Improved diagnostic accuracy with three lung tumor markers compared to six-marker panel.

Background: Combining multiple tumor markers increases sensitivity for lung cancer diagnosis in the cost of false positive. However, some would like to check as many as tumor markers in the fear of missing cancer. We though to propose a panel of fewer tumor markers for lung cancer diagnosis. Methods: Patients with suspected lung cancer who simultaneously underwent all six tests [carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA), squamous cell carcinoma-associated antigen (SCC), neuron-specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP), and sialyl Lewis-X antigen (SLX)] were included. Tumor markers with significant impact on the lung cancer in a logistic regression model were included in our panel. Area under the curve (AUC) was compared between our panel and the panel of all six. Results: We included 1,733 [median 72 years, 1,128 men, 605 women, 779 (45%) confirmed lung cancer]. Logistic regression analysis suggested CEA, CYFRA, and NSE were independently associated with the lung cancer diagnosis. The panel of these three tumor markers [AUC =0.656, 95% confidence interval (CI): 0.630-0.682, sensitivity 0.650, specificity 0.662] had better (P<0.001) diagnostic performance than six tumor markers (AUC =0.575, 95% CI: 0.548-0.602, sensitivity 0.829, specificity 0.321). Conclusions: Compared to applying all six markers (at least one marker above the upper limit of normal), the panel with three markers (at least one marker above the upper limit of normal) led to a better predictive value by lowering the risk of false positives.

ILD-GAP combined with the monocyte ratio could be a better prognostic prediction model than ILD-GAP in patients with interstitial lung diseases.

BACKGROUND: The ILD-GAP scoring system is known to be useful in predicting prognosis in patients with interstitial lung disease (ILD). An elevated monocyte count was associated with increased risks of IPF poor prognosis. We examined whether the ILD-GAP scoring system combined with the monocyte ratio (ILD-GAPM) is superior to the conventional ILD-GAP model in predicting ILD prognosis. METHODS: In patients with ILD treated between April 2013 and April 2017, we were retrospectively assessed the relationships between baseline clinical parameters, including age, sex, Charlson Comorbidity Index score (CCIS), ILD diagnosis, blood biomarkers, pulmonary function test results, and disease outcomes. In ILD patients were included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD). We also assessed the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPM models. RESULTS: A total of 179 patients (mean age, 73 years) were assessed. All of them were taken pulmonary function test, including percentage predicted diffusion capacity for carbon monoxide. ILD patients included 56 IPF cases, 112 iNSIP and CVD-IP cases, 6 CHP cases and 5 UC-ILD cases. ILD-GAPM provided a greater area under the receiver-operating characteristic curve (0.747) than ILD-GAP (0.710) for predicting 3-year ILD-related events. Furthermore, the log-rank test showed that the Kaplan-Meier curves in ILD-GAPM were significantly different by stage (P = 0.015), but not by stage in ILD-GAP (P = 0.074). CONCLUSIONS: The ILD-GAPM model may be a more accurate predictor of prognosis for ILD patients than the ILD-GAP model.

Serum heme oxygenase-1 as a prognostic biomarker in patients with acute exacerbation of interstitial lung disease.

Serum heme oxygenase (HO)-1 level has been reported as a clinically reliable diagnostic biomarker for acute exacerbation of interstitial lung disease (ILD); however, its utility for predicting mortality among these patients is unclear. Serum HO-1 levels of patients newly diagnosed with acute exacerbation of ILD were measured at the time of initiating steroid pulse therapy. The relationship between serum HO-1 and various other serum biomarkers, change in HRCT findings, and disease prognosis at 12 weeks after diagnosis of acute exacerbation was evaluated in 51 patients, of whom 17 (33%) had idiopathic pulmonary fibrosis (IPF). Serum HO-1 was higher in patients with acute exacerbation of IPF than in patients with acute exacerbation of other ILDs. Serum HO-1 levels were higher in patients who died within these 12 weeks than in survivors. Among age, sex, comorbidities, IPF diagnosis, HRCT findings, and blood biomarkers, serum HO-1 was a primary predictor of 12-week mortality. In 41 patients who underwent repeat HRCT, serum HO-1 was higher in patients with honeycomb progression than in those without. Serum HO-1 measurement could be useful for evaluating disease mortality and morbidity of patients with acute exacerbation of ILDs.

Limited efficacy of low-dose dexamethasone for the treatment of severe COVID-19 pneumonia: A retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Its symptoms range from mild to severe, with the latter often being life-threatening. This study aims to assess the effects of low-dose dexamethasone (DEX) in mild-to-severe COVID-19 pneumonia and examine the final clinical outcomes to identify the optimal therapeutic dose. METHODS: Clinical data from 132 patients hospitalized for COVID-19 pneumonia between January and October 2021 at Yamato Municipal Hospital were retrospectively analyzed. Based on the ratio of peripheral arterial oxygen saturation (SpO2) to inspired fraction of oxygen (FiO2), patients were categorized into the mild (>450, n = 65), moderate (315-450, n = 55), and severe (<315, n = 12) pneumonia groups. The event of interest was defined as the worsening of the patient's condition during treatment (need to increase FiO2 > 0.1). Patients were treated with low-dose DEX (6.6 mg/day) for 10 days. RESULTS: The event-free survival rate decreased significantly in patients with severe pneumonia compared with in those with mild and moderate pneumonia (Bonferroni-adjusted p < 0.02). A total of 16 patients were treated with high-dose corticosteroids because of severe hypoxia. Recovery was observed in all discharged patients with respiratory condition improvement. Low SpO2/FiO2 at admission was significantly associated with serum C-reactive protein levels. CONCLUSIONS: For Japanese patients with COVID-19, severe pneumonia, and SpO2/FiO2 of <315, it may be necessary to administer a dose of corticosteroids of >6.6 mg DEX.

