Longitudinal association between polypharmacy and development of pruritus: a Nationwide Cohort Study in a Japanese Population.

BACKGROUND: Although polypharmacy is known to cause side-effects due to drug-drug interactions, dermatological symptoms triggered by polypharmacy are not fully addressed. OBJECTIVE: To investigate whether polypharmacy is associated with the risk of pruritus. METHOD: A cohort study was performed to examine cross-sectional and longitudinal relationships between polypharmacy and pruritus in a general population. Data were collected from the Norm Study conducted in 2016 and 2017, which is a nationwide survey based on a self-administered questionnaire with Japanese representative participants aged 16-84 years. Presence of polypharmacy which was defined as concurrent use of ≥5 prescribed drugs. Primary outcomes were the presence of severe pruritus at baseline for the cross-sectional analysis and the development of severe pruritus after one year for the longitudinal analysis. Multivariable modified Poisson regression analyses were performed to estimate risk ratios (RRs) and 95% confidence intervals (95%CIs) with adjustment for potential confounders (age, gender, smoking habits, drinking habits, depressive symptoms, moderate activities based on IPAQ score and presence of 11 comorbid conditions including skin disease). RESULTS: The study included 3126 participants (mean age, 48.7 years); nearly half (49.8%) were male. In all, 332 participants (10.3%) had polypharmacy in the cross-sectional analysis. Participants with polypharmacy were more likely to present with severe pruritus at baseline than those who were not using drugs (adjusted RR = 1.52 [95%CI 1.15-2.01, P = 0.003]). The longitudinal analysis (n = 1803) was limited to those without severe pruritus at baseline; participants with polypharmacy at baseline were more likely to develop severe pruritus after a one-year follow-up period than those not using drugs (adjusted RR = 1.46 [95%CI 1.14-1.87, P = 0.002]). CONCLUSION: Polypharmacy was associated with the presence of pruritus at baseline and may predict the future risk of developing pruritus.

Utility of a diffusion kurtosis model in the differential diagnosis of orofacial tumours.

AIM: To compare the goodness of fit and correlations between diffusion kurtosis imaging (DKI) and a mono-exponential (ME) model, to compare the corrected apparent diffusion coefficient (Dapp) and apparent kurtosis (Kapp) of the DKI model, and the apparent diffusion coefficient (ADC) of the ME model among the various orofacial lesions, and to evaluate the diagnostic performances between the two models. MATERIALS AND METHODS: A total of 100 orofacial lesions underwent echo-planar diffusion magnetic resonance imaging (MRI) with four b-values. The goodness of fit was evaluated using Akaike information criterion. The correlations of the diffusion-derived parameters were evaluated. The diagnostic performance was analysed by receiver operating characteristics (ROC). RESULTS: The DKI model showed a significantly better goodness of fit than the ME model (p<0.0001). The Kapp had a strongly negative correlation with the Dapp (ρ=-0.749) and ADC (ρ=-0.938). A strongly positive correlation existed between the Dapp and ADC (ρ=0.906). All parameters differed significantly between benign tumours and malignant tumours (p<0.05). In differentiating benign tumours from the malignant tumours, the AUC of Dapp (0.871) was larger than that of ADC (0.805); however, a significant difference was not found (p=0.102). CONCLUSION: The DKI model had better goodness of fit than the ME model. Furthermore, the Dapp and Kapp were also characteristic for each pathological category; however, the DKI model did not yield a significantly higher diagnostic performance than the ME model, which might be related to the high correlation among the diffusion-derived parameters and wide variation among categories.

SARC-F Validation and SARC-F+EBM Derivation in Musculoskeletal Disease: The SPSS-OK Study.

