Niro Okimoto

Clinical Utility of the QuantiFERON TB-2G Test for Elderly Patients With Active Tuberculosis

OBJECTIVE To evaluate the response to the QuantiFERON-TB-2 Gold (QFT-2G) test (Cellestis Ltd; Carnegie, VIC, Australia) in elderly patients with active tuberculosis (TB) to determine whether the QFT-2G test might be a feasible method for diagnosing TB infection in this group of patients. METHODS The subjects were 30 elderly patients with active TB and 100 younger patients with active TB. The QFT-2G test results were analyzed in relation to combined and separate responses to early secretory antigenic target 6-kD (ESAT-6) protein and culture filtrate protein 10 (CFP-10) antigens. RESULTS Of the 30 elderly patients with active TB, 27% had a positive tuberculin skin test (TST) result and 77% had a positive QFT-2G test result. Of the 100 younger patients with active TB, 70% had a positive TST result and 87% had a positive QFT-2G test result. Although there was no significant difference between the two patient groups in the positive rate for the QFT-2G test results (p = 0.185), there was a significant difference in the rates of positive TST results between the elderly and younger patients (p = 0.012). The positive test result rate for both ESAT-6 and CFP-10 antigens in the elderly patients (17%) was significantly lower than that in younger patients (37%; p = 0.038). There was an indeterminate result for the QFT-2G test in five elderly patients, and this might have been related to the presence of lymphocytopenia due to underlying disease. A negative result on the QFT-2G test was detected in two elderly patients, and this might have been related to the severity of the active TB. CONCLUSION We confirmed that the QFT-2G test might be a more useful method of diagnosing TB infection than the TST for elderly patients if peripheral lymphocyte counts have been preserved.

Phase I/II study of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer.

Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age ⩽75 years, and adequate organ function were eligible. Both docetaxel and cisplatin were given on days 1, 8, 29, and 36. Doses of docetaxel/cisplatin (mg m−2) in the phase I study portion were escalated as follows: 20/30, 25/30, 30/30, 30/35, 30/40, 35/40, 40/40, and 45/40. Beginning on day 1 of chemotherapy, thoracic radiotherapy was given at a total dose of 60 Gy with 2 Gy per fraction over 6 weeks. In the phase I portion, the maximum tolerated doses (MTD) among 33 patients were docetaxel 45 mg m−2 and cisplatin 40 mg m−2. The major dose-limiting toxicity (DLT) was radiation oesophagitis. The recommended doses (RDs) for the phase II study were docetaxel 40 mg m−2 and cisplatin 40 mg m−2. A total of 42 patients were entered in the phase II portion. Common toxicities were leukopenia, granulocytopenia, anaemia, and radiation oesophagitis, with frequencies of grade ⩾3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66–91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.

Macrolide-Resistant Mycoplasma pneumoniae Pneumonia in Adolescents and Adults: Clinical Findings, Drug Susceptibility, and Therapeutic Efficacy

ABSTRACT We investigated differences in the clinical findings between 30 patients with macrolide-resistant Mycoplasma pneumoniae pneumonia and 43 patients with macrolide-sensitive M. pneumoniae pneumonia in adolescents and adults. No differences in clinical presentation were observed between the two groups. Among patients with macrolide-resistant Mycoplasma pneumoniae pneumonia, treatment was more effective in the groups that received quinolones and minocycline than in the group that received macrolides (P = 0.0361 and P = 0.0237, respectively).

Setting a standard for the initiation of steroid therapy in refractory or severe Mycoplasma pneumoniae pneumonia in adolescents and adults.

Serum interleukin (IL)-18 level was thought to be a useful as a predictor of refractory or severe Mycoplasma pneumoniae pneumonia, and steroid administration is reported to be effective in this situation. The serum levels of IL-18 correlated significantly with those of lactate dehydrogenase (LDH). The purpose of this study was to set a standard for the initiation of steroid therapy in M. pneumoniae pneumonia using a simple serum marker. We analyzed 41 adolescent and adult patients with refractory or severe M. pneumoniae pneumonia who received steroid therapy, and compared them with 108 patients with M. pneumoniae pneumonia who responded to treatment promptly (control group). Serum LDH levels were significantly higher in the refractory and severe group than in the control group at the initiation of steroid therapy (723 vs 210 IU/L, respectively; p < 0.0001). From receiver operating characteristic curve analysis, we calculated serum LDH cut-off levels of 364 IU/L at initiation of steroid therapy and 302 IU/L at 1-3 days before the initiation of steroid therapy. The administration of steroids to patients in the refractory and severe group resulted in the rapid improvement of symptoms and a decrease in serum LDH levels in all patients. Serum LDH level can be used as a useful parameter to determine the initiation of steroid therapy in refractory or severe M. pneumoniae pneumonia. A serum LDH level of 302-364 IU/L seems to be an appropriate criterion for the initiation of steroid therapy.

Diagnostic sensitivity of a rapid antigen test for the detection of Mycoplasma pneumoniae: Comparison with real-time PCR.

