Factors associated with COVID-19 booster vaccine hesitancy: a nationwide, cross-sectional survey in Japan.

OBJECTIVES: COVID-19 vaccine hesitancy/fatigue is increasing as the pandemic enters the endemic phase. The present study aimed to explore current perceptions about COVID-19 booster vaccination among the Japanese public. STUDY DESIGN: This was a cross-sectional study. METHODS: This cross-sectional study used data from the Japan COVID-19 and Society Internet Survey conducted in September 2021 and September 2022. The public's perceptions of COVID-19 vaccination and factors associated with COVID-19 booster vaccine hesitancy were analyzed. RESULTS: In total, 56,735 respondents were included. In the Japan COVID-19 and Society Internet Survey 2021, 75.1% of the participants (21,126/28,118) had completed the primary vaccination series. In the 2022 survey, 74.1% of the respondents (21,216/28,617) completed the primary series of vaccination with booster doses. The proportion of fear toward COVID-19 and obtaining information about COVID-19 has decreased from 2021 to 2022. Factors independently associated with booster vaccine hesitancy were young age (range: 18-29 years; adjusted odds ratio [aOR]: 6.56), history of COVID-19 (aOR: 1.82), distrust of the Japanese government's COVID-19 prevention measures (aOR: 1.55), lack of confidence in COVID-19 vaccine efficacy (aOR: 1.30), lack of confidence in COVID-19 vaccine safety (aOR: 1.62), low reliance on the COVID-19 vaccine (aOR: 1.92), and belief in COVID-19 conspiracy theories (aOR: 1.77). CONCLUSIONS: Providing clear and trustworthy information is critically important, especially targeted and tailored messages for the young generation, to promoting COVID-19 booster vaccination. Policymakers should therefore develop consistent and transparent communication strategies and the ability to respond promptly and flexibly to mitigate the negative impact of COVID-19 on the public while preparing for the next pandemic.

EFFECT OF ADDING HOME-BASED MODERATE-INTENSITY EXERCISE ON METABOLIC FUNCTIONS IN OLDER ADULTS WITH NON-COMMUNICABLE DISEASES WHO REGULARLY PERFORM GYM-BASED MODERATE-INTENSITY EXERCISE.

CONTEXT: Physical activity is important for the management of metabolic functions; however, little is known whether performing home-based moderate-intensity exercise (MIE) obtains further improvement on metabolic functions in adults with non-communicable diseases (NCDs) who already perform regular gym-based MIE. OBJECTIVE: The purpose of this study was to examine the effect of adding home-based MIE on metabolic functions in older adults with NCDs who have regularly performed gym-based MIE. DESIGN: This was a single-center randomized controlled study. The observation period was set for 24 weeks. SUBJECTS AND METHODS: Twenty-one older adults (age, 60-79 years) with uncomplicated NCDs, who have performed 30-40 min MIE, 2-3 days/week at a hospital gym for over 1 year, were randomly divided into two groups: performing home-based MIE, comprising aerobic and resistance exercises, at least 20 min/day, 3 days/week (HOME, n = 11), or not performing home-based MIE (CON, n = 10). All participants completed the study and continued their gym-based MIE as usual. RESULTS: After 24 weeks, there were no significant differences in the values of any outcomes. Conversely, the decrease in waist circumference (WC) was larger in the HOME group (-2.17 [-3.98, -0.36] cm) than in the CON group (0.57 [-1.42, 2.56] cm) (p < 0.05), although not in other outcomes. CONCLUSIONS: Although further studies are needed, we found that adding home-based MIE had a positive effect on WC, but little effect on other metabolic functions in older adults with NCDs who have continued regular gym-based MIE.

Risk factors for Clostridioides difficile infection in hospitalized patients and associated mortality in Japan: a multi-centre prospective cohort study.

BACKGROUND: Although population characteristics and antimicrobial prescribing practices suggest that the hospitalized population in Japan is at high risk of Clostridioides difficile infection (CDI), the epidemiology of CDI in Japan is poorly understood. AIM: This prospective cohort study aimed to investigate the epidemiology of CDI at 12 hospitals in Japan. METHODS: Patients with clinically significant diarrhoea (CSD) were enrolled. Stool specimens were tested for C. difficile by toxin A and/or B enzyme immunoassay (EIA) in the hospital laboratories, and a toxigenic culture and nucleic acid amplification tests were performed at a central laboratory. The risk factors of CDI and the impact of CDI on mortality were investigated. FINDINGS: In total, 566 patients with CSD were included in the analyses. A total of 152 patients received the diagnosis of CDI by Toxin A/B EIA, toxigenic culture, or nucleic acid amplification test. Factors associated with CDI included low albumin (adjusted odds ratio (aOR): 1.56; 95% confidence interval (CI): 1.03-2.34) and length of hospital stay before stool collection >18 days (aOR: 1.73; 95% CI: 1.09-2.75). CDI was associated with an increased mortality on univariate analysis (OR: 1.6, 95% CI: 1.0-2.6) but was not associated with an increased risk of mortality on multivariable analysis. CONCLUSION: Risk factors for CDI in Japan were similar to those identified in the USA and Europe. However, CDI was not associated with an increased risk of mortality in this population of patients with CSD.

Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity.

Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading-mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas-NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.

Differences between primary central nervous system lymphoma and glioblastoma: topographic analysis using voxel-based morphometry.

AIM: To evaluate the diagnostic feasibility of probabilistic analysis using voxel-based morphometry (VBM) in differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma (GBM). MATERIALS AND METHODS: In total, 118 patients with GBM (57 males, 61 females; mean [± standard deviation] age, 56.9±19.3 years; median, 61 years) and 52 patients with PCNSL (37 males, 15 females; mean age, 62±13.3 years, median, 66 years) were studied retrospectively. Each patient underwent preoperative contrast-enhanced T1-weighted imaging (CE-T1WI) using a 1.5 or 3 T magnetic resonance imaging (MRI) system. To assess preferential occurrence sites, images from CE-T1WI were co-registered and spatially normalised using the MNI152 T1 template. Subsequently, a region of interest (ROI) was placed in the centre of the enhancing tumour in normalised images with 1-mm isotropic resolution. The same ROI between normalised and T1 template images was set up using an ROI manager function in ImageJ software. A spherical volume of interest (VOI) with a radius of 10 mm was determined. A probability map was created by overlaying each image with the VOI. Each VOI was removed from T1 template images for VBM analysis. VBM analysis was performed using statistical parametric mapping (SPM) 12 software under default settings. RESULTS: VBM analysis showed significantly higher frequency in the splenium of the corpus callosum among PCNSL patients than among GBM patients (p<0.05; family-wise error correction). CONCLUSION: Topographic analysis using VBM provides useful information for differentiating PCNSL from GBM.

Intravoxel Incoherent Motion MR Imaging of Pediatric Intracranial Tumors: Correlation with Histology and Diagnostic Utility.

BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging, which simultaneously measures diffusion and perfusion parameters, is promising for brain tumor grading. However, intravoxel incoherent motion imaging has not been tested in children. The purpose of this study was to evaluate the correlation between intravoxel incoherent motion parameters and histology to assess the accuracy of intravoxel incoherent motion imaging for pediatric intracranial tumor grading. MATERIALS AND METHODS: Between April 2013 and September 2015, 17 children (11 boys, 6 girls; 2 months to 15 years of age) with intracranial tumors were included in this retrospective study. Intravoxel incoherent motion parameters were fitted using 13 b-values for a biexponential model. The perfusion-free diffusion coefficient, pseudodiffusion coefficient, and perfusion fraction were measured in high- and low-grade tumors. These intravoxel incoherent motion parameters and the ADC were compared using the unpaired t test. The correlations between the intravoxel incoherent motion parameters and microvessel density or the MIB-1 index were analyzed using the Spearman correlation test. Receiver operating characteristic analysis was used to evaluate diagnostic performance. RESULTS: The perfusion-free diffusion coefficient and ADC were lower in high-grade than in low-grade tumors (perfusion-free diffusion coefficient, 0.85 ± 0.40 versus 1.53 ± 0.21 × 10-3 mm2/s, P < .001; ADC, 1.04 ± 0.33 versus 1.60 ± 0.21 × 10-3 mm2/s, P < .001). The pseudodiffusion coefficient showed no difference between the groups. The perfusion fraction was higher in high-grade than in low-grade tumors (21.7 ± 8.2% versus 7.6 ± 4.3%, P < .001). Receiver operating characteristic analysis found that the combined perfusion-free diffusion coefficient and perfusion fraction had the best diagnostic performance for tumor differentiation (area under the curve = 0.986). CONCLUSIONS: Intravoxel incoherent motion imaging reflects tumor histology and may be a helpful, noninvasive method for pediatric intracranial tumor grading.

Image quality and radiation dose of renal perfusion CT with low-dose contrast agent: a comparison with conventional CT using a 320-row system.

