Functional analysis of a first hindlimb positioning enhancer via Gdf11 expression.

During the early development of tetrapods, including humans, the embryonic body elongates caudally once the anterior-posterior axis is established. During this process, region-specific vertebral morphogenesis occurs, with the determination of limb positioning along the anterior-posterior axis. We previously reported that Gdf11 functions as an anatomical integration system that determines the positioning of hindlimbs and sacral vertebrae where Gdf11 is expressed. However, the molecular mechanisms underlying induction of Gdf11 expression remain unclear. In this study, we searched for non-coding regions near the Gdf11 locus that were conserved across species to elucidate the regulatory mechanisms of Gdf11 expression. We identified an enhancer of the Gdf11 gene in intron 1 and named it highly conserved region (HCR). In HCR knockout mice, the expression level of endogenous Gdf11 was decreased, and the position of the sacral-hindlimb unit was shifted posteriorly. We also searched for factors upstream of Gdf11 based on the predicted transcription factor binding sites within the HCR. We found that inhibition of FGF signaling increased endogenous Gdf11 expression, suggesting that FGF signaling negatively regulates Gdf11 expression. However, FGF signaling does not regulate HCR activity. Our results suggest that there are species-specific Gdf11 enhancers other than HCR and that FGF signaling regulates Gdf11 expression independent of HCR.

Evaluation of the Simple Suspension Method for Oral Anticancer Drugs.

The simple suspension method (SSM) involves administering tablets or capsules using a tube after disintegration and suspension in hot water without crushing or opening the capsule. Particularly, for anticancer drugs, it is an excellent method of administration that reduces the risk of exposure during dispensing. In contrast, information on SSM for individual drugs is insufficient. Anticancer drugs present a therapeutic challenge because their information is limited. We investigated whether SSM is possible with 36 anticancer drugs. Furthermore, we examined the pH of the suspension of these drugs, for which no information on SSM is available. We found that suspension was possible for 24 of the 36 drugs. Furthermore, the pH of the suspension was measured, which provided important information when considering dissolution solutions other than hot water. Little changes in the pH were observed before or after passing through the tube. The results of this study may improve medication adherence in patients with cancer experiencing dysphagia.

Accuracy of aortic valve calcification volume score for identification of significant aortic stenosis on non-electrocardiographic-gated computed tomography compared to the Agatston scoring system.

BACKGROUND: Considering the absence of reports validating the precision of the volume score and the relationship between the volume and Agatston scores, this study evaluated the accuracy of the volume score compared to the Agatston score for the quantitative measurement of aortic valve calcification (AVC) on non-electrocardiographic-gated computed tomography (CT). METHODS: We retrospectively analysed the AVC scores of 5385 patients who underwent transthoracic echocardiography between March 1, 2013 and December 26, 2019 â€‹at our institution, using non-contrast non-electrocardiographic-gated CT. The thresholds for significant aortic stenosis (AS) were computed using receiver operating characteristic curves based on the AVC scores. The area under the curve (AUC) of the Agatston and volume scores for significant AS were compared to evaluate the accuracy of the scoring method. RESULTS: All sex-specific AVC thresholds of the volume score for significant AS (moderate and high AS severity, moderate and high AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.978-0.996; sensitivity, 94.2-98.4%; specificity, 90.1-100%). No significant differences in the AUC were observed between the Agatston and volume scores for significant AS in male and female patients. CONCLUSION: All volume score threshold values showed high sensitivity and specificity for identifying significant AS. The accuracy of the test for AVC thresholds of the volume score for significant AS was comparable to that of the Agatston score. Our findings raise questions about the significance of weighting calcium density in the Agatston score for assessing AS severity.

Successful retrieval of a foreign body in an infant's right pulmonary artery using the new boomerang loop-snare technique: A case report.

