Incidence of Tracheal Stenosis in ICU Hospitalized COVID-19 Patients: Results from a Prospective, Observational, Multicenter Study.

Background: Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis. Study design and methods: In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022. Results: In the study period, 24 patients (8.5%, CI 5.6-12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%, p = 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold (p = 0.047; IC 0.99-6.8) and 5.4-fold (p = 0.002; CI 1.9-16), respectively. Conclusions: In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.

Nano- to Global-Scale Uncertainties in Terrestrial Enhanced Weathering.

Enhanced weathering (EW) is one of the most promising negative emissions technologies urgently needed to limit global warming to at least below 2 °C, a goal recently reaffirmed at the UN Global Climate Change conference (i.e., COP26). EW relies on the accelerated dissolution of crushed silicate rocks applied to soils and is considered a sustainable solution requiring limited technology. While EW has a high theoretical potential of sequestering CO2, research is still needed to provide accurate estimates of carbon (C) sequestration when applying different silicate materials across distinct climates and major soil types in combination with a variety of plants. Here we elaborate on fundamental advances that must be addressed before EW can be extensively adopted. These include identifying the most suitable environmental conditions, improving estimates of field dissolution rates and efficacy of CO2 removal, and identifying alternative sources of silicate materials to meet future EW demands. We conclude with considerations on the necessity of integrated modeling-experimental approaches to better coordinate future field experiments and measurements of CO2 removal, as well as on the importance of seamlessly coordinating EW with cropland and forest management.

Predictors of Malignancy in Patients With Haemoptysis

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Long-term prognostic outcomes in patients with haemoptysis.

BACKGROUND: Haemoptysis is a challenging symptom that can be associated with potentially life-threatening medical conditions. Follow-up is key in these patients to promptly detect new or misdiagnosed pathologic findings. Few prospective studies have evaluated long-term prognostic outcomes in patients with haemoptysis. Furthermore, the role played by antiplatelet and anticoagulant drugs on mortality and recurrence rates is unclear. The aim of this study was to assess mortality after 18 months of follow-up. Furthermore, the incidence of recurrence and the risk factors for recurrence and death were evaluated (including the role played by anticoagulant and antiplatelet drugs). METHODS: Observational, prospective, multicentre, Italian study. RESULTS: 451/606 (74.4%) recruited patients with haemoptysis completed the 18 months follow-up. 22/604 (3.6%) diagnoses changed from baseline to the end of the follow-up. 83/604 (13.7%) patients died. In 52/83 (62.7%) patients, death was the outcome of the disease which caused haemoptysis at baseline. Only the diagnosis of lung neoplasm was associated with death (OR (95%CI): 38.2 (4.2-347.5); p-value: 0.0001). 166 recurrences were recorded in 103/604 (17%) patients. The diagnosis of bronchiectasis was significantly associated with the occurrence of a recurrence (OR (95% CI): 2.6 (1.5-4.3)); p-value < 0.0001). Anticoagulant, antiaggregant, and anticoagulant plus antiaggregant drugs were not associated with an increased risk of death and recurrence. CONCLUSIONS: Our study showed a low mortality rate in patients with haemoptysis followed-up for 18 months. Pulmonary malignancy was the main aetiology and the main predictor of death, whereas bronchiectasis was the most frequent diagnosis associated with recurrence. Antiplatelet and/or anticoagulant therapy did not change the risk of death or recurrence. Follow-up is recommended in patients initially diagnosed with lower airways infections and idiopathic bleeding. TRIAL REGISTRATION: NCT02045394.

Chest X-ray findings in a large cohort of 1117 patients with SARS-CoV-2 infection: a multicenter study during COVID-19 outbreak in Italy.

