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Background: Benign tracheal stenosis may relapse after management. Objectives: This study aimed to assess the value of dyspnea and spirometry in detecting relapse of benign tracheal stenosis. Methods: Patients with benign tracheal stenosis were evaluated post-management, at regular follow-up and emergency visits, with the Medical Research Council (MRC) dyspnea scale, spirometry, and flexible bronchoscopy. Patient visits were categorized and compared, in terms of change in clinical and functional parameters, in 2 groups: visits with relapse (case group) and visits with no relapse (control group). The ability of the MRC dyspnea scale and spirometry to predict relapse was evaluated. Results: Thirty-five patients with benign tracheal stenosis were included. Mean follow-up duration was 3.2 years (standard deviation = 3.3). Spirometry data were analyzed from 43 relapse visits (23 patients) versus 90 nonrelapse visits. The MRC dyspnea score and most spirometric indices were associated with relapse. In the receiver operating characteristic analysis, forced expiratory volume in 1 s, forced expiratory flow when 25% of forced vital capacity has been expired, peak expiratory flow (PEF), and total peak flow were superior to the MRC dyspnea score in predicting relapse. Among spirometric indices, >10.8% of PEF reduction has been very sensitive and specific. Conclusions: This study supports the role of dyspnea and spirometry in monitoring benign tracheal stenosis, with spirometry predicting relapse even in clinically stable patients. PEF being a very sensitive index has the additional advantage of being assessed by peak flow meter and could potentially be used for remote monitoring.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR

For the various asthma-specific beneficial effects of physical activity, daily physical activity (DPA) and the potential of asthma therapies on DPA require better characterization. Hence, we aimed to determine (a) the DPA of asthma patients, and (b) the effect of add-on mepolizumab on the DPA of severe asthma patients. Methods: Adult outpatients with mild-to-moderate or severe asthma had accelerometer assessment of DPA. Severe asthma patients who were commenced on mepolizumab had their DPA reassessed after 12 months. Results: For the total cohort (n = 36), daily step count, time in moderate-to-vigorous physical activity (MVPA), MVPA volume and Movement Intensity (MI) were 7806 ± 3823 steps, 123 (interquartile range, 63) min, 657 ± 255 MET·min and 1.96 (0.45) m/s2, respectively. All patients met at least one recommendation for DPA but less than half met recommendations for vigorous DPA. Patients on mepolizumab therapy increased daily step count (646 steps; 9%), time in MVPA (20 min; 21%), MVPA volume (87 MET·min; 17%) and MI (0.11 m/s2; 6%) for the same amount of moving time; lung function, asthma control and health-related quality of life also improved. Conclusions: Analysis of the first national data on DPA in asthma and novel comparison against current applicable guidelines and identified beneficial thresholds showed borderline levels of DPA with room for improvement especially for severe asthma patients. In a non-sedentary cohort of severe asthma patients, mepolizumab conferred significant and meaningful improvements in DPA.

Introduction: Community-acquired pneumonia (CAP) presents high mortality rates and high healthcare costs worldwide. C-reactive protein (CRP) has been widely used as a biomarker for the management of CAP. We evaluated the performance of CRP threshold values and ΔCRP as predictors of CAP survival and length of hospital stay. Methods: A total of 173 adult patients with CAP were followed for up to 30 days. We measured serum CRP levels on days 1, 4, and 7 (D1, D4, and D7) of hospitalization, and their variations between different days were calculated (ΔCRP). A multivariate logistic regression model was created with CAP 30-day survival and length of hospital stay as dependent variables, and absolute CRP values and ΔCRP, age, sex, smoking habit (pack-years), pO2/FiO2 ratio on D1, WBC on D1, and CURB-65 score as independent variables. Results: A total of six patients with CAP died (30-day mortality 3.47%). No difference was found in CRP levels and ΔCRP between survivors and non-survivors. Using a cut-off level of 9 mg/dL, the AUC (95% CI) for the prediction of survival of CRP on D4 and D7 were 0.765 (0.538–0.992) and 0.784 (0.580–0.989), respectively. A correlation between CRP values on any day and length of hospital stay was found, with it being stronger for CRPD4 and CRPD7 (p < 0.0001 and p = 0.0024, respectively). A reduction of CRP > 50% from D1 to D4 was associated with 4.11 fewer days of hospitalization (p = 0.0308). Conclusions: CRP levels on D4 and D7, but not ΔCRP, could fairly predict CAP survival. A reduction of CRP > 50% by the fourth day of hospitalization could predict a shorter hospital stay.

Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid–femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.

BACKGROUND: Accurate mediastinal staging in patients with non-small cell lung cancer (NSCLC) is crucial for the determination of optimal treatment management. METHODS: This was a real-life prospective study enrolling 140 patients between December 2016 and August 2018. We aimed to determine the clinical utility of EBUS/EUS-b in mediastinal staging of patients with NSCLC in comparison with integrated PET/CT. Furthermore, SUV(max) cut-off value with the highest specificity/accuracy was evaluated. Subgroup analysis according to histological type was performed. RESULTS: One hundred and thirty patients were eligible for analysis (mean age ± SD: 67.6±7.6, males 97). Three hundred different lymph node stations were sampled (272 through EBUS-TBNA and 28 through EUS-b FNA). Mean SUV(max) of all malignant lymph nodes was 7.46 (SD =5.54). Sensitivity, specificity, PPV and NPV of EBUS/EUS-b for the identification of mediastinal malignant lymph nodes was 93.8%, 100%, 100%, and 93.4%, respectively. Accordingly, PET/CT yielded 92.2% sensitivity, 43.9% specificity, 64.8% PPV and 83.3% NPV. For adenocarcinoma (n=76) NPV were 86.2% with EBUS/EUS-b and 75% with PET/CT. NPV for squamous cell (n=46) was 100% with EBUS/EUS-b and 90.9% with PET/CT. EBUS/EUS-b staging yielded excellent agreement with final staging (97.5%, Tau 0.94, P

The notion of Exclusive Economic Zone (EEZ) is a relatively new one. Its gestation during the second half of the 20th century was slow and arduous. But, after its birth, it gained a very important and crucial place within the sector of International Law and especially the branch of the Law of the Sea. Furthermore, it implicates strong and unprecedented geopolitical issues, emerged between a lot of neighbouring states. Pursuant to the rule establishing its notion, the EEZ confers upon a State a sovereign right, subject to a number of restrictions, which do not, nevertheless, affect the core of its integrity. But, in real international life this integrity is seriously jeopardized. International Law, because of its particularity, cannot be equipped by and enjoy the means of forced execution, which are inherent to the national legal system of every sovereign State. The EEZ, as it is provided by the International Law and especially the United Nations Convention on the Law Of the Sea, is not in reality a sovereign right of a State. It depends on the consensus of the State with adjacent coast and overlapping EEZ, which is a ‘prerequisite’ legally not existing.

Objective Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. Methods Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2, Graphical abstract Image 1

Despite that COPD remains one of the most common respiratory diseases worldwide, it can be managed effectively with certain treatments and, more importantly, be prevented by the early implementation of various measures. The pathology and pathophysiology of this disease continue to be studied, with new pharmacological and invasive therapies emerging. In this consensus paper, the Working Group of the Hellenic Thoracic Society aimed to consolidate the up-to-date information and new advances in the treatment of COPD. Local and international data on its prevalence are presented, with revised strategies on the diagnostic approach and the evaluation of risk assessment and disease severity classification. Emphasis is placed on the management and therapy of patients with COPD, covering both common principles, specialized modalities, and algorithms to distinguish between home care and the need for hospitalization. Although pharmacological treatment is commonly recognized in COPD, an integrative approach of pulmonary rehabilitation, physical activity, patient education, and self-assessment should be encountered for a comprehensive treatment, prevention of exacerbations, and increased quality of life in patients.

Background Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders. In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients’ symptoms and history of exacerbations (ABCD assessment approach). Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece. Methods This was a cross-sectional observational study. Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece). Results The mean age at the time of initial COPD diagnosis was 63.8 (± 10.2). Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach. The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A. Conclusion Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder with a course that is not uniform for all COPD patients. Although smoking is considered as the major cause of the disease, persistent or recurrent infections seem to play a particular role in the disease establishment and progression. COPD is characterized by dysregulated immunity that has been associated with the bacterial colonization and infections. The establishment of culture-independent techniques has shed new light on the relationships between bacterial ecology and health status and expanded our knowledge on the lung microbiome. Interactions between the host and lung microbiome result in inflammation and activation of resident cells. The lung microbiome contains populations of symbionts and pathobionts in balance which lose their equilibrium and disturb the balance of T-helper and regulatory T-cells (Treg) upon infection, or lung disease. In COPD factors such as disease severity, exacerbations, degree of inflammation, and type of treatment used (e.g inhaled or systemic steroids and antibiotics) affect the composition of lung microbiota. Recent data indicate that the presence of specific bacterial taxa in the airways has the potential to influence the host immune response and possibly to interfere with disease phenotype. Although, there is a growing body of evidence for the role of microbiome in COPD several unanswered questions still exist for its clinical relevance.