AIM: To compare perfusion computed tomography (CT) with reconstructed image from source data using low-dose contrast agent and conventional 320-row CT for the evaluation of renal tumours. MATERIALS AND METHODS: Twenty-eight patients underwent conventional CT (C-CT) and 26 patients underwent perfusion CT with low-dose (40 ml) contrast agent. Image noise, arterial visualisation, the sharpness of the corticomedullary junction (CMJ), and overall image quality were each assessed using a four-point scale. The tumour detection rate for lesions <4 cm (n=66) was also evaluated. Quantitative image parameters including image noise and the contrast-to-noise ratios (CNRs) of the renal artery and CMJ were measured. The volume CT dose index (CTDI), dose-length product (DLP), and size-specific dose estimate (SSDE) were also recorded. RESULTS: Although the image noise of perfusion CT was higher than that of C-CT and the overall image quality of perfusion CT was lower than that of C-CT, the arterial visualisation score of perfusion CT was significantly higher than that of C-CT. The CMJ sharpness scores of the two techniques were equivalent. Sensitivity and positive predictive values were also equivalent with respect to tumour detection. The CNRs of both the left and right renal arteries were significantly higher on perfusion CT than on C-CT. The CTDI, DLP, and SSDE of perfusion CT were significantly lower than those of C-CT. CONCLUSION: Perfusion CT using low-dose contrast agent preserved arterial visualisation and the tumour detection rate and achieved a low radiation dose despite image quality degradation and image noise.

Predicting TERT promoter mutation using MR images in patients with wild-type IDH1 glioblastoma.

PURPOSE: The purpose of this study was to identify magnetic resonance imaging (MRI) features that are associated with telomerase reverse transcriptase promoter mutation (TERTm) in glioblastoma. MATERIALS AND METHODS: A total of 112 patients with glioblastoma who had MRI at 1.5- or 3.0-T were retrospectively included. There were 43 patients with glioblastoma with wild-type TERT (TERTw) (22 men, 21 women; mean age, 47±25 [SD] years; age range: 3-84 years) and 69 patients with glioblastoma with TERTm (34 men, 35 women; mean age 64±11 [SD] years; age range, 41--85 years). The feature vectors consist of 11 input units for two clinical parameters (age and gender) and nine MRI characteristics (tumor location, subventricular extension, cortical extension, multiplicity, enhancing volume, necrosis volume, the percentage of necrosis volume, minimum apparent diffusion coefficient [ADC] and normalized ADC). First, the diagnostic performance using univariate and multivariate logistic regression analyses was evaluated. Second, the cross-validation of the support vector machine (SVM) was performed by using leave-one-out method with 43 TERTw and 69 TERTm to evaluate the diagnostic performance. In addition, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for the differentiation between TERTw and TERTm were compared between logistic regression analysis and SVM. RESULTS: With multivariate analysis, the percentage of necrosis volume and age were significantly greater in TERTm glioblastoma than in TERTw glioblastoma. SVM allowed discriminating between TERTw glioblastoma and TERTm glioblastoma with sensitivity, specificity, PPV, NPV, and accuracy of 85.7% [60/70; 95% confidence interval (CI): 75.3-92.9%], 54.8% (23/42; 95% CI: 38.7-70.2%), 75.9% (60/79; 95% CI: 69.1-81.7%), 69.7% (23/33; 95% CI: 54.9-81.3%) and 74.1% (83/112; 95% CI: 65.0-81.9%), respectively. CONCLUSION: The percentage of necrosis volume and age may surrogate for predicting TERT mutation status in glioblastoma.

A Qualitative and Quantitative Correlation Study of Lumbar Intervertebral Disc Degeneration Using Glycosaminoglycan Chemical Exchange Saturation Transfer, Pfirrmann Grade, and T1-ρ.

BACKGROUND AND PURPOSE: Glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging allows the direct measurement and mapping of glycosaminoglycans. In this study, we aimed to evaluate the usefulness of gagCEST imaging in the quantitative assessment of intervertebral disc degeneration in a comparison with Pfirrmann grade and T1-ρ measurements. MATERIALS AND METHODS: Ninety-six lumbar intervertebral discs in 24 volunteers (36.0 ± 8.5 years of age, 21 men and 3 women) were examined with both gagCEST imaging and T1-ρ measurements. The gagCEST imaging was performed at 3T with a saturation pulse with 1.0-second duration and the B1 amplitude of 0.8 µT followed by imaging by a 2D fast spin-echo sequence. The Z-spectra were obtained at 25 frequency offsets from -3 to +3 ppm (step, 0.25 ppm). A point-by-point B0 correction was performed with a B0 map. The gagCEST signal and T1-ρ values were measured in the nucleus pulposus in each intervertebral disc. The Pfirrmann grades were assessed on T2-weighted images. RESULTS: The gagCEST signal at grade I (5.36% ± 2.79%) was significantly higher than those at Pfirrmann grade II (3.15% ± 1.40%, P = .0006), grade III (0.14% ± 1.03%, P < .0001), grade IV (-1.75% ± 2.82%, P < .0001), and grade V (-1.47% ± 0.36%, P < .0001). The gagCEST signal at grade II was significantly higher than those of grade III (P < .0001), grade IV (P < .0001), and grade V (P < .0001). The gagCEST signal was significantly correlated negatively with Pfirrmann grade (P < .0001) and positively correlated with T1-ρ (P < .0001). CONCLUSIONS: GagCEST imaging could be a reliable and quantitative technique for assessing intervertebral disc degeneration.

