Stress-strain curve and elastic behavior of the fibrotic lung with usual interstitial pneumonia pattern during protective mechanical ventilation.

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress-strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient's stress-strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8-33.2] cmH2O versus 11.4 [10.3-14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress-strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

Integrated endoscopic treatment of primitive unresectable tracheal tumor: the INTACT retrospective cohort study.

Background: Primitive tracheal tumors represent a rare entity whose management, when unresectable, remains challenging. Primary aim of this study was to explore the survival and the factors influencing prognosis of patients with unresectable primitive tracheal tumor undergoing multimodal treatment integrating interventional bronchoscopy and radiotherapy. Methods: This retrospective cohort study was conducted at the University Hospital of Modena (Italy) over a 12-year period (January 2010 to January 2022) analyzing patients with unresectable primary tracheal tumor receiving interventional bronchoscopy treatment followed by radiotherapy. Survival analysis was conducted for the whole population and according to histology, development of metastasis, stent placement and the onset of disease relapse. The raw and independent association between potential risk factor and 5-year mortality and the reported complications were investigated. Results: A total of 12 patients were included. Five-year survival rate was 42% with a median survival time of 26.7 (interquartile range, 4.1-82) months. Survivors showed a higher prevalence of cystic-adenoid histology (80% vs. 14%), while patients who were dead at 5 years were those with a more advanced T (prevalence of T2: 71% vs. 0%) and a lower response to first line treatment (57% vs. 0%). Treatment complications accounted for stent dislocation (33%) and the onset of granuloma (18%), while no major side effects were reported. The presence of cystic-adenoid histology resulted in significantly improved 5-year survival rate (80% vs. 14%). The onset of distal metastasis, the occurrence of disease relapse and the placement of tracheal stent did not result significantly associated with lower survival. Among analysed variables, only the presence of cystic-adenoid histology resulted independently associated with survival (odds ratio =0.1, P=0.04). Conclusions: Multimodal treatment including interventional bronchoscopy and associated radiotherapy for unresectable primary tracheal tumors seems not burdened by significant complications and may provide benefits in terms of survival for those patients with cystic-adenoid histology.

When sarcoidosis hits down: a case of prostatic sarcoidosis.

A 69-year-old North African male with established diagnosis of sarcoidosis underwent a stereotactic prostate biopsy with fusion technique. At the histological analysis, non-necrotizing micro-granulomas were highlighted in 2 samples, while the immunohistochemical staining resulted negative for CK903/p63/racemase. To the best of our knowledge, only 16 cases of prostatic sarcoidosis have been reported in literature. With this case report we describe an incidental diagnosis of prostatic involvement of sarcoidotic disease and briefly review and discuss the available literature on the topic.

Efficacy of Respiratory Muscle Training in the Immediate Postoperative Period of Cardiac Surgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: This study aimed to evaluate the efficacy of respiratory muscle training during the immediate postoperative period of cardiac surgery on respiratory muscle strength, pulmonary function, functional capacity, and length of hospital stay. METHODS: This is a systematic review and meta-analysis. A comprehensive search on PubMed®, Excerpta Medica Database (or Embase), Cumulative Index of Nursing and Allied Health Literature (or CINAHL), Latin American and Caribbean Health Sciences Literature (or LILACS), Scientific Electronic Library Online (or SciELO), Physiotherapy Evidence Database (or PEDro), and Cochrane Central Register of Controlled Trials databases was performed. A combination of free-text words and indexed terms referring to cardiac surgery, coronary artery bypass grafting, respiratory muscle training, and clinical trials was used. A total of 792 studies were identified; after careful selection, six studies were evaluated. RESULTS: The studies found significant improvement after inspiratory muscle training (IMT) (n = 165, 95% confidence interval [CI] 9.68, 21.99) and expiratory muscle training (EMT) (n = 135, 95% CI 8.59, 27.07) of maximal inspiratory pressure and maximal expiratory pressure, respectively. Also, IMT increased significantly (95% CI 19.59, 349.82, n = 85) the tidal volume. However, no differences were found in the peak expiratory flow, functional capacity, and length of hospital stay after EMT and IMT. CONCLUSION: IMT and EMT demonstrated efficacy in improving respiratory muscle strength during the immediate postoperative period of cardiac surgery. There was no evidence indicating the efficacy of IMT for pulmonary function and length of hospital stay and the efficacy of EMT for functional capacity.

