Language：Japanese   Publisher：(NPO)日本肺癌学会  

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DOI： 10.1016/j.sleep.2023.07.005

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Language：Japanese   Publisher：日本睡眠学会・日本時間生物学会  

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INTRODUCTION: A study is eagerly awaited that will reveal the unknown mechanisms of multiple system atrophy (MSA), in which the risk of sudden death is the greatest during sleep. The blunted pulse response to nocturnal respiratory events suggests an abnormal cardiac response to a sleep-related breathing disorder. Patients with MSA have a lower pulse event index (PEI), despite a greater hypoxic burden and a similar frequency of respiratory events. However, the evidence is speculative and not directly proven, and many limitations require further study. METHODS: We conducted a retrospective analysis of 26 patients with MSA who had undergone overnight oximetry between April 2016 and December 2022. RESULTS: The median 4% oxyhemoglobin desaturation index (ODI) was 11.6/h, the 6-bpm PEI was 8.9/h, and the PEI/ODI ratio was as low as 0.91. There were three patients with suspected sudden death; all had low PEI/ODI ratios. The PEI/ODI ratio was followed over time in seven patients, all of whom had a decrease in the ratio. However, the PEI was higher than the ODI in 12/26 (46%) of the patients. CONCLUSION: A low PEI/ODI ratio, reflecting a blunted pulse response to nocturnal respiratory events in patients with MSA, may indicate a worse prognosis. This finding and the significance of the longitudinal decrease in the PEI/ODI ratio will require a prospective study.

DOI： 10.1016/j.parkreldis.2023.105817

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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BACKGROUND: Chronic intermittent hypoxia (IH) plays a significant role in the pathogenesis of obstructive sleep apnea (OSA) comorbidities. The prevalence of chronic kidney disease is higher in patients with OSA than the general population, and renal function decline is well correlated with renal tubular injury. However, little is known about the impact of OSA-induced chronic IH on the renal tubules. METHODS: We conducted a retrospective survey of clinical records performing multiple regression analysis and cluster analysis with particular attention to the 3% oxygen desaturation index (ODI) and urinary N-acetyl-β-d-glucosaminidase (NAG). RESULTS: In patients with suspicion of OSA, urinary NAG creatinine ratio (UNCR) was elevated as their 3% ODI increased (n = 197, p < 0.001), and the elevated UNCR decreased following CPAP treatment in patients with OSA (n = 46, p = 0.014). Multiple regression analysis showed that 3% ODI was associated with UNCR. Cluster analysis identified three clusters of patients with OSA, including two younger age clusters, one of which was characterized by high BMI, high 3% ODI, and high prevalence of major comorbidities. In a comparative analysis of younger age cases (age ≤ 55, n = 82), the UNCR level was higher in patients with severe 3% ODI (3% ODI > 40 events/h, n = 24) (p = 0.014). CONCLUSIONS: Our results indicate that even at younger ages, OSA patients with severe chronic IH and major comorbidities are susceptible to renal tubular damage. Early treatment with CPAP may attenuate renal tubular injury and progression toward end-stage renal disease.

DOI： 10.1016/j.sleep.2023.03.028

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Nasal breathing disorders are associated with obstructive sleep apnea (OSA) syndrome and influence the availability of continuous positive airway pressure (CPAP) therapy. However, information is scarce about the impact of nasal resistance assessed by rhinomanometry on CPAP therapy. This study aimed to examine the relationship between CPAP adherence and nasal resistance evaluated by rhinomanometry, and to identify clinical findings that can affect adherence to CPAP therapy for patients with OSA. This study included 260 patients (199 men, 61 women; age 58 [interquartile ranges (IQR) 50-66] years) with a new diagnosis of OSA who underwent rhinomanometry (before, and 1 and 3 months after CPAP introduction) between January 2011 and December 2018. CPAP use was recorded, and the good and poor CPAP adherence groups at the time of patient registration were compared. Furthermore, those with improved and unimproved pre-CPAP high rhinomanometry values were also compared. Their apnea-hypopnea index (AHI) by polysomnography at diagnosis was 45.6 (IQR 33.7-61.6)/hour, but the residual respiratory event (estimated AHI) at enrollment was 2.5 (IQR 1.4-3.9)/hour and the usage time was 318 (IQR 226-397) minutes, indicating that CPAP was effective and adherence was good. CPAP adherence was negatively correlated with nasal resistance (r = -0.188, p = 0.002). The participants were divided into good (n = 153) and poor (n = 107) CPAP adherence groups. In the poor adherence group, rhinomanometry values before CPAP introduction were worse (inspiration, p = 0.003; expiration, p = 0.006). There was no significant difference in patient background when comparing those with improved (n = 16) and unimproved (n = 12) pre-CPAP high rhinomanometry values. However, CPAP usage time was significantly longer in the improved group 1 month (p = 0.002) and 3 months (p = 0.026) after CPAP introduction. The results suggest that nasal resistance evaluated by rhinomanometry is a useful predictor of CPAP adherence, and that improved rhinomanometry values may contribute to extending the duration of CPAP use.

DOI： 10.1371/journal.pone.0283070

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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INTRODUCTION: This study aimed to examine the factors associated with cytomegalovirus (CMV) antigenemia and the time of onset of CMV antigenemia among patients with rheumatic diseases. METHODS: A single-center, retrospective, observational study was conducted in our institution from January 2009 to December 2017. This study included patients with rheumatic diseases who had at least one CMV antigen measurement. Multivariate analysis and receiver operating characteristic analysis was performed. RESULTS: A total of 249 patients underwent CMV antigenemia assay, and 84 (33.7%) patients tested positive. When the association between CMV antigenemia and possible associated factors was investigated, multivariate analysis showed that daily steroid dose increased the odds of having CMV [odds ratio 16.25, 95% confidence interval (CI), 5.360-49.253]. In this study, the cutoff value of daily steroid dose found in this study (0.45 mg/kg/day) was reasonable in clinical practice, and the area under the curve of the steroid dose was 0.838 [95% CI 0.781-0.882], which was the largest of the known indicators. Moreover, the median time from the start of immunosuppressive therapy to the onset of CMV antigenemia was 30 (interquartile range, 21-44) days, and most of the daily steroid users (85.7%) developed CMV antigenemia within 60 days. CONCLUSIONS: The daily steroid dose is the most important factor associated with CMV antigenemia. Therefore, monitoring and treatment strategies based on the steroid dose, especially in the initial 2 months, are important.

