Pseudo-Meigs' Syndrome With Eosinophilic Pleural Effusion.

We present a rare case of a 45-year-old woman with pseudo-Meigs' syndrome and eosinophilic pleural effusion (EPE). She experienced cough, sputum, and dyspnea with a large right pleural effusion. Laboratory tests showed eosinophilia in the blood and pleural fluid. An ovarian tumor and ascites were also detected. After left salpingo-oophorectomy, the tumor was diagnosed as a mature cystic teratoma of the left ovary. The right-sided pleural effusion gradually resolved. Pseudo-Meigs' syndrome is characterized by benign ovarian tumor, ascites, and pleural effusion. Typically, it is associated with exudate pleural effusion characterized by a predominance of mononuclear cells. The occurrence of eosinophilic pleural effusion in our patient may be exceptionally rare.

Video gamers demonstrate superior bronchoscopy skills among beginners.

While previous research has explored the connection between video gaming and medical procedures, studies on the connection between video gaming and bronchoscopy techniques are lacking. This study aimed to investigate how video gaming experience influences bronchoscopy skills, particularly among beginners. This study was conducted at Fukujuji Hospital from January 2021 to October 2023. Twenty-three participants were assigned to the inexperienced group, and eighteen participants were assigned to the experienced group. The observational time during bronchoscopy, measured using a simulator, and the playing time of SPLATOON 2 (NINTENDO Co. Ltd., Japan) were analyzed. Video gaming skills were assessed based on game completion time, with shorter times indicating faster task completion. Participants were also divided into gamer and nongamer subgroups for further comparisons. A moderate linear relationship existed between bronchoscopic observation time and game completion time in the inexperienced group (r = 0.453, p = 0.030). However, no correlation was found in the experienced group (r = 0.268, p = 0.283). Among the inexperienced group, the gamer subgroup (n = 12) exhibited significantly shorter bronchoscopic observation times than did the nongamer subgroup (n = 11) (median [range]: 200 [129-229] s) vs. 281 [184-342] s, p = 0.005). This study demonstrated a relationship between bronchoscopy technique and video gaming skills among individuals with little bronchoscopy experience.

Diagnostic flowchart for tuberculous pleurisy, pleural infection, and malignant pleural effusion.

BACKGROUND: Several markers for the diagnosis of pleural effusion have been reported; however, a comprehensive evaluation using those markers has not been performed. Therefore, this study aimed to develop a diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases by using these markers. METHODS: We retrospectively collected data from 174 patients with tuberculous pleurisy, 215 patients with pleural infection other than tuberculous pleurisy, 360 patients with malignant pleural effusion, and 209 patients with other diseases at Fukujuji Hospital from January 2012 to October 2022. The diagnostic flowchart for four diseases was developed by using several previously reported markers. RESULTS: The flowchart was developed by including seven markers: pleural ADA ≥40 IU/L, pleural fluid LDH <825 IU/L, pleural fluid ADA/TP < 14, neutrophil predominance or cell degeneration, peripheral blood WBC ≥9200/µL or serum CRP ≥12 mg/dL, pleural amylase ≥75 U/L, and the presence of pneumothorax according to the algorithm of a decision tree. The accuracy ratio of the flowchart was 71.7 % for the diagnosis of the four diseases, with 79.3 % sensitivity and 75.4 % positive predictive value (PPV) for tuberculosis pleurisy, 75.8 % sensitivity and 83.2 % PPV for pleural infection, 88.6 % sensitivity and 68.8 % PPV for malignant pleural effusion, and 33.0 % sensitivity and 60.0 % PPV for other diseases in the flowchart. The misdiagnosis ratios were 4.6 % for tuberculosis pleurisy, 6.8 % for pleural infection, and 8.3 % for malignant pleural effusion. CONCLUSION: This study developed a useful diagnostic flowchart for tuberculous pleurisy, pleural infection, malignant pleural effusion, and other diseases.

Serum MMP3 and IL1-RA levels may be useful biomarkers for detecting asthma and chronic obstructive pulmonary disease overlap in patients with asthma.

