BJD and CWD lost some important mathematic properties as marginals, on the contrary PSWVD remains unchanged. BJD showed results comparable with CWD. During arousal episodes, analogous energy distribution and spectral indexes were obtained by the three time-frequency representations. Arousals with chin activity presented stronger changes in RR intervals and LF (related to sympathetic activity) component, being statistically different with respect to arousal without chin activity, only around the period of maximum change in beta activity on the EEG. These results suggest a more evident stress for the heart when an arousal is related to external muscular activity.

Background: A strong association between obstructive sleep apnea (OSA) and the risk for cardiovascular and cerebrovascular diseases has been reported. Continuous positive airway pressure (CPAP) is the first-line therapy for OSA, able not only to reduce daytime sleepiness but also to improve cardiovascular and metabolic outcomes. Autoadjusting CPAP (APAP), an alternative treatment to CPAP, can reduce OSA symptoms while increasing long-term CPAP compliance without the high costs of CPAP titration. However, no data are available on the effects of APAP on cardiovascular risk factors, Methods: We performed standard full polysomnography; obtained plasma levels of glucose, insulin, and C-reactive protein (CRP); and measured systolic BP (SBP) and diastolic BP (DBP) in 31 patients with newly diagnosed, severe OSA. After standard CPAP titration, all subjects were randomized to CPAP or APAP treatment. Measurements were obtained at baseline and after 3 months of treatment., Results: The two groups were similar in terms of age, sex, body mass index (BMI), and severity of OSA. SBP, DBP, heart rate (HR), homeostasis model assessment index (HOMA-IR), and CRP were similar in the two groups. After 3 months of treatment, BMI, HR, and compliance to therapy were also comparable. OSA indexes were significantly reduced in both groups. Significant reductions in SBP, DBP, and HOMA-IR were observed in the CPAP group but not in the APAP group, while CRP plasma levels were similarly reduced., Conclusions: Our results suggest that CPAP and APAP, despite significant effects on OSA indexes and symptoms, do not improve cardiovascular risk factors in the same fashion.

The goal of this work was to apply a time-varying spectral approach to study the dynamic changes in Heart Rate Variability (HRV) produced by the arousal from sleep in obese patients with and without Obstructive Sleep Apnea (OSA). We studies 10 subjects, group I without OSA and group II with OSA diagnostic. RR intervals series was obtained from ECG records. HRV spectral indexes (HF & LF component) were computed from a time variant AR model. In general, group II has more variability than group I. Results are in agreement with literature for group I. However, group II results don't show statistical differences. Our preliminary results are comparable to others reported. Therefore, this technique allows characterizing transitory phenomena like cardiovascular response to arousals.

39 subjects aged 53-85 years suffering from COPD, admitted to our Unit, were enrolled in our study: four patients were diagnosed as having CAP; 35 patients meet the criteria of COPD exacerbation. The enrolled patients had been receiving clarithromycin (CLA) 500 mg i.v. every 12 hours; switching to oral therapy was decided on the basis of Ramirez's criteria. The mean total duration (SD) of treatment with CLA was 9.56 (1.87) days. During the study, 2 patients dropped out because of the detection of malignant tumoral cells in the sputum in one case and admission to the Intensive Care Unit because of pulmonary thromboembolism in the other. The clinical assessment made 24-72 hours after the end of the treatment confirmed the clinical efficacy of CLA (cure + improvement) in 35 out of 37 evaluable patients (94.59%). At the first follow-up visit, clinical efficacy was confirmed in 34 patients (91.89%). At the long-term follow-up visit, performed 30-45 days after the end of the study, none of the 34 "cured" patients had relapsed. Local and systemic tolerability was excellent in all patients, and no side effect attributable to the drug was reported. Our experience with switched clarithromycin therapy in patients with LRTIs confirms the validity of this approach.