DOI： 10.1016/j.jiac.2022.07.004

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Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

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Language：Japanese   Publisher：日本感染症学会東日本地方会・日本化学療法学会東日本支部  

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Language：Japanese   Publisher：日本感染症学会東日本地方会・日本化学療法学会東日本支部  

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Language：Japanese   Publisher：(一社)日本睡眠学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Procalcitonin (PCT) is a serological marker whose utility has been established in infectious disease areas. Although serum calcitonin is a prognostic predictor in patients with medullary thyroid carcinoma, the clinical usefulness of PCT remains unclear in lung cancer patients. METHODS: As a discovery cohort, we retrospectively analyzed consecutive patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) who received first-line chemotherapy at our institution, and PCT blood levels were measured. As the validation cohort, PCT blood levels were prospectively evaluated in SCLC patients before first-line chemotherapy. The correlation between a PCT increase and prognosis was examined in the discovery and validation cohorts. RESULTS: Twenty-three SCLC patients and 26 NSCLC patients were enrolled as the discovery cohort, and 30 SCLC patients were enrolled as the validation cohort. The PCT level in SCLC patients was significantly higher than that in NSCLC patients. The PCT level was not associated with WBC count and weakly associated with the CRP level. In both the discovery and validation cohorts, the median survival time was significantly shorter in SCLC patients with PCT-high than in SCLC patients with PCT-normal (discovery; 11.7 vs. 89.7 months, P<0.005, validation; 9.6 vs. 22.6 months, P<0.005). CONCLUSIONS: It may be difficult to differentiate bacterial infections in SCLC patients by PCT, as PCT is elevated even in SCLC patients without infectious diseases. This is the first study to prospectively verify that pretreatment PCT levels have a significant negative correlation with prognosis in SCLC patients.

DOI： 10.21037/tlcr-21-838

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

背景.気管支静脈瘤は稀な疾患であり,その治療法は確立されていない.症例.78歳,女性.小児期より気管支拡張症を罹患し,膿胸の既往があった.6年前から喀血を繰り返し,計3回の気管支動脈塞栓術が行われていた.今回,喀血を契機に入院し,止血薬投与を受けたが大量喀血を来したため,気管挿管の上で人工呼吸管理となった.左下横隔動脈と左気管支動脈をゼラチンスポンジで塞栓し,止血を得た.その際の選択的動脈造影で左下横隔動脈と肺静脈との動静脈シャントを認めた.気管支鏡で観察すると,左上下葉支分岐部に気管支静脈瘤がみられ,出血源と考えられた.動脈塞栓術の2週後の気管支鏡では同部位の瘤は退縮していた.その後,再喀血なく自宅退院した.結論.気管支静脈瘤は気管支拡張症や動脈塞栓に関連して発症する可能性があり,喀血時は気管支鏡による確認が必要である.治療として異常シャントの塞栓術が有効と考えられた.(著者抄録)

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Lymphodepleting cytotoxic regimens enhance the antitumor effects of adoptively transferred effector and naïve T cells. Although the mechanisms of antitumor immunity augmentation by lymphodepletion have been intensively investigated, the effects of lymphodepletion followed by T cell transfer on immune checkpoints in the tumor microenvironment remain unclear. The current study demonstrated that the expression of immune checkpoint molecules on transferred donor CD4+ and CD8+ T cells was significantly decreased in lymphodepleted tumor-bearing mice. In contrast, lymphodepletion did not reduce immune checkpoint molecule levels on recipient CD4+ and CD8+ T cells. Administration of anti-PD-1 antibodies after lymphodepletion and adoptive transfer of T cells significantly inhibited tumor progression. Further analysis revealed that transfer of both donor CD4+ and CD8+ T cells was responsible for the antitumor effects of a combination therapy consisting of lymphodepletion, T cell transfer and anti-PD-1 treatment. Our findings indicate that a possible mechanism underlying the antitumor effects of lymphodepletion followed by T cell transfer is the prevention of donor T cell exhaustion and dysfunction. PD-1 blockade may reinvigorate exhausted recipient T cells and augment the antitumor effects of lymphodepletion and adoptive T cell transfer.

DOI： 10.1007/s00262-021-03078-0

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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An outbreak of serotype 19A Streptococcus pneumoniae occurred among the residents of a relief facility. Pneumonia developed in 5 of 99 residents (attack rate, 5.1%). We obtained pharyngeal specimens from non-onset residents, and S. pneumoniae was isolated from 6 individuals (6.4%), 5 of whom had serotype 19A.

DOI： 10.1017/ice.2021.328

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Background: Although immune checkpoint inhibitors (ICIs) are effective for advanced non-small cell lung cancer (NSCLC), ICIs may cause interstitial lung disease (ILD), which results in treatment discontinuation and is sometimes fatal. Despite the high incidence of ICI-related ILD, there are few cancer treatment options for patients. This study aimed to evaluate the safety and efficacy of subsequent systemic cancer therapy in NSCLC patients with ICI-related ILD. Methods: We retrospectively assessed NSCLC patients who received programmed cell death-1 (PD-1) inhibitors as first- to third-line therapy at participating institutions of the Niigata Lung Cancer Treatment Group from January 2016 to October 2017. Results: This analysis included 231 patients, 32 (14%) of whom developed ICI-related ILD. Of these patients, 16 (7%) received subsequent systemic cancer treatments. The median overall survival (OS) tended to be longer in the systemic cancer therapy group than in the no systemic cancer therapy group [22.2 months (95% CI: 1-NE) vs. 4.5 months (95% CI: 1-NE); P=0.067]. ICI-related ILD recurred in half of the patients who received systemic cancer therapy, and the median OS tended to be shorter in patients with recurrent ICI-related ILD [22.0 months (95% CI: 1-NE) vs. 7.0 months (95% CI: 1-NE); P=0.3154]. Conclusions: According to the current study, systemic cancer treatment is effective in patients with ICI-related ILD; however, its safety is uncertain because of the high risk of ICI-related ILD recurrence and poor survival outcome following ILD recurrence.