Background: Asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO) is characterized by concurrent features of asthma and COPD. Since disease pathogenesis, severities, and treatments differ between asthma and ACO, it is important to differentiate them. Objective: To clarify and compare the characteristics of ACO and asthma and identify the serum biomarkers for differentiating them, especially in older patients. Methods: This study used the data of 639 participants from the nationwide cohort study, the NHOM-Asthma study, an asthma registry in Japan, with complete information on smoking history, respiratory function, and serum biomarkers. ACO was defined as the self-reported comorbidity of COPD or emphysema, or with obstructive pulmonary function and smoking history (pack-years≥10). The clinical characteristics of patients with ACO and asthma without COPD were compared. The serum biomarkers for differentiation were examined using receiver operating characteristic curves and multivariable analysis. The associations between the biomarkers and age were also analyzed. Results: Of the 639 asthma patients, 125 (19.6%) were diagnosed with ACO; these patients were older and male-dominant and had a higher prevalence of comorbidities such as hypertension, diabetes, and stroke. Among the serum biomarkers that were significantly different between ACO and asthma without COPD, the YKL-40/CHI3L1, MMP3, and IL-1RA levels showed a high area under the curve for discriminating ACO. Only the MMP3 and IL-1RA levels were significantly higher among ACO patients, regardless of age and sex; the YKL-40/CHI3L1 levels were not different due to the effect of age. Conclusion: MMP3 and IL-1RA may be useful serum biomarkers for distinguishing ACO from asthma.

Analysis of the utility of transbronchial lung biopsy culture under endobronchial ultrasonography with a guide-sheath.

Transbronchial lung biopsy (TBLB) culture is not common in clinical practice, and TBLB culture for patients with mycobacterial disease provide limited value because the diagnostic accuracy of TBLB culture is very low. Recently, bronchoscopic devices have been further developed, such as endobronchial ultrasonography with a guide-sheath (EBUS-GS). Therefore, this study investigated the utility of TBLB culture obtained by using EBUS-GS compared to washing cultures. A total of 31 patients who underwent TBLB culture by using EBUS-GS (GS-TBLB) were collected retrospectively at Fukujuji Hospital from January 2018 to December 2022. The diagnostic accuracies of GS-TBLB culture and bronchial and device washing cultures (namely, washing culture) were compared. The patients comprised 13 individuals with nontuberculous mycobacteriosis, 7 with pulmonary aspergillosis, 6 with lung abscess, and 5 with pulmonary tuberculosis. The diagnostic accuracy of GS-TBLB culture was lower to that of TBLB culture than those of washing culture (n = 11 [35.5%] vs. n = 20 [64.5%], p = 0.016), and there was only one patient with positive GS-TBLB culture results and negative washing culture results. Comparing between patients with mycobacteria and non-mycobacteria, GS-TBLB culture positivity were no significant difference between patients with mycobacteria and non-mycobacteria (n = 6 [33.3%] vs. n = 5 [38.5%], p = 1.000), however, patients with mycobacteria diagnosed by washing culture more than those with non-mycobacteria (n = 15 [83.3%] vs. n = 5 [38.5%], p = 0.021). Our results demonstrate that the utility of TBLB culture for the diagnosis of pulmonary infections might provide limited value even if EBUS-GS is performed and lung tissue is successfully obtained.

Multiple bacterial culture positivity reflects the severity and prognosis as bronchiectasis in Mycobacterium avium complex pulmonary disease.