The purpose of the study was to examine the effect of an exercise program on the quality of life and self-esteem of inmates in Greek prisons. Sixty male inmates randomly assigned in two groups (control and experiment). The duration of the training program for the exercise group was 12 weeks. Control group individuals did not participate in the exercise program. SF-12 quality of life questionnaire and the Rosenberg self-esteem scale were administered to both groups prior and after exercise intervention. The findings of this study support the beneficial effect of exercise on quality of life and self-esteem of inmates in Greek prison settings. The research for this paper was financially supported by a PhD Research Fellowship from the General Secretariat for Research and Technology (GSRT) and Hellenic Foundation for Research and Innovation (HFRI).

Introduction: The age of asthma onset is often implicated in clinical manifestation, diagnosis, and management of the disease.Aim: To define demographic, clinical and functional features and inflam...

Background Chronic obstructive pulmonary disease (COPD) is a multifactorial clinical condition, characterized by chronic progressive (or worsening) respiratory symptoms, structural pulmonary abnormalities, and impaired lung function, and is often accompanied by multiple, clinically significant comorbid disorders. In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) issued a new report on COPD prevention, diagnosis and management, aiming at personalizing the maintenance therapeutic approach of the stable disease, based on the patients’ symptoms and history of exacerbations (ABCD assessment approach). Our objective was to evaluate the implementation of GOLD suggestions in everyday clinical practice in Greece. Methods This was a cross-sectional observational study. Sixty-five different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, vaccination data, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, COPD treatments) were collected from 3615 nation-wide COPD patients (Greece). Results The mean age at the time of initial COPD diagnosis was 63.8 (+/- 10.2). Almost 60% of the subjects were classified into group B, while the remaining patients were falling into groups A (18%) and D (21%), and only a small minority of patients belonged to Group C, according to the ABCD assessment approach. The compliance of respiratory physicians to the GOLD 2017 therapeutic suggestions is problematic, especially when it comes to COPD patients belonging to Group A. Conclusion Our data provide valuable information regarding the demographic and medical profile of COPD patients in Greece, the domains which the revised ABCD assessment approach may show some clinical significance on, and the necessity for medical practitioners dealing with COPD patients to adhere closer to international recommendations for the proper management of the disease.

Background We performed metabolomic profiling to identify metabolites that correlate with disease progression and death. Methods We performed a study of adults hospitalized with Influenza A(H1N1)pdm09. Cases (n = 32) were defined by a composite outcome of death or transfer to the intensive care unit during the 60-day follow-up period. Controls (n = 64) were survivors who did not require transfer to the ICU. Four hundred and eight metabolites from eight families were measured on plasma sample at enrollment using a mass spectrometry based Biocrates platform. Conditional logistic regression was used to summarize the association of the individual metabolites and families with the composite outcome and its major two components. Results The ten metabolites with the strongest association with disease progression belonged to five different metabolite families with sphingolipids being the most common. The acylcarnitines, glycerides, sphingolipids and biogenic metabolite families had the largest odds ratios based on the composite endpoint. The tryptophan odds ratio for the composite is largely associated with death (OR 17.33: 95% CI, 1.60–187.76). Conclusions Individuals that develop disease progression when infected with Influenza H1N1 have a metabolite signature that differs from survivors. Low levels of tryptophan had a strong association with death. Registry ClinicalTrials.gov Identifier: NCT01056185

