Implementation of Non-Linear Non-Parametric Persistent Scatterer Interferometry and Its Robustness for Displacement Monitoring.

To derive surface displacement, interferometric stacking with synthetic aperture radar (SAR) data is commonly used, and this technique is now in the implementation phase in the real world. Persistent scatterer interferometry (PSI) is one of the most universal approaches among in- terferometric stacking techniques, and non-linear non-parametric PSI (NN-PSI) was proposed to overcome the drawbacks of PSI approaches. The estimation of the non-linear displacements was successfully conducted using NN-PSI. However, the estimation of NN-PSI is not always stable with certain displacements because wider range of the velocity spectrum is used in NN-PSI than the conventional approaches; therefore, a calculation procedure and parameter optimization are needed to consider. In this paper, optimized parameters and procedures of NN-PSI are proposed, and real data processing with Sentinel-1 in the Kanto region in Japan was conducted. We confirmed that the displacement estimation was comparable to the measurement of the permanent global positioning system (GPS) stations, and the root mean square error between the GPS measurement and NN-PSI estimation was less than 3 mm in two years. The displacement over 2π ambiguity, which the conventional PSI approach wrongly reconstructed, was also quantitatively validated and successfully estimated by NN-PSI. As a result of the real data processing, periodical displacements were also reconstructed through NN-PSI. We concluded that the NN-PSI approach with the proposed parameters and method enabled the estimation of several types of surface displacements that conventional PSI approaches could not reconstruct.

Evaluation of the Trend of Deformation around the Kanto Region Estimated Using the Time Series of PALSAR-2 Data.

In the Kanto region of Japan, a large quantity of natural gas is dissolved in brine. The large-scale production of gas and iodine in the region has caused large-scale land subsidence in the past. Therefore, continuous and accurate monitoring for subsidence using satellite remote sensing is essential to prevent extreme subsidence and ensure the safety of residences. This study focused on the small baseline subset (SBAS) method to assess ground deformation trends around the Kanto region. Data for the SBAS method was acquired by the Advanced Land Observing Satellite (ALOS)-2 Phased Array type L-band Synthetic Aperture Radar (PALSAR)-2 from 2015 to 2019. A comparison of our results with reference levelling data shows that the SBAS method underestimates displacement. We corrected our results using linear regression and determined the maximum displacement around the Kujyukuri area to be approximately 20 mm/year; the mean displacement rate for 2015-2019 was -7.9 ± 2.9 mm/year. These values exceed those obtained using past PALSAR observations owing to the horizontal displacement after the Great East Japan Earthquake of 2011. Moreover, fewer points were acquired, and the root mean-squared error of each time-series displacement value was larger in our results. Further analysis is needed to address these bias errors.

Mycobacterium abscessus ssp. abscessus infection progressing to empyema from vertebral osteomyelitis in an immunocompetent patient without pulmonary disease: a case report.

BACKGROUND: Pleural involvement by non-tuberculous mycobacteria (NTM) in patients without distinct pulmonary disease is extremely rare. Vertebral osteomyelitis (VO) with or without pulmonary disease is also a rare clinical presentation of NTM infection, and pleural spread of NTM from VO has not been reported. CASE PRESENTATION: A 63-year-old woman was admitted to our hospital with back pain persisting for 4 months and a 2-day history of fever and right chest pain. The patient was initially treated as right-sided empyema due to general bacteria. However, after removal of the chest tube, a previously overlooked paravertebral lesion was observed on CT. MRI confirmed VO at T7/8. Mycobacterium abscessus ssp. abscessus was detected in both the thoracic cavity and the paravertebral lesion. Both VO and the paravertebral abscess were improved by antimycobacterial treatment. CONCLUSION: VO of the thoracic spine due to non-tuberculous mycobacterial infection should be considered as a cause of pleuritis or empyema without pulmonary disease, especially in patients with back pain.

Disseminated tuberculosis after pregnancy progressed to paradoxical response to the treatment: report of two cases.

BACKGROUND: Early postpartum women are more likely to develop tuberculosis than nonpregnant women mainly due to immune reconstitution after delivery. Paradoxical response (PR) during antituberculosis treatment also arises via recovery from immunosuppression. However, no study focused on PR during antituberculosis treatment in a postpartum patient has been reported. CASE PRESENTATION: We present two sequential cases (Patient 1: 26-year-old; Patient 2: 29-year-old) of postpartum tuberculosis with pulmonary and extrapulmonary lesions (Patient 1: peritonitis; Patient 2: psoas abscess secondary to spondylitis). Both cases progressed to PR (worsening of pre-existing lung infiltrations (Patients 1, 2) and new contralateral effusion (Patient 2)) in a relatively short time after initiation of treatment (Patient 1: 1 week; Patient 2: 3 weeks), suggesting that immune modulations during pregnancy and delivery may contribute to the pathogenesis of both disseminated tuberculosis and its PR. The pulmonary lesions and effusion of both cases gradually improved without change of chemotherapy regimen. CONCLUSION: Physicians should recognize PR in tuberculosis patients with postpartum and then evaluate treatment efficacy.

