Developing Artificial Intelligence Models for Extracting Oncologic Outcomes from Japanese Electronic Health Records.

INTRODUCTION: A framework that extracts oncological outcomes from large-scale databases using artificial intelligence (AI) is not well established. Thus, we aimed to develop AI models to extract outcomes in patients with lung cancer using unstructured text data from electronic health records of multiple hospitals. METHODS: We constructed AI models (Bidirectional Encoder Representations from Transformers [BERT], Naïve Bayes, and Longformer) for tumor evaluation using the University of Miyazaki Hospital (UMH) database. This data included both structured and unstructured data from progress notes, radiology reports, and discharge summaries. The BERT model was applied to the Life Data Initiative (LDI) data set of six hospitals. Study outcomes included the performance of AI models and time to progression of disease (TTP) for each line of treatment based on the treatment response extracted by AI models. RESULTS: For the UMH data set, the BERT model exhibited higher precision accuracy compared to the Naïve Bayes or the Longformer models, respectively (precision [0.42 vs. 0.47 or 0.22], recall [0.63 vs. 0.46 or 0.33] and F1 scores [0.50 vs. 0.46 or 0.27]). When this BERT model was applied to LDI data, prediction accuracy remained quite similar. The Kaplan-Meier plots of TTP (months) showed similar trends for the first (median 14.9 [95% confidence interval 11.5, 21.1] and 16.8 [12.6, 21.8]), the second (7.8 [6.7, 10.7] and 7.8 [6.7, 10.7]), and the later lines of treatment for the predicted data by the BERT model and the manually curated data. CONCLUSION: We developed AI models to extract treatment responses in patients with lung cancer using a large EHR database; however, the model requires further improvement.

The use of artificial intelligence (AI) to derive health outcomes from large electronic health records is not well established. Thus, we built three different AI models: Bidirectional Encoder Representations from Transformers (BERT), Naïve Bayes, and Longformer to serve this purpose. Initially, we developed these models based on data from the University of Miyazaki Hospital (UMH) and later improved them using the Life Data Initiative (LDI) data set of six hospitals. The performance of the BERT model was better than the other two, and it showed similar results when it was applied to the LDI data set. The Kaplan­Meier plots of time to progression of disease for the predicted data by the BERT model showed similar trends to those for the manually curated data. In summary, we developed an AI model to extract health outcomes using a large electronic health database in this study; however, the performance of the AI model could be improved using more training data.

Absolute Quantification of Pure Free Radical Reagents by Combination of the Effective Magnetic Moment Method and Quantitative Electron Paramagnetic Resonance Method.

An absolute quantitative analysis of free radicals by combining the effective magnetic moment method and the quantitative electron paramagnetic resonance [qEPR] method is proposed. This combined method utilizes the advantages of both the analytical methods and compensates for their disadvantages. In the effective magnetic moment method, the magnetic moment under a constant magnetic field is measured accurately using a superconducting quantum interference device. The qEPR method compares a "primary standard sample" and "secondary standard sample". The effective magnetic moment method was used to determine the purity of the primary standard sample. The qEPR method realizes a simple purity analysis of free-radical reagents with traceability to the International System of Units (SI). The purity of the free radicals by the qEPR method for pure 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl benzoate [4HTB], 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine [TEMPOL], and di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium [DPPH] reagents was obtained with a relative expanded uncertainty of 0.7% for 4HTB to 1.5% for the DPPH. These small uncertainties were almost equal to those of the purity of the primary standard samples and were achieved by adopting in-plane positioning of the measured sample perpendicular to the cylindrical axis of the sample space of the superconducting quantum interference device. Some purity values of the free radicals for these reagents differed from those stated by the manufacturers. This combined method enables short-time quality control of pure radical reagents, instead of quality control by separation analytical methods or titrations.

Combined detection of lymphocyte clonality and MALT1 translocations in bronchoalveolar lavage fluid for diagnosing pulmonary lymphomas.

