Massive pleural effusion in porous diaphragm syndrome due to lymphatic leakage after pelvic surgery.

We present the case of a patient who developed a massive right pleural effusion after pelvic surgery, not thoracic surgery. Lymphatic leakage into the abdominal cavity after pelvic surgery can cause massive pleural effusion when complicated with porous diaphragm syndrome.

Severe Atelectasis due to Aspirated Valproic Acid Tablet.

A 60-year-old man treated with valproic acid (VPA) for epilepsy developed atelectasis and respiratory failure after an accidentally aspirated VPA tablet-induced mucus hypersecretion. Following bronchoscopic removal of the aspirated tablet, his respiratory status improved and massive sputum production did not recur. We hypothesized that the aspirated VPA tablet increased the expression of mucin-related genes, thereby increasing mucus production. Our in vitro experiments using a human respiratory epithelial cell line revealed that VPA directly upregulates the airway mucin-related genes. We believe that this is the first case report of aspirated VPA-induced severe atelectasis and respiratory failure, which were successfully treated with the bronchoscopic removal of the VPA tablet.

IgG4-related retroperitoneal fibrosis induced by nivolumab and ipilimumab in a patient with non-small cell lung cancer: A case report.

IgG4-related diseases are adverse events that occur after receiving treatment with immune checkpoint inhibitors (ICI). This study reports the first case of IgG4-related retroperitoneal fibrosis after the administration of chemotherapy with nivolumab and ipilimumab (NI therapy). An 80-year-old man developed lower abdominal pain eight months after NI therapy was initiated. Although the primary lesion maintained its reduced size on computed tomography, there was an increase in the soft tissue shadows intensity around the abdominal aorta, bladder, and seminal vesicles, suggesting retroperitoneal fibrosis. Blood tests showed elevated IgG4 levels. Computed tomography-guided biopsy of the retroperitoneum showed B cell-dominant lymphocyte infiltration consistent with IgG4-related retroperitoneal fibrosis and characteristic CD8-positive lymphocyte infiltration, suggestive of the involvement of cytotoxic T cells. Based on the clinical, imaging, and pathological findings, the patient was diagnosed with IgG4-related retroperitoneal fibrosis due to ICI. Immunotherapy discontinuation alone did not result in improvement; therefore, steroid therapy was initiated. In clinical practice, IgG4-related retroperitoneal fibrosis can occur as an immune-related adverse event when administering anti-PD-1 and anti-CTLA-4 antibodies for cancer immunotherapy. Early steroid therapy could be effective in controlling this immune-related adverse event.

Successful Chemotherapy for Diffuse Cystic Lung Metastases during Targeted Therapy with Osimertinib in a Patient with Non-Small-Cell Lung Cancer: A Literature Review and a Rare Case Report.

Introduction: Diffuse lung cysts occur owing to several diseases; however, diffuse cystic lung metastases are very rare in the case of lung cancer. We report a rare case of diffuse cystic lung metastases from lung adenocarcinoma and reviewed previously reported cases of cystic lung metastases for lung cancer and determined their characteristics. Case Presentation: A 78-year-old Japanese woman with advanced lung adenocarcinoma was positive for the epidermal growth factor receptor gene mutation exon 21 L858R and had been treated with osimertinib. She presented with multiple bilaterally positioned thin-walled lung cysts and pneumothorax. Lung cysts were diagnosed as cystic lung metastases from lung cancer, and carboplatin, pemetrexed, and pembrolizumab were subsequently administered. All cysts markedly decreased in size, and some disappeared. Conclusion: Effective treatment methods for cystic lung metastases from lung cancer have not been reported. To our knowledge, this is the first case of cystic lung metastases that were successfully treated with chemotherapy.

Successful Treatment of Granulomatous-lymphocytic Interstitial Lung Disease in a Patient with CTLA-4 Deficiency.

