Factors associated with patient satisfaction with antiretroviral therapy in Japan: A cross-sectional, multicenter study.

BACKGROUND: Current antiretroviral therapy (ART) regimens are highly effective; therefore, to differentiate between various regimens, considering patient-reported outcomes is essential. This study aimed to assess patient satisfaction with their current ART regimens and investigate factors associated with the Human Immunodeficiency Virus Treatment Satisfaction Questionnaire: Status (HIVTSQs) score. METHODS: This cross-sectional, multicenter study was conducted in Japan between April and December 2021. Patient-reported satisfaction with ART was assessed using the Japanese version of the HIVTSQs. Binary logistic regression was used to identify factors associated with a low total HIVTSQs score. RESULTS: A total of 679 patients completed the questionnaire. The median total HIVTSQs score was 58 (interquartile range: 52.5-64). In the multivariable logistic regression analyses, a total HIVTSQs score in the lowest quartile (indicating low satisfaction) was independently associated with twice- or thrice-daily regimens compared with single-tablet, once-daily regimens (adjusted odds ratio: 2.80, 95% confidence interval: 1.29-6.06, p = 0.009) and depression (adjusted odds ratio: 2.30, 95% confidence interval: 1.32-4.01, p = 0.003). CONCLUSIONS: Satisfaction with the current ART regimen was high. Depression and twice- or thrice-daily ART regimen were associated with low HIVTSQ. Switching to a single-tablet, once-daily regimen may improve patient satisfaction in patients receiving twice- or thrice-daily regimens.

Comparison of lung CT number and airway dimension evaluation capabilities of ultra-high-resolution CT, using different scan modes and reconstruction methods including deep learning reconstruction, with those of multi-detector CT in a QIBA phantom study.

OBJECTIVE: Ultra-high-resolution CT (UHR-CT), which can be applied normal resolution (NR), high-resolution (HR), and super-high-resolution (SHR) modes, has become available as in conjunction with multi-detector CT (MDCT). Moreover, deep learning reconstruction (DLR) method, as well as filtered back projection (FBP), hybrid-type iterative reconstruction (IR), and model-based IR methods, has been clinically used. The purpose of this study was to directly compare lung CT number and airway dimension evaluation capabilities of UHR-CT using different scan modes with those of MDCT with different reconstruction methods as investigated in a lung density and airway phantom design recommended by QIBA. MATERIALS AND METHODS: Lung CT number, inner diameter (ID), inner area (IA), and wall thickness (WT) were measured, and mean differences between measured CT number, ID, IA, WT, and standard reference were compared by means of Tukey's HSD test between all UHR-CT data and MDCT reconstructed with FBP as 1.0-mm section thickness. RESULTS: For each reconstruction method, mean differences in lung CT numbers and all airway parameters on 0.5-mm and 1-mm section thickness CTs obtained with SHR and HR modes showed significant differences with those obtained with the NR mode on UHR-CT and MDCT (p < 0.05). Moreover, the mean differences on all UHR-CTs obtained with SHR, HR, or NR modes were significantly different from those of 1.0-mm section thickness MDCTs reconstructed with FBP (p < 0.05). CONCLUSION: Scan modes and reconstruction methods used for UHR-CT were found to significantly affect lung CT number and airway dimension evaluations as did reconstruction methods used for MDCT. KEY POINTS: • Scan and reconstruction methods used for UHR-CT showed significantly higher CT numbers and smaller airway dimension evaluations as did those for MDCT in a QIBA phantom study (p < 0.05). • Mean differences in lung CT number for 0.25-mm, 0.5-mm, and 1.0-mm section thickness CT images obtained with SHR and HR modes were significantly larger than those for CT images at 1.0-mm section thickness obtained with MDCT and reconstructed with FBP (p < 0.05). • Mean differences in inner diameter (ID), inner area (IA), and wall thickness (WT) measured with SHR and HR modes on 0.5- and 1.0-mm section thickness CT images were significantly smaller than those obtained with NR mode on UHR-CT and MDCT (p < 0.05).

A Bayesian estimation method for cerebral blood flow measurement by area-detector CT perfusion imaging.