Diagnosis of pulmonary lymphoma using small tissue samples is difficult and often requires surgical procedures; thus, a less invasive sampling method is desirable. We previously showed that pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma can be diagnosed by detecting MALT lymphoma translocation gene 1 (MALT1) translocations in bronchoalveolar lavage fluid (BALF) cells. Analysis of B-cell clonality based on immunoglobulin heavy chain (IGH) gene rearrangements was also reportedly useful for diagnosing pulmonary lymphoma. The aim of this prospective multicenter study was to evaluate the yet unknown diagnostic potential of combined detection of MALT1 translocations and clonality using BALF. We analyzed B- and T-cell clonality based on IGH and T-cell receptor (TCR) rearrangements together with MALT1 translocations using BALF of patients with clinically suspected pulmonary lymphomas. In total, 39 patients were evaluated and categorized into three groups: B-cell lymphoma, lymphoproliferative disorders, and other diseases. IGH rearrangement detection for B-cell lymphoma diagnosis exhibited sensitivity and specificity of 88.9% and 90.0%, respectively. TCR rearrangements were not observed in patients with B-cell lymphomas. The presence of IGH rearrangements together with the absence of TCR rearrangements indicated 96.0% specificity for the diagnosis of B-cell lymphoma. The sensitivity and specificity of MALT1 translocations for diagnosing MALT lymphoma were 28.6% and 100%, respectively. The combined detection of lymphocyte clonality and MALT1 translocations using BALF is suitable for screening and diagnosis of B-cell lymphomas. Analysis of specific genes such as MALT1 should improve the precision of B-cell lymphoma diagnosis.

Transition From Distinct Types of KRAS Mutation-Harboring Multifocal Lung Adenocarcinoma to Rhabdoid Tumor: A Longitudinal Follow-Up.

BACKGROUND Rhabdoid tumor (RT) of the lung is a rare and aggressive malignancy. The origin of and the mutation responsible for RT are entirely unknown. The distinction between RT associated with subtypes of lung cancer and SMARCA4-deficient thoracic sarcomas is also unknown. CASE REPORT Three pulmonary subsolid nodules in the right S6, left S6, and left S8 were identified in a 78-year-old Japanese woman. At 3 and 9 months later, a chest CT showed unchanged sizes, but at 15 months the development of a 37-mm mass in the right S6 was observed. The patient's systemic condition deteriorated rapidly, and she died 1 month later. An autopsy revealed that the mass consisted of 90% RT and 10% lung adenocarcinoma. There were another 2 adenocarcinoma lesions in the left lung. KRAS mutation analyses revealed the same KRAS mutation (G12D) in the adenocarcinoma and RT components in the identical mass and metastatic RT, indicating that all of these components had the same clonality. A different KRAS mutation in each of the 3 adenocarcinoma lesions was detected (right S6: G12D, left S6: A59G, left S8: G12C), indicating that the multiple adenocarcinoma lesions were truly multifocal lung adenocarcinoma. The adenocarcinoma and RT components retained SMARCA4 expression. CONCLUSIONS This is the first evidence of RT originating from multifocal lung adenocarcinoma. KRAS mutation is thought to be responsible for the RT's emergence via the epithelial-mesenchymal transition. Patients with multiple subsolid nodules should be followed closely; aggressive surgical intervention should be considered given concerns about the evolution of this aggressive malignancy.

Clinico-radiologic Characteristics of Pulmonary Visceral Larva Migrans Caused by Ascaris suum.

Objective Visceral larva migrans (VLM) caused by Ascaris suum is a major health problem in pig farming regions. The clinical characteristics of pulmonary VLM caused by A. suum, however, are unclear. We assessed the clinico-radiologic features of this disease. Methods Medical records, including the results of chest radiography and high-resolution computed tomography (HRCT), were retrospectively reviewed from January 2000 through June 2019, at the University of Miyazaki Hospital and Kyoritsuiin Hospital in Miyazaki Prefecture, Japan. Results Seven patients with VLM caused by A. suum were identified. All seven patients had a unique habit of consuming raw foods, such as organic vegetables, chicken, turkey, wild boar, and venison. All but one patient, who had eosinophilic pneumonia with a fever and severe fatigue, had only mild or no respiratory symptoms. All 7 patients had remarkable eosinophilia (median, 1,960/µL) and high serum IgE levels (median, 1,346 IU/mL). Chest HRCT revealed multiple nodules and multiple nodular ground-glass opacities in 57% and 29% of the patients, respectively. The pulmonary lesions were located predominantly in subpleural areas. All seven patients were treated with albendazole, which led to improvement within two to three months. Neither eggs nor parasites were detected in the feces or sputum of any patient. Conclusion Consumption of raw organic vegetables or raw meat is a possible route of A. suum infection. Infected patients exhibit mild respiratory symptoms, and multiple nodules with a halo in the subpleural area are a common finding on chest HRCT. Treatment with albendazole was effective in these cases.

A case of bilateral invasive mucinous adenocarcinoma of the lung with severe productive cough and dyspnea successfully treated with palliative lung lobectomy.