BACKGROUND: Bacterial coinfections are observed in 19-66% of patients with Mycobacterium avium complex pulmonary disease (MAC-PD) during the entire duration of the disease. The impact of bacterial coinfection at diagnosis on the clinical course of MAC-PD has not been reported. METHODS: Among 558 patients diagnosed with MAC-PD between January 2016 and December 2020, 218 patients who underwent sputum culture tests twice or more within one year before and after diagnosis were included. We compared the patient characteristics and disease courses between the patients who had the same bacterial species detected twice or more (bacterial culture positive group: BCP group) and those who never had bacteria cultured (bacterial culture negative group: BCN group). RESULTS: We included 70 patients in the BCP group and 74 in the BCN group. The radiological findings showed that BCP at diagnosis correlated with a high modified Reiff score. During the median follow-up period of 42 months, the patients in the BCP group were more likely to accomplish spontaneous sputum conversion of MAC. The treatment initiation rate for MAC-PD in the BCP group was lower than that in the BCN group (41.4% vs. 67.6%, P = 0.003). In contrast, the time to the first bronchiectasis exacerbation in the BCP group was shorter than that in the BCN group, and the frequency of bronchiectasis exacerbations was higher in the BCP group. CONCLUSIONS: Patients with BCP at diagnosis are less likely to initiate treatment for MAC-PD and more likely to develop bronchiectasis exacerbation.

A case of disseminated M. bovis bacillus Calmette-Guérin (BCG) disease after one month of BCG bladder infusion therapy and analysis of 77 cases of suspected BCG infection in Japan, 2017-2022.

Bacillus Calmette-Guerin (BCG) intravesical injections are used as adjuvant therapy for superficial bladder cancer. We report a case of a 78-year-old man who developed disseminated M. bovis BCG disease mimicking miliary tuberculosis early after BCG intravesical infusion. He started coughing after receiving three rounds of BCG for superficial bladder tumors, following transurethral resection of the tumors, approximately one month after initiation. Computerized tomography (CT) images showed diffuse nodular shadows in the bilateral lung fields with a random pattern. Consequently, disseminated BCG disease was diagnosed. Treatment with isoniazid, rifampicin, and ethambutol was initiated. Nine months after initiating treatment, CT showed the disappearance of the miliary shadows. We also discussed 77 cases of suspected BCG infection and the requests for Mycobacterium bovis BCG identification at our institution from 2017 to October 2022. Of these, 76 cases were M. bovis BCG, and 1 case was M. tuberculosis. Since M. tuberculosis can be identified in some patients with suspected BCG infection, it is crucial to distinguish between the two based on pathogenicity.

Usefulness of gastric aspirates for diagnosing nontuberculous mycobacteriosis.

Distinguishing between nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis (TB) is difficult. We aimed to evaluate the usefulness of gastric aspirate examination for NTM-PD diagnosis and for differentiating NTM-PD from other diseases, including pulmonary TB. We retrospectively collected data for 491 patients with negative sputum smears or a lack of sputum production at Fukujuji Hospital. We compared 31 patients with NTM-PD to 218 patients with other diseases (excluding 203 with pulmonary TB). Additionally, we compared 81 patients with NTM cultured from at least one sputum or bronchoscopy sample to the other 410 patients. Gastric aspirate examination for NTM-PD diagnosis showed 74.2% sensitivity and 99.0% specificity for culture positivity. There was no significant difference between the nodular bronchiectatic disease and cavitary disease types for culture positivity (p = 0.515). The significance of NTM isolation from gastric aspirate showed 64.2% sensitivity and 99.8% specificity for culture positivity. Gastric aspirate examination revealed NTM in one TB patient, allowing TB to be ruled out in 98.1% of patients with NTM cultured from gastric aspirates. Gastric aspirate examination is helpful for early-stage NTM diagnosis and ruling out pulmonary TB. This could lead to more accurate and timely treatment.

Anti-Mi-2 antibody-positive lung cancer-associated polymyositis.

After a 75-year-old man was diagnosed with lung cancer, proximal weakness and myalgia in the bilateral lower extremities developed, and the creatinine kinase (CK) level was elevated. The anti-Mi-2 antibody test was positive, muscle T2-weighted/fat-suppressed magnetic resonance imaging showed high intensity, and there were no skin lesions. Therefore, he was diagnosed with lung cancer-associated polymyositis (PM). The lung tumour shrank after chemotherapy, accompanied by gradual improvement of his PM-derived symptoms and CK level. Although positive anti-Mi-2 antibody tests rarely indicate PM and cancer, examining myositis-specific autoantibodies, including anti-Mi-2, should be considered if the CK level increases after a cancer diagnosis.

Causative antigens of humidifier lung in vapor from a humidifier: A case report.

