Assessment of Daily Food and Nutrient Intake in Japanese Type 2 Diabetes Mellitus Patients Using Dietary Reference Intakes

Medical nutrition therapy for the management of diabetes plays an important role in preventing diabetes complications and managing metabolic control. However, little is known about actual eating habits of individuals with type 2 diabetic mellitus (T2DM), especially in Japan. Therefore, we sought to (1) assess the dietary intake of individuals with T2DM, and (2) characterize their intake relative to national recommendations. This cross-sectional study involved 149 patients (77 males and 72 females) aged 40–79 years with T2DM recruited at a Kyoto hospital. Dietary intake was assessed using a validated self-administered diet history questionnaire. Under-consumption, adequacy, and over-consumption, of nutrients were compared to the age- and sex-based standards of the Japanese Dietary Reference Intakes. Among the results, most notable are (1) the inadequacy of diets in men with respect to intake of vitamins and minerals, likely owing to low intake of vegetables and fruits; (2) excess contributions of fat intake to total energy in both sexes; and (3) excess consumption of sweets and beverages relative to the national average. The prevalence of diabetes complications may be increasing because of a major gap between the typical dietary intake of individuals with T2DM and dietary recommendation.     

Cucurbitacin B potently suppresses non-small-cell lung cancer growth: Identification of intracellular thiols as critical targets

Cucurbitacin B (CuB), has recently emerged as a potent anticancer agent; however, its efficacy in non-small-cell lung cancer (NSCLC) and the mechanism(s) initiating its biological effects remain largely unclear. In this study, CuB potently suppressed the growth of four NSCLC cells (H1299, A549, HCC-827 and H661) in vitro and the highly aggressive H1299 xenograft in vivo. CuB significantly altered the actin cytoskeletal assembly, induced G2/M cell-cycle arrest and mitochondrial apoptosis through the modulation of several key molecular targets mediating the aforementioned processes. Interestingly, all cellular effects of CuB were completely attenuated only by the thiol antioxidant N-acetylcysteine (NAC). Furthermore, pretreatment with glutathione synthesis inhibitor butithione-sulfoxime (BSO), significantly exacerbated CuB’s cytotoxic effects. To this end, cells treated with CuB revealed a rapid and significant decrease in the levels of protein thiols and GSH/GSSG ratio, suggesting disruption of cellular redox balance as the primary event in CuB’s cytotoxic arsenal. Using UV and FTICR mass spectrometry we also demonstrate for the first time a physical interaction of CuB with NAC and GSH in a cell-free system suggesting that CuB interacts with and modulates cellular thiols to mediate its anti-cancer effects. Collectively, our data sheds new light on the working mechanisms of CuB and demonstrate its therapeutic potential against NSCLC.     