Impact of Frailty on Symptom Burden in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD), the sixth leading cause of death in the United States in 2022 and the third leading cause of death in England and Wales in 2022, is associated with high symptom burden, particularly dyspnoea. Frailty is a complex clinical syndrome associated with an increased vulnerability to adverse health outcomes. The aim of this review was to explore the current evidence of the influence of frailty on symptoms in patients with a confirmed diagnosis of COPD according to GOLD guidelines. Fourteen studies report a positive association between frailty and symptoms, including dyspnoea, assessed with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) scale. Data were analysed in a pooled a random-effects meta-analysis of mean differences (MDs). There was an association between COPD patients living with frailty and increased CAT score versus COPD patients without frailty [pooled SMD, 1.79 (95% CI 0.72-2.87); I2 = 99%]. A lower association was found between frailty and dyspnoea measured by the mMRC scale versus COPD patients without frailty [pooled SMD, 1.91 (95% CI 1.15-2.66); I2 = 98%]. The prevalence of frailty ranged from 8.8% to 82% and that of pre-frailty from 30.4% to 73.7% in people living with COPD. The available evidence supports the role of frailty in worsening symptom burden in COPD patients living with frailty. The review shows that frailty is common in patients with COPD. Future research is needed to have further details related to the data from CAT to improve our knowledge of the frailty impact in this population.

Home noninvasive ventilation in severe COPD: in whom does it work and how?

Background: Not all hypercapnic COPD patients benefit from home noninvasive ventilation (NIV), and mechanisms through which NIV improves clinical outcomes remain uncertain. We aimed to identify "responders" to home NIV, denoted by a beneficial effect of NIV on arterial partial pressure of carbon dioxide (PaCO2), health-related quality of life (HRQoL) and survival, and investigated whether NIV achieves its beneficial effect through an improved PaCO2. Methods: We used individual patient data from previous published trials collated for a systematic review. Linear mixed-effect models were conducted to compare the effect of NIV on PaCO2, HRQoL and survival, within subgroups defined by patient and treatment characteristics. Secondly, we conducted a causal mediation analysis to investigate whether the effect of NIV is mediated by a change in PaCO2. Findings: Data of 1142 participants from 16 studies were used. Participants treated with lower pressure support (<14 versus ≥14 cmH2O) and with lower adherence (<5 versus ≥5 h·day-1) had less improvement in PaCO2 (mean difference (MD) -0.30 kPa, p<0.001 and -0.29 kPa, p<0.001, respectively) and HRQoL (standardised MD 0.10, p=0.002 and 0.11, p=0.02, respectively), but this effect did not persist to survival. PaCO2 improved more in patients with severe dyspnoea (MD -0.30, p=0.02), and HRQoL improved only in participants with fewer than three exacerbations (standardised MD 0.52, p=0.03). The results of the mediation analysis showed that the effect on HRQoL is mediated partially (23%) by a change in PaCO2. Interpretation: With greater pressure support and better daily NIV usage, a larger improvement in PaCO2 and HRQoL is achieved. Importantly, we demonstrated that the beneficial effect of home NIV on HRQoL is only partially mediated through a reduction in diurnal PaCO2.

Effect of high flow nasal oxygen on inspiratory effort of patients with acute hypoxic respiratory failure and do not intubate orders.