Miliary pulmonary nodules due to Mycobacterium xenopi in a steroid-induced immunocompromised patient successfully treated with chemotherapy: a case report.

BACKGROUND: Mycobacterium xenopi-infected patients have a high prevalence of pulmonary cavities and nodules. However, the clinical course for patients with miliary nodules due to M. xenopi has not yet been reported. CASE PRESENTATION: We encountered a case of miliary nodules with gradually worsening coughing and sputum production in a 44-year-old male who had renal dysfunction due to glomerulosclerosis with a decade-long history of steroid therapy. Although we started anti-tuberculosis treatment on clinical suspicion of miliary tuberculosis, cultures of sputum and bronchial lavage were both positive for M. xenopi. The patient was successfully treated with rifampin, ethambutol and clarithromycin, without fibrosis. It was unclear whether the miliary pattern was induced by hematogenous or endobronchial spread of the M. xenopi infection. CONCLUSION: Even when clinical and radiological disease manifestations are similar to those of miliary tuberculosis, M. xenopi infection should be considered in the differential diagnosis of miliary nodules.

[A Case of Acute Respiratory Distress Syndrome (ARDS) Accompanied with Influenza (H1N1) 2009 Successfully Treated with Polymyxin B-immobilized Fiber Column-direct Hemoperfusion (PMX-DHP)].

A 51-year-old man was admitted to our hospital because of fever and diarrhea. Chest X-ray revealed consolidation in the left lower lung field. Ceftriaxone and minocycline were given empirically, under the suspicion of bacterial or atypical pneumonia. In spite of treatment with antibiotics, the disease rapidly progressed to systemic inflammatory response syndrome. The diagnosis of acute respiratory distress syndrome (ARDS) accompanied with influenza (H1N1) 2009 was made because of positive findings of real-time polymerase chain reaction. While multidisciplinary treatment was performed, his condition was further deteriorated suggesting the excessive pro-inflammatory mediators. To remove them, we conducted polymyxin-B immobilized column-direct hemoperfusion (PMX-DHP), and his general condition recovered successfully. PMX-DHP may be a useful treatment choice for ARDS accompanied with influenza.

BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6.

BACKGROUND: Pneumonitis is a rare complication of bacillus Calmette-Guerin (BCG) immunotherapy seen in patients with urothelial cancer following the repeated administration of BCG. However, no case of BCG-induced pleurisy has been reported. CASE PRESENTATION: We here report the first case of pneumonitis with lymphocytic pleurisy following bacillus Calmette-Guerin (BCG) immunotherapy. Although marked T helper cell alveolitis was found by bronchoalveolar lavage and transbronchial biopsies, no acid-fast bacillus could be identified in recovered BALF or pleural effusion. The lymphocyte stimulation test of BCG was strongly positive. However, levels of serum and bronchoalveolar lavage fluid KL-6, a useful marker for hypersensitivity pneumonitis (HP), were within normal ranges. CONCLUSION: We speculate that the pathogenesis of our case may be a hypersensitive reaction to the proteic component of BCG entering the lung and pleural space, which is different from the etiology of the common type of HP.

Asymptomatic primary tuberculous pleurisy with intense 18-fluorodeoxyglucose uptake mimicking malignant mesothelioma.

BACKGROUND: The pathogenesis of primary tuberculous pleurisy is a delayed-type hypersensitivity immunogenic reaction to a few mycobacterial antigens entering the pleural space rather than direct tissue destruction by mycobacterial proliferation. Although it has been shown that pulmonary tuberculosis induces 18-fluorodeoxyglucose (FDG) uptake in active lesions, little is known about the application of FDG positron emission/computed tomography (FDG PET/CT) to the management of primary tuberculous pleurisy. CASE PRESENTATION: We report a case of asymptomatic primary tuberculous pleurisy presenting with diffuse nodular pleural thickening without distinct pleural effusion and parenchymal lung lesions mimicking malignant mesothelioma. An initial FDG PET/CT scan demonstrated multiple lesions of intense FDG uptake in the right pleura and thoracoscopic biopsy of pleural tissue revealed caseous granulomatous inflammation. The patient received antituberculous therapy for 6 months, with clearly decreased positive signals on a repeated FDG PET/CT scan. CONCLUSION: FDG PET/CT imaging may be useful for evaluating disease activity in tuberculous pleurisy patients with an unknown time of onset.