MRI of diffuse liver disease: characteristics of acute and chronic diseases

Diffuse liver disease, including chronic liver disease, affects tens of millions of people worldwide, and there is a growing need for diagnostic evaluation as treatments become more readily available, particularly for viral liver diseases. Magnetic resonance imaging (MRI) provides unique capabilities for noninvasive characterization of the liver tissue that rival or surpass the diagnostic utility of liver biopsies. There has been incremental improvement in the use of standardized MRI sequences, acquired before and after administration of a contrast agent, for the evaluation of diffuse liver disease and the study of the liver parenchyma and blood supply. More recent developments have led to methods for quantifying important liver metabolites, including lipids and iron, and liver fibrosis, the hallmark of chronic liver disease. Here, we review the MRI techniques and diagnostic features associated with acute and chronic liver disease.Magnetic resonance imaging (MRI) provides superior characterization of disease processes and masses in the liver compared with computed tomography (CT) (1) but requires attention to details regarding the optimal technique needed to achieve this relative performance. Routine MRI examination of the liver should include both single shot T2-weighted and breath-hold T1-weighted images (2), as well as gadolinium enhancement with the acquisition of multiple phases. The T1-weighted precontrast images must include in-phase and out-of-phase acquisitions to assess hepatic lipid or iron content. T1-weighted pre- and postgadolinium enhanced images are acquired using a fat-suppressed three-dimensional gradient-echo (3D GRE) sequence (3). These images are most commonly acquired in the axial plane with approximately 2 mm in-plane resolution and 2–3 mm resolution in the z-axis. Using various acceleration techniques, including parallel processing and under sampling, 3D GRE images covering the entire liver from the lung bases to below the kidneys can be acquired under 15 s during a single breath hold. Dynamically enhanced postgadolinium images are acquired to characterize tumors and diffuse liver disease. The timing of the arterial phase images is critical to providing unique diagnostic information for determining the perfusion characteristics of hepatic lesions and revealing hemodynamic changes related to active liver disease. The venous and delayed recirculation phase images, sometimes referred to as “equilibrium” phase images, are used for detecting other characteristic features delineating different tumor types and for grading hepatic fibrosis related to chronic liver disease. In chronic liver disease, dynamic postgadolinium images are critical for the detection and characterization of regenerative or dysplastic nodules and hepatocellular carcinoma. The same sequences that are useful for liver evaluation allow the comprehensive evaluation of all soft tissues of the abdomen and the depiction of most of the important diseases, and thus, they facilitate the use of a universal protocol for abdominal imaging.Various etiologies have been described for diffuse liver disease (4). This review article discusses acute and chronic liver disease processes in light of the MRI features and techniques that are used for the evaluation of diffuse liver diseases.     

A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato® alprazolam for rapid seizure termination

Objective

Alprazolam administered via the Staccato® breath-actuated device is delivered into the deep lung for rapid systemic exposure and is a potential therapy for rapid epileptic seizure termination (REST). We conducted an inpatient study (ENGAGE-E-001 [NCT03478982]) in patients with stereotypic seizure episodes with prolonged or repetitive seizures to determine whether Staccato alprazolam rapidly terminates seizures in a small observed population after administration under direct supervision.

Methods

Adult patients with established diagnosis of focal and/or generalized epilepsy with a documented history of seizure episodes with a predictable pattern were enrolled. They were randomized 1:1:1 to double-blind treatment of a single seizure event with one dose of Staccato alprazolam 1.0 mg or 2.0 mg, or Staccato placebo in an inpatient unit. The primary end point of the study was the proportion of responders in each treatment group achieving seizure activity cessation within 2 min after administration of study drug and no recurrence of seizure activity within 2 h.

Results

A total of 273 patients were screened, and 116 randomized patients received treatment with the study drug in the double-blind part. The proportion of treated patients who were responders was 65.8% for each of Staccato alprazolam 1.0 mg (n = 38; p = .0392) and 2.0 mg (n = 38; p = .0392), compared with 42.5% for Staccato placebo (n = 40). Staccato alprazolam was well tolerated when administered as a single dose of 1.0 or 2.0 mg: cough and somnolence were the most common adverse events (AEs) (both 14.5%), followed by dysgeusia (13.2%). AEs were mostly mild or moderate in intensity; there were no treatment-related serious AEs.

Significance

Both 1.0 mg and 2.0 mg doses of Staccato alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated. The next step is a Phase 3 confirmatory study to demonstrate efficacy and safety of Staccato alprazolam for rapid cessation of seizures in an outpatient setting.     

Evaluation of the ARCHITECT urine NGAL assay: Assay performance,specimen handling requirements and biological variability

Objectives:NGAL (Neutrophil Gelatinase-Associated Lipocalin) has emerged as a new biomarker for the identification of acute kidney injury. Reliable clinical evaluations require a simple, robust test method for NGAL, and knowledge of specimen handling and specimen stability characteristics. We evaluated the performance of a new urine NGAL assay on the ARCHITECT analyzer.Methods:Assay performance characteristics were evaluated using standard protocols. Urine specimen storage requirements were determined and biological variability was assessed in a self-declared apparently healthy population.Results:Assay performance data showed good precision, sensitivity and lot-to-lot reproducibility. There was good short term 2–8 °C sample stability, however, long term storage samples must be kept at ? 70 °C or colder. The largest variance component in a biological variance study was within-day.Conclusions:The ARCHITECT NGAL assay proved to be a precise and reproducible assay for the determination of urine NGAL.     