We report successful percutaneous retrieval of a foreign body located in an infant's right pulmonary artery using the new boomerang loop-snare technique. The case was an 18-month-old girl. A central venous catheter for chemotherapy was inserted from the right subclavian vein during treatment for myelodysplastic syndrome at another hospital. A postprocedural chest X-ray showed a foreign body in her right lung, and contrast-enhanced computed tomography confirmed the linear foreign body was located in the right pulmonary artery. The patient was transferred to our hospital to retrieve the foreign body. Under cooperation with pediatric cardiologists, a 6 Fr sheath was inserted via the right femoral vein, and a guiding catheter was advanced into the right pulmonary artery. Owing to the risk of vascular injury when using endoscopic forceps, we decided to use the loop-snare technique. We successfully crossed over the foreign body using a steerable microcatheter and a long microguidewire. The microguidewire was reinserted into the guiding catheter, and a loop was created by grasping the end of the wire using a microsnare catheter, which was inserted coaxially within the guiding catheter. By pulling the microsnare catheter, we were able to pull the foreign body into the guiding catheter and successfully retrieved it. There were no complications, such as pulmonary artery injuries or thrombi. The recovered foreign body was a piece of a guidewire. The boomerang loop-snare technique using a small-diameter system is useful for the retrieval of a foreign body in infants.

Differentiating gallbladder cancer from polyps using non-enhanced magnetic resonance imaging.

Purpose: This retrospective cohort study assessed the efficiency of non-enhanced magnetic resonance imaging (MRI) for differentiating gallbladder cancer (GBC) from gallbladder polyps (GBPs) measuring ≥ 10 mm. Material and methods: Patients diagnosed with GBCs or GBPs ≥ 10 mm and GBC ≤ T2 stage were eligible for inclusion. Two independent blinded readers assessed the continuity of the mucosal and muscular layers (CMML; present or absent) and normalised signal intensity ratio (NIR) on the apparent diffusion coefficient map (NIR-ADC), T1-weighted image (NIR-T1WI), and T2-weighted half-Fourier acquisition single-shot turbo spin-echo image. Univariate and multivariate logistic regression analyses and interobserver agreement analyses were performed to detect predictive variables differentiating GBCs from GBPs. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance. A reproducibility test was performed to verify the predictive variables. Results: Multivariate analysis showed significant differences in CMML, NIR-ADC, and NIR-T1WI (p < 0.001). The positive predictive value (PPV) and specificity of the absence of CMML were approximately 100%. The CMML showed the best specificity, accuracy, and PPV in the reproducibility study. The sensitivity of CMML alone was approximately 50%, whereas it increased to approximately 70% when combined with NIR-ADC. The diagnostic performance of the combination, including sensitivity, was almost like that of tumour size. The combined tumour size and CMML assessment showed higher diagnostic performance than tumour size alone. Conclusions: The absence of CMML and NIR-ADC ≤ 1.86 helped in differentiating GBCs from GBPs. Evaluation of the absence of CMML and measurement of tumour size could better aid in determining between the two than measurement of tumour size alone.

Current research on mechanisms of limb bud development, and challenges for the next decade.

The developmental mechanisms of limb buds have been studied in developmental biology as an excellent model of pattern formation. Chick embryos have contributed to the discovery of new principles in developmental biology, as it is easy to observe live embryos and manipulate embryonic tissues. Herein, I outline recent findings and future issues over the next decade regarding three themes, based on my research: limb positioning, proximal-distal limb elongation and digit identity determination. First, how hindlimb position is determined at the molecular level is described, with a focus on the transforming growth factor-ß signaling molecule GDF11. Second, I explain how the cell population in the limb bud deforms with developmental progress, shaping the limb bud with elongation along the proximal-distal axis. Finally, I describe the developmental mechanisms that determine digit identity through the interdigits.

Membrane molecule bouncer regulates sperm binding activity in immature oocytes in the viviparous teleost species Poecilia reticulata (guppy).

Generally, in vertebrates, the first step toward fertilization is the ovulation of mature oocytes, followed by their binding to sperm cells outside of the ovary. Exceptionally, the oocytes of poeciliid fish are fertilized by sperm cells within the follicle, and the developmental embryo is subsequently released into the ovarian lumen before delivery. In the present study, we aimed to identify the factor(s) responsible for intrafollicular fertilization in a viviparous teleost species, Poecilia reticulata (guppy). Sperm tracking analysis in this regard indicated that in this species, sperm cells reached immature oocytes including the germinal vesicle, and the insemination assay indicated that the immature oocytes robustly adhered to the sperm cells; similar binding was not observed in Danio rerio (zebrafish) and Oryzias latipes (medaka). We also identified the Ly6/uPAR protein bouncer as the factor responsible for the observed sperm binding activity of the immature oocytes in this species. The recombinant bouncer peptide acted as an inhibitory decoy for the sperm-oocyte binding in guppy. On the other hand, ectopic expression of guppy bouncer in zebrafish oocytes resulted in interspecific sperm-oocyte binding. These results argue that bouncer is responsible for sperm-immature oocyte binding. Our findings highlight the unique reproductive strategies of guppy fish and enhance our understanding of the diverse reproductive mechanisms in vertebrates.