Background: Patients with severe eosinophilic asthma (SEA) frequently have comorbid chronic rhinosinusitis with nasal polyposis (CRSwNP). In this pilot study we aimed to assess the effect of mepolizumab on rhinitic symptoms and nasal hypersensitivity, as well as NP. Methods: Fifteen patients with SEA (eight patients with rhinitis/rhinosinusitis and seven patients with NP) have been included as yet. All patients underwent skin prick testing (SPTs), facial CT scan, nasal Peak Inspiratory Flow Rate (nPIFR) measurements, and nasal provocation testing (NPT) before, 6 months, and one year after mepolizumab treatment for SEA. Daily nasal symptoms were recorded, along with SNOT 22. Nasal secretion samples were collected at each point of nasal provocation and stored for the quantification of inflammatory mediators. Results: Ten patients had positive SPTs to common aeroallergens. Total IgE mean serum levels were 175 IU/mL (range 10-555 IU/mL) with mean blood eosinophil count 345 k/μL (range 100-540 k/μL). Four patients had a positive provocation test which turned to negative in three patients after one year of treatment. There was a significant decrease in daily symptom scores after six months (mean±SD, 4.5±3 vs 1.7±1, p=0.007) and a year of treatment (2.8±1, p=0.08), with SNOT-22 score significantly improving after a year of treatment (56±16 vs 32±24, p=0.048). In five patients NP was significantly improved. Mediators’ measurements are pending. Conclusions: In SEA patients with CRSwNP a positive effect in reducing symptoms, nasal hypersensitivity and NP was seen however, a larger number of patients is needed in order to have conclusive results

Introduction: Pulmonary rehabilitation (PR) guidelines recommend education be offered as a standard component of a comprehensive PR program. Patient response to disease specific knowledge following PR is often unknown Aim: To assess response to self-management knowledge following COPD disease specific education Methods: 29 patients with stable COPD (GOLD II-ΙV), (FEV1%pred: 49) age 68 ± 7 years, randomly assigned to a 3-month 3 times/week PR program. 16 to intervention group (IG) (exercise + 4 hourly sessions of disease specific education); 13 control group (CG) (exercise + written material). Educational topics included: disease knowledge, symptom management, medication, smoking cessation, exacerbation management, exercise and physical activity. Disease-specific knowledge was assessed with the Bristol COPD Knowledge Questionnaire (BCKQ) before and after the completion of PR Results: At baseline there was no differences between groups in BCKQ overall score. Post-PR, both groups demonstrated significant knowledge improvement, pre-PR vs post-PR: IG (30.5 vs 35.7, p Conclusion: PR programs can improve disease-specific knowledge in patients with COPD. Studies required to assess the impact of medication knowledge on exacerbation rate, hospitalization and medication adherence

Introduction: Accurate mediastinal staging in patients with non-small cell lung cancer (NSCLC) is crucial for the determination of optimal treatment management. Aim: To compare the diagnostic accuracy of EBUS/EUS-b with PET-CT in mediastinal staging of potentially operable NSCLC patients. Methods: This was a prospective study enrolling 140 patients between 1/7/2016 and 31/8/2018. Results: 130 patients were eligible for analysis (mean age ± SD:67,6 ±7,6, males 97). 304 different lymph node (LN) stations were sampled (276 through EBUS and 28 through EUS-b). Sensitivity, specificity, PPV and NPV of EBUS/EUS-b for the identification of mediastinal malignant LN’s was 93,8%, 100%, 100% and 93,4% respectively. Accordingly, PET-CT yielded 92,2% sensitivity, 43,9% specificity, 64,8% PPV and 83,3% NPV. NPV for adenocarcinoma (n=76) was 86,2% with EBUS/EUS-b and 75% with PET-CT. NPV for squamous cell (n=46) was 100% with EBUS/EUS-b and 90,9% with PET-CT. Thoracic endosonography staging yielded excellent agreement with final staging (97,5%, Tau 0,94, p Conclusion: Thoracic endosonography is a safe, minimally invasive procedure with high sensitivity and diagnostic accuracy in patients with potentially operable NSCLC. Implementation of both EBUS/EUS-b and PET-CT is necessary in order to avoid futile thoracotomies.

Asthma is the commonest respiratory disease and one of unceasingly increasing prevalence and burden. As such, asthma has attracted a major share or scientific interest and clinical attention. With the various clinical and pathophysiological aspects of asthma having been extensively investigated, the important association between asthma and physical activity remains underappreciated and insufficiently explored. Asthma impacts adversely on physical activity. Likewise, poor physical activity may lead to worse asthma outcomes. This concise clinical review presents the current recommendations for physical activity, discusses the available evidence on physical activity in asthma, and examines the causes of low physical activity in adult asthmatic patients. It also reviews the effect of daily physical activity and exercise training on the pathology and clinical outcomes of asthma. Finally, it summarizes the evidence on interventions targeting physical activity in asthma.