[Exacerbation of cranial nerurological symptoms by platelet transfusion before the diagnosis of thrombotic thrombocytopenic purpura].

A 47-year-old woman was transported to our hospital because of vomiting and syncope after breakfast. Physical examination revealed icterus and anemia of bulbar conjunctivas, and abnormal neurological findings were detected. Laboratory data indicated marked anemia and thrombocytopenia (Hb 5.2 g/dl, Plt. 0.6×10(4)/µl), but no leukocyte abnormalities were found. Transaminase was slightly elevated, and serum indirect bilirubin in was also elevated. Based on these data, we initially suspected Evan's syndrome, which involves idiopathic thrombocytopenic purpura with autoimmune hemolytic anemia. So we transfused red blood cells, performed platelet transfusion, and administered steroids, but there was no response to these therapies. On the 4th day of admission, she developed a stroke followed by coma. After the stroke, we diagnosed the case as thrombotic thrombocytopenic purpura (TTP) because laboratory findings showed diminished activity of ADAMTS 13 (a disintegrin-like metalloproteinase with thrombospondin type 1 motifs 13) and ADAMTS 13 antigen. It is important to suspect TTP when hemolytic anemia with thrombocytopenia is observed, and to check the activity and antigen of ADAMTS13 immediately for the diagnosis. Platelet transfusion should be done cautiously in these cases.

A randomized phase II study of docetaxel or pemetrexed with or without the continuation of gefitinib after disease progression in elderly patients with non-small cell lung cancer harboring EGFR mutations (JMTO LC12-01).

BACKGROUND: Gefitinib (G) is a recommended molecular-targeted agent for elderly patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Docetaxel (Doc) and pemetrexed (Pem) have similar efficacies, and either is often used as the sole agent during treatment. The efficacy of continuing G after progressive disease (PD) develops has been reported. It remains unclear whether the continuation of G in combination with a single cytotoxic agent beyond PD is beneficial for elderly patients. Here, we conducted a randomized phase II study to assess the efficacy and safety of cytotoxic chemotherapy with G for elderly patients with progressive EGFR-mutant NSCLC. METHODS: Elderly patients with EGFR-mutant NSCLC with PD previously treated with G were enrolled. Patients received Pem 500 mg/m or Doc 60 mg/m every 21 days and were randomly assigned to receive chemotherapy with 250 mg G (G+ Doc/Pem arm) or without G (Doc/Pem arm) until further disease progression or unacceptable toxicity. RESULTS: This trial was terminated early owing to slow accrual. A group of 22 patients underwent analysis. The primary endpoint, progression-free survival (PFS), was significantly longer in the G + Doc/Pem arm (median: 1.6 months vs. 5.6 months, hazard ratio = 0.40, 95% CI: 0.16-0.99, p = 0.0391). Adverse events ≥ grade 3 were more frequent in the G + Doc/Pem arm (45.5% vs. 90.9%, p = 0.032). CONCLUSIONS: Patients on G and Pem or Doc beyond PD showed a longer PFS than those on single-agent chemotherapy; however, it was associated with increased toxicity.

Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established. CASE: A 65-year-old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD-L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3-positive T cells and CD138-positive plasma cells. Second-line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing. CONCLUSION: Pembrolizumab may be used as a treatment option for pulmonary LCNEC.

[A case of pulmonary nontuberculous mycobacteriosis induced by tocilizumab treatment for rheumatoid arthritis].

A 65-year-old woman whose rheumatoid arthritis was treated with tocilizumab (TCZ) was found in chest radiography to have a new consolidation in the right lower lung field. Positive Mycobacterium intracellulare and Mycobacterium avium cultures in sputum and bronchial secretions yielded a diagnosis of pulmonary nontuberculous mycobacteriosis. The most common adverse TCZ effect is infection. This case highlights the fact that those treated with TCZ should be considered at elevated risk for developing nontuberculous mycobacteriosis.

[Two cases of drug-induced intrathoracic lesions caused by mesalazine in patients with ulcerative colitis].