Effect of Inhaled Ciclesonide in Non-Critically Ill Hospitalized Patients With Coronavirus Disease 2019: A Multicenter Observational Study in Japan.

Background: Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. Although systemic steroids play an important role in treating patients with severe COVID-19, the role of inhaled corticosteroids in non-critically ill, hospitalized patients with COVID-19 remains unclear. Methods: We analyzed findings in non-critically ill, hospitalized patients with COVID-19 who were >18 years old and were admitted to 64 Japanese hospitals between January and September 2020. We performed propensity score matching analysis to evaluate 28-day and in-hospital mortality rates with or without inhaled ciclesonide within 2 days of admission. Sensitivity analyses using inverse probability weighting analysis, and generalized estimating equation method were also performed. Results: Eligible patients (n = 3638) were divided into ciclesonide (n = 290) and control (n = 3, 393) groups. The 1-to-4 propensity score matching analysis included 271 ciclesonide users and 1084 nonusers. There were no significant differences between the 2 groups for 28-day (3.3% vs 2.3%; risk difference, 1.0% [95% confidence interval, -1.2 to 3.3]) or in-hospital (4.8% vs 2.6%; risk difference, 2.2 [-.5 to 4.9]) mortality rates. The sensitivity analysis showed similar outcomes. Conclusions: From this multicenter observational study in Japan, inhaled ciclesonide did not decrease 28-day or in-hospital mortality rates in non-critically ill, hospitalized patients with COVID-19. Future large, multinational, randomized trials are required to confirm our results.

An archetype and scaling of developmental tissue dynamics across species.

Morphometric studies have revealed the existence of simple geometric relationships among various animal shapes. However, we have little knowledge of the mathematical principles behind the morphogenetic dynamics that form the organ/body shapes of different species. Here, we address this issue by focusing on limb morphogenesis in Gallus gallus domesticus (chicken) and Xenopus laevis (African clawed frog). To compare the deformation dynamics between tissues with different sizes/shapes as well as their developmental rates, we introduce a species-specific rescaled spatial coordinate and a common clock necessary for cross-species synchronization of developmental times. We find that tissue dynamics are well conserved across species under this spacetime coordinate system, at least from the early stages of development through the phase when basic digit patterning is established. For this developmental period, we also reveal that the tissue dynamics of both species are mapped with each other through a time-variant linear transformation in real physical space, from which hypotheses on a species-independent archetype of tissue dynamics and morphogenetic scaling are proposed.

Immediate effects of verbal instructions with internal focus of attention and external focus of attention on forward reach movement while standing.

[Purpose] This study aimed to examine the immediate effects of verbal instructions with an internal and external focus of attention on forward reach movement while standing. [Participants and Methods] Thirty-seven healthy young males performed reach movement in three conditions: control, internal focus of attention, and external focus of attention. The measurements recorded were the movement distance of the third metacarpal bone (reach distance), the distance of the center of pressure, and the movement angles between the acromion and malleolus lateralis and between the acromion and trochanter major. [Results] Compared to the control condition, the internal focus of attention condition had a lower reach distance, angles between the acromion and malleolus lateralis and between the acromion and trochanter major, and center of pressure distance. In contrast, compared to the control condition, the external focus of attention condition showed higher reach distance and angles between the acromion and malleolus lateralis and between the acromion and trochanter major. The change rate of reach distance in the internal and external focus of attention conditions correlated significantly with the change rates of the angles between the acromion and malleolus lateralis and between the acromion and trochanter major. [Conclusion] Verbal instructions with attentional focus resulted in the simultaneous adjustment of the positional relationship between trunk and hip and immediately affected the reach distance. Our findings suggest that verbal instruction with attentional focus is an important factor affecting reach movement.