DOI： 10.21037/tlcr-21-198

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A 31-year-old woman who was clinically diagnosed with Silver-Russell syndrome (SRS) in childhood was admitted with complaints of dyspnea. She had hypercapnic respiratory failure accompanied by nocturnal hypoventilation. Computed tomography revealed systemic muscle atrophy and superior mesenteric artery syndrome; however, the bilateral lung fields were normal. She was treated with nocturnal noninvasive positive pressure ventilation and showed improvement of respiratory failure. In this case, loss of methylation on chromosome 11p15 and maternal uniparental disomy of chromosome 7, which are the common causes of SRS, were not detected. This is a rare case of adult SRS manifesting as chronic hypercapnic respiratory failure.

DOI： 10.2169/internalmedicine.5479-20

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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We herein report the case of a 20 year-old-man who developed bronchiolitis obliterans after living-donor renal transplantation. The patient presented with dyspnea on exertion and wheezing two years after renal transplantation, and spirometry showed an obstructive pattern. Surgical lung biopsy revealed subepithelial fibrosis that constricted and obstructed the intrabronchiolar space. Based on these findings, the patient was diagnosed with bronchiolitis obliterans. He was prescribed bronchodilators and azithromycin, and he achieved stable respiratory function for two years. The differential diagnosis of respiratory symptoms after renal transplantation includes opportunistic infection and drug-induced lung injury; however, bronchiolitis obliterans should also be considered.

DOI： 10.1016/j.resinv.2020.12.003

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

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Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

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Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

DOI： 10.1038/s41598-020-80853-6

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.5396-20

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BACKGROUND: Each of the currently available (1→3)-β-D-glucan (BDG) measurement kits follows a different measurement method and cut-off value. Comparisons of diagnostic performance for invasive fungal infections (IFIs) are desirable. Additionally, ecological considerations are becoming increasingly important in the development of new measurement kits. METHODS: The plasma BDG levels in clinical samples were measured using the following currently available kits: the Fungitec G test MKII, the Fungitec G test ES, Fungitell, the β-Glucan test Wako, and the newly developed Wako kit (Wako-Eu). Wako-Eu uses a pre-treatment solution that conforms to European regulations for the registration, evaluation, authorisation, and restriction of chemicals. The values obtained for the samples using each kit were studied and compared. RESULTS: Of the 165 patients evaluated, 12 had IFIs, including pneumocystis pneumonia, aspergillosis, and candidiasis. BDG values obtained using the kits were moderately correlated with each other. Clinical diagnoses of the evaluated cases indicated that 21 false positives were diagnosed by at least one kit. The sensitivity of the Fungitell kit was relatively low, but those of the other four were over 90%. The specificity was above 90% for all kits. For positive predictive value, the Wako and the Wako-Eu methods were superior to the others owing to fewer false positive results. CONCLUSIONS: The newly developed Wako-Eu method, which considers ecological concerns, shows diagnostic performance equivalent to that of its predecessor. To improve the diagnostic accuracy of IFIs, it is necessary to interpret the results carefully, giving due consideration to the characteristics of each measurement kit.

DOI： 10.1371/journal.pone.0255172

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Objectives: Although immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs. Methods: We retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors. Results: Of 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4-NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4-NE); p = 0.031]. Conclusion: The current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

DOI： 10.3389/fonc.2021.704475

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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DOI： 10.1186/s12885-019-6398-2

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

[目的]国内3種の(1→3)-β-D-グルカン(以下β-D-グルカン)測定試薬における測定結果と患者の臨床背景を比較し,深在性真菌症の診断における有用性および試薬間での測定結果の乖離,偽陽性の要因について評価する.[方法]新潟大学医歯学総合病院において2017年8月から2017年11月にかけてβ-D-グルカン検査が提出された患者を対象とし,測定残余血漿を用いて以下の3試薬について測定した.(1)ファンギテックGテストMKII「ニッスイ」(以下MKII法),(2)ファンギテックGテストES「ニッスイ」(以下ES法),(3)β-グルカンテストワコー(以下ワコー法).[成績]171患者,245検体が対象となった.深在性真菌症患者は疑診を含め7例であった.β-D-グルカン測定値は,同一検体間の比較でMKII法が最も高く,次いでES法,ワコー法の順であったが,互いに有意に相関していた.感度,特異度,陽性的中率,陰性的中率などの診断特性は各試薬によって異なっていた.MKII法で偽陽性を比較的多く認めたものの,深在性真菌症(疑診含む)診断におけるROC曲線下面積には有意差はなかった.いずれかの試薬による偽陽性を呈した14例について,階層型クラスター分析を用いて分類したところ,偽陽性のパターンに一定の傾向が認められた.[結論]各測定試薬によるβ-D-グルカン測定の結果は概ね相関しているが,測定値は大きく異なっており,異なる試薬同士の比較は困難である.深在性真菌症診断における差は小さいが,それぞれの試薬の診断特性を理解し使用するべきである.また試薬によって偽陽性の原因が異なる可能性が示唆された.(著者抄録)

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DOI： 10.1186/s12879-019-3888-4

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4+ T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3+ cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4+ T cells (P = 0.005; HR<0.001, 95% CI <0.001 to 0.28) and a high density of Foxp3+ cells (P = 0.003; HR<0.001, 95% CI NA) in tumor tissues were strongly correlated with better progression-free survival. In contrast to previous studies in wild type EGFR NSCLCs, PD-L1 expression was not associated with the clinical benefit of anti-PD-1 treatment in EGFR-mutated NSCLCs. The current study indicated that immune status in the tumor microenvironment may be important for the effectiveness of nivolumab in NSCLC patients with EGFR mutations.