ALK-Rearranged NSCLC With Concomitant HER2-Mutant Breast Cancer Patient Treated With Alectinib, Trastuzumab, and Pertuzumab: A Case Report.

Multiple cancers are a common occurrence, and the choice of treatment can be a challenging decision. The current case report describes a 71-year-old woman with overlapping anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma and HER2-mutant breast cancer, who achieved improvement with concurrent use of the molecularly targeted agents Alectinib, Trastuzumab, and Pertuzumab. A 71-year-old woman was diagnosed with lung adenocarcinoma and brain metastases, and invasive ductal carcinoma of the right breast, HER2-mutant type. In March 2021, a biopsy confirmed the presence of the ALK fusion gene in lung cancer. In April 2021, he started Alectinib and showed shrinkage of lung cancer; in December 2021, a metastatic liver tumor was found, and a liver biopsy diagnosed liver metastasis of breast cancer. Therefore, Alectinib was discontinued in February 2022, and Trastuzumab, Pertuzumab, and Docetaxel were started as chemotherapy for breast cancer. She continued treatment with Trastuzumab and Pertuzumab, but in July 2022, she developed an increase in lung cancer. Her metastatic liver tumor continued shrinking, and she was started on Trastuzumab, Pertuzumab, and Alectinib. After six months of treatment, the patient showed a sustained reduction in both lung cancer, breast cancer, and brain metastases with no adverse events. ALK rearrangement lung cancer often develops in young women, and similarly, breast cancer often develops in women. Therefore, those cancers may occur simultaneously. In such cases, the choice of treatment can be difficult, as both cancers require different approaches. Alectinib has been shown to have a high response rate and prolonged progression-free survival in ALK-rearranged non-small cell lung cancer (NSCLC). Trastuzumab and Pertuzumab are commonly used for the treatment of HER2-mutant breast cancer and have been shown to significantly improve progression-free survival and overall survival. This case report provides evidence that the concurrent use of Alectinib, Trastuzumab, and Pertuzumab can be an effective treatment for patients with overlapping ALK-rearranged NSCLC and HER2-mutant breast cancer. It is important to consider concurrent treatment in patients with multiple cancers to optimize treatment outcomes and improve quality of life. However, further studies are needed to establish the safety and efficacy of this combination of drugs for the treatment of overlapping cancers.

Entrectinib-Induced Heart Failure in a Patient With Metastatic Lung Adenocarcinoma: A Case Report.

Entrectinib is a recently approved multikinase inhibitor to treat advanced c-ros oncogene1 (ROS1) positive non-small cell lung cancer (NSCLC). Although molecular targeted therapy is generally well tolerated, cardiovascular adverse events have been described in recent years. We report a case of NSCLC with ROS1 rearrangement where the patient developed drug-induced heart failure after receiving entrectinib. A 74-year-old non-smoker female patient was diagnosed with stage IVB lung adenocarcinoma with ROS-1 positive and right breast cancer stage I. We started on entrectinib as the first-line therapy for lung cancer. Five days after, she developed oral dysesthesia and blood creatinine increased. These findings gradually worsened, so we temporarily discontinued entrectinib. After withholding the drug for 14 days, these findings improved, and we resumed entrectinib at a reduced dose. On day 19 of the reduced entrectinib dose, she presented to the outpatient with shortness of breath and bilateral lower extremity edema, accompanied by respiratory failure. Laboratory evaluation revealed elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), troponin I, creatine kinase (CK), and C reactive protein (CRP), and transthoracic echocardiogram showed congestive heart failure (CHF) with a preserved ejection fraction (HFpEF). She did not complain of chest pain and fever, so we did not consider ischemic heart disease and viral myocarditis in the initial evaluation. There was no other causative cause of CHF. Therefore, we suspected entrectinib-related heart failure. Her symptoms improved and she recovered her cardiac function to baseline within a week of discontinuation of entrectinib and standard heart failure treatment. She developed heart failure after a one-step dose reduction and was prone to cardiotoxicity due to entrectinib. Considering that she could be treated with crizotinib, we decided discontinuation of entrectinib permanently. This case report highlights the potential cardiotoxicity of entrectinib and suggests the need for close monitoring of the cardiac functions of patients receiving entrectinib.

Plasmid Profiles and Prevalence of Intermediately Virulent Rhodococcus equi from Pigs in Nakhonpathom Province, Thailand: Identification of a New Variant of the 70-kb Virulence Plasmid, Type 18.

The prevalence of intermediately virulent Rhodococcus equi isolates from pig submaxillary lymph nodes from four slaughterhouses in Nakhonpathom province, Thailand, was investigated. The isolates were tested for the presence of virulence plasmids and the 20-kDa virulence-associated protein antigen (VapB) gene by PCR. Of the 734 submaxillary lymph nodes tested, 19 (2.6%) produced positive cultures of R. equi. All 19 isolates were positive for the VapB gene and contained virulence plasmids that were identified as type 1 (six isolates), type 6 (two isolates), type 7 (one isolate), type 16 (two isolates), and a new variant (eight isolates). Based on the restriction digestion patterns of the plasmid DNAs, we tentatively designated the variant as type 18. Investigation of the prevalence and plasmid profiles of VapB-positive R. equi in pigs should be extended throughout Thailand to evaluate potential sources of zoonotic infections.