PURPOSE: Bayesian estimation with advanced noise reduction (BEANR) in CT perfusion (CTP) could deliver more reliable cerebral blood flow (CBF) measurements than the commonly used reformulated singular value decomposition (rSVD). We compared the efficacy of CBF measurement by CTP using BEANR and rSVD, evaluating both relative to N-isopropyl-p-[(123) I]- iodoamphetamine (123I-IMP) single-photon emission computed tomography (SPECT) as a reference standard, in patients with cerebrovascular disease. METHODS: Thirty-one patients with suspected cerebrovascular disease underwent both CTP on a 320 detector-row CT system and SPECT. We applied rSVD and BEANR in the ischemic and contralateral regions to create CBF maps and calculate CBF ratios from the ischemic side to the healthy contralateral side (CBF index). The analysis involved comparing the CBF index between CTP methods and SPECT using Pearson's correlation and limits of agreement determined with Bland-Altman analyses, before comparing the mean difference in the CBF index between each CTP method and SPECT using the Wilcoxon matched pairs signed-rank test. RESULTS: The CBF indices of BEANR and 123I-IMP SPECT were significantly and positively correlated (r = 0.55, p < 0.0001), but there was no significant correlation between the rSVD method and SPECT (r = 0.15, p > 0.05). BEANR produced smaller limits of agreement for CBF than rSVD. The mean difference in the CBF index between BEANR and SPECT differed significantly from that between rSVD and SPECT (p < 0.001). CONCLUSIONS: BEANR has a better potential utility for CBF measurement in CTP than rSVD compared to SPECT in patients with cerebrovascular disease.

Assessment of satisfaction with antiretroviral drugs and the need for long-acting injectable medicines among people living with HIV in Japan and its associated factors: a prospective multicenter cross-sectional observational study.

BACKGROUND: Long-acting injectable formulations for HIV infection have been approved and are now available in Japan. Although not currently recommended as first-line drugs in Japanese or overseas guidelines, use of such formulations may increase, in accordance with patient conditions and preference. We determine the level of satisfaction with current anti-HIV drugs and analyzed the preferences of patients who favor long-acting injectable drugs based on their satisfaction level with the present anti-HIV drugs. METHODS: People living with HIV (PLWH) who had received antiretroviral therapy (ART) for at least one month and consented to the study between 1 April and 31 December 2021 were included in a survey conducted using a self-administered questionnaire. The content of the survey included satisfaction with seven items (tablet size, ease and feeling when taking the medicine, color, taste, portability, daily oral therapy, and co-payment) related to the anti-HIV drugs they were taking and their need for future drugs (dosage form, frequency of dosing, long-acting injectable, etc.). In addition, factors related to the need for long-acting injectable medications were analyzed with regard to the relationship with satisfaction with anti-HIV drugs. RESULTS: Overall, 667 patients available for analysis were included in this study. Satisfaction with anti-HIV drugs was highest with regard to "co-payment" and lowest with "daily oral therapy". Regarding the need for long-acting injectable medications, logistic regression analysis indicated that tablet size and daily oral therapy were significant predictors of patient preference for a once-every-eight-weeks intramuscular formulation in terms of their requirement for long-acting injectable medications (tablet size, OR = 2.14, 95%CI 1.030-4.430, p = 0.042; and daily oral therapy, OR = 1.75, 95%CI 1.010-3.030, p = 0.044). CONCLUSIONS: Patients currently receiving anti-HIV drugs who express dissatisfaction with tablet size and daily oral therapy may prefer a long-acting injectable formulation, taking into consideration patient age, employment status, ART history, frequency of daily dosage and concomitant medications other than ART.

Thermoregulatory and cardiovascular responses in the elderly towards a broad range of gradual air temperature changes.

