Yu Hara

Stereotactic body radiotherapy for chronic obstructive pulmonary disease patients undergoing or eligible for long-term domiciliary oxygen therapy.

A major cause of death in patients undergoing long-term domiciliary oxygen therapy (LTOT) is lung cancer progression. In our institution, we actively perform stereotactic body radiotherapy (SBRT) on patients with early-stage non–small-cell lung cancer undergoing LTOT. In this study, we retrospectively analyzed the treatment efficacy and safety of SBRT for patients with T1-3N0M0 non–small-cell lung cancer who had been prescribed LTOT for treatment of chronic obstructive pulmonary disease (COPD). A total of 24 patients were studied. Their median age was 74 years (range, 63–87 years). The median duration from the start of LTOT to SBRT was 23 months (range, 0–85 months). Four of the 24 patients underwent lobectomy due to lung cancer. The median follow-up duration was 29 months (range, 5–79 months). One patient had a local recurrence. The median survival time was 30 months. The 3-year overall survival was 49%. In 6 of the 24 patients (25%), COPD presented with interstitial pneumonia. The 3-year overall survival for patients with COPD without interstitial pneumonia was significantly better than that for patients with both COPD and interstitial pneumonia (67% and 0%, respectively; P < 0.0001). Grade 5 radiation pneumonitis occurred in one patient (4%) with COPD with interstitial pneumonia. SBRT was tolerated by patients with early-stage non–small-cell lung cancer undergoing LTOT. SBRT should be considered for patients undergoing LTOT. However, clinicians should consider the risk of severe radiation pneumonitis in patients with interstitial pneumonia.

Successful diagnosis of tuberculous lymphadenitis by loop-mediated isothermal amplification of cutaneous samples from an ulcerated surface lesion: a case report

IntroductionTuberculous lymphadenitis is the most frequent form of extrapulmonary tuberculous. Although nucleic acid amplification assays such as polymerase chain reaction have recently become mainstream techniques for diagnosing tuberculous lymphadenitis, they are still not routinely performed in developing countries because of their high costs and complicated procedures.Case presentationWe describe a case of tuberculous lymphadenitis in a 79-year-old Japanese man who had been on continuous hemodialysis for end-stage renal disease. We employed loop-mediated isothermal amplification and the procedure for ultrarapid extraction to develop a fast and easy-to-perform procedure for diagnosing tuberculous lymphadenitis.ConclusionsThe commercially available loop-mediated isothermal amplification assay kit and a rapid purification procedure enabled us to identify and amplify a Mycobacterium tuberculosis–specific gene within just 1.5 hours.

Mortality and severity evaluation by routine pneumonia prediction models among Japanese patients with 2009 pandemic influenza A (H1N1) pneumonia.

BACKGROUND Influenza-related pneumonia, referred to as influenza pneumonia, was reported relatively more frequently during a recent influenza pandemic in 2009. The validity of adapting routine pneumonia severity prediction models for various types of pneumonia is unclear. METHODS We conducted a nationwide survey to evaluate influenza pneumonia among adult patients in Japan. Questionnaires were sent to physicians working in departments of respiratory medicine at 2491 hospitals. Both the outcome and pneumonia severity, using invasive positive pressure ventilation (IPPV) as an indicator, were evaluated by routine pneumonia severity index (PSI), CURB-65 (confusion, urea, respiratory rate, blood pressure, and age ≥ 65 years), and A-DROP (age, dehydration, respiration, disorientation, and blood pressure). RESULTS Data collected from 320 patients with influenza pneumonia, including 25 cases (7.8%) of death and 43 (13.4%) of IPPV, were analyzed. Although all routine prediction models showed that higher mortality tended to be associated with a higher risk class/grade, the actual mortality rates were higher than predicted. The risk class of mortality calculated by the PSI was influenced by pneumonia patterns. Although pneumonia severity was similarly predicted, the types of pneumonia also affected severity in all prediction models. A-DROP showed the highest accuracy on receiver operating characteristic analysis for both mortality and severity. CONCLUSIONS CURB-65 and A-DROP are fair predictors of mortality regardless of pneumonia patterns. However, the current pneumonia prediction models may underestimate the severity and appropriate site of care for patients with influenza pneumonia.

Clarithromycin mitigates radiation pneumonitis in patients with lung cancer treated with stereotactic body radiotherapy

Background Radiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT). Methods Among consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ≥6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis. Results Five hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ≥ grade 2 and ≥ grade 3 were significantly lower in CAM-era (grade ≥2, 16% vs. 9.6%, P=0.047; grade ≥3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ≥ grade 3 was significantly lower, and that of grade ≥2 had a lower tendency (grade ≥3, 7.2% vs. 0%, P=0.011; grade ≥2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ≥ grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ≥ grade 2 and ≥ grade 3. Conclusions CAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be confirmed in prospective studies.