Silver-Mixed Port Reduces Venous Access Port Related Infection Rate Compared to Non-Silver-mixed Port: A Single-center Retrospective Analysis.

PURPOSE: Totally implantable venous access ports (TIVAPs) are increasingly used as safe and convenient central venous access devices. However, several TIVAP-related complications occur, with port/catheter infection being most common. Silver-mixed ports have recently been introduced in anticipation of reducing TIVAP infection. This study aimed to investigate the efficacy of this device in reducing port infection by examining groups with and without silver-mixed devices. MATERIALS AND METHODS: From April 2017 to July 2022, silver-mixed ports (S group) and non-silver-mixed port group (NS group) were reviewed at our institution. The incidence of TIVAP-related infections, patient characteristics, and bacteriological data were evaluated. Univariate and multivariate analyses were used to evaluate risk factors for TIVAP-related infection. RESULTS: A total of 607 patients (S group, n = 203; NS group, n = 404) were enrolled. The rates of TIVAP-related infection were 3.0% (n = 6) and 7.7% (n = 31) in the S and NS groups, respectively. The incidence of total infection per 1000 catheter-days were 0.114 and 0.214 the S and NS groups, respectively. In the entire group, the rates of infection were 6.1% (n = 37) and the incidence of total infection per 1000 catheter-days was 0.187. Univariate and multivariate analyses revealed a significantly lower TIVAP-related infection rate in S group than NS group (p = 0.0216, odds ratio = 2.88 confidence interval: 1.17-7.08). No gram-negative rods were detected in the S group as port infection. CONCLUSION: Silver-mixed port may be feasible in preventing port infection. LEVEL OF EVIDENCE: Level 3, Local non-random sample.

3D-OSEM versus FORE + OSEM: Optimal Reconstruction Algorithm for FDG PET with a Short Acquisition Time.

Objective In this study, we investigated the optimal reconstruction algorithm in fluorodeoxyglucose (FDG) positron emission tomography (PET) with a short acquisition time. Materials and Methods In the phantom study, six spheres filled with FDG solution (sphere size: 6.23-37 mm; radioactivity ratio of spheres to background = 8:1) and placed in a National Electrical Manufacturers Association phantom were evaluated. Image acquisition time was 15 to 180 seconds, and the obtained image data were reconstructed using each of the Fourier rebinning (FORE) + ordered subsets expectation-maximization (OSEM) and 3D-OSEM algorithms. In the clinical study, mid-abdominal images of 19 patients were evaluated using regions of interest placed on areas of low, intermediate, and high radioactivity. All obtained images were investigated visually, and quantitatively using maximum standardized uptake value (SUV) and coefficient of variation (CV). Results In the phantom study, FORE + OSEM images with a short acquisition time had large CVs (poor image quality) but comparatively constant maximum SUVs. 3D-OSEM images showed comparatively constant CVs (good image quality) but significantly low maximum SUVs. The results of visual evaluation were well correlated with those of quantitative evaluation. Small spheres were obscured on 3D-OSEM images with short acquisition time, but image quality was not greatly deteriorated. The clinical and phantom studies yielded similar results. Conclusion FDG PET images with a short acquisition time reconstructed by FORE + OSEM showed poorer image quality than by 3D-OSEM. However, images obtained with a short acquisition time and reconstructed with FORE + OSEM showed clearer FDG uptake and more useful than 3D-OSEM in the light of the detection of lesions.

Deciphering viscoelastic cell manipulation in rectangular microchannels.