The ventilatory and arterial blood pressure (ABP) responses to isocapnic hypoxia during wakefulness progressively increased in normal subjects staying 4 wk at 5,050 m (Insalaco G, Romano S, Salvaggio A, Braghiroli A, Lanfranchi P, Patruno V, Donner CF, and Bonsignore G; J Appl Physiol 80: 1724-1730, 1996). In the same subjects (n = 5, age 28-34 yr) and expedition, nocturnal polysomnography with ABP and heart rate (HR) recordings were obtained during the 1st and 4th week to study the cardiovascular effects of phasic (i.e., periodic breathing-dependent) vs. tonic (i. e., acclimatization-dependent) hypoxia during sleep. Both ABP and HR fluctuated during non-rapid eye movement sleep periodic breathing. None of the subjects exhibited an ABP increase during the ventilatory phases that correlated with the lowest arterial oxygen saturation of the preceding pauses. Despite attenuation of hypoxemia, ABP and HR behaviors during sleep in the 4th wk were similar to those in the 1st wk. Because ABP during periodic breathing in the ventilatory phase increased similarly to the ABP response to progressive hypoxia during wakefulness, ABP variations during ventilatory phases may reflect ABP responsiveness to peripheral chemoreflex sensitivity rather than the absolute value of hypoxemia, suggesting a major tonic effect of hypoxia on cardiorespiratory control at high altitude.

Chronic heart failure (CHF) patients frequently show sleep-disordered breathing consisting of periodic breathing (PB) and Cheyne-Stokes respiration (CSR) with central sleep apnoea (CSA). Since the diagnosis of sleep-disordered breathing, in CHF patients, can be made only by means of full polysomnography, the aim of the present study was to evaluate whether or not daytime respiratory function can identify patients at risk of nocturnal PB and/or CSR/CSA. Twenty-seven patients (mean age 54 +/- 8.5 yrs), eight New York Heart Association Functional Class (NYHAFC) II, 17 NYHAFC III and two NYHAFC IV, with severe cardiac failure (cardiac output 2.0 +/- 0.66 L.min-1, ejection fraction 22.5 +/- 5.77%, pulmonary capillary wedge/pressure 23 +/- 9.05 mmHg). Mouth occlusion pressure (P0.1)/maximal inspiratory pressure (MIP) was significantly higher in patients with nocturnal CSR/CSA (5.04 +/- 1.49 versus 3.24 +/- 2.13%, analysis of variance (ANOVA) 0.03), whereas their arterial carbon dioxide tension (Pa,CO2) was significantly lower (4.15 +/- 0.56 (31.2 +/- 4.23 mmHg) versus 4.67 +/- 0.53 kPa (35.1 +/- 4 mmHg), ANOVA 0.02). Logistic regression analysis demonstrated that CSR/CSA occurrence may be predicted by daytime measurement of P0.1/MIP and Pa,CO2 (p = 0.04 and 0.01 respectively; odds ratio 1.93 and 0.76 respectively). The sensitivity was 70%, specificity 76.5%, false positive rate 36.4%, false negative rate 18.8%, positive predictive value 71.4% and negative predictive value 85%. This model seems useful for predicting respiratory pattern changes in chronic heart failure patients and the authors suggest that polysomnography be performed only in high-risk patients, saving costs and the resources of sleep laboratories.

This study aimed to investigate the effect of periodic breathing (PB) at high altitude on sleep structure and arterial oxygen saturation (Sa,O2). Five healthy subjects underwent polysomnographic studies at sea level, and during the first and the fourth week of sojourn at 5,050 m. Their breathing pattern, sleep architecture and Sa,O2 were analysed. PB was detected in the high-altitude studies during nonrapid eye movement (NREM) sleep and tended to increase from the first to the fourth week. Stages 3-4 were absent in four subjects at the first week, but only in one at the fourth week, irrespective of the amount of PB. The arousal index was 11.6+/-3.8 at sea level, 30.1+/-15.5 at the first week at altitude and 33.0+/-18.2 at the fourth week. At altitude, arousal index in NREM sleep was higher during PB than during regular breathing. In NREM sleep, the mean highest Sa,O2 levels in NREM epochs with PB were higher than in those with regular breathing by 2.8+/-1.7% at the first week and 2.9+/-1.5% at the fourth week (p<0.025). From the first to the fourth week, mean Sa,O2 increased significantly during wakefulness (5.6%), NREM (5.2% with regular breathing and 5.3% with PB) and rapid eye movement sleep (7.6%). The data demonstrate a slight role of periodic breathing in altering sleep architecture at high altitude and also show that periodic breathing induces only a minor improvement in arterial oxygen saturation during nonrapid eye movement sleep.