High flow nasal oxygen (HFNO) is recommended as a first-line respiratory support during acute hypoxic respiratory failure (AHRF) and represents a proportionate treatment option for patients with do not intubate (DNI) orders. The aim of the study is to assess the effect of HFNO on inspiratory effort as assessed by esophageal manometry in a population of DNI patients suffering from AHRF. Patients with AHRF and DNI orders admitted to Respiratory intermediate Care Unit between January 1st, 2018 and May 31st, 2023 to receive HFNO and subjected to esophageal manometry were enrolled. Esophageal pressure swing (ΔPes), clinical variables before and after 2 h of HFNO and clinical outcome (including HFNO failure) were collected and compared as appropriate. The change in physiological and clinical parameters according to the intensity of baseline breathing effort was assessed and the correlation between baseline ΔPes values and the relative change in breathing effort and clinical variables after 2 h of HFNO was explored. Eighty-two consecutive patients were enrolled according to sample size calculation. Two hours after HFNO start, patients presented significant improvement in ΔPes (12 VS 16 cmH2O, p < 0.0001), respiratory rate (RR) (22 VS 28 bpm, p < 0.0001), PaO2/FiO2 (133 VS 126 mmHg, p < 0.0001), Heart rate, Acidosis, Consciousness, Oxygenation and respiratory rate (HACOR) score, (4 VS 6, p < 0.0001), Respiratory rate Oxygenation (ROX) index (8.5 VS 6.1, p < 0.0001) and BORG (1 VS 4, p < 000.1). Patients with baseline ΔPes below 20 cmH2O where those who improved all the explored variables, while patients with baseline ΔPes above 30 cmH2O did not report significant changes in physiological or clinical features. A significant correlation was found between baseline ΔPes values and after 2 h of HFNO (R2 = 0.9, p < 0.0001). ΔPes change 2 h after HFNO significantly correlated with change in BORG (p < 0.0001), ROX index (p < 0.0001), HACOR score (p < 0.001) and RR (p < 0.001). In DNI patients with AHRF, HFNO was effective in reducing breathing effort and improving respiratory and clinical variables only for those patients with not excessive inspiratory effort.

Efficacy of Respiratory Muscle Training in the Immediate Postoperative Period of Cardiac Surgery: A Systematic Review and Meta-Analysis

ABSTRACT Introduction: This study aimed to evaluate the efficacy of respiratory muscle training during the immediate postoperative period of cardiac surgery on respiratory muscle strength, pulmonary function, functional capacity, and length of hospital stay. Methods: This is a systematic review and meta-analysis. A comprehensive search on PubMed®, Excerpta Medica Database (or Embase), Cumulative Index of Nursing and Allied Health Literature (or CINAHL), Latin American and Caribbean Health Sciences Literature (or LILACS), Scientific Electronic Library Online (or SciELO), Physiotherapy Evidence Database (or PEDro), and Cochrane Central Register of Controlled Trials databases was performed. A combination of free-text words and indexed terms referring to cardiac surgery, coronary artery bypass grafting, respiratory muscle training, and clinical trials was used. A total of 792 studies were identified; after careful selection, six studies were evaluated. Results: The studies found significant improvement after inspiratory muscle training (IMT) (n = 165, 95% confidence interval [CI] 9.68, 21.99) and expiratory muscle training (EMT) (n = 135, 95% CI 8.59, 27.07) of maximal inspiratory pressure and maximal expiratory pressure, respectively. Also, IMT increased significantly (95% CI 19.59, 349.82, n = 85) the tidal volume. However, no differences were found in the peak expiratory flow, functional capacity, and length of hospital stay after EMT and IMT. Conclusion: IMT and EMT demonstrated efficacy in improving respiratory muscle strength during the immediate postoperative period of cardiac surgery. There was no evidence indicating the efficacy of IMT for pulmonary function and length of hospital stay and the efficacy of EMT for functional capacity.

COVID-19, A New Possible Mimicker of Interstitial Lung Disease Related to Primary Sjögren's Syndrome.

Introduction. Acute exacerbation of interstitial lung disease (ILD) and COVID-19 pneumonia show many similarities, but also COVID-19 sequelae, mainly when fibrotic features are present, can be difficult to distinguish from chronic ILD observed in connective tissue diseases. Case Report. In 2018, a 52-year-old woman, was diagnosed with primary Sjogren's syndrome (pSS). The patient did not show respiratory symptoms, and a chest X-ray was normal. During March 2020, the patient was hospitalized for acute respiratory failure related to COVID-19 pneumonia. Three months later, follow-up chest high-resolution computed tomography (HRCT) showed ground glass opacity (GGO) and interlobular interstitial thickening. Pulmonary function tests (PFTs) showed slight restrictive deficit and mild reduction in diffusion lung of carbon monoxide (DLCO). The patient complained of asthenia and exertional dyspnoea. A multidisciplinary discussion including rheumatologist, pulmonologist, and thoracic radiologist did not allow a definitive differential diagnosis between COVID-19 persisting abnormalities and a previous or new-onset pSS-ILD. A "wait and see" approach was decided, monitoring clinical conditions, PFTs, and chest HRCT over time. Only 2 years after the hospitalization, improvement of clinical symptoms was reported; PFT also improved, and HRCT showed almost complete resolution of GGO and interlobular interstitial thickening, confirming the diagnostic hypothesis of long-COVID lung manifestations. Discussion. In the above-reported case report, 3 differential diagnoses were possible: a COVID-19-related ILD, a preexisting pSS-ILD, or a new-onset pSS-ILD triggered by COVID-19. Regardless of the diagnosis, the persistence of clinical and PFT alterations, suggested a chronic disease but, surprisingly, clinical and radiologic manifestations disappeared 2 years later.

