Kentaro Sakashita

Evaluation of QuantiFERON-TB Gold Plus for Detection of Mycobacterium tuberculosis infection in Japan

Performance of interferon-γ (IFN-γ) release assays still needs to be improved. The data on the performance of QuantiFERON-TB Gold Plus (QFT-Plus), a new-generation of QFT assay are limited. This study evaluated the diagnostic performance of QFT-Plus, and compared to that of QuantiFERON-TB Gold In-Tube (QFT-GIT). Blood samples were collected from 162 bacteriologically confirmed tuberculosis (TB) patients and 212 Mycobacterium tuberculosis-uninfected volunteers; these samples were then tested with QFT-GIT and QFT-Plus. The IFN-γ concentration of QFT-Plus was lower than that of QFT-GIT in TB patients (p < 0.001). Receiver operating characteristic curves were compared between QFT-GIT and QFT-Plus. Both assays showed area under the curve values over 0.99 without significant difference. Using the conventional cut-off (0.35 IU/mL) for QFT-GIT, QFT-Plus had a lower sensitivity of 91.1% compared to 96.2% (p = 0.008) at its optimum cut-off (0.168 IU/mL) with the same specificity. Moreover, IFN-γ values were significantly reduced with age in QFT-GIT (p = 0.035) but not in QFT-Plus. The diagnostic performance of QFT-Plus was as accurate as that of QFT-GIT despite a lack of TB7.7 antigen and despite the decrease in quantitative values. However, the cut-off value for QFT-Plus should be considered independently from that of QFT-GIT to obtain the best sensitivity without compromising specificity.

An anterior mediastinal lesion in TAFRO syndrome showing complete remission after glucocorticoid and tocilizumab therapy

Thrombocytopenia (T), anasarca (A), myelofibrosis (F), renal dysfunction (R), and organomegaly (O) (TAFRO) syndrome is a variant of multicentric Castlemans disease. We describe here a 57‐year‐old man who presented with persistent fever, pleural effusion, and ascites. He was negative for human immunodeficiency virus and human herpes virus‐8. A computed tomography scan showed an anterior mediastinal mass and small inguinal lymphadenopathy. Although a biopsy of the anterior mediastinum showed fatty tissue infiltrated with CD20 + and CD45RO + lymphocytes, a biopsy of the left inguinal lymph node revealed a hyaline vascular type of Castlemans disease. He subsequently developed severe thrombocytopenia and renal dysfunction. In addition, his bone marrow biopsy showed myelofibrosis. TAFRO syndrome was diagnosed based on the lymph node pathology and the characteristic manifestations of the syndrome. Tocilizumab and glucocorticoid therapy achieved complete remission and regression of the mediastinal mass. To our knowledge, this is the first report of TAFRO syndrome accompanied by an anterior mediastinal mass, which responded very well to therapy.

TAFRO syndrome: current perspectives

Multicentric Castleman’s disease (MCD), a distinct subtype of Castleman’s disease, is a rare, nonneoplastic, lymphoproliferative disorder. Patients with MCD present with systemic symptoms and multiple lymphadenopathy. Lymph node biopsy is necessary for the diagnosis of various histological MCD patterns including hyaline vascular, plasma cell, and mixed types. Human herpesvirus 8 (HHV8) infection was identified as an important etiology of MCD among immunocompromised patients such as those positive for human immunodeficiency virus. Although HHV8-negative MCD was reported in immunocompetent patients, the underlying etiology remains unknown. Several experts speculate that MCD in immunocompetent patients might be due to proinflammatory hypercytokinemia because of infection by a virus other than HHV8, inflammation, or neoplastic disease. In 2010, a distinct variant of HHV8-negative MCD reported in Japan was characterized by thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Recent case reports and a systematic review suggest that TAFRO syndrome might have a unique pathogenesis among HHV8-negative MCD variants. This review introduces TAFRO syndrome as a subtype of HHV8-negative MCD and offers an overview of the current perspectives on this syndrome.

Implication of Immunohistochemistry for Propionibacterium acnes in Differential Diagnosis of Necrotizing Granuloma

Propionibacterium acnes (P. acnes) have been reported to have an etiologic link with sarcoidosis. A 45-year-old Japanese woman complaining of cough for 1 month presented to our hospital. Chest computed tomography showed an irregular nodular shadow in the right upper pulmonary lobe, a finding suggestive of either pulmonary sarcoidosis or tuberculosis. Biopsy specimens from the pulmonary shadow showed necrotizing granulomas, and there were no other findings from the initial laboratory examinations that could provide a definitive diagnosis. However, immunohistochemical staining using a P. acnes-specific monoclonal antibody revealed small round bodies within the granulomas. Based on these results, we diagnosed the patient clinically with sarcoidosis, and orally inhaled ciclesonide was administered. At a 7-month follow up, the patient had improved clinically and radiologically. The outcome of this case indicates that immunohistochemical evaluation using a P. acnes antibody may be useful for diagnosing necrotizing granuloma.