DOI： 10.1371/journal.pone.0215292

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Language：Japanese   Publisher：(NPO)日本肺癌学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 52-year-old man with chronic myelogenous leukemia (CML) received dasatinib after the failure of imatinib and nilotinib therapy. Two years after the initiation of dasatinib, he developed shortness of breath that gradually worsened. Chest X-ray and computed tomography scan showed pulmonary infiltrative shadows and bilateral pleural effusion. We performed a transbronchial lung biopsy and diagnosed organizing pneumonia caused by dasatinib treatment. Corticosteroid therapy was initiated after the discontinuation of dasatinib and all his symptoms were significantly improved. Because of the exacerbation of CML, the patient was treated with imatinib and then nilotinib; however, these drugs failed to decrease the leukemic cells. Re - administration of dasatinib in combination with corticosteroid therapy successfully controlled CML without recurrence of organizing pneumonia.

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Background: Interferon-γ neutralizing autoantibodies (nIFNγ-autoAbs) are reported in patients with disseminated nontuberculous mycobacteria (NTM) infection and may function by increasing the infection risk. Notwithstanding, the prevalence of nIFNγ-autoAbs as well as the clinical presentation, diagnosis, and natural history of disseminated NTM infection in these patients is poorly understood. Methods: In this retrospective observational study, data and sera for 331 Japanese subjects with mycobacterial infection were collected and analyzed. IFNγ-autoAb titers in sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry. Results: Disseminated NTM was identified in 50 human immunodeficiency virus-uninfected patients. Of these, 30 of 37 (81%) immunocompetent patients had an increased nIFNγ-autoAb titer whereas only 1 of 13 (7.7%) immunodeficient patients had an increased nIFNγ-autoAb titer (P < .0001, χ2 test). Presenting symptoms were nonspecific and NTM infection was not included in the differential diagnosis in most cases. All patients with disseminated NTM and an increased serum nIFNγ-autoAb level received prolonged antimicrobial therapy. In 6 cases when antibiotic treatment was discontinued, NTM infection recurred and required resumption of antibiotic therapy for infection control. The mortality rate was 3.2% in disseminated NTM patients with nIFNγ-autoAbs and 21% in those without. Conclusions: nIFNγ-autoAbs were present in most patients with disseminated NTM infection without a diagnosis of clinical immunodeficiency. Diagnosis of disseminated NTM requires a high degree of suspicion and can be improved by measuring serum nIFNγ-autoAb titer. Long-term antibiotic therapy helps prevent recrudescent NTM infection.

DOI： 10.1093/cid/cix996

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(NPO)日本肺癌学会  

目的. サルコイドーシスやサルコイド反応は肺門・縦隔リンパ節腫大を呈し、これらを合併した肺癌症例には、リンパ節病変の評価が治療方針決定上で問題となる。本研究では、これらサルコイド反応合併肺癌症例の病期診断におけるEBUS-TBNAの有用性を検討した。対象と方法. 2009年1月から2016年12月に気管支鏡検査を実施され、サルコイドーシス/サルコイド反応と肺癌の合併と診断された症例におけるEBUS-TBNAの有効性について検討した。結果. EBUS-TBNAにより、サルコイドーシス/サルコイド反応と肺癌との合併と診断された症例は4例であった。造影CT、FDG-PET/CTでは癌のリンパ節転移とサルコイドーシス/サルコイド反応の鑑別は困難であった。4例中3例はI期の非小細胞肺癌と診断され、2例は手術が施行された。術後検体でも転移はなく、granulomaが認められたことから、サルコイド反応と診断された。4例中1例は全身性サルコイドーシスに合併したIII期の肺癌症例であった。結論. サルコイドーシス/サルコイド反応合併肺癌症例におけるN因子の評価に、EBUS-TBNAは有用であると考えられる。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01244&link_issn=&doc_id=20180515270004&doc_link_id=%2Fec7jaluc%2F2018%2F005802%2F004%2F0088-0092%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fec7jaluc%2F2018%2F005802%2F004%2F0088-0092%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)日本化学療法学会  

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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Language：Japanese   Publisher：(一社)日本エイズ学会  

継続的に受診していたHIV感染症患者(2009年29人、2011年31人、2013年41人、2014年38人)を臨床群、HIVおよび慢性疾患に罹患していない92人を対照群とした。[情緒的ソーシャルサポート]、[現実的ソーシャルサポート]、[対他的孤独感]、[実存的孤独感]、[孤独不安耐性]の信頼性係数は十分な値であった。ウェルチの検定で、[希死念慮うつ傾向]と[情緒的ソーシャルサポート]、[対他的孤独感]において有意差を認めた。ウェルチの検定の結果も踏まえれば、臨床群は対照群との平均値の比較において、[希死念慮うつ傾向]は高く、[情緒的ソーシャルサポート]は低く、[他的孤独感]は高いことが有意にいえるがその差はわずかであった。GHQ30の陽性判定の繰り返しに注目し、その説明因子やリスクについて検討し、希死念慮や抑うつ気分を持つかどうかが、メンタルヘルス不調の反復性を説明する上で重要であることが示された。メンタルヘルスのリスク因子と考えられる[希死念慮うつ傾向]に対しては、[対他的孤独感]が促進的影響、[孤独不安耐性]が抑制的影響を与えることが示された。