A 68-year-old man exhibited fever and cough three weeks prior to hospital admission after three months of ultrasonic humidifier usage. Chest computed tomography showed bilateral ground-glass opacities, lymphocyte levels in the bronchoalveolar lavage fluid were elevated (60.8%), and the histological examination of a transbronchial lung biopsy showed lymphocytic alveolitis. He gradually improved without medication after he stopped using the humidifier. Accordingly, humidifier lung was the diagnosis. Humidifier water and vapor collected from the patient's humidifier were investigated. Humidifier vapor was obtained by collecting the condensed moisture. Laboratory examinations exhibited gram-negative rods and a high concentration of endotoxin and (1 â†’ 3)-ß-D-glucan in both vapor and water. The serum-precipitating antibodies showed a stronger reaction against humidifier vapor than against humidifier water. 16S rRNA metagenomic analysis revealed a high percentage of sequences of Spirosoma lacussanchae and Sphingomonas spp. in both the humidifier vapor and water. The percentages of sequence reads were lower in humidifier vapor than in water; conversely, sequences of Pseudomonas spp. and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium were more concentrated in the humidifier vapor than in humidifier water. Although the reason for the different bacterial ratios between humidifier vapor and water is uncertain, the bacteria that were more concentrated in humidifier vapor than in humidifier water might have been the causative antigen underlying the humidifier lung diagnosis. This is the first report to indicate the presence of causative antigens in humidifier vapor.

Genetic and histopathological analysis of spermatogenesis after short-term testicular torsion in rats.

BACKGROUND: Patients with testicular torsion (TT) may exhibit impaired spermatogenesis from reperfusion injury after detorsion surgery. Alteration in the expressions of spermatogenesis-related genes induced by TT have not been fully elucidated. METHODS: Eight-week-old Sprague-Dawley rats were grouped as follows: group 1 (sham-operated), group 2 (TT without reperfusion) and group 3 (TT with reperfusion). TT was induced by rotating the left testis 720° for 1 h. Testicular reperfusion proceeded for 24 h. Histopathological examination, oxidative stress biomarker measurements, RNA sequencing and RT-PCR were performed. RESULTS: Testicular ischemia/reperfusion injury induced marked histopathological changes. Germ cell apoptosis was significantly increased in group 3 compared with group 1 and 2 (mean apoptotic index: 26.22 vs. 0.64 and 0.56; p = 0.024, and p = 0.024, respectively). Johnsen score in group 3 was smaller than that in group 1 and 2 (mean: 8.81 vs 9.45 and 9.47 points/tubule; p = 0.001, p < 0.001, respectively). Testicular ischemia/reperfusion injury significantly upregulated the expression of genes associated with apoptosis and antioxidant enzymes and significantly downregulated the expression of genes associated with spermatogenesis. CONCLUSION: One hour of TT followed by reperfusion injury caused histopathological testicular damage. The relatively high Johnsen score indicated spermatogenesis was maintained. Genes associated with spermatogenesis were downregulated in the TT rat model. IMPACT: How ischemia/reperfusion injury in testicular torsion (TT) affects the expressions of genes associated with spermatogenesis has not been fully elucidated. This is the first study to report comprehensive gene expression profiles using next generation sequencing for an animal model of TT. Our results revealed that ischemia/reperfusion injury downregulated the expression of genes associated with spermatogenesis and sperm function in addition to histopathological damage, even though the duration of ischemia was short.

Differences in Pleural Fluid Amylase Levels in Patients with Malignant Pleural Effusion Based on Cancer Type, Histologic Type, and Epidermal Growth Factor Receptor Mutations.