A rapid antigen kit for the detection of the Mycoplasma pneumoniae ribosomal protein L7/L12 using an immunochromatographic assay, Ribotest Mycoplasma, became available in Japan in 2013. To determine the sensitivity of Ribotest compared with real-time polymerase chain reaction (PCR), we prospectively performed these two tests simultaneously in adolescent and adult patients with community-acquired pneumonia (CAP). In addition, we retrospectively analyzed the theoretical sensitivity of Ribotest using M. pneumoniae PCR-positive specimens from previous studies. In prospective study, 118 CAP cases were enrolled, and 16 cases were diagnosed as M. pneumoniae pneumonia; eight cases were PCR-positive, one case was culture positive, and all cases demonstrated a four-fold increase in antibody titer. Ribotest was positive in 15 cases; five cases were PCR positive and 10 cases were PCR negative. For the PCR was control test, the sensitivity, specificity, and overall agreement with Ribotest were 62.5%, 90.9%, and 88.9%, respectively. In the retrospective study, we used 1110 M. pneumoniae PCR-positive specimens, which are collected from pediatric patients with respiratory tract infection who visited 65 institutions throughout Japan. Using a cut-off level for the Ribotest of 8.3 × 10(4) copy/mL in transport medium, 667 (60.0%) specimens were theoretically positive. In conclusion, our prospective and retrospective results demonstrated that the diagnostic sensitivity of Ribotest compared with PCR was not high, at approximately 60%. Thus, treatment decisions about M. pneumoniae pneumonia should be based on clinical findings such as Japanese Respiratory Society scoring system and not on Ribotest results alone.

QuantiFERON TB-2G test for patients with active tuberculosis stratified by age groups

We evaluated the usefulness of the QuantiFERON TB-2G (QFT-2G) test and the tuberculin skin test (TST) in patients with active tuberculosis (TB) disease stratified by age in 10-year increments. Although the positive rate on TST was over 80% in younger patients aged ≤9 years, it decreased to 55% in patients of aged 70–79 years and 33% in patients aged over 80 years. However, the positive rate on QFT-2G test was over 80% for the age groups between 10–19 and 60–69 years, excluding younger patients aged ≤9 years. Furthermore, the rate was 79% in patients aged 70–79 years and 75% in patients over 80 years of age. The positive response rate of the QFT-2G test was significantly higher than that of the TST in patients over 50 years of age. The indeterminate result of the QFT-2G test increased with age and it is suggested that this result is concerned with the severity of underlying diseases in patients with active TB disease. Although the positive rate on QFT-2G test decreased with age in adults, it is thought to be a useful supportive diagnostic method for active TB disease compared to the TST, except in younger patients aged ≤9 years old.

Clinical evaluation for diagnosing active TB disease and transitional change of two commercial blood tests

We compared the usefulness of TST, QFT-TB and T-SPOT.TB for the identification of patients with active tuberculosis (TB) disease and investigated transitional change in both tests during anti-tuberculous treatment. The subjects were 50 healthy volunteers and 48 patients with active TB disease between October 2005 and December 2006. Among active TB disease patients, 60% had a positive TST result, 81% had a positive QFT-TB result, and 87% had a positive T-SPOT.TB result. Indeterminate results of QFT-TB and T-SPOT.TB were recognized in 12% and 6% of patients, respectively. Negative results on QFT-TB and T-SPOT.TB were 6% each. QFT-TB had a sensitivity of 81% for active TB disease. T-SPOT.TB had a sensitivity of 88% for active TB disease. With regard to transitional changes in QFT-TB results and T-SPOT.TB results, both test results showed a positive response in over 40% of patients 12 months after anti-tuberculous treatment. In conclusion, both blood assays seemed to be more useful than TST for the identification of patients with active TB disease. However, neither of the 2 blood tests appears to provide any certainty regarding the cure of infection.

Fractionated administration of irinotecan and cisplatin for treatment of non-small-cell lung cancer: a phase II study of Okayama Lung Cancer Study Group

A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg m–2 was given first and followed by CPT-11 at a dose of 50 mg m–2. Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32–63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities.

Urinastatin (Kunitz-Type Proteinase Inhibitor) Reducing Cisplatin Nephrotoxicity

The authors investigated the reductive effects of a Kunitz-type proteinase inhibitor, urinastatin, on the nephrotoxicity seen in lung cancer patients treated with cisplatin by measuring N-acetyl-beta-D-glucosaminidase (NAG) activity and beta 2-microglobulin (BMG) content in 24 hour urine, creatinine clearance, blood urea nitrogen (BUN), serum creatinine, uric acid, and BMG as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental urinastatin, the 24 hour urine NAG and BMG levels increased more than three-fold over the pretreatment levels, 3 days after anticancer therapy, respectively. Creatinine clearance significantly decreased and levels of BUN, serum uric acid, and BMG in control patients significantly increased over the corresponding pretreatment levels, 3 days after anticancer therapy. However, supplemental urinastatin reduced abnormalities in levels of all these factors 3 days after therapy. These results suggest that supplemental urinastatin protects from cisplatin-induced nephrotoxicity, especially proximal tubular damage.

Clinical features of Q fever pneumonia

Abstract:  The aim of the study was to assess the clinical features of Q fever pneumonia in Japan. Four cases of Q fever pneumonia (a female aged 21 and males aged 53, 74 and 87 years) who were diagnosed using the PanBio ELISA test kit, were assessed and their clinical features are described. The frequency of Q fever pneumonia among our cases of community‐acquired pneumonia was 1.4% (4/284). A 21‐year‐old female had a typical case of the disease with (i) a history of owning a cat, (ii) onset with fever and dry cough, (iii) multiple soft infiltrative shadows on CXR, (iv) a normal white blood cell count, and (v) good response to clarithromycin. The pneumonias in the other three cases were considered mixed infections with bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Their clinical features included the following: (i) an elderly person with an underlying disease, (ii) onset with fever and purulent sputum, (iii) coarse crackles on auscultation, (iv) infiltrative shadows and pleural effusion on CXR, (v) increased white blood cells with elevated BUN and hyponatraemia, and (vi) modest responses to combined therapy with carbapenem and minocycline. Our observations suggest that two types of pneumonia caused by Coxiella burnetti exist; one with the usual features of atypical pneumonia, and the other presenting with the clinical features of bacterial pneumonia in the elderly due to mixed bacterial infection.