The Platelet Count can Predict In-hospital Death in HIV-negative Smear-positive Pulmonary Tuberculosis Inpatients

Objective This retrospective cohort study investigated whether the three components of the blood cell count have prognostic implications in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis. Methods We reviewed patients who were treated by the isoniazid, rifampicin, pyrazinamide, and ethambutol regimen or by the isoniazid, rifampicin, and ethambutol regimen. The association between the patient data on admission and the survival outcome was evaluated. Results We reviewed 367 consecutive patients (male, 60.5%) with a median age of 72 [interquartile range (IQR), 54-82] years. While the white blood cell count did not differ between the two groups, (discharged alive: 7,000/μL; IQR, 5,500-9,300; died in hospital: 7,200/μL; IQR, 5,600-9,400; p=0.797), hemoglobin level (discharged alive: 11.5 g/dL; IQR, 10.0-13.1; died in hospital: 9.9 g/dL; IQR, 8.6-11.3; p<0.001) and the platelet count (discharged alive: 275,000/μL; IQR, 206,000-345,000; died in hospital: 149,000/μL; IQR, 93,000-236,000; p<0.001) were lower in patients who died in hospital. After dividing patients into hemoglobin- and platelet-based quantiles, the lower quantile class tended to show poorer survival (log-rank test for trend p<0.001 for both). A multi-variable Cox proportional hazards model revealed that hazard ratio for in-hospital death for every 1,000/μL increase of platelet count was 0.997 (95%CI, 0.995-0.999; p=0.010); the hazard ratio for the hemoglobin level was not significant. Conclusion A low platelet count was clearly related to a poor life prognosis in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis.

Acute eosinophilic pneumonia caused by camostat mesilate: The first case report

Camostat mesilate is in widespread clinical use mainly to treat chronic pancreatitis, and drug-induced lung injury has not been previously reported. However, pulmonary infiltration with peripheral blood eosinophilia appeared after taking camostat mesilate for ten days. The histological findings showed eosinophilic infiltration into the alveolar space and interstitum, and drug lymphocyte stimulation test of peripheral blood was positive. Both peripheral blood eosinophilia and pulmonary involvements improved two weeks later with the cessation of this drug. To the best of our knowledge, this case is the first report of camostat mesilate-induced acute eosinophilic pneumonia.

HbA1c level cannot predict the treatment outcome of smear-positive non-multi-drug-resistant HIV-negative pulmonary tuberculosis inpatients

We conducted a single-center retrospective cohort study to evaluate whether the HbA1c level on admission could predict the in-hospital treatment outcome of smear-positive non-multi-drug-resistant HIV-negative culture-proven pulmonary tuberculosis inpatients. Our standard regimens under the direct observation were HRZE or HRE for the first two months followed by combination therapy with isoniazid and rifampicin. Our cohort consisted of consecutive 239 patients consisted of 147 men and 92 women with a median age of 73 years. The HbA1c level of patients whose HbA1c was above 7.0% on admission showed clear declining trends after admission. HbA1c on admission had no Spearman’s rank correlation with time to discharge alive (r = 0.17) and time to becoming non-infective (r = 0.17). By Kaplan-Meier curves and a log-rank trend test, HbA1c quartile subgroups showed no association with times to discharge alive (p = 0.431), becoming non-infective (p = 0.113), and in-hospital death (p = 0.427). Based on multi-variate Cox analysis, HbA1c on admission had no significant impact on time to discharge alive (hazard ratio = 1.03, 95% CI 0.89–1.20, p = 0.659), becoming non-infective (hazard ratio = 0.93, 95% CI 0.80–1.06, p = 0.277), and in-hospital death (hazard ratio = 0.68, 0.43–1.07, p = 0.097). In conclusion, the HbA1c level on admission did not seem to affect in-hospital tuberculosis treatment outcomes in Japanese cohort.

Human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient presenting with relapsing and remitting hyponatraemia.

We report a case of human herpes virus-8-associated multicentric Castleman’s disease in an HIV-positive patient with hyponatraemia. A 65-year-old man was admitted with relapsing and remitting fever, scattered skin eruptions and hepatosplenomegaly following combination antiretroviral therapy for his HIV infection. Based on histopathological findings, he was diagnosed as having human herpes virus-8-associated multicentric Castleman’s disease and was treated with four-weekly infusions of rituximab. Prior to receiving chemotherapy, we observed several suspected biomarkers of disease activity, positive correlations between plasma human herpes virus-8 viral load and the levels of plasma interleukin-6, C-reactive protein and soluble interleukin-2 receptor, and negative correlations between platelet count, albumin levels and especially serum sodium levels. We hypothesize that non-osmotic release of plasma antidiuretic hormone is a cause of hyponatraemia in human herpes virus-8-associated multicentric Castleman’s disease and that relapsing and remitting hyponatraemia could be correlated with plasma human herpes virus-8 viral load.

Biomarkers for Staging and Evaluating the Therapy for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a form of chronic fibrosing interstitial lung disease of unknown etiology and poor prognosis. The clinical course of IPF varies considerably in the severity and the rate of progression. Potential prognostic biomarkers have been suggested as markers of severity or progression, including surfactant apoproteins, matrix metalloprotease-7, circulating fibrocytes, and composite scoring systems that include biochemical, physiological, and demographic data. Biomarkers for evaluating the effects of therapy are not as well characterized, although in clinical trials, all causes of mortality, changes in the forced vital capacity, and the frequency of acute exacerbations have been used to evaluate novel therapies. Other candidate biomarkers of IPF progression that affect the deposition of extracellular matrix have also been evaluated. There is currently no consensus as to the most informative measurements that would indicate the IPF severity or predict progression and response to therapy.