Invasive mucinous adenocarcinoma (IMA) of the lung is a chemo-refractory type of lung cancer with frequent intrapulmonary dissemination. Patients with IMA of the lung often suffer from a productive cough and rapid deterioration of performance status (PS). There is currently no standard therapeutic strategy against this unrelenting condition. Here we report a patient with bilateral IMA of the lung with severe productive cough and dyspnea successfully controlled by palliative lung lobectomy. A 67-year-old Japanese man presented with a 3-month history of productive cough. Chest computed tomography (CT) revealed a mass lesion in the left lower lobe and a small nodule and multiple thin-walled cystic lesions in the right lung. He was diagnosed with stage IIB IMA of the lung. Over the next two weeks, his productive cough and dyspnea drastically worsened and his PS declined from 0 to 4. Chest CT showed increases in size of both the nodule and cystic lesions in the right lung and the mass lesion in the left lower lobe. He was re-diagnosed as stage IVA. Given the extreme heterogeneity of the tumor distribution, we decided to perform palliative resection of the left lower lobe. After the surgery, he experienced complete relief of respiratory symptoms, and his PS improved dramatically, enabling chemotherapy. Thirty-one months after surgery, he maintains good PS. In conclusion, our report suggests that aggressive introduction of palliative lung lobectomy played a substantial role for in the excellent outcome of our patient with relatively well confined, advanced-stage IMA.

Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome.

Fibrotic scarring is an important prognostic factor of acute respiratory distress syndrome (ARDS). There are currently no antifibrotic drugs or other therapeutic agents for ARDS. Lysyl oxidase-like 2 (LOXL2), an amine oxidase, contributes to fibrotic scarring by facilitating collagen cross-linking. Recent clinical trials revealed that a monoclonal inhibitory antibody against LOXL2 failed to show benefit over placebo in patients with fibrotic disorders involving the lungs. These clinical results raise the possibility that targeting the extracellular enzymic activity of LOXL2 is not in itself sufficient to prevent fibrotic scarring. We investigated the role of LOXL2 in the pathogenesis of ARDS in vivo, in vitro, and in samples from patients with ARDS. After lung injury, LOXL2 was unevenly expressed in the nuclei of lung fibroblasts and myofibroblasts in the fibrotic phase. Nuclear LOXL2 expression was upregulated in lung fibroblasts after transforming growth factor-beta1 (TGF-ß1)-treatment. LOXL2 silencing abrogated the TGF-ß1-induced expression of a myofibrogenic-progenitor marker, the appearance of proto-myofibroblasts, and the evolution of differentiated myofibroblasts in lung fibroblasts. Nuclear upregulation of Snail was evident in myofibroblasts during the fibrotic phase after lung injury. We detected high levels of LOXL2 protein in the lungs of ARDS patients, specifically during the proliferative and fibrotic phases. Our results highlight nuclear LOXL2 in fibroblasts as a primary causative driver of cell-fate decision toward myofibroblasts and of the progression of fibrotic scarring. A nuclear-LOXL2-targeted agent could be a promising therapeutic strategy against fibrotic disorders including ARDS.

Role of FK506 Binding Protein on Tacrolimus Distribution in Red Blood Cells.

PURPOSE: Tacrolimus is distributed mainly in red blood cells (RBCs) after transfer into blood. This study aimed to evaluate the effect of FK506-binding proteins (FKBPs) on RBC distribution of tacrolimus in a physiological environment. METHODS: Human RBCs were isolated from fresh blood samples from healthy volunteers. The effect of FKBPs on each process of the RBC distribution of tacrolimus was evaluated in vitro. Effect of intracellular FKBPs was assessed by inhibition experiment with rapamycin, which competitively inhibits the binding of tacrolimus to FKBPs. Effect of extracellular FKBPs was examined by pre-exposure of RBCs to FKBP and preincubation of tacrolimus with FKBP. RESULTS: Pretreatment with rapamycin significantly reduced the rate of tacrolimus distribution in RBCs in a concentration-dependent manner. Pre-exposure of RBCs to FKBP12 followed by exposure to tacrolimus significantly decreased tacrolimus distribution in RBCs in a concentration-dependent manner. In addition, preincubation of tacrolimus with FKBP12 significantly reduced the rate of tacrolimus distribution in RBCs. CONCLUSIONS: FKBP played an important role in the distribution of tacrolimus in RBCs. The effect of intracellular and extracellular FKBPs on RBC distribution of tacrolimus in circulating blood was substantial. FKBP was shown as a potential biomarker for predicting the pharmacokinetics and pharmacodynamics of tacrolimus.

