Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis

Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

Background Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13). Case presentation An 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13. Conclusions It is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay

Predicting Therapeutic Effects using PET/CT

This study investigated the usefulness of [18F]-3’-deoxy-3’-fluorothymidine (18F-FLT) and [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for predicting the therapeutic efficacy of non-small cell lung cancer (NSCLC) irradiation at an early stage after radiation treatment. Mice were xenografted with the human lung adenocarcinoma line A549 or large cell lung cancer line FT821. Tumour uptake of 18F-FLT and 18F-FDG was imaged using PET/CT before and 1 week after irradiation. In A549 tumours, 18F-FLT uptake was significantly decreased, and 18F-FDG uptake was unchanged post-irradiation compared with pre-irradiation. In FT821 tumours, uptake of both 18F-FLT and 18F-FDG uptake was substantially decreased post-irradiation compared with pre-irradiation. In both xenografts, tumour volumes in the irradiated groups were significantly decreased compared with those in the control group. 18F-FLT is expected to contribute to individual NSCLC therapy because it accurately evaluates the decrease in tumour activity that cannot be captured by 18F-FDG. 18F-FDG may be useful for evaluating surviving cells without being affected by the inflammatory reaction at an extremely early stage, approximately 1 week after irradiation. Combined use of 18F-FLT and 18F-FDG PET/CT imaging may increase the accurate prediction of radiotherapy efficacy, which may lead to improved patient outcomes and minimally invasive personalised therapy

Macrophage colony-stimulating factor enhances rituximab-dependent cellular cytotoxicity by monocytes

医薬保健研究域医学系Recent studies suggest that monocytes are the dominant effectors by which rituximab induces cell death in B-cell lymphoma. Because macrophage colony-stimulating factor (M-CSF) can enhance the cytotoxicity of monocytes, the authors examined whether this growth factor can enhance their ability to kill lymphoma cells in vitro. Monocytes derived from a healthy volunteer were cultured for 48 h in the presence or absence of M-CSF. Monocytes stimul ated with M-CSF were significantly more cytotoxic to Daudi B-cell lymphomas than unstimulated monocytes. Flow cytometry revealed that M-CSF increased monocyte expression of Fcγ receptors III and I by 1.6- and 1.5-fold, whereas the expression of Fcγ receptor II remained unchanged. These results suggest that pretreatment with M-CSF can improve the therapeutic efficacy of rituximab against intractable CD20+ lymphoma. © 2007 Japanese Cancer Association

Second Seminar and Workshop

The Second International Seminar and Workshop (ISW) on Technological Competency as Caring in the Health Sciences was offered by the Rozzano Locsin Institute for Advancing the Theory of Technological Competency as Caring in Nursing, and held from August 17- 19, 2018 at Tokushima University in Tokushima, Japan. The ISW was envisioned to provide a platform for sharing research and scholarly works into innovative design and developments on studying and applying the theory of Technological Competency as Caring in the Health Sciences. This ISW was founded on the theory of Technological Competency as Caring in Nursing (TCCN) (Locsin, 2005). The ISW, as aimed broadened the influence of theory, research, and practice through the advancements in technology, caring, and nursing, as espoused in the theory of Technological Competency as Caring particularly within the Health Sciences. This report illuminates the contents of the ISW and its outcomes, and reveals the direction of the theory, its development, and future implications through formalized activities

Efficacy of osimertinib in epidermal growth factor receptor-mutated non-small-cell lung cancer patients with pleural effusion

Background: Osimertinib is a standard first-line treatment for advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Although malignant pleural effusion (PE) is a common clinical problem in NSCLC, information about the efficacy of osimertinib in patients with PE is limited, especially regarding its efficacy in EGFR T790M-negative patients with PE remains unclear. Methods: We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who were treated with osimertinib in our institution between May 2016 and December 2020. Results: A total of 63 patients with EGFR mutated NSCLC were treated with osimertinib; 33 (12 with PE) had no EGFR T790M mutation, while 30 (12 with PE) had EGFR T790M mutation. In EGFR T790M-negative NSCLC, the progression-free survival (PFS) of the patients with PE was comparable to that of the patients without PE (median PFS 19.8 vs. 19.8 months, p = 0.693). In EGFR T790M- positive NSCLC, the PFS and overall survival (OS) of the patients with PE were significantly shorter than those of the patients without PE (median PFS 16.8 vs. 8.3 months, p = 0.003; median OS 44.9 vs. 14.2 months, p = 0.007). In the multivariate analysis, the presence of PE was independently associated with shorter PFS and OS in EGFR T790M-positive NSCLC patients, but not EGFR T790M-negative patients. Conclusions: These data suggest the efficacy of osimertinib may differ between EGFR T790M-positive and -negative NSCLC patients with PE

A case of pulmonary pleomorphic carcinoma with malignant phenotypes induced by ZEB1-associated epithelial-mesenchymal transition

A 60-year-old man was admitted to our hospital with non-small cell lung cancer (NSCLC). Imaging and pathological studies revealed NSCLC, not otherwise specified (NOS), at clinical stage T3N1M0 stage IIIA. We started radiotherapy alone because of obstructive pneumonia and end-stage renal disease, but the tumors progressed rapidly and resulted in death due to air obstruction by pharyngeal metastasis. The cancer was diagnosed as pleomorphic carcinoma in an autopsy. Viable lung tumor cells, which were resistant to radiotherapy, and the pharyngeal metastasis had mesenchymal phenotypes and expressed ZEB1 but not SNAI1. These observations indicated that ZEB1-associated epithelial-mesenchymal transition has malignant features including resistance to radiotherapy and aggressive metastatic potential. ZEB1-associated EMT may be an important mechanism to understand the pathophysiology of pleomorphic carcinoma

A sporadic case of CTLA4 haploinsufficiency manifesting as Epstein–Barr virus-positive diffuse large B-cell lymphoma

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is a coinhibitory receptor that plays an essential role in maintaining immune system homeostasis by suppressing T-cell activation. We report a sporadic case of CTLA4 haploinsufficiency in a patient with Epstein-Barr virus-positive diffuse large B-cell lymphoma and subsequent benign lymphadenopathy. A missense mutation in exon 2 of the CTLA4 gene (c.251T>C, p.V84A) was found in the patient's peripheral blood and buccal cell DNA, but not in her parents' DNA. CTLA4 expression decreased in the peripheral regulatory T cells upon stimulation, whereas CTLA4 and PD-1-positive T cell subsets increased, possibly to compensate for the defective CTLA4 function. This case suggests that some adult lymphoma patients with no remarkable medical history have primary immune disorder. As immune-targeted therapies are now widely used for the treatment of malignancies, it is increasingly important to recognize the underlying primary immune disorders to properly manage the disease and avoid unexpected complications of immunotherapies