A Case of MET Exon 14 Skipping Mutation: Positive Lung Adenocarcinoma Complicated by Paraneoplastic Neurological Syndrome.

A 67-year-old man with cervical spondylotic myelopathy undergoing conservative treatment presented with subacute progression of fine motor and ambulatory disturbances, leading to admission at a previous hospital. Pre-cervical laminoplasty chest computed tomography (CT) revealed a tumor in the left upper lobe of the lung, prompting transfer to our institution. Transbronchial biopsy findings were consistent with adenocarcinoma, diagnosed as clinical stage T2bN0M0, Stage IIA. The neurological abnormalities could not be solely attributed to cervical spondylotic myelopathy, leading to a diagnosis of concurrent paraneoplastic neurological syndrome (PNS). During hospitalization, the patient's condition progressed to a state of constant bed rest within two weeks. On the 17th hospital day, a left upper lobectomy was performed, resulting in significant improvement, allowing the patient to ambulate with assistance after two weeks, and transfer to a convalescent rehabilitation hospital on the 58th hospital day. Subsequent cancer multigene panel testing revealed a positive MET exon 14 skipping mutation. Given the absence of reports on this mutation in lung adenocarcinoma associated with PNS, we consider it rare and thus report this case.

Infectious Pulmonary Artery Pseudoaneurysm Secondary to a Lung Abscess Treated With Pulmonary Artery Coil Embolization: A Case Report.

Pulmonary artery pseudoaneurysms (PAPs) are uncommon, yet they frequently result in hemoptysis and are associated with a poor prognosis. We report a case of an 87-year-old male patient. Initially, he was admitted to a previous hospital, and diagnosed with a lung abscess in the left lower lobe. On the second hospital day, he developed hemoptysis. A contrast-enhanced chest computed tomography (CT) identified an infectious pulmonary artery pseudoaneurysm. On the ninth hospital day, pulmonary artery coil embolization was successfully performed, significantly improving the patient's condition.

A randomized double-blind placebo-controlled trial of an inhibitor of plasminogen activator inhibitor-1 (TM5614) in mild to moderate COVID-19.

An inhibitor of plasminogen activator inhibitor (PAI)-1, TM5614, inhibited thrombosis, inflammation, and fibrosis in several experimental mouse models. To evaluate the efficacy and safety of TM5614 in human COVID-19 pneumonia, phase IIa and IIb trials were conducted. In an open-label, single-arm trial, 26 Japanese COVID-19 patients with mild to moderate pneumonia were treated with 120-180 mg of TM5614 daily, and all were discharged without any notable side effects. Then, a randomized, double-blind, placebo-controlled trial was conducted in Japanese COVID-19 patients with mild to moderate pneumonia. The number of study participants was set to be 50 in each arm. Even after extension of the enrollment period, the number of study participants did not reach the initially intended sample size, and 75 patients were enrolled in the study. The total oxygenation scale from Day 1 to Day 14 as the primary endpoint was 1.5 in the TM5614 group vs 4.0 in the placebo group (p = 0.22), and the number of days of oxygen administration required as the secondary endpoint was 2.0 days in the TM5614 group vs 3.5 days in the placebo group (p = 0.34). Further studies will be necessary to verify the efficacy of PAI-1 inhibition for the treatment of COVID-19 pneumonia.Clinical trial registration: Two studies were conducted: a prospective, multicenter, open-label phase II study at https://jrct.niph.go.jp (jRCT2021200018) (First registration date 18/08/2020) and a prospective, multicenter, randomized, double-blind, placebo-controlled, phase II study at https://jrct.niph.go.jp (jRCT2021210006) (First registration date 28/05/2021).

Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study.

BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID. METHODS: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. RESULTS: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma. CONCLUSIONS: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.

Impairment of Social-Related Quality of Life in COVID-19 Pneumonia Survivors: A Prospective Longitudinal Study.

The post-acute sequelae of SARS-CoV-2 (PASC) pose a threat to patients' health-related quality of life (HRQOL). Here, the impact of COVID-19 on HRQOL and the clinical factors associated with impaired HRQOL were examined. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and the SF-36 questionnaire at these two time points and underwent pulmonary function testing at 6 months after disease onset. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months, and 26% reported respiratory symptoms at 6 months after disease onset. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with lower RCS tended to have respiratory sequelae or a relatively lower forced vital capacity. The CT score that reflected the extent of COVID-19 pneumonia was inversely correlated with the RCS score (3 months, p = 0.0024; 6 months, p = 0.0464). A high CT score (≥10 points) predicted a low RCS score at 6 months (p = 0.013). This study highlights the impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19.

A phase II feasibility study of carboplatin and nab-paclitaxel for advanced non-small cell lung cancer patients with interstitial lung disease (YLOG0114).