This study aimed to determine age-related differences in thermoregulatory and cardiovascular responses to a wide range of gradual ambient temperature (Ta) changes. Morphologically matched normotensive elderly and young males participated. The participants wearing only shorts rested during the 3-h experiment. After 30 min of baseline at 28 °C, Ta increased linearly to 43 °C in 30 min (warming) and then gradually decreased to 13 °C in 60 min (cooling). Ta was rewarmed to 28 °C in 30 min (rewarming), and that temperature was maintained for an additional 30 min (second baseline). During the warming phase, there were no age-related differences in blood pressure (BP) and rectal temperature (Tre), despite a significantly lower cutaneous vascular conductance and heart rate in the elderly (P < 0.05). At the end of the cooling phase, systolic blood pressure (SBP) in the elderly was significantly higher than the young (155.8 ± 16.1 and 125.0 ± 12.5 mmHg, P < 0.01). There was a consistent age group difference in SBP during rewarming. Mean skin temperature was significantly lower in the elderly during rewarming (P < 0.05). Tre decreased more in the elderly and was significantly lower at the end of the experiment than the younger participants (36.78 ± 0.34 and 37.01 ± 0.15 °C, P < 0.05). However, there were no age group differences in thermal sensation. In conclusion, even normotensive elderly participants have a greater and more persistent BP response to cold than younger adults, suggesting that the elderly might be at a higher risk of cardiac events during cooling and subsequent rewarming.

OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis).

OBJECTIVE: To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS: This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or ß3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS: In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P < 0.001), and significantly greater improvement for all secondary end-points (P < 0.05). Urinary tract infection, dysuria, urinary retention and post-void residual urine volume increased represented adverse events occurring at a higher rate in the onabotulinumtoxinA group. The majority of these were mild or moderate in severity. CONCLUSIONS: Statistically significant and clinically relevant improvements in symptoms and patient-reported outcomes, and tolerability were seen in patients with overactive bladder and urinary incontinence who had been inadequately managed with overactive bladder medications after using onabotulinumtoxinA.

PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.

Coenzyme Q10 (CoQ10) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ10 supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10 are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10 supplements are commercially available, however, their kinetic difference is still unclear. In order to conduct in vivo analysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing 11C-labeled ubiquinol-10 ([11C]UQL) and ubiquinone-10 ([11C]UQN), respectively. In the present study, we aimed to investigate the kinetics of [11C]UQL and [11C]UQN, both of which were administered via the tail vein of 8-week-old male Sprague-Dawley rats. Whole-body positron emission tomography (PET) imaging was performed to follow the time course of accumulation in the liver, spleen, brain, and other organs. Then, at the two typical time points at 20 or 90 min after injection, we conducted the biodistribution study. Various organs/tissues and blood were collected, weighed and counted with a gamma counter. Percent injected dose per gram of tissue (%ID/g) was calculated as the indicator of the accumulation of each compound. As the results, at both time points, %ID/g of [11C]UQL in the cerebrum, cerebellum, white adipose tissue, muscle, kidney, and testis were higher (P < 0.05) than that of [11C]UQN: at 90-min time point, %ID/g of [11C]UQL in the brown adipose tissue was higher (P < 0.05) than that of [11C]UQN: on the contrary, %ID/g of [11C]UQL in the spleen was lower (P < 0.05) than that of [11C]UQN at 90 min. In a separate study of the metabolite analysis in the plasma, UQL injected into the tail vein of rats was almost unchanged during the PET scanning time, but UQN was gradually converted to the reduced form UQL. Therefore, the uptake values of UQL into the tissues and organs were rather accurate but those of UQN might be the sum of UQN uptake and partly converted UQL uptake. These studies suggested that the accumulation level of administered CoQ10 differs depending on its redox state, and that CoQ10 redox state could be crucial for optimization of the effective supplementation.

Synthesis of 11 C-labeled ubiquinone and ubiquinol via Pd0 -mediated rapid C-[11 C]methylation using [11 C]methyl iodide and 39-demethyl-39-(pinacolboryl)ubiquinone.