OBJECTIVES: To validate the SARC-F questionnaire for sarcopenia screening in musculoskeletal disease setting, and to assess improvements in diagnostic accuracy by adding "EBM" (elderly and body mass index information) to the SARC-F. DESIGN: Diagnostic accuracy study. SETTING AND PARTICIPANTS: The center involved in this study was located in an urban area of Kobe City, Japan. People with musculoskeletal disease in the knee, hip, or spine who were scheduled for surgical treatment were included. MEASUREMENTS: Sarcopenia was evaluated using the Asian Working Group for Sarcopenia (AWGS) and the European Working Group on Sarcopenia in Older People (EWGSOP2), which included bioimpedance, handgrip strength, and gait speed. Patients answered the SARC-F questionnaire and their body mass index was measured. SARC-F and "EBM" information were combined into an original score. The sensitivities, specificities, and areas under the receiver operating characteristic curve (AUC) were estimated and compared to identify sarcopenia. RESULTS: A total of 959 patients were included. Sarcopenia by AWGS criteria was identified in 36 (3.8%) patients. SARC-F had a sensitivity of 41.7% and specificity of 68.5%. SARC-F+EBM had a sensitivity of 77.8% and specificity of 69.6%, with substantial improvement in sensitivity (P<0.001). The AUCs for SARC-F and SARC-F+EBM were 0.557 (95% confidence interval [CI] 0.452-0.662) and 0.824 (95% CI 0.762-0.886), respectively (P<0.001). Similar results were obtained when EWGSOP2 criteria were used as the reference standard. CONCLUSION: The SARC-F alone is not adequate for finding cases in musculoskeletal disease settings. SARC-F+EBM significantly improved the sensitivity and overall diagnostic accuracy of the SARC-F for screening sarcopenia. SARC-F+EBM is potentially useful for screening sarcopenia in different ethnic and disease settings.

Anterior mediastinal solid tumours in adults: characterisation using dynamic contrast-enhanced MRI, diffusion-weighted MRI, and FDG-PET/CT.

AIM: To find significant parameters to characterise anterior mediastinal solid tumours in adults using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted MRI (DWI), and combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: Forty-eight histologically confirmed anterior mediastinal solid tumours in 48 patients (24 men, 24 women; age range 21-83 years, mean 50.7 years) were examined. The parameters analysed were maximal diameter, presence of capsule/septa on T2-weighted images, time-signal intensity curves (TICs), apparent diffusion coefficient (ADC), and maximum standardised uptake value (SUVmax). Also examined was whether any differences between histological types could be seen in these parameters. In a validation study, 42 anterior mediastinal solid tumours in 42 patients were examined consecutively. RESULTS: The washout pattern on TIC was seen only in thymic epithelial tumours (20/32). SUVmax of lymphoma (mean, 17.9), malignant germ cell tumours (14.2), and thymic carcinomas (15.6) were significantly higher than that of thymomas (6.1). The mean maximal diameter of thymic epithelial tumours was significantly smaller than that of lymphomas (p<0.01) and malignant germ cell tumours (p<0.05). The validation study also yielded high accuracy (38/42, 91%) in differentiation among the anterior mediastinal solid tumours. CONCLUSION: The SUVmax, TIC pattern on DCE-MRI, and maximal diameter might be useful to differentiate anterior mediastinal solid tumours in adults.

Low-dose CT screening using hybrid iterative reconstruction: confidence ratings of diagnoses of simulated lesions other than lung cancer.

OBJECTIVE: To evaluate the confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose screening CT with hybrid iterative reconstruction (IR). METHODS: Simulated lesions (emphysema, mediastinal masses and interstitial pneumonia) in a chest phantom were scanned by a 320-row area detector CT. The scans were performed by 64-row and 160-row helical scans at various dose levels and were reconstructed by filtered back projection (FBP) and IR. Emphysema, honeycombing and reticular opacity were visually scored on a four-point scale by six thoracic radiologists. The ground-glass opacity as a percentage of total lung volume (%GGO), CT value and contrast-to-noise ratio (CNR) of mediastinal masses were calculated. These scores and values were compared between FBP and IR. Wilcoxon's signed-rank test was used (p < 0.05). Interobserver agreements were evaluated by κ statistics. RESULTS: There were no significant differences in visual assessment. Interobserver agreement was almost perfect. CT values were almost equivalent between FBP and IR, whereas CNR with IR was significantly higher than that with FBP. %GGO significantly increased at low-dose levels with FBP; however, IR suppressed the elevation. CONCLUSION: The confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose CT screening were not degraded with hybrid IR compared with FBP. ADVANCES IN KNOWLEDGE: Hybrid IR did not degrade the confidence ratings of diagnoses on visual assessment and differential diagnoses based on CT value of mediastinal masses, and it showed the advantage of higher GGO conspicuity at low-dose level. Radiologists can analyse images of hybrid IR alone on low-dose CT screening for lung cancer.

Dynamic contrast-enhanced MRI of oral squamous cell carcinoma: a preliminary study of the correlations between quantitative parameters and the clinical stage.