Objective High pleural amylase levels have been reported in patients with malignant pleural effusion; however, the characteristics of this association are uncertain. Therefore, this study investigated the factors, such as cancer type and oncogenic drivers, related to pleural amylase levels in patients with malignant pleural effusion. Methods We retrospectively collected the data of 362 cancer patients [lung adenocarcinoma (n=256), lung squamous carcinoma (n=12), small-cell lung carcinoma (n=32), other lung cancers (n=5), mesothelioma (n=31), and metastatic cancer (n=26)] with malignant pleural effusion at Fukujuji Hospital from January 2012 to October 2022. Pleural amylase levels were compared. Results Pleural amylase levels were significantly higher in patients with lung adenocarcinoma [median 58.6 IU/L (interquartile range (IQR) 33.8-139.3)] than in those with small-cell lung carcinoma [median 37.2 IU/L (IQR 26.3-63.7), p=0.012]. The median pleural amylase level was higher in patients with lung adenocarcinoma than in those with other cancer or histologic types, although the difference was not significant. Pleural amylase levels were higher in epidermal growth factor receptor (EGFR) mutation-positive patients than in EGFR mutation-negative patients [median 95.8 IU/L (IQR 52.7-246.5) vs. median 51.2 IU/L (IQR 27.8-96.9), p<0.001]. The Kaplan-Meier survival curves of pleural amylase ≥75 IU/L were higher than those of pleural amylase <75 IU/L [log-rank test p<0.001, hazard ratio 0.54 (95% confidence interval: 0.41-0.71)]. Conclusion This study demonstrates that pleural amylase levels were elevated in patients with lung adenocarcinoma and EGFR mutations. Furthermore, a high pleural amylase level was associated with a good prognosis.

Characterization and cluster analyses of elderly asthma in comparison with nonelderly patients with asthma in Japan.

BACKGROUND: Asthma is a heterogeneous disease with multiple phenotypes that are useful in precision medicine. As the population ages, the elderly asthma (EA, aged ≥ 65 years) population is growing, and EA is now a major health problem worldwide. OBJECTIVE: To characterize EA and identify its phenotypes. METHODS: In adult patients with asthma (aged ≥ 18 years) who had been diagnosed with having asthma at least 1 year before study enrollment, 1925 were included in the NHOM-Asthma (registered in UMIN-CTR; UMIN000027776), and the data were used for this study, JFGE-Asthma (registered in UMIN-CTR; UMIN000036912). Data from EA and non-EA (NEA) groups were compared, and Ward's minimum-variance hierarchical clustering method and principal component analysis were performed. RESULTS: EA was characterized by older asthma onset, longer asthma duration and smoking history, more comorbidities, lower pulmonary function, less atopic, lower adherence, and more hospital admissions because of asthma. In contrast, the number of eosinophils, total immunoglobulin E level, oral corticosteroid use, and asthma control questionnaire scores were equivalent between EA and NEA. There were 3 distinct phenotypes in EA, which are as follows: EA1: youngest, late onset, short duration, mild; EA2: early onset, long duration, atopic, low lung function, moderate; and EA3: oldest, eosinophilic, overweight, low lung function, most severe. The classification factors of the EA phenotypes included the age of onset and asthma control questionnaire-6. Similarities were observed between EA and NEA phenotypes after principal component analysis. CONCLUSION: The EA in Japan may be unique because of the population's high longevity. Characterization of EA phenotypes from the present cohort indicated the need for distinct precision medicine for EA. TRIAL REGISTRATION: JFGE-Asthma registered in UMIN-CTR (https://www.umin.ac.jp/ctr/); UMIN000036912.

Impact of hydrogen gas inhalation during therapeutic hypothermia on cerebral hemodynamics and oxygenation in the asphyxiated piglet.

We previously reported the neuroprotective potential of combined hydrogen (H2) gas ventilation therapy and therapeutic hypothermia (TH) by assessing the short-term neurological outcomes and histological findings of 5-day neonatal hypoxic-ischemic (HI) encephalopathy piglets. However, the effects of H2 gas on cerebral circulation and oxygen metabolism and on prognosis were unknown. Here, we used near-infrared time-resolved spectroscopy to compare combined H2 gas ventilation and TH with TH alone. Piglets were divided into three groups: HI insult with normothermia (NT, n = 10), HI insult with hypothermia (TH, 33.5 ± 0.5 °C, n = 8), and HI insult with hypothermia plus H2 ventilation (TH + H2, 2.1-2.7%, n = 8). H2 ventilation and TH were administered and the cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation (ScO2) were recorded for 24 h after the insult. CBV was significantly higher at 24 h after the insult in the TH + H2 group than in the other groups. ScO2 was significantly lower throughout the 24 h after the insult in the TH + H2 group than in the NT group. In conclusion, combined H2 gas ventilation and TH increased CBV and decreased ScO2, which may reflect elevated cerebral blood flow to meet greater oxygen demand for the surviving neurons, compared with TH alone.