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BACKGROUND: Presepsin is a widely recognized biomarker for sepsis. However, little is known about the usefulness of presepsin in invasive fungal infection. The aim of this study was to determine the plasma levels of presepsin in fungal bloodstream infections and to investigate whether it reflects the disease severity, similar to its utility in bacterial infections. METHODS: We prospectively measured presepsin in plasma samples from participants with fungemia from April 2016 to December 2017. The associations of C-reactive protein, procalcitonin, and presepsin concentrations with the severity of fungemia were statistically analyzed. In vitro assay was performed by incubating Escherichia coli, Candida albicans, and lipopolysaccharide to whole blood cells collected from healthy subjects; after 3 h, the presepsin concentration was measured in the supernatant and was compared among the bacteria, fungi, and LPS groups. RESULTS: Presepsin was increased in 11 patients with fungal bloodstream infections. Serial measurement of presepsin levels demonstrated a prompt decrease in 7 patients in whom treatment was effective, but no decrease or further increase in the patients with poor improvement. Additionally, presepsin concentrations were significantly correlated with the Sequential Organ Failure Assessment score (r = 0.89, p < 0.001). In vitro assay with co-incubation of C. albicans and human whole blood cells indicated that the viable cells of C. albicans caused an increase in presepsin, as seen with E. coli. CONCLUSIONS: Plasma presepsin levels increased in patients with fungal bloodstream infection, with positive association with the disease severity. Presepsin could be a useful biomarker of sepsis secondary to fungal infections.

DOI： 10.1371/journal.pone.0206089

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Lung Cancer Society  

Objective. Sarcoidosis is a systemic disease that causes the formation of noncaseating epithelioid granuloma in various organs and which often exhibits hilar and mediastinal lymphadenopathy. Among lung cancer patients with sarcoidosis or sarcoid reactions, it is difficult to evaluate the lymph node status and stage by CT and FDG-PET/CT scans. In this study, we examined the usefulness of EBUS-TBNA in the staging of the lung cancer in patients with sarcoidosis or sarcoid reactions. Materials and Methods. We evaluated the effectiveness of EBUS-TBNA in lung cancer patients with sarcoidosis or sarcoid reactions from January 2009 to December 2016. Results. We found 4 patients who were diagnosed with lung cancer accompanied by sarcoidosis and sarcoid reactions by EBUS-TBNA. All of these patients had hilar and mediastinal lymphadenopathy. EBUS-TBNA was useful for the differential diagnosis of lymph-node metastasis of lung cancer. Three of the 4 patients were diagnosed with stage I non-small cell lung cancer and surgery was performed in 2 cases. The histopathological examination of the surgical specimens confirmed that these patients had sarcoid reactions with no lymph-node metastasis. One of the 4 patients was diagnosed with stage III non-small cell lung cancer with systemic sarcoidosis. Conclusion. EBUS-TBNA seems to be useful for the evaluation of the lymph-node status of lung cancer patients with sarcoidosis and sarcoid reactions.

DOI： 10.2482/haigan.58.88

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Nursing and healthcare-associated pneumonia (NHCAP) is a category of healthcare-associated pneumonia that was modified for the healthcare system of Japan. The NHCAP guidelines stated the difficulty in assessing the severity classifications, for instance, A-DROP. We compared the usefulness of different severity classifications (A-DROP, CURB-65, PSI, and I-ROAD) in predicting the prognosis of nursing and healthcare-associated pneumonia.
We conducted a retrospective analysis on 303 adult patients hospitalized for nursing healthcare-associated pneumonia and community-acquired pneumonia, which were diagnosed at the Department of Respiratory Medicine of Niigata General City Hospital between January 2012 and December 2014.
We evaluated 159 patients with community-acquired pneumonia and 144 with nursing and healthcare-associated pneumonia. In the nursing and healthcare-associated pneumonia group, 30-days mortality and in-hospital mortality rates were 6.5% and 8.7%, respectively, in severe cases and 16.1% and 25.0%, respectively, in the most severe cases, based on A-DROP. With I-ROAD, these rates were 11.1% and 11.1%, respectively, in group B and 14.9% and 20.7%, respectively, in group C. With PSI, the rates were 2.3% and 6.8%, respectively, in class IV and 14.3% and 19.8%, respectively, in class V. Despite some variability due to the small sample size, both the 30-days and in-hospital mortality rates increased as the severity increased.
In this study, both the 30-days mortality and in-hospital mortality rates in the nursing and healthcare-associated pneumonia group tended to increase in severity with the A-DROP. We found that A-DROP was useful in predicting the prognosis of nursing and healthcare-associated pneumonia. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2017.04.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naive T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naive T cells that are able to differentiate into tumor-specific effector T cells remains difficult. To establish culture methods to obtain a large number of polyclonal T cells that are capable of differentiating into tumor-specific effector T cells, naive T cells were activated with anti-CD3 mAbs in vitro. These cells were stimulated with IL-2 and IL-7 for the CD8 subset or with IL-7 and IL-23 for the CD4 subset. Transfer of these hyperexpanded T cells after lymphodepletion showed significant antitumor efficacy, and tumor-specific effector T cells were primed from these expanded T cells in tumor-bearing hosts. Moreover, these ex vivo-D expanded T cells maintained T cell receptor diversity and showed long-term persistence of memory against specific tumors. Further analyses revealed that combination therapy consisting of vaccination with dendritic cells that were co-cultured with irradiated whole tumor cells and the transfer of ex vivo D expanded T cells significantly enhanced antitumor immunity. These results indicate that the transfer of ex vivo D expanded polyclonal T cells can be combined with other immunotherapies and augment antitumor effects.