BACKGROUND: A standard treatment regimen for advanced non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) has not been established since most clinical trials exclude such patients because of the high risk of acute exacerbation of ILD. This study aimed to prospectively investigate the efficacy and safety of carboplatin and nab-paclitaxel as a first-line regimen for NSCLC patients with ILD. METHODS: The enrolled patients had treatment-naïve advanced NSCLC with ILD. The patients received 4-6 cycles of carboplatin (area under the curve = 5) on day 1 and nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 every 4 weeks. The primary endpoint was the completion rate of four or more cycles. Secondary endpoints included toxicity, overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-five patients were enrolled in this study. Nine patients had adenocarcinoma, 11 had squamous cell carcinoma, one had large cell carcinoma, and four had NSCLC, not otherwise specified. The completion rate of ≥4 cycles was 76% (95% confidence interval: 56.2%-88.8%), which met the primary endpoint. The ORR and DCR were 44% and 88%, respectively. The median PFS and OS were 5.8 months and 15.8 months, respectively. Three patients experienced grade ≥2 pneumonitis, and one patient met the acute exacerbation criteria. CONCLUSION: The 4-week modified regimen of carboplatin and nab-paclitaxel showed tolerable toxicity with favorable efficacy in NSCLC patients with ILD. This regimen may be an effective treatment option for patients in real clinical settings.

ALK-Positive Squamous Cell Carcinoma Dramatically Responded to Alectinib.

Anaplastic lymphoma kinase (ALK) rearrangement is usually observed in patients with adenocarcinoma. Herein, we report a case of squamous cell carcinoma (SCC) with ALK rearrangement treated with alectinib. The patient was a 73-year-old woman without a smoking history. She consulted us with nonproductive cough and loss of appetite. Computed tomography scan revealed a mass in the left lower lobe of the lung. According to the pathological examinations, we diagnosed the tumor as SCC. Because the patient had never smoked, we searched for driver mutations and found that the tumor harbored ALK rearrangement. We began treatment with alectinib, and the tumor remarkably reduced in volume. No severe adverse events were observed. Although there are only few reports of SCC with ALK rearrangement, this case implies that clinicians should consider searching for driver mutations in patients with SCC when there are atypical findings or characteristics.

Successful treatment of refractory aortitis in antineutrophil cytoplasmic antibody-associated vasculitis using tocilizumab.

A 47-year-old Japanese woman developed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) complicated by a rare combination of aortitis and hypertrophic pachymeningitis. Despite the therapy with prednisolone and cyclophosphamide, the aortitis was not ameliorated. However, after cyclophosphamide was replaced with intravenous tocilizumab, the aortitis was improved, and the prednisolone dose was successfully tapered to 4 mg/day without elevation in C-reactive protein and myeloperoxidase ANCA (MPO-ANCA) levels. Several studies have reported that tocilizumab is effective for aortitis associated with Takayasu's arteritis and giant cell arteritis. On the other hand, we succeeded to improve the aortitis in AAV with monthly administration of tocilizumab. Moreover, we successfully controlled disease activity and enabled the tapering of prednisolone to 4 mg/day without relapses of AAV symptoms and elevated MPO-ANCA levels. It indicates that tocilizumab may be therapeutically beneficial for not only aortitis but also AAV itself. In conclusion, tocilizumab was effective in treating glucocorticoid- and cyclophosphamide-resistant AAV-associated aortitis. This is the first report demonstrating the successful treatment of AAV-associated aortitis using tocilizumab.

Cytokeratin expression profiling is useful for distinguishing between primary squamous cell carcinoma of the lung and pulmonary metastases from tongue cancer.

It can be difficult to distinguish between primary and metastatic squamous cell carcinoma (SCC) in the lung. Surgical specimens were obtained from two groups of patients, 26 lung SCC patients without histories of any other cancer (the definite primary group) and 17 patients who had undergone surgical removal of SCC emerging in the lung after surgery for tongue SCC (the unknown group). From the former, 26 primary lung SCC were obtained. From the latter, 17 lung tumors and 15 primary tumors of the tongue were obtained. Eleven of the 17 lung tumors from the unknown group were metastatic lung SCC. All specimens were immunostained with cytokeratin (CK)5/6, CK7, CAM5.2, CK19 and p63 antibodies. The frequency of CAM5.2 and CK19 expression was significantly higher in the lung SCC of the definite primary group (21 of 26, 81% and 20 of 26, 78%, respectively) than in the metastatic lung SCC (1 of 11, 9% (P < 0.001) and 2 of 11, 18% (P = 0.003), respectively) or primary SCC of the tongue (5 of 15, 33% (P = 0.002) and 2 of 15, 13% (P < 0.001), respectively). CAM5.2 and CK19 are useful for distinguishing between primary SCC of the lung and metastases from tongue cancer.