Imprisonment is clearly associated with mental health problems among prisoners. Evidence across research literature shows that exercise in detention environments improves mental health. The purpose of the study was to examine the effect of an exercise program on mood profile and anxiety of inmates in Greek prisons. Sixty male inmates randomly assigned in two groups (control and experiment). Individuals of the exercise group received a 12 weeks training program at a frequency of three (3) training sessions each week of 60 minutes per session. Control group individuals did not participate in the exercise program. The Profile of Mood States (POMS) and The State-Trait Anxiety Inventory (STAI) were administered to both groups prior and after exercise intervention. The findings of this study support the beneficial effect of exercise on mood and anxiety of inmates in Greek prison settings. The research for this paper was financially supported by a PhD Research Fellowship from the General Secretariat for Research and Technology (GSRT) and Hellenic Foundation for Research and Innovation (HFRI).

Background: Sestrin 2, Endocan, and Sirtuin 1 are distinct molecules with some biologic actions associated with asthma pathophysiology. The aim of the present study was to determine the molecular level differences attributable to underlying asthma severity. Methods: We initially recruited 85 asthmatics with a wide spectrum of severity. All of the patients were optimally treated according to current guidelines. Demographics, test results of lung function, and treatment regimes of all patients were recorded. Sestrin 2, Endocan, and Sirtuin 1 were measured in different biological samples (sputum with two processing methods and serum). Results: A total of 60 patients (35 with severe asthma) were analyzed, since 25 patients failed to produce an adequate sample of sputum. Patients with severe asthma showed significantly higher values for Sestrin 2 [pg/mL], measured in both sputum supernatant and cell pellet, compared to those with mild to moderate asthma [9524 (5696, 12,373) vs. 7476 (4265, 9273) p = 0.029, and 23,748 (15,280, 32,742) vs. 10,084 (3349, 21,784), p = 0.008, respectively]. No other significant differences were observed. No significant associations were observed between biomarkers, inflammatory cells, and lung function. Conclusion: Sestrin 2 is increased in patients with severe asthma as part of a mechanism that may modify structural alterations through the imbalance between oxidative stress and antioxidant activity.

Daily sedation interruption (DSI) is a method used since the beginning of the millennium to streamline sedation in critically ill patients under mechanical ventilation and improve clinical outcomes. The purpose was to assess whether there is a correlation between DSI and weaning from mechanical ventilation. We designed a literature review via searching PubMed, UpToDate and Google Scholar for relevant key terms from inception until March 2019. Literature retrieved included nine randomized controlled trials. When compared to usual practice, it is superior in terms of duration of mechanical ventilation, stay in the intensive care unit, hospitalization, adverse effect occurrence and total cost of therapy. Comparison with other sedation protocols produces conflicting results. DSI, and protocolized sedation in general, are safe methods to perform to facilitate earlier weaning and improved clinical outcomes. Future research should focus on minimizing bias by conducting double-blinded studies and studying different patient subgroups.

Key Points Question Is the receipt of colchicine among patients hospitalized with symptomatic coronavirus disease 2019 associated with clinical benefit? Findings In this randomized clinical trial of 105 patients, the rate of the primary clinical end point (clinical deterioration) was higher in the control group than in the colchicine group, and the time to clinical deterioration was shorter in the control group than in the colchicine arm. No difference was observed in the primary biochemical end point (high-sensitivity troponin concentration), but patients in the colchicine group had a smaller increase in dimerized plasma fragment D compared with patients in the control group. Meaning The hypothesis-generating findings of this study suggest a role for colchicine in the treatment of patients with coronavirus disease 2019., This randomized clinical trial evaluates the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19)., Importance Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. Objective To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). Design, Setting, and Participants In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. Intervention Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. Main Outcomes and Measures Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. Results A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). Conclusions and Relevance In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. Trial Registration ClinicalTrials.gov Identifier: NCT04326790

Background Nintedanib represents an antifibrotic compound able to slow down disease progression of patients with idiopathic pulmonary fibrosis (IPF). Objective To investigate the safety and efficacy of nintedanib in patients with IPF in a real-life setting. Methods This was a multicentre, retrospective, observational, real-life study for patients with IPF receiving nintedanib between October 2014 and October 2016. Results We identified 94 patients with IPF receiving nintedanib (72 males, mean age±SD: 73.8 ± 7.5, mean%FVC±SD = 68.1 ± 18.3, mean%DLCo±SD = 44.4 ± 14.5). Diarrhea (n = 52, 55.3%) was the most commonly reported adverse event. Twenty patients (21.2%) had to permanently discontinue nintedanib due to severe adverse events. In the 6-months follow-up, median decline in %FVC predicted and %DLCO predicted were 1.36 (95%Cl: 0 to 2.97) and 4.00 (95%Cl: 2.01 to 6.20), respectively, when deaths were censored and excluded from the analysis. At 12 months, mean%FVC±SD and mean%DLCo±SD were 64.5 ± 19.1 and 43.7 ± 15.4, respectively. With regards to mortality, 17 patients (18.1%) died over a study period of 730 days. Conclusion Nintedanib demonstrated an acceptable safety and efficacy profile in our real-world observational study. Prospective observational studies in the context of registries that collect well-defined supporting data over time are sorely needed to answer residual questions on drug's performance.