A case of impaired consciousness due to large cystic metastatic brain tumors from lung adenocarcinoma successfully controlled with Ommaya reservoir placement.

Large cystic brain metastases from lung cancer are rare but cause substantial central nervous system symptoms that often deprive patients of opportunities to receive anticancer therapy. There are no standard therapeutic strategies against this relentless condition. Here we report a patient with large cystic brain metastases from lung adenocarcinoma successfully controlled with Ommaya reservoir placement and subsequent gamma knife surgery (GKS). A 62-year-old Japanese man presented with left upper extremity paresis. Magnetic resonance imaging revealed large cystic masses in both cerebral hemispheres and multiple brain nodules. Computed tomography of the chest showed irregular nodular shadows in the lower lobe of the right lung with multiple swollen lymph nodes. His performance status (PS) and level of consciousness worsened rapidly. Thus, at that time, we could not perform bronchoscopy with the goal of establishing a pathological diagnosis. Intracystic placement of an Ommaya reservoir followed by GKS dramatically improved his PS and level of consciousness. We were subsequently able to perform bronchoscopy, which resulted in a diagnosis of lung adenocarcinoma with 100% positivity of programmed cell death-1 ligand-1 expression. The patient was started on a 3-week cycle of pembrolizumab. Substantial reduction in tumor size was observed after one course of pembrolizumab treatment. The patient had a partial remission. He has been still receiving pembrolizumab with long-term efficacy. In conclusion, our report suggests that aggressive Ommaya reservoir placement should be considered for large cystic metastatic brain tumors, even in patients with undiagnosed cancer, poor PS, and impaired consciousness.

Elevated levels of periostin and TGF-ß1 in the bronchoalveolar lavage fluid of patients with idiopathic eosinophilic pneumonia.

BACKGROUND: Periostin is induced in bronchial epithelial cells and fibroblasts by various stimuli including interleukin (IL)13 and transforming growth factor (TGF)-ß1, and is involved in allergic diseases such as asthma and atopic dermatitis, playing an important role in tissue remodeling and fibrosis. The role of periostin in the pathogenesis of eosinophilic lung diseases, however, is unclear. OBJECTIVE: To examine the contribution of periostin to eosinophilic inflammation of the lung in humans, we evaluated periostin, IL-13, and TGF-ß1 levels in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP). METHODS: Periostin, IL-13, and TGF-ß1 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute EP, chronic EP, idiopathic pulmonary fibrosis (IPF), and sarcoidosis. Further, we analyzed the relationship between periostin, IL-13, and TGFß-1, levels and the number of inflammatory cells in the BALF. RESULTS: The absolute number of eosinophils, and the periostin, IL-13, and TGF-ß1 levels in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. Concentrations of periostin significantly correlated with the concentrations of TGF-ß1, but not those of IL-13, in the BALF of patients with EP. Periostin levels also significantly correlated with the absolute number of eosinophils in the BALF of patients with IPF, but not EP. CONCLUSIONS: Our findings suggest that TGF-ß1 might increase the production of periostin in the lungs of patients with EP. Periostin might contribute the pathogenesis of not only EP, but also IPF.

Allergic bronchopulmonary aspergillosis complicated by eosinophilic chronic rhinosinusitis successfully treated with mepolizumab.

A 67-year-old woman was admitted to our hospital because of frequent asthma attacks and refractory chronic rhinosinusitis. She was diagnosed with allergic bronchopulmonary aspergillosis (ABPA) concomitant with eosinophilic chronic rhinosinusitis (ECRS) on the basis of peripheral blood eosinophilia, precipitating antibodies against Aspergillus fumigatus, elevated total serum IgE, pulmonary infiltration, central bronchiectasis, mucoid impaction, and bilateral rhinosinusitis with nasal polyps, which showed remarkable eosinophil accumulation histologically, especially in the ethmoid sinuses. Treatment with mepolizumab, 100 mg every 4 weeks, was initiated for both the ABPA and ECRS. Consistent with the decrease in the peripheral eosinophil count, the asthma and rhinosinusitis symptoms were drastically ameliorated. Not only her airway symptoms but also her exercise tolerance and pulmonary function test results remarkably improved. Mepolizumab therapy enhanced the quality of life for this patient with intractable ABPA and ECRS.