OBJECTIVE: To probe the utility of dynamic contrast-enhanced MRI (DCE-MRI) parameters in assessing the clinical characteristics of oral squamous cell carcinoma. METHODS: A total of 85 tumours were included. We applied the Tofts and Kermode model for the DCE-MRI data and obtained three dependent parameters: the influx forward volume transfer constant into the extravascular extracellular space (EES) from the plasma (K(trans)), the fractional volume of EES per unit volume of tissue (ve) and the fractional volume of plasma (vp). We evaluated the correlations between these parameters and the clinical stages. RESULTS: The T stage showed a negative correlation with the K(trans) (r = -0.2272; p = 0.0365), but it did not show a significant correlation with the other parameters. The N stage showed a negative correlation with K(trans) (r = -0.1948; p = 0.0404), and there were significant differences between N1 and N2+3 (0.119 ± 0.027 vs 0.096 ± 0.023 min(-1); p = 0.0198) and between N0 and N2+3 (0.114 ± 0.29 vs 0.096 ± 0.023 min(-1); p = 0.0288). CONCLUSION: A decrease in the K(trans) at the primary site was found in advanced N stage cases, which might indicate that the hypoxic status cause a high possibility of the metastasis. ADVANCES IN KNOWLEDGE: A decrease in the K(trans) at the primary site suggested the high possibility of an advanced N stage.

Detectability of simulated interstitial pneumonia on chest radiographs: comparison between irradiation side sampling indirect flat-panel detector and computed radiography.

OBJECTIVE: To compare the detectability of simulated interstitial pneumonia on chest radiographs between an irradiation side sampling indirect flat-panel detector (ISS-FPD) and computed radiography (CR). METHODS: Simulated interstitial pneumonia findings (ground-glass opacity, reticular opacity and honeycomb lung) were superimposed on an anthropomorphic chest phantom. Chest radiographs were acquired under three exposure levels (4.0, 3.2 and 2.0 mAs) with an ISS-FPD and with CR. 5 thoracic radiologists evaluated 72 images for the presence or absence of a lesion over each of 6 areas. A total of 1296 observations were analysed in a receiver-operating characteristic analysis. A jackknife method was used for the statistical analysis. RESULTS: The areas under the curves (AUCs) for the detection of simulated honeycomb lung obtained with the ISS-FPD were significantly larger than those obtained with CR at all exposure conditions. For the detection of simulated ground-glass opacity and reticular opacity, there were no significant differences between the two systems. In addition, the AUCs for the detectability of simulated honeycomb lung obtained with the ISS-FPD at all exposure levels were significantly larger than those obtained with CR at 4 mAs. CONCLUSION: The ISS-FPD was superior to CR for the detection of simulated honeycomb lung. Provided that the chosen model is representative of interstitial pneumonia, the use of an ISS-FPD might reduce a patient's exposure dose during the detection of interstitial pneumonia. ADVANCES IN KNOWLEDGE: The ISS-FPD has shown its advantage compared with CR in the detection of honeycombing, one sign of interstitial pneumonia.

Evaluation of the extent of ground-glass opacity on high-resolution CT in patients with interstitial pneumonia associated with systemic sclerosis: comparison between quantitative and qualitative analysis.

AIM: To verify whether quantitative analysis of the extent of ground-glass opacity (GGO) on high-resolution computed tomography (HRCT) could show a stronger correlation with the therapeutic response of interstitial pneumonia (IP) associated with systemic sclerosis (SSc) compared with qualitative analysis. MATERIALS AND METHODS: Seventeen patients with IP associated with SSc received autologous peripheral blood stem cell transplantation (auto-PBSCT) and were followed up using HRCT and pulmonary function tests. Two thoracic radiologists assessed the extent of GGO on HRCT using a workstation. Therapeutic effect was assessed using the change of vital capacity (VC) and diffusing capacity of the lung for carbon monoxide (DLco) before and 12 months after PBSCT. Interobserver agreement was assessed using Spearman's rank correlation coefficient and the Bland-Altman method. Correlation with the therapeutic response between quantitative and qualitative analysis was assessed with Pearson's correlation coefficients. RESULTS: Spearman's rank correlation coefficient showed good agreement, but Bland-Altman plots showed that proportional error could be suspected. Quantitative analysis showed stronger correlation than the qualitative analysis based on the relationships between the change in extent of GGO and VC, and change in extent of GGO and DLco. CONCLUSION: Quantitative analysis of the change in extent of GGO showed stronger correlation with the therapeutic response of IP with SSc after auto-PBSCT than with the qualitative analysis.

Apparent diffusion coefficient calculated with relatively high b-values correlates with local failure of head and neck squamous cell carcinoma treated with radiotherapy.

