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Lung Cancer (Amsterdam, Netherlands) Jul 2023Screening reduces lung cancer mortality of high-risk populations. Currently proposed screening eligibility criteria only identify half of those individuals, who later...
INTRODUCTION
Screening reduces lung cancer mortality of high-risk populations. Currently proposed screening eligibility criteria only identify half of those individuals, who later develop lung cancer. This study aimed to develop and validate a sensitive and simple model for predicting 10-year lung cancer risk.
METHODS
Using the 1991-94 examination of The Copenhagen City Heart Study in Denmark, 6,820 former or current smokers from the general population were followed for lung cancer within 10 years after examination. Logistic regression of baseline variables (age, sex, education, chronic obstructive pulmonary disease, family history of lung cancer, smoking status and cumulative smoking, secondhand smoking, occupational exposures to dust and fume, body mass index, lung function, plasma C-reactive protein, and AHRR(cg05575921) methylation) identified the best predictive model. The model was validated among 3,740 former or current smokers from the 2001-03 examination, also followed for 10 years. A simple risk chart was developed with Poisson regression.
RESULTS
Age, sex, education, smoking status, cumulative smoking, and AHRR(cg05575921) methylation identified 65 of 88 individuals who developed lung cancer in the validation cohort. The highest risk group, consisting of less educated men aged >65 with current smoking status and cumulative smoking >20 pack-years, had absolute 10-year risks varying from 4% to 16% by AHRR(cg05575921) methylation.
CONCLUSION
A simple risk chart including age, sex, education, smoking status, cumulative smoking, and AHRR(cg05575921) methylation, identifies individuals with 10-year lung cancer risk from below 1% to 16%. Including AHRR(cg05575921) methylation in the eligibility criteria for screening identifies smokers who would benefit the most from screening.
Topics: Humans; Male; Basic Helix-Loop-Helix Transcription Factors; DNA Methylation; Lung; Lung Neoplasms; Repressor Proteins; Risk Factors; Smoking; Female; Aged
PubMed: 37150141
DOI: 10.1016/j.lungcan.2023.107229 -
JAMA Internal Medicine Jul 2023Low-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in...
IMPORTANCE
Low-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in patients undergoing LDCT lung screening. However, the exact nature of these SIF findings has not been described.
OBJECTIVE
To describe SIFs reported in the LDCT arm of the National Lung Screening Trial and classify SIFs as reportable or not reportable to the referring clinician (RC) using the American College of Radiology's white papers on incidental findings.
DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective case series study of 26 455 participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT. The trial was conducted from 2002 to 2009, and data were collected at 33 US academic medical centers.
MAIN OUTCOMES AND MEASURES
Significant incident findings were defined as a final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer or a positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm.
RESULTS
Of 26 455 participants, 10 833 (41.0%) were women, the mean (SD) age was 61.4 (5.0) years, and there were 1179 (4.5%) Black, 470 (1.8%) Hispanic/Latino, and 24 123 (91.2%) White individuals. Participants were scheduled to undergo 3 screenings during the course of the trial; the present study included 75 126 LDCT screening examinations performed for 26 455 participants. A SIF was reported for 8954 (33.8%) of 26 455 participants who were screened with LDCT. Of screening tests with a SIF detected, 12 228 (89.1%) had a SIF considered reportable to the RC, with a higher proportion of reportable SIFs among those with a positive screen result for lung cancer (7632 [94.1%]) compared with those with a negative screen result (4596 [81.8%]). The most common SIFs reported included emphysema (8677 [43.0%] of 20 156 SIFs reported), coronary artery calcium (2432 [12.1%]), and masses or suspicious lesions (1493 [7.4%]). Masses included kidney (647 [3.2%]), liver (420 [2.1%]), adrenal (265 [1.3%]), and breast (161 [0.8%]) abnormalities. Classification was based on free-text comments; 2205 of 13 299 comments (16.6%) could not be classified. The hierarchical reporting of final diagnosis in NLST may have been associated with an overestimate of severe emphysema in participants with a positive screen result for lung cancer.
CONCLUSIONS AND RELEVANCE
This case series study found that SIFs were commonly reported in the LDCT arm of the National Lung Screening Trial, and most of these SIFs were considered reportable to the RC and likely to require follow-up. Future screening trials should standardize SIF reporting.
Topics: Humans; Female; Middle Aged; Male; Incidental Findings; Retrospective Studies; Lung Neoplasms; Mass Screening; Early Detection of Cancer; Lung; Emphysema
PubMed: 37155190
DOI: 10.1001/jamainternmed.2023.1116 -
PLoS Neglected Tropical Diseases Oct 2023Excretory/secretory products (ESPs) derived from helminths have been reported to effectively control allergic inflammation, which have better therapeutic prospects than...
INTRODUCTION
Excretory/secretory products (ESPs) derived from helminths have been reported to effectively control allergic inflammation, which have better therapeutic prospects than live parasite infections. However, it remains unknown whether ESPs from schistosome eggs can protect against allergies, despite reports alleging that schistosome infection could alleviate disordered allergic inflammation.