To enable positron emission tomography (PET) imaging of the in vivo kinetics of ubiquinone and ubiquinol, which is referred to as coenzyme Q10 , their 11 C-radiolabeled counterparts were synthesized herein. 11 C-Labeled ubiquinone [11 C]-1 was realized by Pd-mediated rapid C-[11 C]methylation of [11 C]CH3 I with 39-demethyl-39-(pinacolboryl)ubiquinone, prepared by Ru-catalyzed olefin metathesis of unradiolabeled ubiquinone with 2-(pinacolboryl)propene. Subsequent reduction of [11 C]-1 using Na2 S2 O4 yielded 11 C-labeled ubiquinol [11 C]-2. The synthesis time and [11 C]CH3 I-based radiochemical yield of [11 C]-1 were within 36 minutes and up to 53%, while those of [11 C]-2 were within 38 minutes and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [11 C]-1 and [11 C]-2 were confirmed to be applicable for animal PET studies. The analytical values of [11 C]-1 and [11 C]-2 are as follows: radioactivity of up to 3.5 and 1.4 GBq, molar activity of 21 to 78 and 48 to 76 GBq/µmol, radiochemical purity of greater than 99% and greater than 95%, and chemical purity of greater than 99% and 77%, respectively. The concept behind this radiolabeling procedure is that unradiolabeled natural ubiquinone can be converted to 11 C-radiolabeled ubiquinone and ubiquinol via a pinacolborane-substituted ubiquinone derivative. Each PET probe was used for molecular imaging using rats to investigate the in vivo kinetics and biodistribution of the coenzyme Q10 .

Long-term clinical results of acute myocardial infarction at the left main trunk requiring percutaneous cardiopulmonary support.

The clinical results of patients with acute myocardial infarction (AMI) at the left main trunk (LMT) remain unclear, especially in cases requiring percutaneous cardiopulmonary support (PCPS). Twenty seven cases of AMI at the LMT requiring emergent PCPS were retrospectively investigated. These 27 patients were aged 44-83 years (65.6 ± 8.6 years) and 20 (81.5%) were men. Peak creatine kinase (CK) leakage ranged from 538 to 34,010 IU/l (13,553 ± 7656 IU/l). Eight (29.6%) patients were discharged without mechanical support. Ten (37.0%) patients underwent left ventricular assist device (LVAD) implantation, five of whom with preoperative organ failure could not survive more than 6 months after implantation. The other nine (33.3%) patients died of low output syndrome or brain damage. The overall survival rates were 53.7, 41.3, 33.0, and 28.3% at 3 months, 6 months, 1 year, and 2 years, respectively. Multivariate analysis showed that Killip class 3/4 at hospital arrival was an independent risk factor for hospital mortality (odds ratio 20.4). Patients with more than 5 days of PCPS support period (n = 6), ≥ 4 h to revascularization (n = 6) or maximum CK leakage ≥20,000 IU/dl (n = 3) were not associated with successful PCPS or IABP weaning. The long-term clinical outcomes of patients with LMT disease requiring PCPS is devastating. Rapid cardiopulmonary resuscitation and coronary revascularization and timely insertion of LVAD before the onset of complications might lead to better survival.

Long-term Effect of Ubiquinol on Exercise Capacity and the Oxidative Stress Regulation System in SAMP1 Mice.

[Purpose] This study examined how exercise capacity and the oxidative stress regulation system are affected by different amounts of dietary Ubiquinol (reduced form of coenzyme Q10, H2CoQ10: QH) over the long term. [Subjects and Methods] Twenty-three senescence-accelerated mouse P1 (SAMP1) mice were randomly divided into two groups: one consuming a relatively high amount of QH (300 mg/kg; Group A) and the other a relatively low amount (30 mg/kg, Group B). Food and tap water were provided ad libitum. Both groups were made to run on a treadmill until exhaustion, and total running duration was measured. For the oxidative stress regulation system, the d-ROM test value (degree of oxidative stress) and BAP test value (antioxidant potential) were measured in a resting state, and then the BAP/d-ROM ratio (B/R ratio) was calculated. The values of plasma QH and plasma ubiquinone (plasma oxidized form of CoQ10) were also measured, and the reduced ratio was calculated. Measurements were taken 3 times: at the start of the study when the animals were 39 weeks old (baseline), after consumption of QH for 7 months (7 mo), and after consumption of QH for 10 months (10 mo). [Results] The senescence score at 10 mo was significantly lower in Group A. Comparison of the mean percentage change in running time showed a difference of 15.1% between the 2 groups. At 10 mo, the d-ROM test value was significantly increased and the B/R ratio was significantly decreased in Group B. Significant increases in the plasma QH value and reduced ratio were seen in Group A. [Conclusion] Group A showed a greater decrease in the d-ROM test and increase in the reduced ratio than Group B. Thus, a dose-dependent effect of QH consumption was demonstrated.

Factors associated with incomplete adherence to integrase strand transfer inhibitor-containing single-tablet regimen among Japanese people living with HIV.

