Biological effects of COVID-19 on lung cancer: can we drive our decisions?

COVID-19 infection caused by SARS-CoV-2 is considered catastrophic because it affects multiple organs, particularly those of the respiratory tract. Although the consequences of this infection are not fully clear, it causes damage to the lungs, the cardiovascular and nervous systems, and other organs, subsequently inducing organ failure. In particular, the effects of SARS-CoV-2-induced inflammation on cancer cells and the tumor microenvironment need to be investigated. COVID-19 may alter the tumor microenvironment, promoting cancer cell proliferation and dormant cancer cell (DCC) reawakening. DCCs reawakened upon infection with SARS-CoV-2 can populate the premetastatic niche in the lungs and other organs, leading to tumor dissemination. DCC reawakening and consequent neutrophil and monocyte/macrophage activation with an uncontrolled cascade of pro-inflammatory cytokines are the most severe clinical effects of COVID-19. Moreover, neutrophil extracellular traps have been demonstrated to activate the dissemination of premetastatic cells into the lungs. Further studies are warranted to better define the roles of COVID-19 in inflammation as well as in tumor development and tumor cell metastasis; the results of these studies will aid in the development of further targeted therapies, both for cancer prevention and the treatment of patients with COVID-19

Exhaled nitric oxide in patients with PiZZ Phenotype-related α 1-anti-trypsin deficiency

AbstractThere is no report of exhaled NO (eNO) in subjects with different phenotypes ofα1 -anti-trypsin (AAT) deficiency.Exhaled nitric oxide was evaluated by means of single-breath chemiluminescence analysis (fractional exhaled concentration at the plateau level [plFENO]) in 40 patients with AAT deficiency. Patients were divided according to the protease inhibitor (Pi) phenotype: PiMZ/MS, n=25; PiSZ n=6; PiZZ, n=9. Nineteen healthy subjects served as controls. Levels of eNO in PiZZ patients were also compared with those of subjects, without AAT deficiency (PiMM), matched for diagnosis, sex, age, smoking habit and forced expiratory volume in 1 sec (FEV1). In AAT deficiency subjects airway hyper-responsiveness to methacholine (PD20FEV1) was also assessed.plFENOwas significantly lower in the PiZZ group (4·5±1·4 ppb) than in matched PiMM subjects (8·2±3·8 ppb), in healthy controls (9·3±2·8 ppb) and in patients of other phenotypes. Dynamic lung volumes and DLCOwere significantly lower in PiZZ than in other AAT-deficient patients. Bronchial hyper-responsiveness was not different among AAT phenotypes.These results suggest that eNO may be significantly reduced in PiZZ as compared to healthy control subjects and to AAT subjects with other phenotypes, independent of the level of airway obstruction. Whether, at least potentially, eNO may be considered as an early marker of lung involvement in AAT deficiency must be confirmed with studies on larger number of subjects

Breathlessness, but not cough, suggests chronic obstructive pulmonary disease in elderly smokers with stable heart failure.

Chronic obstructive pulmonary disease (COPD) is a common comorbidity of heart failure (HF), but remains often undiagnosed, and we aimed to identify symptoms predicting COPD in HF. As part of an observational, prospective study, we investigated stable smokers with a confirmed diagnosis of HF, using the 8-item COPD-Assessment-Test (CAT) questionnaire to assess symptoms. All the items were correlated with the presence of COPD, and logistic regression models were used to identify independent predictors. 96 HF patients were included, aged 74, 33% with COPD. Patients with HF and COPD were more symptomatic, but only breathlessness when walking up a hill was an independent predictor of COPD (odds ratio=1.33, p=0.0484). Interestingly, COPD-specific symptoms such as cough and phlegm were not significant. Thus, in elderly smokers with stable HF, significant breathlessness when walking up a hill is most indicative of associated COPD, and may indicate the need for further lung function evaluation

Differences between acute exacerbations of idiopathic pulmonary fibrosis and other interstitial lung diseases.

Interstitial lung diseases (ILDs) comprise a wide group of pulmonary parenchymal disorders. These patients may experience acute respiratory deteriorations of their respiratory condition, termed “acute exacerbation” (AE). Incidence of AE-ILD seems to be lower than idiopathic pulmonary fibrosis (IPF), but prognosis and prognostic factors are largely unrecognized. We retrospectively analyzed a cohort of 158 consecutive adult patients hospitalized for AE-ILD in two Italian University hospitals from 2009 to 2016. Patients included in the analysis has been divided into two groups: non-IPF (62%) and IPF (38%). Among ILDs included in the non-IPF group, the most frequent diagnoses were non-specific interstitial pneumonia (NSIP) (42%) and connective tissue disease (CTD)-ILD (20%). Mortality during hospitalization was significantly different between the two groups, respectively 19% in non-IPF group and 43% in IPF group. AEs of ILDs are difficult-to-predict events and are burdened by relevant mortality. Increased inflammatory markers with neutrophilia on differential blood cell count (HR 1.02 [CI 1.01 – 1.04]), presence of pulmonary hypertension (HR 1.85 – [CI 1.17 – 2.92]) and diagnosis of IPF (HR 2.31 [CI 1.55 – 3.46]) resulted negative prognostic factors in our analysis, while lymphocytosis on differential count seemed to act as a protective prognostic factor (OR 0.938 [CI 0.884 – 0.995]). Further prospective, large-scale, real-world data are needed to support and confirm the impact of our findings