METHOD
In the present study, we investigated the protective effects of ESPs from Schistosoma japonicum eggs (ESP-SJE) on asthmatic inflammation. Firstly, we successfully established an allergic airway inflammation model in mice by alum-adjuvanted ovalbumin (OVA) sensitization and challenge. ESP-SJE were administered intraperitoneally on days -1 and 13 (before sensitization), on day 20 (before challenge), and on days 21-24 (challenge phase).
RESULTS
The results showed that ESP-SJE treatment significantly reduced the infiltration of inflammatory cells, especially eosinophils into the lung tissue, inhibited the production of the total and OVA-specific IgE during OVA-sensitized and -challenged phases, respectively, and suppressed the secretion of Th2-type inflammatory cytokines (IL-4). Additionally, ESP-SJE treatment significantly upregulated the regulatory T cells (Tregs) in the lung tissue during OVA challenge. Furthermore, using liquid chromatography-mass spectrometry analysis and Treg induction experiments in vitro, we might identify nine potential therapeutic proteins against allergic inflammation in ESP-SJE. The targets of these candidate proteins included glutathione S-transferase, egg protein CP422 precursor, tubulin alpha-2/alpha-4 chain, actin-2, T-complex protein 1 subunit beta, histone H₄, whey acidic protein core region, and molecular chaperone HtpG.
CONCLUSION
Taken together, the results discussed herein demonstrated that ESP-SJE could significantly alleviate OVA-induced asthmatic inflammation in a murine model, which might be mediated by the upregulation of Treg in lung tissues that may be induced by the potential modulatory proteins. Therefore, potential proteins in ESP-SJE might be the best candidates to be tested for therapeutic application of asthma, thus pointing out to a possible new therapy for allergic airway inflammation.
Topics: Animals; Mice; Ovalbumin; Schistosoma japonicum; Egg Hypersensitivity; Asthma; Lung; Cytokines; Inflammation; Mice, Inbred BALB C; Bronchoalveolar Lavage Fluid; Disease Models, Animal
PubMed: 37788409
DOI: 10.1371/journal.pntd.0011625 -
Life (Basel, Switzerland) Sep 2023Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, characterized by progressive parenchymal fibrosis and respiratory...
Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaze (Bovhyaluronidase Azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaze was administered at different doses by intranasal and intramuscular routes. Histology, hematology, and enzyme-linked immunosorbent assay were used in the study. The use of Longidaze reduced pulmonary fibrosis, as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue, and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaze inhibited the inflammatory response in pulmonary fibrosis, and decreased the levels of IL-6, TNF-α, and hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaze at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaze is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.
PubMed: 37763335
DOI: 10.3390/life13091932 -
Journal of Veterinary Internal Medicine Apr 2024An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution...
An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low-molecular-weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension. On Day 13, contrast-enhanced computed tomography identified extensive contrast defects in the pulmonary arteries, and IV monteplase was administered on Days 14 and 18, with marked improvement in respiratory status and exertional dyspnea on Day 20. Right ventricular function and McConnell signs also improved, and tricuspid regurgitation velocity and pulmonary vascular resistance decreased. On Day 250, echocardiography indicated further improvement in pulmonary hypertension pathophysiology. The patient was still progressing well with antithrombotic and pulmonary vasodilator treatment 400 days later.
PubMed: 38662965
DOI: 10.1111/jvim.17089 -
Thorax Sep 2023Although obstructive airway disease has been shown to be associated with prematurity, other spirometry phenotypes are less well described.
INTRODUCTION
Although obstructive airway disease has been shown to be associated with prematurity, other spirometry phenotypes are less well described.
OBJECTIVES
We characterised abnormal spirometry phenotypes in preterm-born children, including prematurity-associated obstructive lung disease (POLD, forced expiratory volume in 1 s (FEV)
METHODS
768 children, aged 7-12 years, underwent FE measurements and spirometry before and after salbutamol. Groups were compared using parametric tests; multinomial regression was used.
RESULTS
22.6% of 544 preterm-born (mean gestation: 31 weeks) and 9.2% of 195 term-born children, with satisfactory data available, were classified into one of four abnormal spirometry groups. Each phenotype was generally more prevalent in preterm-born children than in the term-born children. For the preterm group, POLD-reversible (4.4%) was associated with increased FE, bronchopulmonary dysplasia (BPD) and intrauterine growth restriction. POLD-fixed group (3.3%) did not have increased FE but was associated with BPD. 41% of the pDysanapsis group (5.9%) had bronchodilator response, 31% had increased FE and was associated with postnatal weight gain. In the pPRISm group (9%), 13% responded to bronchodilators, FE was not increased and was non-significantly associated with body mass index (p=0.064).
CONCLUSIONS
Further to airway obstruction, we describe airway dysanapsis and pPRISm spirometry phenotypes in survivors of prematurity, both of which have poor outlook in other disease groups. By identifying specific phenotypes, targeted therapy can be developed to improve long-term outcomes.