Diffusion-weighted magnetic resonance imaging of extraocular muscles in patients with Grave's ophthalmopathy using turbo field echo with diffusion-sensitized driven-equilibrium preparation.

PURPOSE: The purpose of this study was to correlate diffusivity of extraocular muscles, measured by three-dimensional turbo field echo (3DTFE) magnetic resonance (MR) imaging using diffusion-sensitized driven-equilibrium preparation, with their size and activity in patients with Grave's ophthalmopathy. MATERIALS AND METHODS: Twenty-three patients with Grave's ophthalmopathy were included. There were 17 women and 6 men with a mean age of 55.8±12.6 (SD) years (range: 26-83 years). 3DTFE with diffusion-sensitized driven-equilibrium MR images were obtained with b-values of 0 and 500s/mm2. The apparent diffusion coefficient (ADC) of extraocular muscles was measured on coronal reformatted MR images. Signal intensities of extraocular muscles on conventional MR images were compared to those of normal-appearing white matter, and cross-sectional areas of the muscles were also measured. The clinical activity score was also evaluated. Statistical analyses were performed with Pearson correlation and Mann-Whitney U tests. RESULTS: On 3DTFE with diffusion-sensitized driven-equilibrium preparation, the mean ADC of the extraocular muscles was 2.23±0.37 (SD)×10-3mm2/s (range: 1.70×10-3-3.11×10-3mm2/s). There was a statistically significant moderate correlation between ADC and the size of the muscles (r=0.61). There were no statistically significant correlations between ADC and signal intensity on conventional MR and the clinical activity score. CONCLUSION: 3DTFE with diffusion-sensitized driven-equilibrium preparation technique allows quantifying diffusivity of extraocular muscles in patients with Grave's ophthalmopathy. The diffusivity of the extraocular muscles on 3DTFE with diffusion-sensitized driven-equilibrium preparation MR images moderately correlates with their size.

Predictors of therapeutic effect of transarterial chemoembolisation using drug-eluting beads for hepatocellular carcinoma.

AIMS: To identify predictors of a therapeutic effect after transarterial chemoembolisation using drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between January 2015 and July 2015, tumour variables and angiographic data were collected for 25 patients (49 target lesions) after they had undergone the DEB-TACE procedure for HCC. The therapeutic effect was evaluated according to the Response Evaluation Criteria in Cancer of the Liver at follow-up dynamic computed tomography (CT) performed within 1-4 months after the procedure. A p<0.05 was considered significant. RESULTS: On a target lesion basis, the objective response (TE3/4) rate was 63.3% (31 of 49). On univariate analysis, larger size (≥2 cm) was a predictor of an objective response (p=0.029). The tumour location of the medial (segment 4) or caudate (segment 1) lobe also indicated a poor therapeutic effect (TE1/2), but not at the level of significance (p=0.051). Multivariate analysis identified tumour size (odds ratio, 8.60; 95% confidence interval, 1.87-62.8) and tumour location (odds ratio, 12.2; 95% confidence interval, 2.12-129.8) as significant factors associated with a therapeutic effect. On a patient basis, 10 of 25 (40%) patients showed complete response/partial response. There were no significant differences between complete response/partial response and stable disease/progressive disease regarding age, gender, tumour markers, history of previous treatment, Child-Pugh class, T-stage, or Barcelona Clinic Liver Cancer Staging. CONCLUSION: A short-term therapeutic effect was associated with tumour size and location on a target lesion basis.

Impact of inadequate initial antimicrobial therapy on mortality in patients with bacteraemic cholangitis: a retrospective cohort study.

