Influence of long-term cigarette smoking on immunoglobulin E-mediated allergy, pulmonary function, and high-resolution computed tomography lung densitometry in elderly patients with asthma

Background Smoking is the most important cause of chronic obstructive pulmonary disease (COPD). However, the influence of cigarette smoking on the pathogenesis of asthma in the elderly remains controversial. This study attempted to clarify the influence of cigarette smoking on elderly asthmatics. Methods Forty‐eight asthmatics over 70 years old (25 ex‐smokers and 23 never‐smokers) and 20 patients with COPD over 70 years old (all ex‐smokers) were studied to determine the influence of cigarette smoking on IgE‐mediated allergy (total IgE, IgE antibodies against inhalant allergens, bronchial hyper‐responsiveness (BHR), generation of leukotriene (LT) B₄ and C₄), pulmonary function, and the relative area of lung showing attenuation values less than ?950 Hounsfield units (RA₉₅₀) on high‐resolution computed tomography scans. Results The incidence of positive IgE antibodies against inhalant allergens, BHR, and the generation of leukotriene B₄ (LTB₄) by leucocytes were significantly increased in patients with a history of smoking compared with those without. Residual volume (%RV) was significantly increased, and diffusing capacity for carbon monoxide was significantly decreased in ex‐smokers with asthma and COPD compared with never‐smokers with asthma. Inspiratory RA₉₅₀ and ratio of expiratory RA₉₅₀ to inspiratory RA₉₅₀ were significantly larger in asthmatics with a smoking history than in those without, and in COPD patients than in asthmatics. Conclusion Cigarette smoking enhances the production of IgE antibodies, BHR, and generation of LTB₄ by leucocytes in elderly asthmatics. Increased hyper‐inflation or emphysematous changes of the lungs expressed by increased RA₉₅₀, closely related to %RV, was more frequently observed in ex‐smokers compared with never‐smokers.     

The first case of adult-onset PFAPA syndrome in Japan

A 26-year-old woman presented with fever and pharyngitis. She previously experienced four periodic febrile episodes at 30- to 40-day intervals. We suspected periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, and prescribed predisolone, thereby her fever rapidly subsided. Her febrile episodes improved after daily cimetidine treatment. Genetic testing results of genomic DNA for periodic fever syndromes were negative, although she was heterozygous for p.Glu148Gln variation in MEFV, supporting the diagnosis of PFAPA syndrome.     

Clinicopathological outline of dementia with Lewy bodies applying the revised criteria: the Hisayama study

To explore the validity of the criteria for dementia with Lewy bodies (DLB) revised in 2005, we examined community based consecutive autopsy cases. 10.3% of the non-demented subjects and 31.2% of the demented subjects showed the Lewy body pathology. Applying the revised pathological criteria to the 205 demented subjects, the types of LB pathology of 11 cases (5.4%) were brainstem-predominant, 24 cases (11.7%) were limbic type and 24 cases (11.7%) were diffuse neocortical type, although there were many subjects not to fit the criteria exactly. The prevalence of Lewy bodies (LBs) was almost same regardless of gender; however, the extent of the LB pathology among females was more severe than that in males. The likelihood of DLB being modified by concomitant Alzheimer's pathology was as follows: 27 cases (13.2%) showed low likelihood, 16 cases (7.8%) showed intermediate likelihood and 16 cases (7.8%) showed high likelihood. Since the numbers of clinical features of DLB were significantly higher in the pathological intermediate and high likelihood DLB groups than in the low likelihood DLB group or no LB group, both the intermediate and high likelihood groups of DLB should be considered as pathological DLB.     

Clinical study with allogeneic cultured dermal substitutes for chronic leg ulcers

BACKGROUND: Clinical studies of the use of allogeneic cultured dermal substitutes (CDSs) have been conducted in 30 medical centers across Japan with the support of the Millennium Project of the Ministry of Health, Labor and Welfare. The CDS is prepared by plating cultured fibroblasts on a spongy matrix made from hyaluronic acid and atelo-collagen. The aim of the present clinical study was to evaluate an allogeneic CDS as cell therapy in which cytokines are released to promote wound healing. MATERIALS AND METHODS: The CDS was applied repeatedly at an interval of 5-7 days to 13 patients being treated with intractable chronic leg ulcers, using the CDS as a dermatological treatment. Intractable leg ulcers, whether venous or arterial, are difficult to heal because they occur as a secondary change of disease. RESULTS: None of these patients had responded to conventional therapies such as topical or surgical methods, but 77% of the patients had an efficacy score of > 80 points for wound healing with allogeneic CDS. A high safety level was obtained: A, 84.6%; B and C, 7.7%; D, 0%. In 92% of the patients, the final assessment of wound healing was good or very good. CONCLUSIONS: For promotion of wound healing, the present CDS is superior to existing topical agents and occlusive dressings.     