A Case Series of Acute Kidney Injury during Anti-tuberculosis Treatment

Objective The standard anti-tuberculosis (TB) regimen occasionally causes acute kidney injury (AKI). The major etiology is rifampicin-induced acute interstitial nephritis. However, the standard management of AKI induced by anti-TB drugs has yet to be established. Methods We retrospectively reviewed patients with TB who developed AKI after starting standard anti-TB treatment between 2006 and 2016 at a single TB center. The clinical characteristics and the management are described. Results Among 1,430 patients with active TB, 15 (1.01%) developed AKI. The mean age (standard deviation) was 61 years (18). The median (interquartile range) time to AKI development was 45 days (21-54 days). The median serum creatinine level before anti-TB treatment was 0.7 mg/dL (0.5-1.4 mg/dL), whereas the median peak serum creatinine level after AKI onset was 4.0 mg/dL (3.08-5.12 mg/dL). Five patients (33.3%) were pathologically confirmed as having acute interstitial nephritis (AIN), and 7 patients (46.7%) had a clinical diagnosis of the disease. All anti-TB drugs were stopped, and steroids were administered to 5 (100%) patients with pathologically confirmed AIN and 3 (42.8%) patients with clinically diagnosed AIN. The renal function was normalized in 12 patients (80.0%) after restarting anti-TB treatment without rifampicin (n=12) or isoniazid (n=1). Two patients died due to severe renal failure after restarting rifampicin. Conclusion Rifampicin is the leading cause of AKI. Levofloxacin may be an alternative to rifampicin thanks to its safety and potency. Restarting anti-TB treatment without rifampicin and short-term steroid administration may be a feasible management for AKI.

Evaluation of PyroMark Q24 pyrosequencing as a method for the identification of mycobacteria

We evaluated PyroMark Q24 (QIAGEN) pyrosequencing as a method for the identification of mycobacteria, with potential application in clinical practice. Sequence data from the hypervariable region A of the 16S rRNA gene (43 and 35bp sequences) were obtained using PyroMark Q24, and a similarity search was performed automatically with PyroMark IdentiFire software. Of the 148 mycobacterial type strains tested, 138 (93.2%) were accurately identified to single or clade species level, including complex level. From the remaining 10 strains, 3 (Mycobacterium gilvum, Mycobacterium goodi, and Mycobacterium thermoresistible) showed poor sequencing quality of homopolymers. For 6 other strains (Mycobacterium cosmeticum, Mycobacterium flavescens, Mycobacterium pallens, Mycobacterium hodleri, Mycobacterium xenopi, and Mycobacterium crocinum), the sequences were unreadable from the middle, and Sanger sequencing indicated biallelic site. Finally, a 40bp sequence for Mycobacterium gordonae could not be obtained despite repeated attempts. PyroMark Q24 provided accurate identification of multiple mycobacterial strains isolated from common clinical settings, but additional gene sequencing is required to distinguish species identified as a group or complex.

Efficiency of the Lung Flute for sputum induction in patients with presumed pulmonary tuberculosis

High quality sputum helps increase the sensitivity of the diagnosis of pulmonary tuberculosis.

Predictor of success in endobronchial occlusion therapy against intractable pneumothoraces

Background: An increasing number of patients have been receiving bronchial occlusion therapies against spontaneous pneumothoraces. However, predicting which patients will benefit from the procedures remains difficult. Methods: This post-hoc analysis used data from a randomized controlled trial of the Endobronchial Watanabe Spigot (EWS) ®and fibrin glue in patients with intractable pneumothoraces. All of the patients received one or more bronchial occlusion therapies (BOTs). The success of the BOT was defined as the termination of air-leakage from the chest tubes and expansion of the affected lungs within a week of the first or second BOT. Results: The study included 22 patients (male/female: 18/4) with a median age of 68 at the initial BOT. The BOT produced the desired outcome in 13 patients. Univariate analysis suggested that a previous history of pneumothoraces and the absence of a history of heavy cigarette smoking, defined as 40 packs per year or more, are predictors of a favorable therapeutic outcome (p=0.046, 0.067). Multivariate analysis demonstrated that the absence of a history of heavy cigarette smoking significantly correlated with a favorable outcome (p=0.043). Conclusion: The results suggested that spontaneous pneumothorax patients without a history of heavy cigarette smoking may benefit from bronchial occlusion therapies using the EWS, or fibrin glue.