Association between Pulmonary Aspergillosis and Cytomegalovirus Reactivation in Critically Ill COVID-19 Patients: A Prospective Observational Cohort Study.

COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the association between CAPA development and the incidence and prognosis of cytomegalovirus (CMV) reactivation in critically ill COVID-19 patients. We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from 25 February 2020 to 8 May 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associated with CAPA and CMV reactivation and the association between CMV recurrence and mortality were estimated using adjusted Cox proportional hazard regression models. CAPA occurred in 96 patients (16.6%) of the 579 patients analyzed. Among the CAPA population, 40 (41.7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7-27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (p = 0.166). The CAPA+CMV group had a longer ICU stay, fewer ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21-4.48, p = 0.011). In critically ill COVID-19 patients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immunosuppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality.

The Association of Procalcitonin and C-Reactive Protein with Bacterial Infections Acquired during Intensive Care Unit Stay in COVID-19 Critically Ill Patients.

In COVID-19 patients, procalcitonin (PCT) and C-reactive protein (CRP) performance in identifying bacterial infections remains unclear. Our study aimed to evaluate the association of PCT and CRP with secondary infections acquired during ICU stay in critically ill COVID-19 patients. This observational study included adult patients admitted to three COVID-19 intensive care units (ICUs) from February 2020 to May 2022 with respiratory failure caused by SARS-CoV-2 infection and ICU stay ≥ 11 days. The values of PCT and CRP collected on the day of infection diagnosis were compared to those collected on day 11 after ICU admission, the median time for infection occurrence, in patients without secondary infection. The receiver operating characteristic curve (ROC) and multivariate logistic model were used to assess PCT and CRP association with secondary infections. Two hundred and seventy-nine patients were included, of whom 169 (60.6%) developed secondary infection after ICU admission. The PCT and CRP values observed on the day of the infection diagnosis were larger (p < 0.001) than those observed on day 11 after ICU admission in patients without secondary infections. The ROC analysis calculated an AUC of 0.744 (95%CI 0.685-0.803) and 0.754 (95%CI 0.695-0.812) for PCT and CRP, respectively. Multivariate logistic models showed that PCT ≥ 0.16 ng/mL and CRP ≥ 1.35 mg/dL were associated (p < 0.001) with infections acquired during ICU stay. Our results indicated that in COVID-19 patients, PCT and CRP values were associated with infections acquired during the ICU stay and can be used to support, together with clinical signs, rather than predict or rule out, the diagnosis of these infections.

Physiological effects of lung-protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study.

BACKGROUND: Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. METHODS: Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero = ZEEP, 4-8 cmH2O = PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure PL,EE = PEEPTITRATED) were used for measurements. RESULTS: Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [- 7.6- - 2.3] cmH2O and lung elastance (EL) 44 [40-51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p = 0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3-1.5] cmH2O and EL to 49 [43-59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEPLOW, respectively). ΔPL decreased at PEEPLOW (p = 0.018) and increased at PEEPTITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and ΔPL. CONCLUSIONS: In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.

Frailty and its influence on mortality and morbidity in COPD: A Systematic Review and Meta-Analysis.

Frailty increases vulnerability to adverse outcomes. Long-term conditions increase the risk of frailty. We searched PubMed, Web of Science, The Cochrane Library, EMBASE from inception to March 2022. Quality assessment was conducted using the NOS. Data was analysed in a pooled a random-effects meta-analysis. Our primary outcome was the impact of frailty on mortality in adults with Chronic Obstructive Pulmonary Disease (COPD) diagnosis according to the guidelines. Secondary outcomes were: frailty and association with readmissions, hospitalisations, exacerbation rates, and prevalence of frailty in COPD. We identified 25 studies, with 5882 participants. The median prevalence of frailty was 47% (IQR, 39.3-66.3%, range 6.4-72%). There was an association between COPD patients living with frailty and increased risk of mortality versus COPD patients without frailty (pooled OR, 4.21 (95% CI 2.99-5.93, I2 55%). A descriptive analysis of relationship between frailty and hospital readmission and all cause hospitalization showed positive associations. The relationship between frailty and the risk of exacerbation showed a pooled OR, 1.45 (95% CI 0.37-5.70, I2 80%). Frailty is significantly associated with higher mortality risk in COPD. Frailty is common in patients with COPD and its measurement should be considered in clinical practice to better characterise COPD.