BACKGROUND AND PURPOSE: Few studies have investigated the relationship between ADC and clinical outcome in HNSCC. Our hypothesis has that relatively high pretreatment ADC would correlate with local failure of HNSCC treated with radiation therapy. MATERIALS AND METHODS: This includes prospective and validation studies. Seventeen patients treated with radiation therapy for primary HNSCC completed the prospective study. Variables considered to affect local failure including MR imaging-related parameters such as ADC and its change ratio were compared between patients with local failure and controls, and those showing difference or association with local failure were further tested by survival analysis. Furthermore, variables were analyzed in 40 patients enrolled in the validation study. RESULTS: Relatively high ADC calculated with b-values (300, 500, 750, and 1000 s/mm(2)) before treatment, high ADC increase ratio, and treatment method (chemoradiotherapy versus radiation therapy alone) revealed significant difference between patients with local failure and controls or association with local failure. In Cox proportional hazard testing, high ADC before treatment alone showed significant association with local failure (P = .0186). In the validation study, tumor volume before treatment, high ADC before treatment, T stage (T12 versus T34), and treatment method showed significance. Tumor volume before treatment (P = .0217) and high ADC before treatment (P = .0001) revealed significant association with local failure in Cox proportional hazard testing. High ADC before treatment was superior to tumor volume before treatment regarding association with local failure. CONCLUSIONS: These results suggest pretreatment ADC obtained at high b-values as well as tumor volume correlate with local failure of HNSCC treated with radiation therapy.

NUB1, an interferon-inducible protein, mediates anti-proliferative actions and apoptosis in renal cell carcinoma cells through cell-cycle regulation.

BACKGROUND: NEDD8 ultimate buster 1 (NUB1) is an interferon (IFN)-inducible protein that downregulates NEDD8 expression and its conjugation system. Although overexpression of NUB1 induces a growth-inhibitory effect in cells, the mechanisms underlying the anti-mitogenic actions of NUB1 in cancer cells remain uncertain. We investigated the anti-cancer effects of NUB1 in human renal cell carcinoma (RCC) cells. METHODS: Nine human RCC cells were used for this study. The proliferation of RCC cells exposed to IFN-alpha was measured by water-soluble tetrazolium salt assay. The expression level of NUB1 in cells was measured by quantitative reverse transcriptase PCR or western blot analysis. Apoptosis and cell-cycle analysis were performed by flow cytometry. Silencing of NUB1 was performed using a small interfering RNA. RESULTS: Both NUB1 messenger RNA and protein were significantly induced by IFN-alpha in seven out of nine selected RCC cell lines, and the NUB1 expressions induced by IFN-alpha correlated positively with cell growth inhibition. Overexpression of NUB1 remarkably induced S-phase transition during cell cycle and apoptosis in IFN-alpha-resistant A498 cells, in which NUB1 is not induced by IFN-alpha. The expression levels of two cell-cycle regulator proteins, cyclin E and p27, were increased under the aforementioned conditions. The knockdown of NUB1 enhanced cell proliferation of IFN-alpha-resistant A498 cells and suppressed IFN-alpha-induced growth inhibition in IFN-alpha-sensitive 4TUHR cells. CONCLUSION: NUB1 may be a key factor involved not only in cell growth inhibition by IFN-alpha in RCC cells but also in the anti-cancer effect against IFN-alpha-resistant RCC cells.

Enhanced vagal modulation and exercise induced ischaemia of the inferoposterior myocardium.

OBJECTIVE: To determine whether the Bezold-Jarisch reflex or enhancement of vagal nerves, which are preferentially distributed in the inferoposterior myocardium, results from exercise induced ischaemia in this region. METHODS: On the basis of exercise myocardial scintigraphy and coronary angiography, 145 patients were classified as follows: group I, 34 patients with inferoposterior ischaemia; group A, 32 with anterior ischaemia; and control, 79 without ischaemia. The relation between ischaemic areas and ECG leads with ST segment changes and vagal modulation assessed by heart rate variability (HRV) (high frequency (HF) component (0.15-0.40 Hz) and coefficient of HF component variance (CCVHF), which is the square root of HF divided by mean RR interval) were assessed. RESULTS: The rate of ST segment depression in any lead did not differ between group I and group A. HF and CCV(HF) were similar before exercise but higher in group I than in group A and the control group after exercise (mean (SEM) HF: 94 (17) ms2, 41 (7) ms2, and 45 (6) ms2, respectively, p = 0.021; CCV(HF): 1.18 (0.09)%, 0.81 (0.07)%, and 0.89 (0.05)%, p = 0.0053). Furthermore, the percentage change in CCV(HF) before and after exercise was higher in group I than in group A or controls (mean (SEM) 22 (10)%, -24 (4)%, and -21 (3)%, p < 0.0001). The optimal cut off for diagnosis of inferoposterior ischaemia was -5% with a sensitivity of 74%, specificity 75%, and accuracy 75%. CONCLUSIONS: Vagal modulation as assessed by HRV analysis was enhanced in association with exercise induced inferoposterior ischaemia. Exercise ECG testing combined with HRV analysis would increase accuracy in the diagnosis of ischaemic areas in selected patients with angina pectoris.