We encountered 2 cases of drug-induced intrathoracic lesions caused by allergic reactions to mesalazine in patients with ulcerative colitis. Case 1: A 26-year-old man had a fever, cough and exertional dyspnea after 1 month of mesalazine treatment. He was hospitalized because of bilateral pulmonary infiltrates on a chest X-ray film. Case 2: A 27-year-old woman complained of fever and left back pain that exacerbated after 2 weeks of mesalazine treatment. She was hospitalized because of bilateral pulmonary effusions on chest CT. Both patients showed a positive reaction to a drug lymphocyte stimulation tests (DLST) for mesalazine. The first case was given a diagnosis of eosinophilic pneumonia by bronchoscopic examination, and responded to steroid therapy after discontinuation of mesalazine. The second case was given a diagnosis of pleuritis and improved on cessation of Mesalazine treatment.

Pulmonary tuberculosis misdiagnosed as extensively drug-resistant tuberculosis due to selection of a nontuberculous mycobacterial colony from a preculture dish used for a drug-susceptibility test.

Drug-susceptibility test (DST) is important for tuberculosis care; however, there are several pitfalls with the procedure. A 70-year-old woman was diagnosed with extensively drug-resistant tuberculosis based on the result of a DST using microdilution method. Because she had no history of medication for tuberculosis and the sputum acid-fast bacillus smear test turned negative during standard treatment, identification of the strain used for DST was performed. Consequently, the strain was found to be M. intracellulare. It was assumed that a colony of M. intracellulare that had existed in the preculture solid medium was selected and used for the DST.

Mycobacterium Shinjukuense Pulmonary Disease Progressed to Pleuritis after Iatrogenic Pneumothorax: A Case Report.

Mycobacterium shinjukuense is a newly identified nontuberculous mycobacteria (NTM) and its gene sequence of 16S rRNA shows high homology to that of Mycobacterium tuberculosis. We present a case of M. shinjukuense pulmonary disease progressed to pleuritis after iatrogenic pneumothorax. The patient was initially diagnosed as tuberculosis based on a positive result for the 16S rRNA of an M. tuberculosis identification kit using scrapings from the cavitary nodule. We need to bear in mind that pneumothorax following bronchoscopy may induce NTM pleuritis and M. shinjukuense infection should be considered in the differential diagnosis of mycobacterial pulmonary disease with effusion.

Autopsy case of rapid progressive atypical carcinoid of the lung discovered with multiple nodular shadows.

We report an autopsy case of rapid progressive atypical carcinoid of the lung discovered as multiple nodular shadows. The patient was an 82-year-old man with non-productive cough. Both chest radiography and computed tomography revealed multiple nodules in both the lung and pleural effusion. Multiple metastases to bone and liver were also noted. Samples from the wall-side pleural lesion were obtained by video-assisted thoracoscopic surgery under local anesthesia, and histological examination led to a diagnosis of atypical carcinoid. Treatment was ineffective and the patient died on day 39 after admission. The primary site was identified as the lung after autopsy. We believe that early detection is crucial in the treatment of atypical carcinoid due to poor prognosis.

Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice.

RATIONALE: Imatinib is an inhibitor of platelet-derived growth factor receptors. We have reported that treatment with imatinib inhibited bleomycin-induced pulmonary fibrosis in mice. However, late treatment with imatinib had no effect. OBJECTIVES: To clarify why imatinib had no antifibrotic effect when its administration was delayed, we focused on alpha(1)-acid glycoprotein (AGP), because it was reported to bind imatinib and mediate drug resistance. METHODS: The concentration of AGP in serum of mice and patients with idiopathic pulmonary fibrosis was measured by radial immunodiffusion testing. The effects of AGP in vitro were evaluated by assaying the growth of lung fibroblasts. We examined the combined effects of erythromycin (EM) or clarithromycin (CAM) on bleomycin-induced pulmonary fibrosis in mice. MEASUREMENTS AND MAIN RESULTS: Addition of AGP abrogated imatinib-mediated inhibition of the growth of fibroblasts. However, treatment with EM or CAM restored the growth-inhibitory effects of imatinib. The elevated level of AGP was detected in serum and lung homogenates in bleomycin-exposed mice and reached a plateau on Day 14. Imatinib alone did not ameliorate pulmonary fibrosis when treatment was started on Day 15, whereas coadministration of imatinib and EM or CAM significantly reduced the fibrogenesis via inhibition of the growth of fibroblasts in vivo. Serum levels of AGP were higher in patients with idiopathic pulmonary fibrosis than in healthy subjects. CONCLUSIONS: AGP is an important regulatory factor modulating the ability of imatinib to prevent pulmonary fibrosis in mice, and combined therapy with imatinib and EM or CAM might be useful for treatment of pulmonary fibrosis.