Autoimmune Pulmonary Alveolar Proteinosis with Suspected Exacerbation after Osimertinib Administration for Lung Cancer.

A 46-year-old woman with lung cancer who received chemotherapy was admitted to our hospital for lower-lobe bilateral ground-glass opacity (GGO). GGO developed after the lung cancer diagnosis, deteriorated after the initiation of osimertinib, and incompletely decreased after interrupting osimertinib; therefore, flexible bronchoscopy was performed. Transbronchial lung biopsy histology and anti-granulocyte/macrophage colony-stimulating factor autoantibody positivity revealed autoimmune pulmonary alveolar proteinosis (aPAP) that did not require treatment. This rare case of aPAP comorbid with lung cancer suggested that using PAP findings to differentiate from drug-induced lung injury or lymphangitis is difficult and that osimertinib was suspected to exacerbate aPAP.

The thickness of erector spinae muscles can be easily measured by computed tomography for the assessment of physical activity: An observational study.

The loss of muscle mass and changes in muscle composition are important factors for assessing skeletal muscle dysfunction. The cross-sectional area (CSA) of muscle is usually used to assess skeletal muscle function. However, the CSA of skeletal muscle can be difficult for clinicians to measure because a specific 3D image analysis system for computed tomography (CT) scans is needed. Therefore, we conducted a study to develop a new method of easily assessing physical activity, in which the thickness of the erector spinae muscles (ESMT) was measured by CT, and to compare ESMT to the CSA of the erector spinae muscles (ESMCSA) in patients with nontuberculous mycobacteria (NTM) pulmonary infections who underwent surgery after some preoperative examinations, such as laboratory tests, chest CT scans, spirometry, and 6-minute walk tests (6MWT). We retrospectively studied adult patients with NTM pulmonary infections who underwent a lobectomy at Fukujuji Hospital from April 2010 to March 2016. We assessed the correlations between ESMT and different variables, including ESMCSA. Sixty-one patients with NTM pulmonary infections were included. The median ESMT and ESMCSA were 1371 mm2 (IQR 1178-1784 mm2) and 28.5 mm (IQR 25.4-31.7 mm), respectively, and a very strong linear correlation was observed between ESMT and ESMCSA (R = 0.858, P < .001). ESMT and ESMCSA were positively associated with body weight (ESMT: R = 0.540, P < .001, ESMCSA: R = 0.714, P < .001), body mass index (ESMT: R = 0.421, P < .001, ESMCSA: R = 0.560, P < .001), the 6MWT value (ESMT: R = 0.413, P = .040, ESMCSA: R = 0.503, P = .010), vital capacity (ESMT: R = 0.527, P < .001, ESMCSA: R = 0.577, P < .001), and the forced expiratory volume in 1 second (ESMT: R = 0.460, P < .001, ESMCSA: R = 0.532, P < .001). We demonstrated that compared to ESMCSA, ESMT is easily measured by CT and can be a useful parameter for clinically evaluating physical activity. Furthermore, ESMT and ESMCSA were related to physical activity, as measured by the 6MWT and spirometry.

Characteristics of pleural effusion with a high adenosine deaminase level: a case-control study.