We present the case of a young adult with type I Arnold-Chiari malformation (AMC1) and syringomyelia who developed central sleep apnoea and chronic respiratory failure, successfully treated with nocturnal noninvasive positive pressure ventilation ventilation (NIPPV). An extensive syringomyelic cavity (from bulbar to L4 segment) with severe impairment of the IX cranial nerve was documented and remains, although reduced, after the neurosurgical treatment. At baseline evaluation, the patient showed a moderate restrictive ventilatory defect, severe hypercapnic respiratory failure, abnormal control of breathing characterized by the absence of response to hypoxia and hypercapnia, and severe nocturnal central apnoeas. Nocturnal NIPPV was then started in the A/C mode with an improvement in blood gas values. Further evaluations were performed 10 and 18 months later. A progressive significant improvement of lung volumes, both in sitting and supine position, associated with a slight improvement of blood-gas values were observed. Nonetheless, the breathing pattern abnormalities persisted. Polysomnographic evaluation during mechanical ventilation showed a normalization of breathing pattern with arterial oxygen saturation (SaO2) > 90% throughout the night.

Recently, to reduce the costs of polysomnography, split-night studies have been introduced into routine practice: the first part of the night is used to make the diagnosis of obstructive sleep apnoea syndrome (OSAS) and the second part to achieve an appropriate level of continuous positive airway pressure. Since this split-night protocol has not yet been validated by the comparison of polysomnographic pictures obtained in the first and second parts of the night, the aim of this study was to evaluate sleep profile and respiratory disturbances in the first part (PSG1) and second (PSG2) portion of a standard full-night polysomnographic examination (PSGtot) in a group of OSAS patients. Twenty nine consecutive OSAS patients, aged 54+/-10 yrs; body mass index (BMI) 40+/-6 kg x m(-2) (mean+/-SD values), were studied by separate analyses of PSG1, PSG2 and PSGtot. PSG1 was found to have a low sensitivity value (66%). A significant difference was found between apnoea-hypopnoea indices (AHI) recorded in PSG1, PSG2 and PSGtot (mean+/-SD, AHI1 33+/-27, AHI2 45+/-28, AHItot 40+/-25 events x h(-1), respectively; p<0.01). A strong correlation was observed between AHItot and AHI1 (r=0.89) and between AHItot and AHI2 (r=0.92), but a weaker correlation between AHI1 and AHI2 (r=0.66). These correlations became weaker when patients were subdivided into two different classes on the basis of disease severity. PSG1 was representative of PSGtot and similar to PSG2 only in those patients with rapid eye movement (REM) phase sleep in the first part of the night. We conclude that split-night protocols are not appropriate for evaluating sleep-disordered breathing in obstructive sleep apnoea syndrome patients when rapid eye movement phase sleep does not occur in the first part of the night.

To assess the effect of chronic hypoxic conditions on ventilatory, heart rate (HR), and blood pressure (BP) responses to acute progressive isocapnic hypoxia, we studied five healthy Caucasian subjects (3 men and 2 women). Each subject performed one rebreathing test at sea level (SL) and two tests at the Pyramid laboratory at Lobuche, Nepal, at the altitude of 5,050 m, 1 day after arrival (HA1) and after 24 days of sojourn (HA2). The effects of progressive isocapnic hypoxia were tested by using a standard rebreathing technique. BP, electrocardiogram, arterial oxygen saturation, airflow and end-tidal CO2 and O2 were recorded. For each subject, the relationships between arterial oxygen saturation and HR, systolic BP and minute ventilation (VE), respectively, were evaluated. At HA1, the majority of subjects showed a significant increase in VE and BP response and a decrease in HR response to progressive isocapnic hypoxia as compared to SL. At HA2, VE and BP responses further increased, whereas the HR response remained similar to that observed at HA1. A significant relationship between hypoxic ventilatory responses and both systolic and diastolic BP responses to progressive hypoxia was found. No significant correlation was found between hypoxic ventilatory and HR responses.