BACKGROUND: People living with human immunodeficiency virus (PLWH) require high rates of medication adherence to antiretroviral therapy (ART) for a successful treatment outcome. Understanding the factors associated with incomplete adherence among those receiving integrase strand transfer inhibitor-containing single-tablet regimens (INSTI-STRs) is crucial for improving treatment outcomes. This study aimed to identify the factors contributing to incomplete ART adherence among Japanese PLWH receiving INSTI-STRs. METHODS: This multicenter cross-sectional study was conducted at 11 Japanese institutions as an anonymous survey. ART adherence was assessed using a self-reported questionnaire. We defined incomplete ART adherence as missing ≥ 1 dose of antiretroviral drugs (ARVs) over the past month. The factors associated with incomplete ART adherence were assessed using logistic regression analysis. Additionally, we investigated the associations between patients' satisfaction score with and need for ARVs and their adherence to ART. RESULTS: The final analysis included data of 387 patients who were treated with INSTI-STRs. Multivariate logistic regression demonstrated significant association of younger age (adjusted odds ratio [aOR], 0.79; 95%confidence interval [CI]: 0.64-0.99 for each 10-year increment) with incomplete ART adherence. Additionally, female sex (aOR, 3.98; 95%CI: 1.36-11.60); depressive symptoms (mild depression: aOR, 1.68; 95%CI: 1.001-2.82, moderate depression: aOR, 2.98; 95%CI: 1.35-6.53, and severe depression: aOR, 8.73; 95%CI: 1.38-55.00 vs. minimal depression); were also significantly associated with incomplete ART adherence when compared with the reference categories. Concomitant medication usage was significantly associated with a lower rate of incomplete ART adherence (1-4 medications: aOR, 0.53; 95%CI: 0.31-0.89 and ≥ 5 medications: aOR, 0.30; 95%CI: 0.13-0.70 vs. no concomitant medication usage). In the incomplete ART adherence group, satisfaction scores for various aspects were significantly lower. Furthermore, a lower proportion of patients in the incomplete ART adherence group preferred the option of "taking tablets daily and visiting the hospital every 3 months," compared to those in the complete ART adherence group (p = 0.008). CONCLUSIONS: This study demonstrated that factors associated with incomplete ART adherence include younger age, female sex, no concomitant medication, and depressive symptoms. Despite ART simplification, incomplete adherence among PLWH receiving INSTI-STRs, remains a challenge, requiring additional actions.

Catalytic NH3 oxidation affected by the nanometric roughness of the platinum overlayer.

Pulsed cathodic arc-plasma deposition was employed to create a few nanometre-thick Pt overlayer on a 50 µm-thick Fe-Cr-Al metal (SUS) foil, resulting in an effective NH3 oxidation catalyst fabrication. This catalyst exhibited a turnover frequency (TOF) exceeding 100 times that of Pt nanoparticles. In this study, Pt overlayer catalysts with varying degrees of surface roughness were fabricated using different metal foil substrates: mirror-polished (Pt/p-SUS), unpolished (Pt/SUS) and roughened by the formation of a surface oxide layer (Pt/Al2O3/SUS). The nanoscale roughness was comprehensively analysed using electron microscopy, laser scanning confocal microscopy and chemisorption techniques. NH3 oxidation activity, measured at 200 °C, followed an increasing trend in the order of Pt/Al2O3/SUS < Pt/SUS < Pt/p-SUS, despite a decrease in the apparent Pt surface area in the same order. Consequently, the calculated TOF was markedly higher for Pt/p-SUS (267 min-1) compared to Pt/SUS (107 min-1) and Pt/Al2O3/SUS (≤22 min-1). The smooth Pt overlayer surface also favoured N2 yield over N2O at this temperature. This discovery enhances our fundamental understanding of high-TOF NH3 oxidation over Pt overlayer catalysts, which holds significance for the advancement and industrial implementation of selective NH3 oxidation processes.

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease and Diabetes.