Successful treatment with mepolizumab in a case of allergic bronchopulmonary aspergillosis complicated with nontuberculous mycobacterial infection.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction that is associated with an allergic immunological response to Aspergillus species via Th2-related inflammation. The long-term use of a systemic corticosteroid is often needed for the treatment of ABPA. However, systemic corticosteroid treatment imposes a risk of the onset of a nontuberculous mycobacterial infection. Here we report the case of a patient with ABPA who required the long-term use of an oral corticosteroid because her repeated asthmatic attacks were successfully treated with mepolizumab, an anti-interleukin-5 monoclonal antibody. The patient, a 60-year-old Japanese female, had been treated with an oral corticoid and itraconazole. Despite the success of the initial treatment for ABPA, it was difficult to discontinue the use of the oral corticosteroid. In addition, Mycobacterium avium was detected from her bronchial lavage. We initiated mepolizumab treatment to taper the amount of corticosteroid and control the asthma condition. The patient's number of blood eosinophils, serum IgE level, fractional exhaled nitric oxide level, dosage of oral prednisolone, and need for inhaled budesonide/formoterol all improved, without an exacerbation of her asthma attacks. Although further research regarding mepolizumab treatment is needed, we believe that mepolizumab could be considered one of the agents for treating refractory ABPA.

Drug-drug interactions among drugs prescribed for nontuberculous mycobacterial infection and epilepsy: A case report.

WHAT IS KNOWN AND OBJECTIVE: Multi-drug combinations often make chemotherapy difficult owing to drug-drug interactions (DDIs). We report a rare and difficult-to-treat case due to DDIs between drugs for Mycobacterium avium complex (MAC) infection and antiepileptic drugs. CASE DESCRIPTION: A 70-year-old Japanese woman was diagnosed as having pulmonary MAC disease. She had a history of symptomatic epilepsy, which was successfully treated with phenytoin and phenobarbital. Serum phenytoin concentrations increased upon the initiation of MAC infection treatment. WHAT IS NEW AND CONCLUSION: We evaluated DDIs and adjusted the dosage of drugs by monitoring the serum drug level.

Improvement of Reproducibility of Magnetic Moment Detected by a SQUID Magnetometer Through Radial Offset Measurement on a YIG Sphere.

We report here on the reproducibility of measurements on a second-order gradiometer superconducting quantum interference device magnetometer of two different yttrium iron garnet spheres, both having a diameter of 1 mm: 1) the National Institute of Standards and Technology magnetic moment standard reference material (SRM) and 2) a commercial sample. It has been suggested that rotating the sample rod around its axis can move the sample center toward the center of the second-order gradiometer coil. The observed value of the magnetic moment will be theoretically a minimum when the radial offset is 0, and this value will increase in a "quadratic" manner with the radial offset. When the magnetic moment of the SRM was repeatedly measured as a function of rotation angle φ from 0° to 360°, we observed a sinusoidal variation in the measured values. The radial offset dependence of the observed magnetic moment was experimentally confirmed by the measurements of the commercial sphere placed in a hole in several cylindrical containers, wherein the distance between the center of the hole and the center of the container was r. The r-dependence of the minimum from each φ-dependent measurement series is qualitatively consistent with the theoretical curve. When the φ-dependent measurements for the SRM in a capsule were repeated 12× over 21 months, the relative standard deviation of the minimums improved up to 0.1%. Knowledge of these facts will be necessary for the accurate measurement of the magnetic moment of other sample forms (e.g., powders).

Factors associated with pneumococcal vaccination in elderly people: a cross-sectional study among elderly club members in Miyakonojo City, Japan.

BACKGROUND: Pneumonia is the third leading cause of death in Japan. All elderly people aged 65 years or older are recommended to receive a pneumococcal vaccine. A subsidy for part of the cost of routine pneumococcal vaccination in this age group was introduced in 2014. Factors related to vaccination behavior among elderly adults have not been well reported. The purpose of this study was to investigate factors associated with vaccine uptake among elderly people in Japan. METHODS: We conducted a cross-sectional study, using a self-administered questionnaire among elderly club members aged 65 years or older in one city of Japan in April 2017. The participants were selected from among all elderly club members in the study area. Variables extracted from the questionnaire were analyzed using logistic regression analysis. RESULTS: A total of 208 elderly club members participated in the study. The mean age (± SD) was 77.2 (± 5.3) years. The pneumococcal vaccination rate was 53.2%. Logistic regression analysis revealed three variables that had a significant association with pneumococcal vaccination: a recommendation for vaccination from medical personnel (aOR 8.42, 95% CI 3.59-19.72, p <  0.001), receiving influenza vaccination in any of the previous three seasons (aOR 3.94, 95% CI 1.70-9.13, p = 0.001), and perception of the severity of pneumonia (aOR 1.23, 95% CI 1.03-1.48, p = 0.026). CONCLUSIONS: Although the pneumococcal vaccination rate in this study was increased compared with previous reports, almost half of study participants had not yet received vaccination. Our findings could be helpful for developing vaccination strategies to increase the vaccine coverage in the elderly population.