Topics: Humans; Infant, Newborn; Bronchodilator Agents; Bronchopulmonary Dysplasia; Forced Expiratory Volume; Lung; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Spirometry; Vital Capacity; Premature Birth; Infant, Premature
PubMed: 36725332
DOI: 10.1136/thorax-2022-219301 -
Journal of the Belgian Society of... 2024Due to the mass-like appearance of pulmonary histoplasmosis in the lung, radiological misdiagnosis may occur. Fungal infections should be considered in the differential...
Due to the mass-like appearance of pulmonary histoplasmosis in the lung, radiological misdiagnosis may occur. Fungal infections should be considered in the differential diagnosis, especially in immune-compromised patients.
PubMed: 38680724
DOI: 10.5334/jbsr.3563 -
Advances in Therapy Dec 2023In the INBUILD trial in patients with progressive pulmonary fibrosis other than idiopathic pulmonary fibrosis (IPF), nintedanib slowed the rate of decline in forced...
INTRODUCTION
In the INBUILD trial in patients with progressive pulmonary fibrosis other than idiopathic pulmonary fibrosis (IPF), nintedanib slowed the rate of decline in forced vital capacity (FVC; mL/year) over 52 weeks compared with placebo. We assessed the efficacy of nintedanib across subgroups in the INBUILD trial by baseline characteristics.
METHODS
We assessed the rate of decline in FVC over 52 weeks and time to progression of interstitial lung disease (ILD) (absolute decline from baseline in FVC % predicted > 10%) or death over the whole trial in subgroups based on sex, age, race, body mass index (BMI), time since diagnosis of ILD, FVC % predicted, diffusing capacity of the lungs for carbon monoxide (DLco) % predicted, composite physiologic index (CPI), GAP (gender, age, lung physiology) stage, use of anti-acid therapy and use of disease-modifying antirheumatic drugs (DMARDs) at baseline.
RESULTS
The effect of nintedanib versus placebo on reducing the rate of decline in FVC over 52 weeks was consistent across the subgroups by baseline characteristics analysed. Interaction p values did not indicate heterogeneity in the treatment effect between these subgroups (p > 0.05). Over the whole trial (median follow-up time ∼19 months), progression of ILD or death occurred in similar or lower proportions of patients treated with nintedanib than placebo across the subgroups analysed, with no heterogeneity detected between the subgroups.
CONCLUSIONS
In the INBUILD trial, no heterogeneity was detected in the effect of nintedanib on reducing the rate of ILD progression across subgroups based on demographics, ILD severity or use of anti-acid therapy or DMARDs. These data support the use of nintedanib as a treatment for progressive pulmonary fibrosis.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov Identifier: NCT02999178.
Topics: Humans; Lung; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Vital Capacity; Treatment Outcome; Antirheumatic Agents; Disease Progression
PubMed: 37751022
DOI: 10.1007/s12325-023-02668-x -
Open Medicine (Warsaw, Poland) 2023Low molecular weight heparin (LMWH) is often used to prevent perioperative venous thrombosis after surgery, but aspirin is also recommended by academics. Studies were... (Review)
Review
Low molecular weight heparin (LMWH) is often used to prevent perioperative venous thrombosis after surgery, but aspirin is also recommended by academics. Studies were searched in electronic databases until February 24, 2023. We performed a meta-analysis to evaluate the safety and efficacy of aspirin and LMWH for venous thromboembolism (VTE) prophylaxis in patients after orthopedic surgery. The outcomes were death from any causes, deep vein thrombosis (DVT), pulmonary embolism (PE), etc. This study was registered with INPLASY, number 202320117. Six randomized controlled trials enrolled 13,851 patients with postoperative joint surgery. The risk of DVT was comparable between the two groups when aspirin was combined with mechanical devices (RR 0.61 [95% CI 0.27-1.39], ² = 62%, = 0.24). No significant differences in all cause death, PE, wound infection, and wound complication were found between the aspirin and LMWH groups. In this meta-analysis, the mortality rate was comparable between the aspirin and LMWH groups. However, aspirin alone had a higher risk of DVT than LMWH. Based on the results of this meta-analysis, we suggest aspirin combined with mechanical devices for VTE prophylaxis in patients after orthopedic surgery.
PubMed: 37663232
DOI: 10.1515/med-2023-0760 -
Journal of Cardiovascular Echography 2023Heart metastatic tumors are more frequent than primary heart tumors. Cardiac metastasis is a rare phenomenon, occurring mainly by direct spread, especially from lung...
Heart metastatic tumors are more frequent than primary heart tumors. Cardiac metastasis is a rare phenomenon, occurring mainly by direct spread, especially from lung cancer. Cardiac metastases may be asymptomatic or cause arrhythmias, nonspecific electrocardiographic alterations, or mimic a myocardial infarction. In this case report, we illustrate a rare case of pulmonary adenocarcinoma, which through the bloodstream developed a stalactite-shaped metastasis within the right ventricle of conspicuous size (20 mm × 34 mm × 12 mm). In addition, the tumor compressed the right pulmonary trunk, causing pulmonary hypertension. It is essential to characterize metastasis with multimodality imaging. Such lesions within the right cavities can cause massive pulmonary embolism, as in our case, leading to the patient's death, thrombolytic therapy not being effective.
PubMed: 38486687
DOI: 10.4103/jcecho.jcecho_46_23