BACKGROUND: Increased pleural fluid adenosine deaminase (ADA) is useful for diagnosing tuberculous pleurisy (TB), but high ADA levels are associated with other diseases. In this study, we compare various disease characteristics in patients with high-ADA pleural effusion. METHODS: We retrospectively collected data for 456 patients with pleural fluid ADA levels of ≥ 40 U/L from January 2012 to October 2021. Cases were classified as TB (n = 203), pleural infection (n = 112), malignant pleural effusion (n = 63), nontuberculous mycobacteria (n = 22), malignant lymphoma (ML) (n = 18), autoimmune diseases (n = 11), and other diseases (n = 27), and data were compared among those diseases. Predictive factors were identified by comparing data for a target disease to those for all other diseases. A diagnostic flowchart for TB was developed based on those factors. RESULTS: The most frequent disease was TB, though 60.0% of patients were diagnosed with other diseases. Median ADA levels in patients with TB were 83.1 U/L (interquartile range [IQR] 67.2-104.1), higher than those of patients with pleural infection (median 60.9 [IQR 45.3-108.0], p = 0.004), malignant pleural effusion (median 54.1 [IQR 44.8-66.7], p < 0.001), or autoimmune diseases (median 48.5 [IQR 45.9-58.2], p = 0.008), with no significant difference from NTM (p = 1.000) or ML (p = 1.000). Pleural fluid lactate dehydrogenase (LDH) levels of < 825 IU/L were beneficial for the diagnosis of TB. Neutrophil predominance or cell degeneration, white blood cell count of ≥ 9200/µL or C-reactive protein levels of ≥ 12 mg/dL helped in diagnosing pleural infection. Pleural fluid amylase levels of ≥ 75 U/L and a pleural fluid ADA/total protein (TP) ratio of < 14 helped in diagnosing malignant pleural effusion. High serum LDH and high serum/pleural fluid eosinophils helped in diagnosing ML and autoimmune diseases, respectively. The flowchart was comprised of the following three factors: pleural fluid LDH < 825 IU/L, pleural fluid ADA/TP of < 14, and neutrophil predominance or cell degeneration, which were decided by a decision tree. The diagnostic accuracy rate, sensitivity, and specificity for the diagnosis of TB were 80.9%, 78.8%, and 82.6%, respectively. CONCLUSION: Cases involving high pleural fluid ADA levels should be investigated using several factors to distinguish TB from other diseases.

Identification of ANXA2 on epithelial cells as a new receptor for secretory IgA using immunoprecipitation and mass spectrometry.

Secretory immunoglobulin A plays an important role in the protection against exogenous pathogens and antigens, but it has also been reported to have pathogenic potential. We previously found that secretory immunoglobulin A accumulated in the peripheral lungs during idiopathic pulmonary fibrosis and that transferrin receptor/CD71 was partially involved in secretory immunoglobulin A-induced inflammatory cytokine production in A549 cells. This study aimed to identify the receptor responsible for the induction of cytokine production by secretory immunoglobulin A-stimulated airway epithelial cells. To this end, immunoprecipitation followed by time-of-flight mass spectrometry and peptide mass fingerprinting were performed and Annexin A2 was detected as a novel receptor for secretory immunoglobulin A. Enzyme-linked immunosorbent assay demonstrated binding of secretory immunoglobulin A to Annexin A2, and flow cytometry showed robust expression of Annexin A2 on the surface of BEAS-2B cells, A549 cells, and normal human bronchial/tracheal epithelial cells. Experiments in A549 cells using Annexin A2 small interfering RNA and neutralizing antibodies suggested that Annexin A2 was partially involved in the production of interleukin-8/CXCL8 and C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 induced by secretory immunoglobulin A. Immunohistochemistry using lung sections revealed clear expression of Annexin A2 on airway epithelial cells, although the staining remained equivalent in idiopathic pulmonary fibrosis, asthma, and healthy control lungs. In conclusion, we identified that Annexin A2 expressed in airway epithelial cells is a novel receptor for secretory immunoglobulin A, which is involved in cytokine synthesis.

Potential Cross-Transmission of Mycobacterium abscessus among Non-Cystic Fibrosis Patients at a Tertiary Hospital in Japan.

