A Prospective Cohort Study to Assess Obstructive Respiratory Disease Phenotypes and Endotypes in Japan: The TRAIT Study Design.

Background: Asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) are complex and heterogeneous diseases that share clinical characteristics (phenotypes) and molecular mechanisms (endotypes). Whilst physicians make clinical decisions on diagnostic groups, for some such as ACO there is no commonly accepted criteria. An alternative approach is to evaluate phenotypes and endotypes that are considered to respond well to a specific type of treatment ("treatable traits") rather than diagnostic labels. Purpose: The prospective, longitudinal, and observational TRAIT study will evaluate disease characteristics, including both phenotypes and endotypes, in relation to the presentation of obstructive respiratory disease characteristics in patients diagnosed with asthma, COPD, or ACO in Japan, with the aim of further understanding the clinical benefit of a treatable traits-based approach. Patients and Methods: A total of 1500 participants will be enrolled into three cohorts according to their treating physician's diagnosis of asthma, COPD, or ACO at screening. Part 1 of the study will involve cross-sectional phenotyping and endotyping at study enrollment. Part 2 of the study will evaluate the progression of clinical characteristics, biomarker profiles, and treatment over a 3-year follow-up period. The follow-up will involve three annual study visits and three telephone calls scheduled at 6-month intervals. A substudy involving 50 participants from the asthma cohort (in which the ratio will be approximately 1:1 including 25 participants with a smoking history of ≥10 pack-years and 25 participants with no smoking history), 100 participants from the ACO cohort, and 100 participants from the COPD cohort will evaluate disease phenotypes using inspiratory and expiratory computed tomography scans. Conclusion: TRAIT will describe clinical characteristics of patients with obstructive respiratory diseases to better understand potential differences and similarities between clinical diagnoses, which will support the improvement of personalized treatment strategies

Narrow band imaging for the detection of gastric intestinal metaplasia and dysplasia during surveillance endoscopy

Background: Surveillance of premalignant gastric lesions relies mainly on random biopsy sampling. Narrow band imaging (NBI) may enhance the accuracy of endoscopic surveillance of intestinal metaplasia (IM) and dysplasia. We aimed to compare the yield of NBI to white light endoscopy (WLE) in the surveillance of patients with IM and dysplasia. Methods: Patients with previously identified gastric IM or dysplasia underwent a surveillance endoscopy. Both WLE and NBI were performed in all patients during a single procedure. The sensitivity of WLE and NBI for the detection of premalignant lesions was calculated by correlating endoscopic findings to histological diagnosis. Results: Forty-three patients (28 males and 15 females, mean age 59 years) were included. IM was diagnosed in 27 patients; 20 were detected by NBI and WLE, four solely by NBI and three by random biopsies only. Dysplasia was detected in seven patients by WLE and NBI and in two patients by random biopsies only. Sixty-eight endoscopically detected lesions contained IM: 47 were detected by WLE and NBI, 21 by NBI only. Nine endoscopically detected lesions demonstrated dysplasia: eight were detected by WLE and NBI, one was detected by NBI only. The sensitivity, specificity, positive and negative predictive values for detection of premalignant lesions were 71, 58, 65 and 65% for NBI and 51, 67, 62 and 55% for WLE, respectively. Conclusions: NBI increases the diagnostic yield for detection of advanced premalignant gastric lesions compared to routine WLE

Direct Synthesis of Azaheterocycles from N-Aryl/Vinyl Amides. Synthesis of 4-(Methylthio)-2-phenylquinazoline and 4-(4-Methoxyphenyl)-2-phenylquinoline

A flame-dried, 300-mL three-necked round-bottomed flask equipped with a 3.0 cm footballshaped stir bar, rubber septum, and low temperature thermometer is charged with benzanilide (1) (Note 1) (6.02 g, 30.5 mmol, 1 equiv), sealed under an argon atmosphere, and fitted with an argon inlet. Anhydrous dichloromethane (Note 2) (60 mL) followed by 2-chloropyridine (Note 3) (5.76 mL, 6.97 g, 61.4 mmol, 2.01 equiv) is added via syringe, and the heterogeneous mixture is vigorously stirred and cooled to <−70 °C (dry-ice–acetone bath, internal temperature). After 10 min, trifluoromethanesulfonic anhydride (Note 4) (Tf[subscript 2]O, 5.60 mL, 9.39 g, 33.3 mmol, 1.09 equiv) is added via syringe over 5 min at <−65 °C (internal temperature). After 15 min, the reaction flask is warmed to 0 °C (ice–water bath). After 5 min, the deep red solution becomes homogeneous and a solution of thiocyanic acid methyl ester (2) (Note 1) (2.52 mL, 2.67 g, 36.5 mmol, 1.20 equiv) in anhydrous dichloromethane (40 mL) is added via cannula over 5 min at 5–6 °C (Note 5). After 10 min, the cold bath is removed, and the reaction mixture is allowed to warm to 23 °C. After 2.5 h, triethylamine (Note 2) (10.0 mL, 7.26 g, 71.7 mmol, 2.35 equiv) is added via syringe over one min. The resulting mixture is concentrated with a rotary evaporator (20 mmHg, 30 °C). The remaining deep red oil is purified by flash column chromatography (Note 6) to afford quinazoline 3 (6.15 g, 80%) as an off-white solid (Note 7).National Institute of General Medical Sciences (U.S.