What is the Optimal Treatment Regimen of Low-MolecularWeight Heparin in Coronavirus Disease 2019 Pneumonia?

OBJECTIVE: The optimal anticoagulant treatment regimen in hospitalized coronavirus disease 2019 (COVID-19) patients is uncertain. This study aimed to compare the rates of disease progression and mortality in patients treated with low-molecular-weight heparin (LMWH) according to baseline d-dimer levels and in those who received a fixed-dose regimen irrespective of the d-dimer level. MATERIAL AND METHODS: This was a retrospective analysis of all patients admitted to a university hospital for COVID-19 pneumonia during a 1-year period. The protocol for d-dimer-driven therapy (on-protocol) was as follows: prophylactic dose when the baseline level is <1000 ng/mL, intermediate dose when the level is between 1000 and 3000 ng/mL, and therapeutic dose when the level is >3000 ng/mL. We compared the progression and mortality rates between the on-protocol and off-protocol treatment groups. The offprotocol group consisted of patients that received a fixed-dose LMWH regimen, which was not in accordance with the defined protocol. RESULTS: Of 384 patients (mean age 61.5 ± 15.9 years, 216 male), 294 patients with complete data composed the study group, and 174 patients were treated on-protocol and 120 patients were treated off-protocol. The on-protocol group had lower C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and d-dimer levels and higher SpO2/FiO2 levels at admission. Disease progression developed in 45/174 on-protocol patients (25.9%) vs. 53/120 off-protocol patients (44.2%) during the follow-up (P = .001), and mortality was 29 (16.7%) vs. 32 (26.7%), respectively (P = .041). Logistic regression analysis was performed and included age, presence of comorbidities, LMWH regimen, baseline SpO2/FiO2, CRP, and LDH levels as independent variables. The presence of cardiac comorbidity, age, CRP, and LDH levels, but not the LMWH treatment regimen, were associated with both disease progression and mortality. CONCLUSION: A d-dimer-driven LMWH treatment protocol is not associated with better clinical outcomes in hospitalized COVID-19 patients.

Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis.

Background: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). Methods: Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. Results: Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045). Interpretation: Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression.

Pneumothoraxes after CT-guided percutaneous transthoracic needle aspiration biopsy of the lung: A single-center experience with 3426 patients.

Introduction: The purpose of this study is to determine how long patients who developed pneumothorax were followed up on in the emergency department, how many patients required chest tube placement, and what factors influenced the need for a chest tube in patients who underwent computed tomography (CT)-guided percutaneous transthoracic fine needle aspiration biopsy (PTFNAB). Materials and Methods: Patients who developed pneumothorax following CT-guided PTFNAB were analyzed retrospectively. In cases with pneumothorax, the relationship between chest tube placement and the size of the lesion, the lesion depth from the pleural surface, the presence of emphysema, and the needle entry angle were investigated. It was determined how long the patients were followed up in the emergency department, when a chest tube was placed, and when patients who did not require chest tube placement were discharged. Result: CT-guided PTFNAB was performed in 3426 patients within two years. Pneumothorax developed in 314 (9%) cases and a chest tube was placed in 117 (37%). The risk factor for chest tube placement was found to be the lesion depth from the pleural surface. The lesion depth from the pleural surface of >24 mm increased the risk of chest tube placement by 4.8 times. Chest tubes were placed at an average of five hours (5.04 ± 5.57). Conclusions: This study has shown that in cases with pneumothorax that required chest tube placement, the lesion depth from the pleural surface is a risk factor. Patients who developed pneumothorax on CT during the procedure had chest tubes placed after an average of five hours.

Detection of Pneumocystis jirovecii by PCR in patients with lung cancer: A preliminary study.

INTRODUCTION: Infection complications in lung cancer (LC), one of the most common cancers in the world, are still among the most important causes of death. Of them, P. jirovecii, which is as an opportunistic infection, causes a life-threatening type of pneumonia in cancer patients. This preliminary study aimed to determine the incidence and clinical status of P. jirovecii by PCR in lung cancer patients compared to the conventional method. MATERIAL AND METHODS: Sixty-nine lung cancer patients and fSorty healthy individuals were included in the study. After sociodemographical and clinical features were recorded, sputum samples were collected from attenders. Firstly, microscopic examination was made with Gomori's methenamine silver stain and then PCR was performed. RESULTS: P. jirovecii was detected in three of 69 lung cancer patients by PCR (4.3%), but not by microscopy. However, healthy individuals were negative for P. jirovecii by both methods. Based on clinical and radiological findings, P. jirovecii was evaluated as probable infection in one patient and colonization in the other two patients. Although PCR is more sensitive than conventional staining methods, it cannot distinguish probable and proven infections from pulmonary colonization. DISCUSSION: It is important to evaluate the decision of infection together with laboratory, clinical and radiological findings. Moreover, PCR may enable to know the colonization and to take precautions such as prophylaxis, due to the risk of colonization turning into an infection in immunocompromised patient groups. Further studies involving larger populations and evaluating the colonization-infection relationship in patients with solid tumors are needed.