Common variable immunodeficiency (CVID) causes granulomatous-lymphocytic interstitial lung disease (GLILD) and has a poor prognosis. We herein report a case of GLILD in a 49-year-old woman with CTLA-4 deficiency-associated CVID. The patient presented with dyspnea that had worsened over the past two years. A laboratory examination revealed hypoglobulinemia and pancytopenia. Chest computed tomography showed diffuse infiltrative and granular shadows in the bilateral interstitium. A flow cytometric analysis of blood cells and genetic testing confirmed CTLA-4 deficiency. We performed video-assisted thoracoscopic surgery for the pathological diagnosis of GLILD and to exclude infection and malignancy. Corticosteroid treatment successfully improved the condition of the patient.

Development of intravascular large B-cell lymphoma during prophylactic antibiotic treatment for anti-interferon-gamma autoantibody syndrome: A case report.

Anti-interferon (IFN)-γ autoantibody-positive syndrome is one of the acquired non-HIV cellular immunodeficiencies, caused by abnormalities in the IFN-γ/interleukin (IL)-12 pathways. It is often diagnosed alongside the onset of disseminated mycobacterium infection, and requires continuous antimycobacterial chemotherapy; however, the detailed pathological mechanisms underlying this syndrome, including its prognosis, are not known. To the best of our knowledge, this is the first reported case of intravascular large B-cell lymphoma complicated by anti-IFN-γ autoantibody syndrome, presented in an 82-year-old woman. The patient had been diagnosed with anti-IFN-γ autoantibody immunodeficiency ten years ago. She had repeated subacute fever of undetermined origin for 13 months that made us suspect infections, such as disseminated mycobacterium disease and other viral and fungal infections, despite receiving prophylactic antimycobacterial chemotherapy with rifampicin and clarithromycin. However, all the screenings performed showed no evidence of infectious diseases; thus, she was finally diagnosed with intravascular large B-cell lymphoma via a random skin biopsy. Unfortunately, the patient debilitated rapidly and died. Evidence supporting a correlation between anti-IFN-γ autoantibody syndrome and carcinogenesis is still lacking, although it is known that patients with anti-IFN-γ autoantibody syndrome are at risk of persistent viral infection-related and T-cell lineage-related carcinogenesis. This case demonstrated that patients with anti-IFN-γ autoantibody syndrome are also at risk of developing B-cell lymphoma, such as intravascular lymphoma. This emphasizes that caution should be paid to increased risk of developing malignancy during the long-term management of anti-IFN-γ autoantibody syndrome with cellular immunodeficiency.

Healthy lifestyle behaviors and transitions in frailty status among independent community-dwelling older adults: The Yabu cohort study.

Frailty is a dynamic condition that can worsen or improve. Although previous studies have identified demographic and intrinsic factors associated with transitions in frailty status, less evidence is available regarding associations with daily activities. This longitudinal study examined associations of behavioral factors with incident frailty, adverse events (e.g. residence in a nursing home, hospitalization, and death), and frailty improvement among older adults. The analysis included data from 3,769 independent older adults aged 65 years or more (mean age, 76.3 ± 7.2years; proportion of frail participants, 30.1%) from the Yabu cohort study (baseline, 2012; follow-up, 2017). The Kaigo-Yobo Checklist, a standardized questionnaire, was used to assess frailty status (non-frail or frail) and seven behavioral factors: farming, shopping, exercise, eating habit, intellectual activity, social participation, and smoking. At the 5-year follow-up survey, the proportions of participants transitioning from non-frail to frail, from non-frail to incident adverse events, from frail to non-frail, and from frail to incident adverse events were 16.8%, 13.9%, 15.2%, and 50.1%, respectively. In the analysis of non-frail participants, farming, exercise, intellectual activity, and social participation were associated with lower odds of becoming frail and experiencing adverse events. In the analysis for frail participants, farming, intellectual activity, and social participation were significantly associated with improvement in frailty status, and farming, shopping, and social participation were associated with lower odds of incident adverse events. These findings suggest that farming, healthy daily activities, and social participation help improve and prevent frailty/adverse events.

[Process and outcome evaluation of community-based strategies for frailty prevention in the elderly with the help of the senior workforce at Silver Human Resources Centers in Yabu City, Japan].