OBJECTIVES: Acute cholangitis is a common cause of bacteraemia resulting in severe sepsis or septic shock. The impact of the appropriate initial antimicrobial therapy on short-term mortality in bacteraemic cholangitis has not been well investigated. METHODS: We conducted a retrospective cohort study of patients with bacteraemic cholangitis at two large tertiary care centres in Tokyo, Japan between 2009 and 2015. We determined the factors associated with 30-day all-cause mortality from the date of drawing the first positive blood culture, using a multivariate logistic regression analysis. RESULTS: We identified 573 patients with bacteraemic cholangitis (median age, 77 years; male, 58.3%). The 30-day all-cause mortality rate was 6.6% (38/573). Inadequate initial antimicrobial therapy occurred in 133 (23.2%) patients. Factors associated with 30-day all-cause mortality included the Charlson co-morbidity index score >3 (adjusted odds ratio (aOR) 4.12; 95% CI 1.18-14.38), jaundice (total bilirubin >2.5 mg/dL) (aOR 3.39; 95% CI 1.46-7.89), septic shock within 48 h of the first positive blood culture (aOR 3.34; 95% CI 1.42-7.89), biliary obstruction due to hepatobiliary malignancy (aOR 8.00; 95% CI 2.92-21.97), and inadequate initial antimicrobial therapy (aOR 2.78; 95% CI 1.27-6.11). CONCLUSIONS: Inadequate initial antimicrobial therapy was an important, modifiable determinant of survival.

Correlations and time-dependent changes of upper arm performance tests, the Japanese Orthopaedic Association score, and a newly developed patient-based outcome measure : the Japanese Orthopaedic Cervical Myelopathy Questionnaire.

AIMS: In this prospective observational study, we investigated the time-dependent changes and correlations of upper arm performance tests (ten-second test and Simple Test for Evaluating Hand Function (STEF), the Japanese Orthopaedic Association (JOA) score, and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) in 31 patients with cervical myelopathy who had undergone surgery. PATIENTS AND METHODS: We hypothesised that all the indices correlate with each other, but show slightly different recovery patterns, and that the newly described JOACMEQ is a sensitive outcome measure. RESULTS: Peak recoveries were achieved one month post-operatively in the ten-second test and JOACMEQ upper extremity function (UEF) subscale, and at three months in the JOA and STEF scores. The recoveries of all indices were maintained until six months post-operatively. The upper extremity function (UEF) subscale in the JOACMEQ showed the strongest correlation with STEF although all the indices correlated with each other. Patients with ≥ 20 and < 20 acquired points in the UEF subscale were classified into the UEF-improved and UEF-unimproved groups. Comparisons between the groups showed that pre-operative evaluation of "coordinated motion" of the STEF was significantly low in the UEF-unimproved group. CONCLUSION: These results indicate that the JOACMEQ is a concise, sensitive, patient-based outcome measure for evaluating functional recovery in patients with cervical myelopathy who have undergone surgery. Cite this article: Bone Joint J 2016;98-B:990-6.

Fatty change in moderately and poorly differentiated hepatocellular carcinoma on MRI: a possible mechanism related to decreased arterial flow.

AIM: To clarify the frequency of fatty change in moderately and poorly differentiated hepatocellular carcinomas (mHCCs and pHCCs) and its relationship to arterial blood flow. MATERIALS AND METHODS: One hundred and thirty-six surgically resected HCC lesions were studied. All patients had undergone dynamic magnetic resonance imaging (MRI) with chemical-shift-encoded water-fat imaging (CSI). The presence of fat was identified by a signal drop-off on CSI and confirmed at pathology. Lesions were classified into four groups in the arterial phase; G1, hypointense; G2, isointense; G3, slightly and heterogeneously hyperintense; G4, markedly and homogeneously hyperintense. The number of cumulative arteries (CAs) in the tumours in the pathology examination were counted. RESULTS: A fat component was observed significantly more frequently in the pHCCs (13/21; 61.9%) compared to the mHCCs (32/101; 31.7%; p=0.013). The numbers of lesions in each group were as follows: (G1, G2, G3, G4) = (18, 9, 23, 4) in the HCCs with fat; (1, 6, 24, 51) in the HCCs without fat (p<0.001); (5, 5, 18, 4) in the mHCCs with fat; (0, 3, 19, 47) in the mHCCs without fat (p<0.001); (11, 0, 2, 0) in the pHCCs with fat; (0, 2, 3, 3) in the pHCCs without fat (p=0.001). The number of CAs in the fat-containing HCCs (5.5±2.9) was significantly lower than that in the HCCs without fat (10.8±5.3; p<0.001). CONCLUSION: A fat component was more commonly observed in the pHCCs than in the mHCCs. The present results showed a possible mechanism of fatty change in mHCCs and pHCCs in relation to decreased arterial blood supply.