Frailty Prevalence and Association with Clinical Outcomes in Interstitial Lung Disease, Asthma, and Pleural Disease.

BACKGROUND: Frailty is a syndrome characterised by increased vulnerability to negative outcomes. Interstitial lung disease (ILD), asthma, and pleural disease are leading causes of morbidity and mortality. We aimed to investigate the prevalence and impact of frailty in adult patients with these diseases. METHODS: We conducted a systematic review and meta-analysis, searching PubMed, Web of Science, The Cochrane Library, and EMBASE for studies reporting on frailty in ILD, asthma, and pleural disease. MeSH terms including interstitial lung disease, Idiopathic Pulmonary Fibrosis, Non-specific Interstitial Pneumonia, Chronic Hypersensitivity Pneumonitis, systemic sclerosis-associated ILD, connective tissue disease-associated ILD, and frailty were used as key words. The primary outcome was prevalence of frailty. Where enough contextually homogeneous studies were included, a pooled random-effects meta-analysis was performed with mortality and hospitalisation as the outcomes. RESULTS: The review found three studies relating to frailty in asthma. No studies relating to pleural disease and frailty were identified. The median prevalence in asthma was 9.5% (IQR, 7.8-11.3). Six relevant studies incorporating 1471 ILD patients (age 68.3 ± SD2.38; 50% male) were identified, which were either cohort or cross-sectional design rated either good or fair. The median prevalence of frailty was 48% (IQR, 25-50). There was a positive association between frail ILD patients and increased risk of long-term mortality (pooled OR, 2.33 95%CI 1.31-4.15, I2 9%). One study reported a hospitalization rate of HR = 1.97(1.32-3.06) within 6 months in frail ILD patients. CONCLUSIONS: Frailty is very common and associated with increased mortality in patients with ILD. There are still minimal data regarding the prevalence of frailty and its influence on the risk in this population.

Critical COVID-19 patients through first, second, and third wave: retrospective observational study comparing outcomes in intensive care unit.

Background: The time-course of the coronavirus disease 2019 (COVID-19) pandemic was characterized by subsequent waves identified by peaks of intensive care unit (ICU) admission rates. During these periods, progressive knowledge of the disease led to the development of specific therapeutic strategies. This retrospective study investigates whether this led to improvement in outcomes of COVID-19 patients admitted to ICU. Methods: Outcomes were evaluated in consecutive adult COVID-19 patients admitted to our ICU, divided into three waves based on the admission period: the first wave from February 25th, 2020, to July 6th, 2020; the second wave from September 20th, 2020, to February 13th, 2021; the third wave from February 14th, 2021 to April 30th, 2021. Differences were assessed comparing outcomes and by using different multivariable Cox models adjusted for variables related to outcome. Further sensitivity analysis was performed in patients undergoing invasive mechanical ventilation (IMV). Results: Overall, 428 patients were included in the analysis: 102, 169, and 157 patients in the first, second, and third wave. The ICU and in-hospital crude mortalities were lower by 7% and 10% in the third wave compared to the other two waves (P>0.05). A higher number of ICU- and hospital-free days at day 90 was found in the third wave when compared to the other two waves (P=0.001). Overall, 62.6% underwent invasive ventilation, with decreasing requirement during the waves (P=0.002). The adjusted Cox model showed no difference in the hazard ratio (HR) for mortality among the waves. In the propensity-matched analysis the hospital mortality rate was reduced by 11% in the third wave (P=0.044). Conclusions: With application of best practice as known by the time of the first three waves of the pandemic, our study failed to identify a significant improvement in mortality rate when comparing the different waves of the COVID-19 pandemic, notwithstanding, the sub-analyses showed a trend in mortality reduction in the third wave. Rather, our study identified a possible positive effect of dexamethasone on mortality rate reduction and the increased risk of death related to bacterial infections in the three waves.