DOI： 10.1371/journal.pone.0183976

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC NEPHROLOGY  

Nephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin. In the clinical setting, cilastatin has been used safely to suppress dehydropeptidase-I-mediated renal metabolism of imipenem, a carbapenem antimicrobial, and thereby limit tubular injury. Here, we tested the hypothesis that cilastatin also blocks megalin-mediated uptake of vancomycin, cisplatin, colistin, and aminoglycosides, thereby limiting the nephrotoxicity of these drugs. Quartz crystal microbalance analysis showed that megalin also binds vancomycin and cisplatin and that cilastatin competes with megalin for binding to gentamicin, colistin, vancomycin, and cisplatin. In kidney specific mosaic megalin knockout mice treated with colistin, vancomycin, or cisplatin, the megalin-replete proximal tubule epithelial cells exhibited signs of injury, whereas the megalin-deficient cells did not. Furthermore, concomitant cilastatin administration suppressed colistin-induced nephrotoxicity in C57BL/6J mice. Notably, cilastatin did not inhibit the antibacterial activity of gentamicin, colistin, or vancomycin in vitro, just as cilastatin did not affect the anticancer activity of cisplatin in previous studies. In conclusion, megalin blockade with cilastatin efficiently suppresses the nephrotoxicity induced by gentamicin, colistin, vancomycin, or cisplatin. Cilastatin may be a promising agent for inhibiting various forms of drug-induced nephrotoxicity mediated via megalin in the clinical setting.

DOI： 10.1681/ASN.2016060606

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese  

Serum (1→3) beta-D-glucan (BG) measurement is a useful test for systemic mycoses, and often used. On the other hand, various factors, including administration of intravenous immunoglobulins (IVIG) may cause false-positives. In the present study, we measured BG concentration of seven IVIG preparations with three lots respectively. BG levels varied with individual IVIG preparations (<3.0 - >300 pg/mL), and contamination from manufacturing processes was suspected.

With serum BG concentration of clinical specimens obtained in Niigata University Medical & Dental Hospital, the difference between before and after administration of IVIG were calculated.

The false-positive rate of BG due to IVIG administration was 9.8 %, and the positive predective value was reduced to 37.5%. Above all, administration of IVIG can complicate the BG test's interpretation, and caution is required.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background: In contrast to community-acquired pneumonia (CAP), no specific severity assessment tools have been developed for healthcare-associated pneumonia (HCAP) in clinical practice. Objectives: In this review, we assessed the clinical significance of severity assessment tools for HCAP. Methods: We identified related articles from the PubMed database. The eligibility criteria were original research articles evaluating severity scoring tools and reporting the outcomes of mortality in patients with HCAP. Results: Eight articles were included in the meta-analysis. The PORT score and CURB-65 were evaluated in 7 and 8 studies, respectively. Using cutoff values of &gt;= IV and V for the PORT score, the diagnostic odds ratios (DORs) were 5.28 (2.49-11.17) and 3.76 (2.88-4.92), respectively, and the areas under the curve (AUCs) were 0.68 (0.64-0.72) and 0.71 (0.67-0.75), respectively. Conversely, the AUCs for &gt;= IV and V were 0.71 (0.67-0.76) and 0.74 (0.70-0.78), respectively, when applied only to nonimmunocompromised patients. In contrast, when using cutoff values of &gt;= 2 and &gt;= 3 for CURB-65, the DORs were 3.35 (2.26-4.97) and 2.65 (2.05-3.43), respectively, and the AUCs were 0.65 (0.61-0.69) and 0.66 (0.62-0.70), respectively. Conversely, the AUCs for &gt;= 2 and &gt;= 3 were 0.65 (0.61-0.69) and 0.68 (0.64-0.72), respectively, when applied only to nonimmunocompromised patients. Conclusions: The PORT score and CURB-65 do not have substantial power compared with the tools for CAP patients, although the PORT score is more useful than CURB-65 for predicting mortality in HCAP patients. According to our results, however, these tools, especially the PORT score, can be more useful when limited to nonimmunocompromised patients. (C) 2017 S. Karger AG, Basel.

DOI： 10.1159/000470915

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Aspiration pneumonia is thought to be associated with a poor outcome in patients with community acquired pneumonia (CAP). However, there has been no systematic review regarding the impact of aspiration pneumonia on the outcomes in patients with CAP. This review was conducted using the MOOSE guidelines: Patients: patients defined CAP. Exposure: aspiration pneumonia defined as pneumonia in patients who have aspiration risk. Comparison: confirmed pneumonia in patients who were not considered to be at high risk for oral aspiration. Outcomes: mortality, hospital readmission or recurrent pneumonia. Three investigators independently identified published cohort studies from PubMed, CENTRAL database, and EMBASE. Nineteen studies were included for this systematic review. Aspiration pneumonia increased in-hospital mortality (relative risk, 3.62; 95% CI, 2.65-4.96; P &lt; 0.001, seven studies) and 30-day mortality (3.57; 2.18-5.86; P &lt; 0.001, five studies). In contrast, aspiration pneumonia was associated with decreased ICU mortality (relative risk, 0.40; 95% CI, 0.26-0.60; P &lt; 0.00001, four studies). Although there are insufficient data to perform a meta-analysis on long-term mortality, recurrent pneumonia, and hospital readmission, the few reported studies suggest that aspiration pneumonia is also associated with these poor outcomes. In conclusion, aspiration pneumonia was associated with both higher in-hospital and 30-day mortality in patients with CAP outside ICU settings.

DOI： 10.1038/srep38097

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Other Link： http://hdl.handle.net/10191/43959

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOCIETY ALLERGOLOGY  

Background: Influenza infection is known to be an exacerbating factor in the control of asthma, therfore its prevention is critical in managing asthma. The aim of this study was to investigate the influenza A H1N1 2009 pandemic virus (H1N1 pdm09) infection in adult asthmatic patients.
Methods: Data were obtained from a questionnaire-based survey of asthmatic patients conducted from September to October 2010 in Niigata Prefecture. Patient background, H1N1 pdm09 infection, vaccination status, and asthma exacerbation due to influenza infection were analyzed.
Results: In total, 2,555 cases were analyzed. The incidence of the infection was 6.7% (95% confidence interval [Cl]: 5.7-7.6), and the rate of vaccination was 63.9% (95% CI: 62.1-65.8). The odds ratio (OR) for vaccination against the infection among adult patients and younger patients (&lt;= the median age) were 0.61 (95% Cl: 0.45-0.84) and 0.62 (95% Cl: 0.42-0.90), respectively. However, OR among the older patient (&gt; median age) were 1.38 (96%Cl: 0.66-2.89). The rate of infection-induced asthma exacerbation was 23.2% (95% CI: 18.6-29.6), and the OR for vaccination against the infection-induced asthma exacerbation was 1.42 (95% Cl: 0.69-2.92).
Conclusions: The effectiveness of the vaccination against the H1N1 pdm09 virus was confirmed during the first pandemic season, but it was limited. Further investigation on H1N1 pdm09 virus infection in asthmatics will be required.

