Tepotinib Improves Prognosis in an Elderly Patient with Poor Performance Status and MET Exon 14 Skipping Mutation-positive Non-small Cell Lung Cancer.

Several target therapies for driver gene mutations related with lung cancer growth are clinically effective in patients with advanced non-small cell lung cancer. Gefitinib and alectinib have been reported as being effective and safe even in those with poor performance status (PS), but little is known about efficacy and tolerability of other TKIs. An 84-year-old man was diagnosed with non-small cell lung cancer (cT3N2M1c stage IVB). During the initial treatment with carboplatin and nab-paclitaxel, his Eastern Cooperative Oncology Group PS increased to 3. He was found to be positive for the mesenchymal-epithelial transition factor (MET) exon 14 skipping mutation, and tepotinib, a c-Met inhibitor, was started. His PS improved to 0-1 and partial response was maintained for 12 months or more. The MET exon 14 skipping mutation is common in the elderly, and TKI treatment may improve prognosis, even in patients with reduced PS.

Effectiveness of pulmonary vasodilators on pulmonary hypertension associated with POEMS syndrome.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare plasma cell disease. Patients with POEMS syndrome are considered to be at a high risk of developing pulmonary hypertension (PH). We report a 51-year-old woman diagnosed with PH associated with POEMS syndrome. She was started on dexamethasone and thalidomide. Although, the plasma vascular endothelial growth factor (VEGF) level decreased, systolic pulmonary artery pressure (sPAP) remained high. Auto-peripheral blood stem cell transplantation improved the plasma VEGF and sPAP levels. Four years later, she presented with dyspnoea on exertion, and elevated plasma VEGF and sPAP levels. Subsequently, on administering sildenafil and macitentan, the plasma VEGF and PH levels improved. Pulmonary vasodilators can be considered when PH remains after treatment of POEMS syndrome.

Surface Modification of Macrophages with Nucleic Acid Aptamers for Enhancing the Immune Response against Tumor Cells.

Antigen-presenting cells play a dominant role in cancer immunotherapy. Tumor cells, however, can still resort to several mechanisms of immune evasion that ultimately lead to the development of tumor tissues. In the current study, we performed surface modification of live macrophages with nucleic acid aptamers with the aim to enhance their affinity for tumor cells. Intercellular adhesion of tumor cells to surface-modified macrophages and the functions of the macrophages when in contact with tumor cells were investigated. To immobilize thiol-terminated nucleic acid aptamers that showed high affinity for the membrane protein of the tumor cells, methacryloyl groups were delivered into the sialic acids of the macrophages via metabolic glycoengineering (MGE). The proposed surface modification was cytocompatible and did not induce any undesirable activation of macrophages. According to the cell proliferation assay, the density of aptamers immobilized on a macrophage was found to decrease over time. However, the presence of aptamers on the cell surface was observed for more than 24 h after the immobilization. The number of adherent tumor cells on aptamer-immobilized macrophages was significantly larger than that of non-immobilized macrophages. Although the number of adherent tumor cells on aptamer-immobilized macrophages was not influenced by the pretreatment of doxorubicin to induce apoptosis in tumor cells, the apoptosis-induced tumor cells were highly phagocytosed by the aptamer-immobilized macrophages. The secretion amount of proinflammatory cytokines (TNF-α and IL-12) from the macrophages was coincident with the phagocytic index, which increased with the phagocytic uptake of tumor cells by the macrophages. In addition, the expression level of the major histocompatibility complex (MHC) class I and II molecules, required for antigen presentation, increased in nucleic acid aptamer-immobilized macrophages. Overall, the surface modification of macrophages with nucleic acid aptamers improved the tumor cell recognition of macrophages, indicating that the combination of cell surface engineering and anticancer drug treatment could constitute a promising strategy for tumor cell elimination.

Long-term clinical course of idiopathic pulmonary haemosiderosis with rheumatoid arthritis.

Idiopathic pulmonary haemosiderosis (IPH) is a rare cause of diffuse alveolar haemorrhage during childhood, and its precise pathophysiology and long-term clinical course remain unclear. A 31-year-old man was diagnosed with IPH at four years of age and had recurrent episodes of haemoptysis. The patient's symptoms responded well to steroids. However, pulmonary fibrosis and the cystic region in the lung progressively worsened. At age 27, the patient developed polyarthritis with positive anti-cyclic citrullinated peptide antibodies. The patient also developed hand synovitis, which was diagnosed with ultrasonography. These results indicate complications from rheumatoid arthritis. The patient's dyspnoea gradually worsened, and at the age of 31, he developed pneumothorax and an acute exacerbation of IPH. The clinical course from ages 4 to 31 included progressive chronic respiratory failure because of pulmonary fibrosis, acute exacerbations, complications with rheumatoid arthritis, and deliberation regarding lung transplantation. The development of rheumatoid arthritis after the onset of IPH supports the theory of an autoimmune mechanism of IPH.

Prospective open-label randomized comparative, non-inferiority study of two initial antibiotic strategies for patients with nursing- and healthcare-associated pneumonia: Guideline-concordant therapy versus empiric therapy.

BACKGROUND AND OBJECTIVE: The nursing- and healthcare-associated pneumonia guideline, proposed by the Japan Respiratory Society, recommends that patients at risk of exposure to drug-resistant pathogens, classified as treatment category C, be treated with antipseudomonal antibiotics. This study aimed to prove the non-inferiority of empirical therapy in our hospital compared with guideline-concordant therapy. METHODS: This was a randomized controlled trial conducted from December 2011 to December 2012. Patients were randomized to the Guideline group receiving guideline-concordant therapy, and the Empiric group treated with sulbactam/ampicillin or ceftriaxone. The primary endpoint was in-hospital relapse of pneumonia and mortality within 30 days, with a predefined non-inferiority margin of 10%. The secondary endpoints included duration, adverse effects, and cost of antibiotic therapy. RESULTS: One hundred and eleven patients were assigned to the Guideline group (n = 55) and the Empiric group (n = 56; 3 of which were excluded). The incidence of relapse and death within 30 days was similar in the Guideline and the Empiric groups (31% vs. 26%, risk difference -4.5%, 95% CI -21.5% to 12.5%). While the duration of antibiotic therapy was slightly shorter in the Guideline group than in the Empiric group (7 vs. 8 days), there were no significant differences in adverse effects or cost. CONCLUSIONS: The efficacy of empiric therapy was comparable to guideline-concordant therapy, although non-inferiority was not proven. The administration of broad-spectrum antibiotics to patients at risk of exposure to drug-resistant pathogens may not necessarily improve the prognosis. TRIAL REGISTRATION: UMIN000006792.

Surface engineering of macrophages with nucleic acid aptamers for the capture of circulating tumor cells.

In order to enhance the interactions between macrophages and cancer cells, thiol-terminated nucleic acid aptamers were immobilized on methacryloyl-functionalised carbohydrates of macrophages. The adhesion of cancer cells on the surface modified macrophages was significantly accelerated.