The Metabolism of Methazolamide in Immortalized Human Keratinocytes, HaCaT Cells.

Objective: Drug therapy is occasionally accompanied by an idiosyncratic severe toxicity, which occurs very rarely, but can lead to patient mortality. Methazolamide, an anti-glaucomatous agent, could cause severe skin eruptions called Stevens-Johnson syndrome/toxic epidermal necrolyis (SJS/TEN). Its precise etiology is still uncertain.

Afatinib successfully treated leptomeningeal metastasis during erlotinib treatment in a patient with EGFR-mutant (Exon18:G719S) lung adenocarcinoma as a second-line chemotherapy.

Exon18 mutations are detected in 3.6% of epidermal growth factor receptor mutations. Exon 18 mutations as driver mutations have higher sensitivities in vitro to second-generation (G)-tyrosine kinase inhibitors (TKIs) than to first G- and third G-TKIs at clinically relevant doses.

Performance evaluation of Xpert MTB/RIF in a moderate tuberculosis incidence compared with TaqMan MTB and TRCRapid M.TB.

Xpert MTB/RIF is an automated nucleic acid amplification test (NAT) that can detect the presence of Mycobacterium tuberculosis complex (MTC) in clinical specimens as well as rifampicin (RIF) resistance resulting from rpoB mutation. Despite its high sensitivity and specificity for diagnosing tuberculosis (TB) with or without RIF resistance, the clinical performance of the test is variable. In this study, we evaluated the performance of Xpert MTB/RIF in a setting of moderate TB burden and high medical resources.

Successful retreatment with osimertinib after osimertinib-induced acute pulmonary embolism in a patient with lung adenocarcinoma: A case report.

Pulmonary embolism (PE) can be life-threatening, and it is challenging to diagnose because of its nonspecific signs and symptoms. PE is also an important potential risk of osimertinib treatment, however, clinical courses regarding retreatment after osimertinib-induced acute pulmonary embolism remain unclear. We described a 77-year-old woman with postoperative recurrent lung adenocarcinoma who developed osimertinib-induced acute PE.

[EXAMINATION OF THE EFFECTIVENESS OF SLOW AND DEEP INHALATION OF FP/FM-pMDI FOR THE SMALL-AIRWAYS DYSFUNCTION OF ADULT-ONSET ASTHMA].

Backgrounds: To date adult-onset asthmatic patients who lack a clear stridor and show prolonged coughs and chest discomfort caused by small-airways dysfunction have increased. We examined the small-airways function of these cases and the effectiveness of slow and deep inhalation of FP/FM-pMDI.

Methods: 62 adult-onset asthmatic patients who had prolonged coughs and chest discomfort with the middle or high dose of ICS/LABA combination agents under well technique (32 of BUD/FM-DPI group and 30 of FP/SM-pMDI group) were included into this study.

Phase II study of erlotinib plus tivantinib (ARQ 197) in patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer just after progression on EGFR-TKI, gefitinib or erlotinib.

Background: Patients with epidermal growth factor receptor (EGFR) activation mutation-positive non-small-cell lung cancer (NSCLC) respond well to EGFR tyrosine kinase inhibitors (EGFR-TKIs), but eventually become resistant in most cases. The hepatocyte growth factor/c-Met (HGF/c-Met) pathway is reported as a poor prognostic factor in various cancers. As c-Met is involved in EGFR-TKI resistance, a c-Met inhibitor and EGFR-TKI combination may reverse the resistance.

Turkish and Japanese Mycobacterium tuberculosis sublineages share a remote common ancestor.

Two geographically distant M. tuberculosis sublineages, Tur from Turkey and T3-Osaka from Japan, exhibit partially identical genotypic signatures (identical 12-loci MIRU-VNTR profiles, distinct spoligotyping patterns). We investigated T3-Osaka and Tur sublineages characteristics and potential genetic relatedness, first using MIRU-VNTR locus analysis on 21 and 25 samples of each sublineage respectively, and second comparing Whole Genome Sequences of 8 new samples to public data from 45 samples uncovering human tuberculosis diversity.

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

Background: Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis.

Methods: In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo.

[THE COMPARISON OF EFFECTIVENESS OF SLOW SPECIFIC ORAL IMMUNOTHERAPY FOR WHEAT ALLERGY USING TWO DIFFERENT INTAKE FREQUENCY].

Objective: We performed a constructive study on the effectiveness of oral immunotherapy for wheat allergy using two different intake frequency, and evaluated the impact of intake frequency.

Subjects: Of all the subjects who had a positive result in an oral food challenge test for udon (wheat noodles), informed consent was obtained from 49 subjects. Forty-one of the subjects successfully completed testing; data was tabulated for only the 16 in each group who complied with their assigned intake frequency.

Endoscopic bronchial occlusion with silicone spigots under virtual bronchoscopic navigation.

A 68-year-old woman with interstitial lung disease related to dermatomyositis and systemic scleroderma was admitted to our hospital with fever and dyspnoea. Although the fever was reduced after antibiotic therapy, a left pneumothorax suddenly occurred on day 27 after admission. A continuous air leak persisted despite chest drainage with three tubes and repeated pleurodesis.

Long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with severe uncontrolled asthma.