DOI： 10.2332/allergolint.13-OA-0609

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Subjects exposed to non-tuberculous mycobacterium (NTM) species do not always develop an active disease, which likely reflects underlying host susceptibility factors. Recent reports have shown that anti interferon gamma (IFN-gamma) neutralizing autoantibodies (IFN-gamma Ab) are associated with the development of disseminated NTM in patients without known evidence of immunodeficiency. The purpose of this study is to establish the screening method if subjects have IFN-gamma Ab. Whole blood was obtained from patients with disseminated NTM, those with pulmonary NTM, and healthy controls. The neutralizing capacity to IFN-y activity was assessed as an inhibition of Signal Transducer and Activation of Transcription 1 (STAT1) phosphorylation in leukocyte after stimulation with exogenous IFN-gamma by flow cytometer. The strength of phosphorylation was described as STAT1 phosphorylation index. Antigen capture assay was performed to measure the relative titer of Immunoglobulin-G fraction of IFN-y Ab. STAT1 phosphorylation by IFN-gamma was significantly inhibited in the leukocytes from patients with disseminated NTM compared to that in healthy subjects, while this inhibition was not observed in patients with pulmonary NTM. All subjects with inhibited STAT1 phosphorylation had high titer of Immunoglobulin-G that reacted with IFN-gamma in the antigen capture assay. The measurement of STAT1 phosphorylation index in whole blood leukocytes and antigen capture assay are simple and useful method for detection of anti-IFN-gamma neutralizing autoantibodies, and is valuable in the pathophysiological diagnosis of disseminated NTM patients without obvious immunodeficiency. (C) 2013, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2013.08.003

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Other Link： http://hdl.handle.net/10191/36221

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)医薬情報研究所  

喘息治療薬についての喘息患者の関心・要望について、新潟喘息治療研究会2010年アンケート調査より検討した。参加施設は新潟県内の医療機関で、200床以上の24病院、200床未満の16病院と56の診療所であった。アンケート回収率は58.0%(4662例中2706例)であった。喘息治療薬の効果、易使用性、コスト・安全性の中では、患者は喘息治療薬の効果を最も重要視した。更に、喘息治療薬の効果に関する項目では、効果発現の早さ、効果の持続の2つともに重要視しているが、喘息症状の完全寛解については理解が乏しかった。易使用性では使用回数に関した要望が高いものの、内服・吸入といった使用経路についての関心が低かった。コスト・安全性では副作用についての要望が高かったものの、予想されたコスト面での要望は低かった。

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Language：Japanese   Publisher：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.35.4_460_1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

In this study, we have evaluated the efficacy of calcium-EDTA (Ca-EDTA) as an inhibitor of bacterial metalloenzymes, such as metallo-beta-lactamase (MBL) and other proteases, in a mouse model of Pseudomonas aeruginosa pneumonia. The simultaneous presence of Ca-EDTA (32 mu g/ml) reduced the MICs of imipenem (IPM) in all MBL-producing P. aeruginosa isolates (IMP-1, -2, -7, and -10 and VIM-2) but not non-MBL-producing strains. In the pneumonia model, mice were intranasally infected with MBL-producing P. aeruginosa and then kept under conditions of hyperoxia to mimic ventilator-associated pneumonia. With both intranasal and subcutaneous administrations, Ca-EDTA significantly potentiated survival benefits of IPM compared to those of IPM alone. Ca-EDTA combination therapy induced a significant reduction of the bacterial burden in the lungs (P &lt; 0.05). Furthermore, the inhibition activity of Ca-EDTA against MBL activity was confirmed by using the purified IMP-1 enzyme, which was characterized by a 50% inhibitory concentration (IC(50)) of 55 +/- 8.2 mu M. Finally, the protective effects of Ca-EDTA were demonstrated by culture supernatant-induced epithelial cell damage and acute lung injury in mice. These data suggest the therapeutic potential of Ca-EDTA not only by the blocking of MBLs but also by neutralizing tissue-damaging metalloproteases in P. aeruginosa infections.

DOI： 10.1128/AAC.00511-10

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Multidrug-resistant Pseudomonas aeruginosa (MDRP) is becoming a serious problem in hospitals, especially in patients on ventilators. Recent data demonstrate that colistin may be effective for these patients, although limited in vitro and in vivo data are available. Our aim was to identify further characteristics of colistin for the therapy of pneumonia caused by MDRP.
The effects of colistin on clinical strains of MDRP were examined by susceptibility test, time-kill assay, lipopolysaccharide (LPS)-blocking assay and a mouse pneumonia model, alone or in combination with other antibiotics. For the pneumonia model, mice were intranasally infected with bacteria and kept in hyperoxic conditions to mimic ventilator-associated pneumonia.
As a single agent, colistin exhibited the strongest activity of the antimicrobial agents tested. In combination, maximum synergy was observed with colistin plus rifampicin. As expected, co-incubation of bacterial culture supernatants with colistin significantly reduced LPS activities with an associated decrease in cellular cytotoxicity. In the pneumonia model, intranasal, but not intravenous, colistin combined with rifampicin produced maximum survival protection. Pharmacokinetic analysis of colistin demonstrated the superiority of intranasal administration, judging from the compartmentalized high concentration and the long half-life in the lungs. Moreover, colistin therapy significantly decreased both production of inflammatory cytokines and LPS activity, even at a dose effecting no change in the bacterial burden in the lung.
These data strongly suggest that colistin may be an important option for combination therapy against critical MDRP infections. For pneumonia especially, intranasal colistin with rifampicin may be beneficial not only for synergistic antibacterial activity, but also for blocking LPS.