Mycobacterium abscessus (M. abscessus) is a highly antimicrobial-resistant pathogen that causes refractory pulmonary disease. Recently, the possibility of M. abscessus cross-transmission among cystic fibrosis (CF) patients has been reported. CF is rare in Asia, but M. abscessus pulmonary disease is common. Therefore, we investigated the possibility of M. abscessus cross-transmission in a Japanese hospital setting. Of 104 M. abscessus isolates, 25 isolates from 24 patients were classified into four clusters based on their variable number of tandem repeat profiles and were subjected to whole-genome sequencing (WGS). The epidemiological linkages among our patients were investigated by integrating the WGS data of previously reported nosocomial outbreak-related M. abscessus clinical isolates in the United Kingdom and the United States. Eight transmissible clusters (TCs) were identified. The United Kingdom and United States isolates were assigned to four clusters (TC1, TC2, TC5, and TC8) and one cluster (TC3), respectively. A total of 12 isolates from our hospital belonged to 4 clusters (TC4, TC5, TC6, and TC7). Epidemiological linkage analysis inferred direct or indirect transmission between patients in our hospital in TC4 and TC5 but not in TC6 and TC7. In TC5, the single nucleotide polymorphism distance between isolates from Japanese and United Kingdom patients was less than 21; however, there was no contact. This study revealed that genetically closely related isolates exist, even in non-CF patients. However, the transmission route remains unclear, and further research is warranted to clarify whether cross-transmission is involved. IMPORTANCE Although the possibility of Mycobacterium abscessus (M. abscessus) cross-transmission in cystic fibrosis (CF) patients has often been reported, it is not clear whether similar events have occurred in Asian non-CF patients. Whole-genome sequencing analysis of M. abscessus isolates from Fukujuji Hospital in Japan indicated that genetically closely related M. abscessus isolates exist. In addition, according to epidemiological linkage analysis, some clusters were suspected of direct or indirect transmission between patients within our hospital. However, the transmission route of M. abscessus remains unclear, because interestingly, one cluster showed a single nucleotide polymorphism distance of less than 21 from the United Kingdom isolates, but no epidemiological linkage was identified.

Evaluation of cytokine levels in response to mitogen among HIV-1-infected blood cells and their relationships to the number of T cells.

BACKGROUND: Human immunodeficiency virus-1 (HIV-1) infection causes loss and anergy of CD4+ and CD8+ T cells, leading to opportunistic infections, including tuberculosis (TB). QuantiFERON®-TB (QFT) is used as a diagnostic tool to detect TB, but it exhibits limited accuracy among subjects with low CD4+ T cell numbers, including HIV-1-infected individuals. The present study aimed to determine the effect of HIV-1 infection and patients' blood T cell numbers on cytokine production in response to mitogen (Mit) stimulation. METHODS: The number of CD4+ and CD8+ T cells in HIV-1-infected individuals was quantified. Levels of various cytokines in Mit-stimulated and un-stimulated (Nil) supernatants of QFT gold "in tube" were assessed using a MAGPIX System. The correlation between cytokine levels and CD4+/CD8+ T cell counts in response to Mit was analyzed. The cytokine levels were compared between HIV-1-infected and healthy subjects. RESULTS: HIV-1-infected individuals (110) and control subjects (27) were enrolled. Interferon (IFN)-γ, interleukin-1 receptor antagonist (IL-1RA), IL-6, IL-8, and regulated on activation, normal T cell expressed and secreted (RANTES) values in Mit-Nil tubes showed a significant correlation with CD4+ T cell counts, while IFN-γ, IL-6, and IFN-γ-induced protein 10 (IP-10) values in Mit-Nil tubes had significant correlation with CD8+ T cell counts. IL-1RA, IL-8, IP-10, platelet-derived growth factor (PDGF)-BB, and RANTES levels in Nil tubes were significantly higher in the HIV-1-infected group. IFN-γ, IL-2, IL-5, IL-6, IP-10, and macrophage inflammatory protein-1ß values in Mit-Nil tubes were significantly higher, and PDGF-BB and RANTES levels were significantly lower in the HIV-1-infected group. CONCLUSION: The functions of HIV-1-infected T cells and uninfected T cells, such as spontaneous and responsive cytokine production in response to Mit, were different. Our findings may be useful for developing new clinical tools for patients with low T cell counts. Additionally, the study provides new insights into the pathogenesis of HIV-1 infection.