Background: Omalizumab is effective and well-tolerated in children with moderate to severe allergic asthma. However, the effects of long-term treatment with omalizumab in this population haven't been well investigated. The objective of this study is to evaluate the long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with uncontrolled severe asthma.

Endoscopic Bronchial Occlusion with Silicon Spigots for the Treatment of an Alveolar-pleural Fistula during Anti-tuberculosis Therapy for Tuberculous Empyema.

A prolonged air leak caused by pulmonary tuberculosis is difficult to treat, and little is known about optimal treatment strategies. We herein report the case of a 60-year-old man who demonstrated tuberculous empyema with a fistula. An air leak from a tuberculous cavity in his left upper lobe persisted for approximately 4 months; surgical repair could not be performed due to a poor physical status and undernourishment.

Vascular Endothelial Growth Factor in Plasma and Pleural Effusion Is a Biomarker for Outcome After Bevacizumab plus Carboplatin-Paclitaxel Treatment for Non-small Cell Lung Cancer with Malignant Pleural Effusion.

Aim: Malignant effusion is associated with high serum and plasma levels of vascular endothelial growth factor (VEGF). There are no biomarkers of outcome for bevacizumab treatment in patients with malignant pleural effusion (MPE). We previously reported that carboplatin-paclitaxel plus bevacizumab was effective for patients with advanced non-squamous non-small cell lung cancer (NSCLC) and MPE, although we did not evaluate the relationship between treatment outcomes and plasma or pleural effusion levels of VEGF.

Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G).

Background: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab.

Patients And Methods: WJOG4407G was a randomized, open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease.

Radial endobronchial ultrasound with a guide sheath for diagnosis of peripheral cavitary lung lesions: a retrospective study.

Background: Radial endobronchial ultrasound with a guide sheath (EBUS-GS) has improved the diagnostic outcomes of peripheral lung lesions. However, to our knowledge, reports on the use of EBUS-GS for diagnosis of cavitary lesions are unavailable. Therefore, this study aimed to assess the effectiveness and safety of EBUS-GS for diagnosis of peripheral cavitary lung lesions (PCLLs).

A heterochronic genetic change from an EGFR mutation to an ALK rearrangement in a patient with lung adenocarcinoma: a case report.

An 87-year-old man with postoperative recurrent lung adenocarcinoma was treated with gefitinib. At the beginning of treatment, surgically resected archived tumor tissue revealed a deletion in exon 19 of the EGFR gene, but no ALK gene rearrangement. After gefitinib treatment for 9 months, the disease progressed.

Chemotherapy for patients with advanced lung cancer receiving long-term oxygen therapy.

Background: Long-term oxygen therapy (LTOT) is sometimes prescribed for patients with advanced lung cancer who are potential candidates for chemotherapy. The aim of this study was to assess the usefulness of chemotherapy for patients with this disease who require LTOT.

Methods: The medical records of 40 patients with advanced lung cancer who received LTOT while undergoing systemic chemotherapy at our institution between January 2009 and December 2014 were retrospectively reviewed.

Bevacizumab beyond disease progression after first-line treatment with bevacizumab plus chemotherapy in advanced nonsquamous non-small cell lung cancer (West Japan Oncology Group 5910L): An open-label, randomized, phase 2 trial.

Background: Bevacizumab combined with platinum-based chemotherapy has been established as a standard treatment option in the first-line setting for advanced nonsquamous non-small cell lung cancer (NSCLC). However, there has been no evidence to support the use of bevacizumab beyond disease progression in such patients.

Methods: West Japan Oncology Group 5910L was designed as a multicenter, open-label, randomized, phase 2 trial of docetaxel versus docetaxel plus bevacizumab every 3 weeks for patients with recurrent or metastatic nonsquamous NSCLC whose disease had progressed after first-line treatment with bevacizumab plus a platinum-based doublet.

Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ hybridisation (FISH) analyses.

Aims: Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7-9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging.

Methods: To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.

Risk of developing active tuberculosis in rheumatoid arthritis patients on adalimumab in Japan.

Setting: Nationwide study in Japan.

Objective: To identify the clinical characteristics of and risk factors for tuberculosis (TB) in rheumatoid arthritis (RA) patients receiving adalimumab.

Design: A post hoc case-control study involving 7755 RA patients evaluated in an all-case post-marketing surveillance of adalimumab from 18 June 2008 to 20 January 2011 and spontaneous report of TB during adalimumab treatment.

Development and validation of asthma questionnaire for assessing and achieving best control in preschool-age children.

Background: Several patient-/caregiver-completed questionnaires have been utilized for the assessment of asthma control. However, due to the diversity in medical/social circumstances, they may not be optimal for use in all countries. The Japanese pediatric asthma guideline (JPGL) aims at higher levels of control compared with other international guidelines, based on a strong social demand for best care.

A phase II study of pemetrexed plus carboplatin followed by maintenance pemetrexed as first-line chemotherapy for elderly patients with advanced non-squamous non-small cell lung cancer.

A phase I study recommended carboplatin (CBDCA, area under the curve = 5) plus pemetrexed (PEM, 500 mg/m(2)) for elderly patients (≥75-years old) with non-squamous non-small cell lung cancer (NSCLC). PEM maintenance therapy was well tolerated. We conducted a multicenter phase II trial to evaluate the efficacy and safety of this regimen in elderly patients with NSCLC.