There is a scarcity of data on clinical outcomes after intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with multivessel disease and diabetes. The Optimal Intravascular Ultrasound Guided Complex Percutaneous Coronary Intervention study multivessel cohort was a prospective, multicenter, single-arm trial enrolling 1,021 patients who underwent multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared the clinical outcomes between those patients with and without diabetes. The primary end point was a composite of death, myocardial infarction, stroke, or any coronary revascularization. There were 560 patients (54.8%) with diabetes and 461 patients (45.2%) without diabetes. The mean age was not different between the 2 groups (70.9 ± 9.7 vs 71.7 ± 10.4 years, p = 0.17). Patients with diabetes more often had chronic kidney disease and complex coronary artery disease, as indicated by the greater total number of stents and longer total stent length. The rate of meeting the OPTIVUS criteria was not different between the 2 groups (61.2% vs 60.7%, p = 0.83). The cumulative 1-year incidence of the primary end point was not different between the 2 groups (10.8% vs 9.8%, log-rank p = 0.65). After adjusting for confounders, the risk of diabetes relative to nondiabetes remained insignificant for the primary end point (hazard ratio 0.97, 95% confidence interval 0.65 to 1.44, p = 0.88). In conclusion, in patients who underwent multivessel IVUS-guided PCI and were managed with contemporary clinical practice, patients with diabetes had similar 1-year outcomes to patients without diabetes.

Cryoglobulinemic Vasculitis Associated with Monoclonal Gammopathy of Undetermined Significance Developed after Sustained Virologic Response of Hepatitis C.

A 72-year-old woman had a history of chronic hepatitis C virus (HCV) infection previously treated with interferon to achieve a sustained virologic response. Thereafter, she developed polyarthritis and purpura of the lower extremities as well as progressive renal dysfunction with hypertension and proteinuria that had occurred in the last three months. Laboratory investigations revealed seropositivity for cryoglobulin but negative findings for HCV RNA. She was ultimately diagnosed with cryoglobulinemic glomerulonephritis complicated by monoclonal gammopathy of undetermined significance (MGUS) based on the pathological findings of the kidney and bone marrow, indicating that MGUS-induced cryoglobulinemic vasculitis may occur even after HCV elimination.

Capability for dose reduction while maintaining nodule detection: Comparison of silver and copper X-ray spectrum modulation filters for chest CT using a phantom study with different reconstruction methods.

PURPOSE: To compare the capability of CTs obtained with a silver or copper x-ray beam spectral modulation filter (Ag filter and Cu filter) and reconstructed with FBP, hybrid-type IR and deep learning reconstruction (DLR) for radiation dose reduction for lung nodule detection using a chest phantom study. MATERIALS AND METHODS: A chest CT phantom was scanned with a 320-detector row CT with Ag filter at 0.6, 1.6 and 2.5 mGy and Cu filters at 0.6, 1.6, 2.5 and 9.6 mGy, and reconstructed with the aforementioned methods. To compare image quality of all the CT data, SNRs and CNRs for any nodule were calculated for all protocols. To compare nodule detection capability among all protocols, the probability of detection of any nodule was assessed with a 5-point visual scoring system. Then, ROC analyses were performed to compare nodule detection capability of Ag and Cu filters for each radiation dose data with the same method and of the three methods for any radiation dose data and obtained with either filter. RESULTS: At any of the doses, SNR, CNR and area under the curve for the Ag filter were significantly higher or larger than those for the Cu filter (p < 0.05). Moreover, with DLR, those values were significantly higher or larger than all the others for CTs obtained with any of the radiation doses and either filter (p < 0.05). CONCLUSION: The Ag filter and DLR can significantly improve image quality and nodule detection capability compared with the Cu filter and other reconstruction methods at each of radiation doses used.

Effectiveness of deep learning reconstruction on standard to ultra-low-dose high-definition chest CT images.