Real‐world data on NGS using the Oncomine DxTT for detecting genetic alterations in non‐small‐cell lung cancer: WJOG13019L

Considering the increasing number of identified driver oncogene alterations, additional genetic tests are required to determine the treatment for advanced non‐small‐cell lung cancer (NSCLC). Next‐generation sequencing can detect multiple driver oncogenes simultaneously, enabling the analysis of limited amounts of biopsied tissue samples. In this retrospective, multicenter study (UMIN ID000039523), we evaluated real‐world clinical data using the Oncomine Dx Target Test Multi‐CDx System (Oncomine DxTT) as a companion diagnostic system. Patients with NSCLC who were tested for a panel of 46 genes using the Oncomine DxTT between June 2019 and January 2020 were eligible for enrollment. Patients from 19 institutions affiliated to the West Japan Oncology Group were recruited. The primary endpoint of the study was the success rate of genetic alteration testing in four driver genes (EGFR, ALK, ROS1, and BRAF) using the Oncomine DxTT. In total, 533 patients were enrolled in the study. The success rate of genetic alteration testing for all four genes was 80.1% (95% CI 76.5%‐83.4%). Surgical resection was associated with the highest success rate (88.0%), which was significantly higher than that for bronchoscopic biopsy (76.8%, P = .005). Multivariate analysis revealed a significant difference for surgical resection alone (P = .006, 95% CI 1.36‐6.18, odds ratio 2.90). Although the success rate of genetic alteration testing immediately after Oncomine DxTT induction was not sufficient in this study, optimizing specimen quantity and quality may improve the use of driver gene testing in clinical settings.     

Role of the NOD2 genotype in the clinical phenotype of Blau syndrome and early‐onset sarcoidosis

Objective

Blau syndrome and its sporadic counterpart, early‐onset sarcoidosis (EOS), share a phenotype featuring the symptom triad of skin rash, arthritis, and uveitis. This systemic inflammatory granulomatosis is associated with mutations in the NOD2 gene. The aim of this study was to describe the clinical manifestations of Blau syndrome/EOS in Japanese patients and to determine whether the NOD2 genotype and its associated basal NF‐κB activity predict the Blau syndrome/EOS clinical phenotype.

Methods

Twenty Japanese patients with Blau syndrome/EOS and NOD2 mutations were recruited. Mutated NOD2 was categorized based on its basal NF‐κB activity, which was defined as the ratio of NF‐κB activity without a NOD2 ligand, muramyldipeptide, to NF‐κB activity with muramyldipeptide.

Results

All 9 mutations, including E383G, a novel mutation that was identified in 20 patients with Blau syndrome/EOS, were detected in the centrally located NOD region and were associated with ligand‐independent NF‐κB activation. The median age of the patients at disease onset was 14 months, although in 2 patients in Blau syndrome families (with mutations R334W and E383G, respectively) the age at onset was 5 years or older. Most patients with Blau syndrome/EOS had the triad of skin, joint, and ocular symptoms, the onset of which was in this order. Clinical manifestations varied even among familial cases and patients with the same mutations. There was no clear relationship between the clinical phenotype and basal NF‐κB activity due to mutated NOD2. However, when attention was focused on the 2 most frequent mutations, R334W and R334Q, R334W tended to cause more obvious visual impairment.

Conclusion

NOD2 genotyping may help predict disease progression in patients with Blau syndrome/EOS.

     

Atypical teratoid/rhabdoid tumor arising from the spinal cord--case report and review of the literature

Spinal atypical teratoid/rhabdoid tumor (AT/RT) is extremely rare. We report this rare case and review the literature of spinal AT/RT. A 10-month-old girl presented with rapidly progressive paraplegia. Magnetic resonance images revealed an intramedullary tumor occupying the entire spinal canal below Th10. An urgent operation, consisting of decompression by laminectomy and biopsy, was performed. Histologically, the tumor specimen had many rhabdoid cells with prominent nuclei and eosinophilic cytoplasmic inclusion. It showed mitosis and necrosis. The tumor cells were immunoreactive for vimentin, desmin, smooth muscle actin, neuron-specific enolase, neurofilament, epithelial membrane antigen, and CAM5.2. Despite chemotherapy and radiotherapy, she died 3 months after admission. The present case is only the third detailed report of spinal AT/RT. Spinal AT/RT carries a poor prognosis, and therefore should be distinguished from other embryonal tumor.