To describe radiographic key patterns on Chest X-ray (CXR) in patients with SARS-CoV-2 infection, assessing the prevalence of radiographic signs of interstitial pneumonia. To evaluate pattern variation between a baseline and a follow-up CXR. 1117 patients tested positive for SARS-CoV-2 infection were retrospectively enrolled from four centers in Lombardy region. All patients underwent a CXR at presentation. Follow-up CXR was performed when clinically indicated. Two radiologists in each center reviewed images and classified them as suggestive or not for interstitial pneumonia, recording the presence of ground-glass opacity (GGO), reticular pattern or consolidation and their distribution. Pearson's χ2 test for categorical variables and McNemar test (χ2 for paired data) were performed. Patients mean age 63.3 years, 767 were males (65.5%). The main result is the large proportion of positive CXR in COVID-19 patients. Baseline CXR was positive in 940 patients (80.3%), with significant differences in age and sex distribution between patients with positive and negative CXR. 382 patients underwent a follow-up CXR. The most frequent pattern on baseline CXR was the GGO (66.1%), on follow-up was consolidation (53.4%). The most common distributions were peripheral and middle-lower lung zone. We described key-patterns and their distribution on CXR in a large cohort of COVID-19 patients: GGO was the most frequent finding on baseline CXR, while we found an increase in the proportion of lung consolidation on follow-up CXR. CXR proved to be a reliable tool in our cohort obtaining positive results in 80.3% of the baseline cases.

Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy.

Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors.

Inpatient Care during the COVID-19 Pandemic: A Survey of Italian Physicians.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. OBJECTIVE: We explored the clinical management of inpatients with COVID-19 in Italy. METHODS: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. RESULTS: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. CONCLUSIONS: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.

First COVID-19 sub-intensive respiratory unit in Europe: the Italian experience.

European SARS-CoV-2 pandemic epicenter was detected in Northern Italy, in a little Italian town of Lodi province, the Lodi Hospital was therefore rapidly saturated, and in particularly the departments of respiratory diseases and Intensive Care Unit had been largely involved. In this paper, we describe how the first Sub-intensive Respiratory Unit in Europe completely dedicated to COVID-19 patients was organized and managed in our hospital. From February 25th to April 30th 2020, 156 patients were admitted to our Respiratory Sub-intensive Unit. Among them, 100 were discharged, 28 dead and 28 transferred to ICU for intubation.

Bronchoscopy to assess patients with hemoptysis: which is the optimal timing?

BACKGROUND: Bronchoscopy plays a key role to diagnose the etiology, to localize the site, and to identify the sources of the bleeding in patients with hemoptysis, but the ideal timing of an endoscopic examination is still unclear. METHODS: We performed a secondary analysis of an observational and multicenter study, aimed at evaluating the epidemiology of hemoptysis in Italy and the diagnostic yield of the most frequently prescribed examinations. The aim of the study was to evaluate whether an early bronchoscopy (i.e., performed during active bleeding/≤48 h after hemoptysis stopped) helps localize bleeding (i.e., site, lobe, lung) and increase diagnostic yield in comparison with a delayed examination. RESULTS: Four hundred eighty-six consecutive adult patients (69.2% males; median [IQR] age: 67 [53-76] years) with hemoptysis requiring an etiological diagnosis and undergoing bronchoscopy were recruited. Bleeding focus could be located more frequently in case of moderate-severe bleedings than in cases of mild hemoptysis (site: 70/154, 45.4%, VS. 73/330, 22.1%; p-value < 0.0001; lobe: 95/155, 61.3%, VS. 95/331, 28.7%; p-value < 0.0001; lung: 101/155, 65.1%, VS. 111/331, 33.5%; p-value < 0.0001). Early bronchoscopy showed a higher detection rate of bleeding source in comparison with delayed examination (site: 76/214, 35.5%, VS. 67/272, 24.6%; p-value = 0.01; lobe: 98/214, 45.8%, VS. 92/272, 33.8%; p-value = 0.007; lung: 110/214, 51.4%, VS. 102/272, 37.5%; p-value = 0.002). Early bronchoscopy did not provide any advantages in terms of increased diagnostic yield, in the total cohort (113/214, 52.8%, VS. 123/272, 45.2%; p-value = 0.10) and in the severity subtypes (mild: 56/128, 43.8%, VS. 88/203, 43.4%; p-value = 0.94; moderate-severe: 57/86, 66.2%, VS. 35/69, 50.7%; p-value = 0.051). CONCLUSIONS: Early bronchoscopy helps detect bleeding sources, particularly in cases of moderate-severe hemoptysis, without increasing diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT02045394 ).