PURPOSE: Deep learning reconstruction (DLR) has been introduced by major vendors, tested for CT examinations of a variety of organs, and compared with other reconstruction methods. The purpose of this study was to compare the capabilities of DLR for image quality improvement and lung texture evaluation with those of hybrid-type iterative reconstruction (IR) for standard-, reduced- and ultra-low-dose CTs (SDCT, RDCT and ULDCT) obtained with high-definition CT (HDCT) and reconstructed at 0.25-mm, 0.5-mm and 1-mm section thicknesses with 512 × 512 or 1024 × 1024 matrixes for patients with various pulmonary diseases. MATERIALS AND METHODS: Forty age-, gender- and body mass index-matched patients with various pulmonary diseases underwent SDCT (CT dose index volume : mean ± standard deviation, 9.0 ± 1.8 mGy), RDCT (CTDIvol: 1.7 ± 0.2 mGy) and ULDCT (CTDIvol: 0.8 ± 0.1 mGy) at a HDCT. All CT data set were then reconstructed with 512 × 512 or 1024 × 1024 matrixes by means of hybrid-type IR and DLR. SNR of lung parenchyma and probabilities of all lung textures were assessed for each CT data set. SNR and detection performance of each lung texture reconstructed with DLR and hybrid-type IR were then compared by means of paired t tests and ROC analyses for all CT data at each section thickness. RESULTS: Data for each radiation dose showed DLR attained significantly higher SNR than hybrid-type IR for each of the CT data (p < 0.0001). On assessments of all findings except consolidation and nodules or masses, areas under the curve (AUCs) for ULDCT with hybrid-type IR for each section thickness (0.91 ≤ AUC ≤ 0.97) were significantly smaller than those with DLR (0.97 ≤ AUC ≤ 1, p < 0.05) and the standard protocol (0.98 ≤ AUC ≤ 1, p < 0.05). CONCLUSION: DLR is potentially more effective for image quality improvement and lung texture evaluation than hybrid-type IR on all radiation dose CTs obtained at HDCT and reconstructed with each section thickness with both matrixes for patients with a variety of pulmonary diseases.

A concomitant case of giant cell arteritis and microscopic polyangiitis with hemoperitoneum by rupture of the gastroepiploic artery.

Giant cell arteritis (GCA) mainly involves large-sized arteries, while microscopic polyangiitis (mPA), characterized by pauci-immune necrotizing vasculitis, mainly affects small-sized vessels. We report a very rare concomitant case of GCA diagnosed by temporal artery biopsy and mPA with a high titer of myeloperoxidase antineutrophil cytoplasmic antibody, exacerbation of interstitial pneumonia, and suspected rapidly progressive glomerulonephritis. The patient died by sudden rupture of the gastroepiploic artery (medium-sized vessel), which may have been triggered by GCA and/or mPA.

Pharmacokinetic and pharmacodynamic properties of the glucokinase activator MK-0941 in rodent models of type 2 diabetes and healthy dogs.

Glucokinase activators (GKAs) are small-molecule agents that enhance glucose sensing by pancreatic ß cells and glucose metabolism by hepatocytes. There is strong interest in these agents as potential therapies for type 2 diabetes. Here, we report key pharmacokinetic and pharmacodynamic findings from preclinical studies of the GKA 3-[[6-(ethylsulfonyl)-3-pyridinyl]oxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (MK-0941). Incubated in vitro with recombinant human glucokinase, 1 µM MK-0941 lowered the S(0.5) of this enzyme for glucose from 6.9 to 1.4 mM and increased the maximum velocity of glucose phosphorylation by 1.5-fold. In 2.5 and 10 mM glucose, the EC(50) values for activation of GK by MK-0941 were 0.240 and 0.065 µM, respectively. Treatment of isolated rat islets of Langerhans and hepatocytes with 10 µM MK-0941 increased insulin secretion by 17-fold and glucose uptake up to 18-fold, respectively. MK-0941 exhibited strong glucose-lowering activity in C57BL/6J mice maintained on a high-fat diet (HFD), db/db mice, HFD plus low-dose streptozotocin-treated mice, and nondiabetic dogs. In both mice and dogs, oral doses of MK-0941 were rapidly absorbed and rapidly cleared from the blood; plasma levels reached maximum within 1 h and fell thereafter with a half-life of ~2 h. During oral glucose tolerance testing in dogs, MK-0941 reduced total area-under-the-curve postchallenge (0-2 h) plasma glucose levels by up to 48% compared with vehicle-treated controls. When administered twice daily to mice for 16 days, and once daily to the dog for 4 days, MK-0941 remained efficacious on successive days. These findings support further investigation of MK-0941 as a potential therapeutic agent for treatment of type 2 diabetes.

Efficacy and safety of onabotulinumtoxinA in patients with overactive bladder: subgroup analyses by sex and by serum prostate-specific antigen levels in men from a randomized controlled trial.

