Early diagnosis of partial interferon-γ receptor 1 deficiency prevents the development of Bacille de Calmette et Guérin osteomyelitis.

We encountered two patients with partial interferon γ receptor 1 (IFN-γR1) deficiency in whom early diagnosis enhanced disease management. Patient 1 was a 44-year-old woman with enlarged lymph nodes diagnosed in a pre-pregnancy checkup, and pathological examination revealed a Mycobacterium avium infection. Based on her history of unknown multiple osteomyelitis during early childhood, mendelian susceptibility to mycobacterial disease was suspected. Genetic analysis revealed a novel heterozygous variant in IFNGR1. Genetic counseling was administered to the patient and her husband before they had their baby. Patient 2 was a 4-month-old boy whose father was previously diagnosed with autosomal dominant IFN-γR1 deficiency owing to Bacille de Calmette et Guérin (BCG) osteomyelitis. Genetic analysis showed that he had the same INFGR1 variant. He avoided BCG vaccination and has been disease-free since then. Early diagnosis is considered to be useful for genetic counseling and essential for preventing BCG osteomyelitis.

[A Case of Pulmonary Enteric Adenocarcinoma with Soleus Muscle Metastasis].

Pulmonary enteric adenocarcinoma is a unique pulmonary adenocarcinoma subtype and has histopathological findings that are similar to those of colorectal adenocarcinoma. A man in his 50s visited our hospital because of discomfort in his right lower leg for the last 9 months. Imaging studies revealed a mass in his right soleus muscle, and needle biopsy was performed. Histological findings revealed adenocarcinoma, and immunohistochemical staining showed that the tumor cells were positive for CK20 and CDX-2. The tumor was first suspected to be metastasis of gastrointestinal malignant tumors. FDG-PET/CT showed increased FDG uptake in the right soleus muscle mass and presented with increased FDG uptake in a right upper lobe mass and right mediastinum lymphadenopathy. There were no findings in other organs. Scraping cytology of a transbronchial biopsy indicated adenocarcinoma. Upper and lower gastrointestinal endoscopy showed no findings of malignancy. He was finally diagnosed with pulmonary enteric adenocarcinoma(cT3N2M1b, Stage ⅣA). Treatment with cisplatin(CDDP), pemetrexed( PEM), and bevacizumab(BEV) was initiated. After 4 courses of the regimen, the tumor was partially reduced, and the patient showed stable disease(SD).

Association study of H2AFZ with schizophrenia in a Japanese case-control sample.

It is widely accepted that malfunction of the N-methyl-D-aspartate (NMDA)-type glutamate receptor may be involved in the pathophysiology of schizophrenia. Several recent microRNA (miRNA) studies have demonstrated that the expression of the glutamate system-related miR-132 and miR-212 is changed in postmortem schizophrenic brains. Here we attempted to obtain further insight into the relationships among schizophrenia, the NMDA receptor, the molecular cascades controlled by these miRNAs and commonly predicted target genes of the two miRNAs. We focused on the H2AFZ (encoding H2A histone family, member Z) gene, whose expression was shown in our screening study to be modified by a schizophrenomimetic NMDA antagonist, phencyclidine. By performing polymerase chain reaction with fluorescent signal detention using the TaqMan system, we examined four tag single nucleotide polymorphisms (SNPs; SNP01-04) located around and within the H2AFZ gene for their genetic association with schizophrenia. The subjects were a Japanese cohort (2,012 patients with schizophrenia and 2,170 control subjects). We did not detect any significant genetic association of these SNPs with schizophrenia in this cohort. However, we observed a significant association of SNP02 (rs2276939) in the male patients with schizophrenia (allelic P = 0.003, genotypic P = 0.008). A haplotype analysis revealed that haplotypes consisting of SNP02-SNP03 (rs10014424)-SNP04 (rs6854536) also showed a significant association in the male patients with schizophrenia (P = 0.018). These associations remained significant even after correction for multiple testing. The present findings suggest that the H2AFZ gene may be a susceptibility factor in male subjects with schizophrenia, and that modification of the H2AFZ signaling pathway warrants further study in terms of the pathophysiology of schizophrenia.

Erratum to: Association study of H2AFZ with schizophrenia in a Japanese case-control sample.

Table 1 contains several errors as originally published. Table 1 should read as follows; the corrected values are shown in italics.

COVID-19 and acute exacerbation of interstitial lung disease.

We conducted a study to examine the effect of COVID-19 on the acute exacerbation of interstitial lung disease (AE-ILD) early in the COVID-19 epidemic (January 1-April 30, 2020). An online questionnaire survey was conducted, which was completed by 134 hospitals. During this period, 854 patients with AE-ILD (including 12 cases of COVID-AE-idiopathic pulmonary fibrosis were hospitalized at 128 hospitals. In comparison, the total number of AE-ILD hospitalizations during the same period in 2019 was 894. The number of hospitalizations increased at 17 hospitals, decreased at 27, and remained the same at 88 hospitals in 2020 compared to the same period in 2019. In 2020, COVID-19-related acute exacerbations had a significantly worse prognosis than non-COVID-19-related acute exacerbations in both 30-day and 90-day mortality. Because the prognosis of AE-ILD associated with COVID-19 is extremely poor, prevention of COVID-19 is especially important for patients with ILD.

Non-inferior clinical outcomes of immune checkpoint inhibitors in non-small cell lung cancer patients with interstitial lung disease.

OBJECTIVES: The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) patients with pre-existing interstitial lung disease (ILD) is unclear. MATERIALS AND METHODS: Retrospective medical data from advanced or recurrent NSCLC patients who were treated with nivolumab or pembrolizumab at ten institutions in Japan between January 2016 and September 2018 were analyzed. Eligible patients were divided into two groups according to the presence of pre-existing ILD. RESULTS: A total of 461 NSCLC patients were enrolled, 412 without ILD (Non-ILD group) and 49 with ILD (ILD group). The response rate (RR) and disease control rate (DCR) of the ILD group were not inferior to those of the Non-ILD group [RR: 49.0 % (24/49) vs. 30.1 % (124/412), P < 0.01 and DCR: 69.4 % (34/49) vs. 51.2 % (211/412), P = 0.016, respectively]. Non-inferior outcomes were also observed with respect to progression-free survival (PFS) and overall survival (OS) (median PFS: 5.9 months vs. 3.5 months, P = 0.14 and median OS: 27.8 months vs. 25.2 months, P = 0.74 in the ILD and Non-ILD groups, respectively). Among immune-related adverse effects (irAEs), checkpoint inhibitor pneumonitis (CIP) was more frequently observed among NSCLC patients in the ILD group [30.6 % (15/49) vs. 9.5 % (39/412), P < 0.01]. The frequency of irAEs other than CIP and infusion reactions was not significantly different between the ILD group and the Non-ILD group. CONCLUSION: These results suggest that the clinical outcomes of ICIs are not significantly affected by pre-existing ILD despite the increased frequency of CIP. NSCLC patients with ILD are therefore probable candidates for ICIs.