Solitary fibrous tumors of the skin: a clinicopathologic study of 10 cases and review of the literature

Solitary fibrous tumor (SFT) is a relatively uncommon neoplasm that most commonly arises in the pleura. However, SFT is now known to affect various other anatomic sites as well, including rare examples in the skin, where the histologic features of this lesion may create diagnostic confusion with a variety of other spindle-cell tumors. In order to further the characterization of cutaneous SFT, all available cases of that entity were retrieved from the authors' institutional files. Immunohistochemical analysis for CD-34, CD-99, vimentin, bcl-2, factor XIIIa, S100 protein, smooth muscle actin, pankeratin, epithelial membrane antigen (EMA) and desmin was performed on those neoplasms and the corresponding clinical information was obtained whenever possible. There were eight men and two women in the study group, with a median age of 43 years. Sites of involvement included the trunk (two cases), cheek (two), scalp (one), forehead (one), lip (one), temple (one), heel (one) and toe (one). All patients were treated with local excision; only one lesion recurred locally, but it required multiple re-excisions. All of the neoplasms were composed of bland spindle cells with a variably fibrous but focally hyalinized collagenous stroma. A variety of case-specific growth patterns were observed. Mitoses were generally rare, ranging from 0 to 3 per 10 x400 microscopic fields. Immunostains showed reactivity for vimentin in all SFTs, CD-34 in 8 of 10 cases, CD-99 and bcl-2 in 4 of 10 (each) and smooth-muscle actin in 3 of 10 cases. None of the lesions was labeled for factor XIIIa, keratin, EMA, desmin or S100 protein. SFT of the skin appears to be a 'borderline' neoplasm that only uncommonly recurs. Immunoreactivity for CD-34, - especially together with bcl-2 or CD-99, or both - is helpful in identifying this tumor.     

Development of Acute Adult T-cell Leukemia Following PD-1 Blockade Therapy for Lung Cancer

Immune checkpoint inhibitors (ICIs) are widely used for the treatment of various cancers. However, paradoxical exacerbation of neoplasms, referred to as “hyperprogressive disease,” has been reported in a proportion of patients treated with anti-programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1) blockade. We herein report a case of acute adult T-cell leukemia (ATL) that developed shortly after the administration of nivolumab, a PD-1 inhibitor, to treat non-small-cell lung cancer. There were no signs of ATL before the administration of nivolumab, and seropositivity for human T-cell leukemia virus type-1 (HTLV-1) was confirmed after the development of acute ATL. We speculate that nivolumab likely contributed to the development of acute ATL.     

A case of anomalous origin of the right coronary artery from the pulmonary trunk: imaging of abnormal flow by Doppler color flow mapping

An asymptomatic 48-year-old woman was admitted to our hospital for evaluation of a precordial continuous murmur. The chest radiograph showed a normal cardiac silhouette. The resting electrocardiogram showed incomplete right bundle branch block. A multistage, graded treadmill exercise test did not affect the ST-T segment. A thallium-201 myocardial perfusion scan with a multistage ergometer exercise test showed no distinct perfusion defect. A two-dimensional echocardiogram disclosed a dilated left coronary artery arising from the left sinus of Valsalva, and a dilated right coronary artery crossing the aorta anteriorly to the pulmonary trunk. Real-time two-dimensional Doppler echocardiography of the same region showed an abnormal jet coming from the right coronary artery into the pulmonary trunk during diastole. A continuous wave Doppler flow study in the pulmonary trunk revealed a high-speed, disturbed flow which began in mid-systole, and continued during diastole. These findings were compatible with anomalous origin of the right coronary artery from the pulmonary trunk. An aortogram confirmed the diagnosis.