PURPOSE: We aimed to assess onabotulinumtoxinA treatment outcomes by sex in patients with overactive bladder (OAB) and then explore the impact of serum prostate-specific antigen (PSA) levels in men. METHODS: Patients inadequately managed with OAB medications were randomized to receive single-dose onabotulinumtoxinA (100 U) or placebo intravesical injection in a phase III trial in Japan. We performed subgroup analyses by sex and post-hoc subgroup analyses using male PSA categories. RESULTS: In women (n = 186), onabotulinumtoxinA demonstrated statistically significant and clinically relevant improvements in all urinary symptoms at Week 12. In men with lower PSA (< 1.5 ng/mL, n = 40), onabotulinumtoxinA also showed numerically greater reductions in urinary symptom frequency than placebo; the between-group differences (onabotulinumtoxinA minus placebo) in change from baseline in the average daily number at Week 12 for urinary incontinence (UI), urgency UI, micturition, urgency, and nocturia were - 1.43, - 1.79, - 2.81, - 2.45, and - 0.32 episodes, respectively. In men with higher PSA (≥ 1.5 ng/mL, n = 22), onabotulinumtoxinA did not reduce urinary symptom frequency. Some patients treated with onabotulinumtoxinA showed elevated post-void residual urine volume at Week 2 (≥ 200 mL): 4 of 91 women, none of the men with lower PSA and 3 of 11 men with higher PSA. CONCLUSIONS: OnabotulinumtoxinA was efficacious and well tolerated in women and in men with lower PSA levels. Given our post-hoc subgroup analyses which suggested that onabotulinumtoxinA treatment is a good treatment option for OAB males with lower PSA levels, future studies having prostate volume data with larger sample size are warranted to verify our findings. CLINICALTRIALS. GOV IDENTIFIER: NCT02820844 (first posted July 1, 2016). https://clinicaltrials.gov/ct2/show/NCT02820844 .

Inspiratory/expiratory xenon-enhanced area-detector CT: Capability for quantitative assessment of lung ventilation changes in surgically treated non-small cell lung cancer patients.

PURPOSE: To evaluate the capability of inspiratory/expiratory Xe-enhanced ADCT for assessment of changes in pulmonary function and regional ventilation of surgically treated NSCLC patients. METHOD AND MATERIALS: Forty consecutive surgically treated NSCLC patients underwent pre- and postoperative inspiratory/expiratory Xe-enhanced ADCT and pulmonary function tests. For each patient, pre- and post-operative data were analyzed and pre- and post-operative wash-in (WI) and wash-out (WO) indexes and ventilation ratio (VR=[WI-WO]/WI) maps generated by means of pixel-by-pixel analyses. Differences between pre- and postoperative WI (ΔWI), WO (ΔWO) and VR (ΔVR) were also determined. To determine the relationship between all ventilation index changes and pulmonary functional loss, Pearson's correlation was used to correlate each ventilation index change with the corresponding pulmonary functional parameter change. In addition, stepwise regression analysis was performed for all ventilation index changes and each corresponding pulmonary functional parameter change. RESULTS: FEV1/FVC% change showed fair or good and significant correlations with ΔWI (r = 0.39, p = 0.01) and ΔVR (r = 0.68, p = 0.001), %FEV1 change good or moderate and significant correlations with ΔWI (r = 0.56, p = 0.0001) and ΔVR (r = 0.76, p < 0.0001), and %VC change moderate yet significant correlation with ΔWI (r = 0.65, p < 0.0001) and ΔVR (r = 0.67, p < 0.0001). Stepwise regression analysis demonstrated that FEV1/FVC% change (r2 = 0.56, p < 0.0001) significantly affected two factors, ΔVR (p < 0.0001) and ΔWI (p = 0.006), as did %FEV1 change (r2 = 0.68, p < 0.0001) [ΔVR (p < 0.0001) and ΔWI (p = 0.0001)], and %VC change (r2 = 0.63, p < 0.0001) [ΔVR (p < 0.0001) and ΔWI (p = 0.0001)]. CONCLUSION: Inspiratory/expiratory Xe-enhanced ADCT has the potential to demonstrate that pre- and postoperative ventilation status of surgically treated NSCLC patients correlates with pulmonary function.