The Spectrum of Infections in Patients with Lung Cancer.

Although diagnostic and therapeutic advances in lung cancer (LC) have increased the survival of patients, infection and its complications are still among the most important causes of mortality. The disruption of tissue caused by tumor mass, management of cancer therapy and alteration in the humoral/cellular immune systems due to both cancer itself and therapy considerably increase susceptibility to infection in cancer patients. Particularly, opportunistic microorganisms should be considered, then applying rapid and sensitive diagnostic methods for them. Thus, cancer patients who are already exposed to difficult, long-term and expensive treatments can be prevented from dying from complications related to infections.

Lung cancer in patients with idiopathic pulmonary fibrosis: A retrospective multicentre study in Europe.

BACKGROUND AND OBJECTIVE: There remains a paucity of large databases for patients with idiopathic pulmonary fibrosis (IPF) and lung cancer. We aimed to create a European registry. METHODS: This was a multicentre, retrospective study across seven European countries between 1 January 2010 and 18 May 2021. RESULTS: We identified 324 patients with lung cancer among 3178 patients with IPF (prevalence = 10.2%). By the end of the 10 year-period following IPF diagnosis, 26.6% of alive patients with IPF had been diagnosed with lung cancer. Patients with IPF and lung cancer experienced increased risk of all-cause mortality than IPF patients without lung cancer (HR: 1.51, [95% CI: 1.22-1.86], p < 0.0001). All-cause mortality was significantly lower for patients with IPF and lung cancer with a monocyte count of either <0.60 or 0.60-<0.95 K/µl than patients with monocyte count ≥0.95 K/µl (HR [<0.60 vs. ≥0.95 K/µl]: 0.35, [95% CI: 0.17-0.72], HR [0.60-<0.95 vs. ≥0.95 K/µl]: 0.42, [95% CI: 0.21-0.82], p = 0.003). Patients with IPF and lung cancer that received antifibrotics presented with decreased all cause-mortality compared to those who did not receive antifibrotics (HR: 0.61, [95% CI: 0.42-0.87], p = 0.006). In the adjusted model, a significantly lower proportion of surgically treated patients with IPF and otherwise technically operable lung cancer experienced all-cause mortality compared to non-surgically treated patients (HR: 0.30 [95% CI: 0.11-0.86], p = 0.02). CONCLUSION: Lung cancer exerts a dramatic impact on patients with IPF. A consensus statement for the management of patients with IPF and lung cancer is sorely needed.

A Pilot Study on the Evaluation of Cryptosporidium Infection in Patients with Lung Cancer: Respiratory Cryptosporidiosis.

Lung carcinoma is one of the most common cancers and the leading cause of cancer-related death worldwide. Increasing evidence has shown that Cryptosporidium spp., an opportunistic parasite, is associated with cancers, causing life-threatening infections. The most common clinical form of Cryptosporidium is intestinal infections. However, respiratory cryptosporidiosis has rarely been documented, although the parasite infects respiratory epithelial cells and gastrointestinal (GIS) epithelial cells. To evaluate respiratory cryptosporidiosis in patients with lung cancer, we investigated Cryptosporidium spp. in patients with lung cancer (n = 69) in comparison with healthy groups (n = 40). Sputum and stool samples were examined microscopically and by polymerase chain reaction (PCR). Two cancer patients were diagnosed with respiratory cryptosporidiosis (2.9%), on PCR examination of the sputum samples. Cryptosporidium spp. was detected in the stool samples of one patient (1.5%) and 2 healthy individuals (5.4%) by PCR and microscopy. First, respiratory cryptosporidiosis was documented in 2 patients with lung cancer. Cryptosporidium is an important agent of the respiratory tract and GIS infections in cancer patients. These new findings highlight the molecular prevalence of Cryptosporidium spp., an opportunistic infection, in patients with lung cancer. Respiratory cryptosporidiosis should also be considered when patients have respiratory symptoms.