Molecular Biology and Therapeutic Targets of Primitive Tracheal Tumors: Focus on Tumors Derived by Salivary Glands and Squamous Cell Carcinoma.

Primary tracheal tumors are rare, constituting approximately 0.1-0.4% of malignant diseases. Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) account for about two-thirds of these tumors. Despite most primary tracheal cancers being eligible for surgery and/or radiotherapy, unresectable, recurrent and metastatic tumors may require systemic treatments. Unfortunately, the poor response to available chemotherapy as well as the lack of other real therapeutic alternatives affects the quality of life and outcome of patients suffering from more advanced disease. In this condition, target therapy against driver mutations could constitute an alternative to chemotherapy, and may help in disease control. The past two decades have seen extraordinary progress in developing novel target treatment options, shifting the treatment paradigm for several cancers such as lung cancer. The improvement of knowledge regarding the genetic and biological alterations, of major primary tracheal tumors, has opened up new treatment perspectives, suggesting the possible role of biological targeted therapies for the treatment of these rare tumors. The purpose of this review is to outline the state of knowledge regarding the molecular biology, and the preliminary data on target treatments of the main primary tracheal tumors, focusing on salivary-gland-derived cancers and squamous cell carcinoma.

Quality of life and intrinsic capacity in patients with post-acute COVID-19 syndrome is in relation to frailty and resilience phenotypes.

The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: "fit/resilient", "fit/non-resilient", "frail/resilient" and "frail/non-resilient". Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Predictors for SF-36 score < 61.60 were the phenotypes "frail/non-resilient" (OR = 4.69, CI 2.08-10.55), "fit/non-resilient" (OR = 2.79, CI 1.00-7.73). Predictors for EQ-5D-5L < 89.7% were the phenotypes "frail/non-resilient" (OR = 5.93, CI 2.64-13.33) and "frail/resilient" (OR = 5.66, CI 1.93-16.54). Predictors of impaired IC (below the mean score value) were "frail/non-resilient" (OR = 7.39, CI 3.20-17.07), and "fit/non-resilient" (OR = 4.34, CI 2.16-8.71) phenotypes. Resilience and frailty phenotypes may have a different impact on wellness and QoL and may be evaluated in people with PACS to identify vulnerable individuals that require suitable interventions.

Case report: Endoscopic closure with double stenting and autologous fascia lata graft of large tracheo-esophageal fistula.

Introduction: Radiotherapy and esophageal stenting are usually employed to manage esophageal localization of distant cancer. However, they are also related to the occurrence of an increased risk of tracheoesophageal fistula. Tracheoesophageal fistula management in these patients involves dealing with poor general conditions and short-term prognosis. This paper presents the first case in literature of bronchoscopic fistula closure through an autologous fascia lata graft placement between two stents. Case report and aim: A 67-years-old male patient was diagnosed with pulmonary squamous cell carcinoma in the inferior lobe of the left lung with mediastinal lymph node metastasis. After a multidisciplinary discussion, bronchoscopic repair of tracheoesophageal fistula with autologous fascia lata was decided without the removal of the esophageal stent due to the high risk on the esophagus possibly related to such a procedure. Oral feeding was progressively introduced without the development of aspiration symptoms. Videofluoroscopy and esophagogastroduodenoscopy were performed at 7 months showing no signs of tracheoesophageal fistula patency. Conclusion: This technique might represent a low risks viable option for patients unsuitable for open surgical approaches.

One-year clinical experience on the use of Nintedanib in systemic sclerosis.

We reviewed 11 patients with systemic sclerosis-related ILD who were referred to our Scleroderma Unit from January 2020 to January 2021 and started Nintedanib. Non-specific interstitial pneumonia (NSIP) was prevalent (45%), usual interstitial pneumonia (UIP) and UIP/NSIP pattern were both 27%. Only one patient had a history of smoking. Eight patients were on mycophenolate mofetil (MMF), eight were treated with corticosteroids (mean dose 5 mg/day of Prednisone or equivalent), and three were on Rituximab. The mean modified British Council Medical Questionnaire (mmRC) decreased from 3 to 2.5. Two patients had to reduce their daily dose to 200 mg/day for severe diarrhoea. Nintedanib was generally well tolerated.