Accumulation of NEDD8 in neuronal and glial inclusions of neurodegenerative disorders.

NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) is a ubiquitin-like protein that controls vital biological events through its conjugation to members of the cullin family, which are components of certain ubiquitin E3 ligases. Recent studies have shown that NEDD8 is incorporated into Lewy bodies (LBs) in Parkinson's disease, Mallory bodies in alcoholic liver disease and Rosenthal fibres in astrocytoma. In order to examine whether NEDD8 plays a role in the formation of ubiquitinated inclusions, we performed immunohistochemical staining of brain tissue from patients with various neurodegenerative disorders, using an affinity-purified polyclonal antibody raised against NEDD8 that did not cross-react with ubiquitin. In LB disease, NEDD8 immunoreactivity was present in almost all of the LBs and Lewy neurites. Moreover, NEDD8 immunoreactivity was found in a variety of ubiquitinated inclusions, including neuronal and oligodendroglial inclusions in multiple system atrophy, neurofibrillary tangles in Alzheimer's disease, ubiquitinated inclusions in motor neurone disease, and intranuclear inclusions in triplet repeat diseases. These findings suggest that NEDD8 is involved in the formation of various ubiquitinated inclusions via the ubiquitin-proteasome system.

Measurement of positron production efficiency from a tungsten monocrystalline target using 4- and 8-GeV electrons.

Intense positron sources are being widely investigated for the next-generation linear colliders and B factories. A new method utilizing an axially oriented crystal as a positron-production target is one of the bright schemes, since it provides a powerful photon source through channeling and coherent bremsstrahlung processes when high-energy electrons penetrate the target. A series of positron-production experiments with tungsten crystals hit by 4- and 8-GeV single-bunch electron beams were carried out at the KEKB 8-GeV injector linac. Three tungsten crystals with different thicknesses (2.2, 5.3, and 9.0 mm) and those combined with amorphous tungsten plates were tested on a precise goniometer. The positron-production yields were measured with a magnetic spectrometer in the positron momentum (P(e(+))) range from 5 to 20 MeV/c. The angle of the <111> crystal axis with respect to the electron-beam direction was controlled by measuring the relative intensities of the produced positrons as a function of the rotational angle of the goniometer. The results show that the enhancements of the positron yield from crystal targets compared to amorphous targets of the same thickness at P(e(+))=20 MeV/c are from 1.5 to 3.7 and from 1.8 to 5.1, depending upon the target thickness for 4- and 8-GeV electrons, respectively.

E-cadherin expression in lymph nodes of three patients with non-Hodgkin's lymphoma.

The E-cadherins are a family of cell-cell adhesion molecules. These molecules exhibit Ca2+ dependent cell adhesion and are expressed on epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. We determined serum E-cadherin levels in 30 patients with non-Hodgkin's lymphoma (NHL) using an enzyme immunoassay and then investigated whether E-cadherin is expressed on lymphoma cells in lymph nodes of three cases selected to analyze from 15 cases of serum E-cadherin levels over mean + 2SD with monoclonal antibody immunohistochemistry. Results indicated that E-cadherin antigen is expressed on the lymphoma cells in these three patients with NHL, and that soluble E-cadherin might be released into blood from lymphoma cells. Expression of E-cadherin may contribute to the morphological appearance of some malignant lymphoma, although no conclusion can be drawn based on such small number of patients analyzed.

Clinical significance of serum E-cadherin levels in patients with haematological malignancies.

E-cadherin is a transmembrane glycoprotein that mediates Ca2+-dependent intracellular adhesion in normal epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. However, the role of E-cadherin in haematopoietic cells is less clear. In this study, serum E-cadherin levels were therefore determined in patients with acute or chronic leukaemia, malignant lymphoma or myelodysplastic syndromes. Significant elevation of serum E-cadherin levels was detected in patients with haematological malignancies, and between types of acute leukaemias or subtypes of myelodysplastic syndromes, stages of malignant lymphoma, and phases of chronic leukaemia, respectively, compared with those in healthy adult volunteers. These findings suggest that E-cadherin might be expressed in malignant haematopoietic cells and might be useful as a diagnostic indicator in haematological malignancies.