Objectives　Preventing frailty is a crucial issue in aging societies such as Japan. In 2011, we launched an action research project in Yabu City, Hyogo Prefecture, to develop effective community-based strategies to prevent frailty in the elderly. We attempted to introduce community-based frailty prevention classes in every administrative district with the help of the senior workforce at Silver Human Resources Centers. This study aimed to evaluate the effectiveness and the applicability to different communities of this strategy, which will be called the "Yabu model."Methods　Using PAIREM (Plan, Adoption, Implementation, Reach, Effectiveness, Maintenance) framework, we evaluated the effectiveness and the applicability to different communities of the Yabu model. To evaluate its effectiveness, we conducted a baseline and follow-up survey of residents aged 65 years or older in 2012 (n=7,287, 90.7% response rate) and 2017 (n=8,157, 85.7%), using a mailed self-administered questionnaire.Results　(1) Plan: The idea was to establish a frailty prevention class (60 min/session, once a week) consisting of resistance exercises and nutritional or psychosocial programs (standard course, six months, 20 sessions/course; short course, one and a half months, 6 sessions/course; after the course, residents continued with the activities themselves). We planned to launch three classes in the first year (2014) and then to increase the number of classes by ten each year after the second year. (2) Adoption: Out of 154 administrative districts, 36 (23.4%) held frailty prevention classes between 2014 and 2017. (3) Implementation: The median attendance rate for the standard or short course (number of times each participant attended/number of frailty prevention class sessions held) was 75.0%. (4) Reach: A total of 719 older people participated in the standard or short course. The participation rate in the administrative districts, where each frailty prevention class was held, was 32.8%, while at the city level it was 8.1%. (5) Effectiveness: Propensity score matching after multiple imputations were performed. While the prevalence of frailty in non-participants increased by 13.7% in the five years from 2012 to 2017, it only increased by 6.8% in participants. Compared to non-participants, program participants had a significantly lower prevalence odds ratio of frailty at the time of the follow-up survey (OR=0.65, 95% confidence interval 0.46-0.93). (6) Maintenance: After the standard or short course, 25 out of 26 communities (96.2%) continued the frailty prevention activities once a week.Conclusion　The frailty prevention classes were adopted across many districts and lowered the participants' risk of frailty. Moreover, participants continued to engage in frailty prevention activities even after the course. These results indicate the Yabu model's effectiveness and its applicability for a different community.

Whole Genome Sequencing of Influenza A and B Viruses With the MinION Sequencer in the Clinical Setting: A Pilot Study.

Introduction: Whole genome sequencing (WGS) of influenza viruses is important for preparing vaccines and coping with newly emerging viruses. However, WGS is difficult to perform using conventional next-generation sequencers in developing countries, where facilities are often inadequate. In this study, we developed a high-throughput WGS method for influenza viruses in clinical specimens with the MinION portable sequencer. Methods: Whole genomes of influenza A and B viruses were amplified by multiplex RT-PCR from 13 clinical specimens collected in Tokyo, Japan. Barcode tags for multiplex MinION sequencing were added with each multiplex RT-PCR amplicon by nested PCR with custom barcoded primers. All barcoded amplicons were mixed and multiplex sequencing using the MinION sequencer with 1D2 sequencing kit. In addition, multiplex RT-PCR amplicons generated from each clinical specimen were sequenced using the Illumina MiSeq platform to validate the performance of MinION sequencer. The accuracy, recall, and precision rates of MinION sequencing were calculated by comparing the results of variant calling in the Illumina MiSeq platform and MinION sequencer. Results: Whole genomes of influenza A and B viruses were successfully amplified by multiplex RT-PCR from 13 clinical samples. We identified 6 samples as influenza type A virus H3N2 subtype and 7 as influenza B virus Yamagata lineage using the Illumina MiSeq platform. The overall accuracy, recall, and precision rates of the MinION sequencer were, respectively 99.95%, 89.41%, and 97.88% from 1D reads and 99.97%, 93.28%, and 99.86% from 1D2 reads. Conclusion: We developed a novel WGS method for influenza A and B viruses. It is necessary to improve read accuracy and analytical tools in order to better utilize the MinION sequencer for real-time monitoring of genetic rearrangements and for evaluation of newly emerging viruses.