Successful treatment of steroid-refractory double-positive ANCA and anti-GBM disease with a combination of plasma exchange and immunosuppression: A case report and literature review.

The concurrence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and anti-glomerular basement membrane (GBM) disease, known as double-positive disease, is rare, but it occurs at a much higher frequency than expected by chance. Double-positive disease has an aggressive clinical course, with no optimal treatment strategy. Here we describe a patient with steroid-refractory double-positive disease who was treated successfully with the addition of plasma exchange (PE) and cyclophosphamide (CPA). A 78-year-old Japanese woman who was diagnosed with diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis received two cycles of pulse steroid therapy. However, her respiratory and renal condition deteriorated. She was found to be positive for both myeloperoxidase-ANCA and anti-GBM antibodies. The combination of PE and CPA improved her systemic condition. This is the first case report of a patient with steroid-refractory double-positive disease who was successfully treated with the addition of PE and CPA. The marked contrast in therapeutic response to corticosteroids alone and the addition of PE and CPA in this case strongly implies that earlier induction of combination therapy aimed at rapid removal of pathogenic autoantibodies and prevention of ongoing antibody production might improve the outcome of this life-threatening disease.

Measuring Number of Free Radicals and Evaluating the Purity of Di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium [DPPH] Reagents by Effective Magnetic Moment Method.

Di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium [DPPH] is widely used as a standard for measuring the number of free radicals. Here, we evaluated the number of free radicals of "DPPH" reagents from three manufacturers by effective magnetic moment method. Interestingly, the reagents from different manufacturers had varying temperature dependencies for both magnetic moment and g-value at low temperatures. As a result, the maximum relative difference among the three reagents on the number of free radicals per unit mass was 20%. Carbon hydrogen nitrogen (CHN) analyses, high-resolution EPR measurements, FT-IR measurement, and NMR measurement confirmed that a major component of only one among the three reagents was "pure" DPPH. The evaluated purity based on free radical content was 0.998 kg kg-1 with expanded uncertainty of 0.036 kg kg-1. The other two reagents were found to be contaminated by several % of benzene in the DPPH crystal structure.

Malignant mesothelioma with squamous differentiation.

AIMS: We report the autopsy findings of a 58-year-old man with malignant mesothelioma in the left pleural cavity. METHODS AND RESULTS: The patient had a history of asbestos exposure, and the chest computed tomography scan on initial admission demonstrated an extrapleural sign, suggesting a nodular lesion in the chest wall. However, no nodular lesions were detectable in either of his lungs. In spite of chemotherapy, he died 4 months after the initial admission. An autopsy revealed markedly thickened pleura in a large section of the left pleural cavity without visible intrapulmonary primary tumour lesions. Histological examination of a biopsy specimen obtained prior to chemotherapy and that of an autopsy specimen showed that the pleural tumour was composed of a mixture of mesothelioma and tumour cells with squamous differentiation mimicking squamous cell carcinoma. CONCLUSIONS: To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in the English-language literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma.

Desquamative interstitial pneumonia complicated by diffuse alveolar haemorrhage.

We report a rare case of desquamative interstitial pneumonia (DIP) with diffuse alveolar haemorrhage (DAH). A 56-year-old man diagnosed with DIP by surgical lung biopsy 2 years ago was admitted to our hospital because of severe acute respiratory failure. The DIP had progressed despite smoking cessation. On admission, the patient appeared extremely ill, and physical examination revealed respiratory distress. The patient required mechanical ventilation. High-resolution computed tomography showed diffuse ground glass opacity in both lungs. The bronchoalveolar lavage fluid was bloody, and numerous haemosiderin-laden alveolar macrophages were detected. Pulse steroid therapy followed by oral prednisolone immediately relieved the respiratory failure and improved the long-term control of the DIP. Paired sera tests confirmed the diagnosis of influenza A/H3N2 virus infection, which was the cause of the DAH. Chronically progressive DIP with acute respiratory failure due to DAH was successfully treated by steroid therapy.