Surfactant proteins (SPs) have been studied in COPD patients as biomarkers of disease severity and as predictive factors of unfavorable outcomes. The aim of this exploratory study was to evaluate serum levels of SP-A, SP-B, SP-C, and SP-D in patients with COPD both during AECOPD and in stability and to test their possible associations with disease severity and with the development of new exacerbation events. 20 consecutive COPD patients hospitalized for AECOPD were included. Serum SP levels were measured on admission, at discharge, and on stability. SP-A levels were significantly lower both on admission and at discharge in patients with early relapse compared to those with late or no relapse (29.2 ± 9.1 vs. 43.9 ± 16.9 ng/ml, p = 0.037, and 24.3 ± 2.8 vs. 39.3 ± 14.2 ng/ml, p = 0.011, respectively). SP-B levels were found to have a trend to be higher at discharge and significantly higher on stability in patients experiencing an early relapse compared to those with late or no relapse (52.5 ± 31.6 vs. 31.4 ± 32.3 ng/ml, p = 0.052 and 64.8 ± 32.6 vs. 32.8 ± 25.6 ng/ml, p = 0.024, respectively). Finally, the ROC analysis showed that serum SP-A, SP-B, and SP-C levels at discharge, seemed to be significant predictors of early relapse. Our conclusion is that serum levels of SPs might be related to disease outcomes in COPD patients.

Background: Osteopontin (OPN) is involved in cancer development and metastasis. Increased sputum OPN was detected in chronic obstructive pulmonary disease (COPD). Methods: We evaluated serum OPN levels in patients with lung cancer (LC) and/or COPD and aimed to determine OPN prognostic performance in 1-year mortality in LC and also its diagnostic performance in LC among COPD patients. We recruited 167 LC patients, 85 with concomitant COPD. 28 COPD patients served as control group. Results: OPN levels were higher in LC compared to COPD alone (P=0.017) and higher in COPD and LC compared to COPD alone (P=0.031). No difference was observed in OPN levels between LC and COPD vs . LC without COPD (P=0.171). Serum OPN ≥50.3 ng/mL was an independent predictor of 1-year mortality in LC. Conclusions: OPN levels ≥35 ng/mL could predict the presence of LC among COPD patients. In patients with LC and/or COPD, LC is the major determinant for serum OPN. Serum OPN might be a promising prognostic biomarker of LC and a diagnostic biomarker of LC among COPD patients.

Angiogenesis is a biological process that involves the formation of new blood vessels from the existing vasculature, and it plays a fundamental role in the development and progression of several types of cancer, including lung cancer. The angiopoietin/Tie2 ligand/receptor system orchestrates vascular integrity. In particular, Angiopoietin-1 activates the endothelial cell (EC)-specific receptor tyrosine kinase,Tie2,which is essential for preserving endothelial quiescence. On the other hand, Angiopoietin-2 acts as an inhibitor of the Angiopoietin-1/Tie2 signaling pathways, thus facilitating the destabilization of quiescent endothelium in cases of inflammation and cancer. Clinical studies have proven that high levels of Angiopoietin-2 indicate the development of non-small-cell lung carcinomas (NSCLC), while high levels of Angiopoietin-2 are strongly related to tumor angiogenesis, lymphangiogenesis, metastasis, and poor prognosis. Interestingly, the association of Angiopoietin-2 levels with the type of surgical approach makes Angiopoietin-2 a valuable factor in selecting the most suitable therapeutic strategy for lung cancer patients. The role of the Angiopoietin-1 and Angiopoietin-4 levels in NSCLC development requires further investigation. The present review focuses on the clinical impact of the Angiopoietin-1, Angiopoietin-2, and Angiopoietin-4 levels in patients diagnosed with NSCLC, emphasizing the interaction between them, and how they affect the development, progression, and metastasis of lung disease. Finally, it estimates the role of angiopoietins levels in the effective therapy of lung cancer patients.