DOI： 10.1093/jac/dkn530

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Multidrug-resistant Pseudomonas aeruginosa (MDRP) is becoming a serious problem in hospitals, especially in patients on ventilators. Recent data demonstrate that colistin may be effective for these patients, although limited in vitro and in vivo data are available. Our aim was to identify further characteristics of colistin for the therapy of pneumonia caused by MDRP.
The effects of colistin on clinical strains of MDRP were examined by susceptibility test, time-kill assay, lipopolysaccharide (LPS)-blocking assay and a mouse pneumonia model, alone or in combination with other antibiotics. For the pneumonia model, mice were intranasally infected with bacteria and kept in hyperoxic conditions to mimic ventilator-associated pneumonia.
As a single agent, colistin exhibited the strongest activity of the antimicrobial agents tested. In combination, maximum synergy was observed with colistin plus rifampicin. As expected, co-incubation of bacterial culture supernatants with colistin significantly reduced LPS activities with an associated decrease in cellular cytotoxicity. In the pneumonia model, intranasal, but not intravenous, colistin combined with rifampicin produced maximum survival protection. Pharmacokinetic analysis of colistin demonstrated the superiority of intranasal administration, judging from the compartmentalized high concentration and the long half-life in the lungs. Moreover, colistin therapy significantly decreased both production of inflammatory cytokines and LPS activity, even at a dose effecting no change in the bacterial burden in the lung.
These data strongly suggest that colistin may be an important option for combination therapy against critical MDRP infections. For pneumonia especially, intranasal colistin with rifampicin may be beneficial not only for synergistic antibacterial activity, but also for blocking LPS.

DOI： 10.1093/jac/dkn530

Web of Science

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Language：Japanese   Publisher：(一社)日本内科学会  

症例1は67歳男性で、Behcet病に伴う皮疹と診断され、8ヵ月前より、皮膚科からプレドニゾロン(PSL)およびジアフェニルスルホン(DDS)が処方されていた。数日前からの頭痛を訴え、室内気でSpO2 89%と低下していた。Hb 7.5g/dlと貧血あり、白血球10950/μl、CRP 20.05mg/dlと高度の炎症所見を認めた。室内気での動脈血液ガス分析(BGA)でSaO2 95.6%であり、SpO2とSaO2の乖離(saturation gap)を認め、メトヘモグロビン(MetHb)3.3%と上昇していた。症例2は69歳男性で、骨髄異形成症候群に伴うSweet病のため、3ヵ月前より皮膚科からPSLおよびDDSが処方されていた。肝機能障害のために入院となり、無症状であったが入院時よりSpO2 90%以下が持続したため、酸素吸入を開始された。その後もSpO2低値が遷延した。酸素吸入下のBGAでSaO2 90.8%と軽度のsaturation gapを認め、MetHb 7.4%と上昇していた。症例3は40歳男性で、潰瘍性大腸炎に伴う壊疽性膿皮症のため、4ヵ月前より皮膚科からDDSが処方されていた。潰瘍性大腸炎の通院治療のために来院した際、無症状であったがSpO2低下を認めたため入院した。室内気でSpO2 92%と低下していた。軽度の炎症反応上昇が認められた。BGAでSaO2 97.7%とSaturation gapを認め、MetHb 3.2%と上昇を認めた。いずれの症例も、皮膚科より処方されていたDDSによる薬剤性MetHb血症を疑い、DDS内服を中止した。その結果、1週後にはMetHb分画の低下と共にSpO2の上昇が認められた。

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01159&link_issn=&doc_id=20210316070034&doc_link_id=10.2169%2Fnaika.110.622&url=https%3A%2F%2Fdoi.org%2F10.2169%2Fnaika.110.622&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：(一社)日本呼吸ケア・リハビリテーション学会  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00990&link_issn=&doc_id=20200413110004&doc_link_id=%2Fdg3nigta%2F2019%2F013303%2F004%2F0108-0109%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2019%2F013303%2F004%2F0108-0109%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本感染症学会  

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症例は52歳、男性。慢性骨髄性白血病(CML)に対してX-4年からメシル酸イマチニブ(imatinib mesylate、以下イマチニブ)、X-2年からニロチニブ、X-1年からダサチニブを開始された。X年11月ごろより息切れが出現し、胸部X線、胸部CTで浸潤影、両側胸水を認めた。抗菌薬と利尿剤を開始されたが改善を認めず、当科を紹介受診した。経気管支肺生検で得られた生検組織で肺胞腔内にポリープ状線維化巣を認め、器質化肺炎と診断した。ダサチニブを中止してステロイド治療を行い、臨床症状、画像所見の改善を認めた。その後CMLに対して、イマチニブ、ニロチニブを投与したが治療効果を認めなかった。ステロイド併用下でダサチニブを再投与し、器質化肺炎の再燃なくCMLをコントロールすることができた。ダサチニブによる器質化肺炎はまれであり、これまで報告はない。ステロイド治療によりダサチニブの再投与が可能であった器質化肺炎の症例を経験したので、文献的考察を含め報告する。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00296&link_issn=&doc_id=20180528410016&doc_link_id=%2Fab8gtkrc%2F2018%2F004505%2F017%2F0851-0854%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fab8gtkrc%2F2018%2F004505%2F017%2F0851-0854%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER THORACIC SOC  

Web of Science

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(NPO)日本呼吸器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

DOI： 10.11477/mf.1542200797

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本結核病学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER THORACIC SOC  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：Japanese   Publisher：(一社)日本結核病学会  

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J-GLOBAL

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER THORACIC SOC  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本呼吸器学会  

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Language：Japanese   Publisher：(一社)日本感染症学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER THORACIC SOC  

Web of Science

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

CiNii Article

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Other Link： http://search.jamas.or.jp/link/ui/2011328810

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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