Development of post-COVID-19 cardiovascular events: An analysis of clinical features and risk factors from a single hospital retrospective study

Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific inter-est. The aim of this study was to analyze the onset of post-COVID-19 cardiovascular events in patients hospitalized in a tertiary care center. This is a retrospective study conducted on patients hospitalized over a period of three months. The patients were older than 18 years of age and had a diagnosis of COVID-19 infection confirmed from a nasopharyngeal swab sample. Anamnestic and clinical-laboratory data were collected. Cardiovascular events at 30 days were defined as follows: arrhythmias, myocardial infarction, myocarditis, and pulmonary embolism. Univariate analysis (Student\u2019s t-test or Mann-Whitney U test, as appropriate) and multivariate analysis (multinomial logistic regression) were applied to the data. A total of 394 patients were included; they were mostly males and had a median age of 65.5 years. Previous cardiovascular disease was present in 14.7% of patients. Oxygen therapy was required for 77.9%, and 53% received anticoagulant therapy. The overall 30-day mortality was 20.3%. A cardiovascular event developed in 15.7% of the subjects. These were mainly pulmonary embolism (9.4%), followed by arrhythmias (3.3%), myocardial infarction (2.3%), and myocarditis (0.8%). Patients who developed cardiovascular events upon univariate analysis were significantly older, with major comorbidities, a more compromised respiratory situation, and a higher mortality rate. Multivariate analysis revealed independent factors that were significantly associated with the development of cardiovascular events: hypertension, endotracheal intubation, and age older than 75 years. In patients with COVID-19, the development of a cardiovascular event occurs quite frequently and is mainly seen in elderly subjects with comorbidities (especially hypertension) in the presence of a severe respiratory picture

Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol.

To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are: a)more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were receiving standard oxygen therapy5.IMV in patients who at randomisation were receiving non-invasive mechanical ventilationb)Similar in terms of major bleeding risk TRIAL DESIGN: Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study

Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome.

Background: A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods: We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results: Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P < .001). Insulin resistance (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.14-1.96), body mass index (OR = 1.14; 95% CI, 1.04-1.24), and the metabolic syndrome (OR = 2.54; 95% CI, 1.13-5.68) were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR = 0.86; 95% CI, .76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions: Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS

Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator.

Objectives: Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference. Methods: This was a retrospective, observational cohort study among patients with severe COVID- 19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death by sex. Interaction was formally tested to compare the risk difference by sex in subsets. Mediation analysis with a binary endpoint IMV or death (yes/no) by end of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted. Results: Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54-77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs 191 mmHg; p=0.023). By 28 days from admission, 49.2% (95% CI: 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent IMV or death (log-rank pvalue<0.0001) and this amounted to a difference in HR of 0.40 (0.26-0.63, p=0.0001). The AUC in Creactive protein (CRP) over the study period appeared to explain 85% of this difference in risk by sex. Conclusions: Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. CRP showed a predominant role to mediate the difference in risk by sex

Efficacy of pulmonary rehabilitation in chronic respiratory failure (CRF) due to chronic obstructive pulmonary disease (COPD): The Maugeri Study.

14noWhile the effectiveness of pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) is well established, its effectiveness in the most severe category of COPD, i.e. patients with chronic respiratory failure (CRF), is less well known. OBJECTIVE: To verify the effects of PR in patients with CRF, and compare the level of improvement with PR in these patients to that of COPDs not affected by CRF. METHODS: A multi-centre study was carried out on COPD patients with versus without CRF. The PR program included educational support, exercise training, and nutritional and psychological counselling. Lung function, arterial gases, walk test (6MWT), dyspnoea (MRC; BDI/TDI), and quality of life (MRF(28); SGRQ) were evaluated. RESULTS: Thousand forty seven consecutive COPD inpatients (327 with CRF) were evaluated. In patients with CRF all parameters improved after PR (0.001). Mean changes: FEV(1), 112 ml; PaO(2), 3.0 mmHg; PaCO(2), 3.3 mmHg; 6MWT, 48 m; MRC, 0.85 units; MRF(28) total score, 11.5 units. These changes were similar to those observed in patients without CRF. CONCLUSIONS: This study, featuring the largest cohort so far reported in the literature, shows that PR is equally effective in the more severe COPD patients, i.e. those with CRF, and supports the prescription of PR also in these patients.nonemixedCARONE M; PATESSIO A; AMBROSINO N; BAIARDI P; BALBI B; BALZANO G; CUOMO V; DONNER CF; FRACCHIA C; NAVA S; NERI M; POZZI E; VITACCA M; SPANEVELLO A.Carone, M; Patessio, A; Ambrosino, N; Baiardi, P; Balbi, B; Balzano, G; Cuomo, V; Donner, Cf; Fracchia, C; Nava, S; Neri, M; Pozzi, E; Vitacca, M; Spanevello, Antoni