Pleuroparenchymal fibroelastosis in idiopathic pulmonary fibrosis: Survival analysis using visual and computer-based computed tomography assessment.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and pleuroparenchymal fibroelastosis (PPFE) are known to have poor outcomes but detailed examinations of prognostic significance of an association between these morphologic processes are lacking. METHODS: Retrospective observational study of independent derivation and validation cohorts of IPF populations. Upper-lobe PPFE extent was scored visually (vPPFE) as categories of absent, moderate, marked. Computerised upper-zone PPFE extent (cPPFE) was examined continuously and using a threshold of 2·5% pleural surface area. vPPFE and cPPFE were evaluated against 1-year FVC decline (estimated using mixed-effects models) and mortality. Multivariable models were adjusted for age, gender, smoking history, antifibrotic treatment and diffusion capacity for carbon monoxide. FINDINGS: PPFE prevalence was 49% (derivation cohort, n = 142) and 72% (validation cohort, n = 145). vPPFE marginally contributed 3-14% to variance in interstitial lung disease (ILD) severity across both cohorts.In multivariable models, marked vPPFE was independently associated with 1-year FVC decline (derivation: regression coefficient 18·3, 95 CI 8·47-28·2%; validation: 7·51, 1·85-13·2%) and mortality (derivation: hazard ratio [HR] 7·70, 95% CI 3·50-16·9; validation: HR 3·01, 1·33-6·81). Similarly, continuous and dichotomised cPPFE were associated with 1-year FVC decline and mortality (cPPFE ≥ 2·5% derivation: HR 5·26, 3·00-9·22; validation: HR 2·06, 1·28-3·31). Individuals with cPPFE ≥ 2·5% or marked vPPFE had the lowest median survival, the cPPFE threshold demonstrated greater discrimination of poor outcomes at two and three years than marked vPPFE. INTERPRETATION: PPFE quantification supports distinction of IPF patients with a worse outcome independent of established ILD severity measures. This has the potential to improve prognostic management and elucidate separate pathways of disease progression. FUNDING: This research was funded in whole or in part by the Wellcome Trust [209,553/Z/17/Z] and the NIHR UCLH Biomedical Research Centre, UK.

Mortality in combined pulmonary fibrosis and emphysema patients is determined by the sum of pulmonary fibrosis and emphysema.

In patients with combined pulmonary fibrosis and emphysema, emphysema and fibrosis do not have a synergistic effect that results in worsened survival when compared to IPF patients without emphysema https://bit.ly/35EJMo6.

Development and Validation of a Clinical Diagnostic Scoring System for the Diagnosis of Idiopathic Pulmonary Fibrosis.

Rationale: Interpreting the radiologic data in conjunction with an objective clinical score could help to harmonize idiopathic pulmonary fibrosis (IPF) diagnosis and improve accuracy. Objectives: We sought to establish and validate a multivariable objective scoring model based on clinical parameters by stratifying the risk of patients having IPF diagnosed versus having other forms of interstitial lung disease (ILD) diagnosis. Methods: A clinical score was derived from review of patients evaluated at the Inova Fairfax ILD Program and validated in three distinct cohorts. On the basis of known IPF clinical characteristics, a multivariable model was created and assessed by using receiver operating characteristic curves. Results: There were 844 patients with ILD with either IPF (n = 347, 41%) or non-IPF ILD (n = 497, 59%) diagnosis. On the basis of calculated odds ratios, a score was assigned to each of the following clinical parameters: age, sex, smoking history, race or ethnicity, ILD family history, exposures, presence of connective tissue disease signs or symptoms, and velcro crackles. The final Fairfax IPF Clinical Score (FICS) ranged from 1 to 25. The clinical diagnostic score system was accurate in predicting IPF, as measured by the area under the curve (0.88) in the derivation cohort, with similar areas under the curve of 0.91, 0.81, and 0.71 being demonstrated in the respective validation cohorts. Conclusions: The FICS appears to be an accurate tool for estimating the pretest probability of IPF in patients with ILD. How the FICS performs in conjunction with the various high-resolution computed tomographic patterns remains to be determined. This model could ultimately be useful for increasing the degree of confidence in the final diagnosis and could help to obviate the need for lung biopsy in cases with non-usual interstitial pneumonia patterns on high-resolution computed tomographic images.