Viscoelastic focusing has emerged as a promising method for label-free and passive manipulation of micro and nanoscale bioparticles. However, the design of microfluidic devices for viscoelastic particle focusing requires a thorough comprehensive understanding of the flow condition and operational parameters that lead to the desired behavior of microparticles. While recent advancements have been made, viscoelastic focusing is not fully understood, particularly in straight microchannels with rectangular cross sections. In this work, we delve into inertial, elastic, and viscoelastic focusing of biological cells in rectangular cross-section microchannels. By systematically varying degrees of fluid elasticity and inertia, we investigate the underlying mechanisms behind cell focusing. Our approach involves injecting cells into devices with a fixed, non-unity aspect ratio and capturing their images from two orientations, enabling the extrapolation of cross-sectional equilibrium positions from two dimensional (2D) projections. We characterized the changes in hydrodynamic focusing behaviors of cells based on factors, such as cell size, flow rate, and fluid characteristics. These findings provide insights into the flow characteristics driving changes in equilibrium positions. Furthermore, they indicate that viscoelastic focusing can enhance the detection accuracy in flow cytometry and the sorting resolution for size-based particle sorting applications. By contributing to the advancement of understanding viscoelastic focusing in rectangular microchannels, this work provides valuable insight and design guidelines for the development of devices that harness viscoelastic focusing. The knowledge gained from this study can aid in the advancement of viscoelastic particle manipulation technique and their application in various fields.

An inducible germ cell ablation chicken model for high-grade germline chimeras.

Chicken embryos are a powerful and widely used animal model in developmental biology studies. Since the development of CRISPR technology, gene-edited chickens have been generated by transferring primordial germ cells (PGCs) into recipients after genetic modifications. However, low inheritance caused by competition between host germ cells and the transferred cells is a common complication and greatly reduces production efficiency. Here, we generated a gene-edited chicken, in which germ cells can be ablated in a drug-dependent manner, as recipients for gene-edited PGC transfer. We used the nitroreductase/metronidazole (NTR/Mtz) system for cell ablation, in which nitroreductase produces cytotoxic alkylating agents from administered metronidazole, causing cell apoptosis. The chicken Vasa homolog (CVH) gene locus was used to drive the expression of the nitroreductase gene in a germ cell-specific manner. In addition, a fluorescent protein gene, mCherry, was also placed in the CVH locus to visualize the PGCs. We named this system 'germ cell-specific autonomous removal induction' (gSAMURAI). gSAMURAI chickens will be an ideal recipient to produce offspring derived from transplanted exogenous germ cells.

VGLL3 confers slow-twitch muscle differentiation via PGC-1α expression in C2C12 myocytes.

Vestigial-like family member 3 (VGLL3) is a cofactor for the TEA-domain transcription factor (TEAD) family. Although VGLL3 influences myogenic differentiation, its involvement in slow- and fast-twitch fiber specification remains unknown. In this study, we established a cell line stably overexpressing VGLL3 and analyzed effects of VGLL3 on the myogenic differentiation of murine myoblast C2C12 cells. We found that VGLL3 expression promotes slow-twitch muscle differentiation. Mechanistically, VGLL3 expression induced the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master transcriptional regulator of slow-twitch muscle development. We also found that VGLL3 proteins are degraded by the proteasome, which causes switching of TEAD cofactors from VGLL3 to Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ). These results suggest that the balance between the two kinds of TEAD cofactors VGLL3 and YAP/TAZ controls muscle fiber-type specification.

Long-term results of Chiari pelvic osteotomy on the preservation of hip function with mean follow-up of more than 30 years and its prognostic factors.

BACKGROUND: Clinical outcomes of Chiari pelvic osteotomy for acetabular dysplasia, including conversion to total hip arthroplasty (THA), have not been adequately explored. The purpose of this study was to examine the long-term results and clinical outcomes of Chiari pelvic osteotomy as the primary outcome and to analyze its prognostic factors as the second outcome. METHODS: This study was a multicenter, retrospective cohort study. Ninety-seven patients underwent Chiari pelvic osteotomy at three hospitals between March 1975 and October 1997. The long-term clinical outcomes of Chiari pelvic osteotomy, including conversion to THA and hip pain, were analyzed using the Kaplan-Meier method. In addition, the prognostic factors for conversion to THA after Chiari pelvic osteotomy were evaluated with clinical variables and radiographic parameters. RESULTS: The study included 51 hips in 45 patients (4 men and 41 women) with long-term follow-up. The survival rates assessed by Kaplan-Meier analysis with conversion to THA as an endpoint, were 90.2% (95% confidence interval (CI) 82.0-98.4%) at 20 years and 73.5% (95% CI 61.1-86.0%) at 30 years. In contrast, the Kaplan-Meier survival rates with the Japanese Orthopaedic Association hip score for pain ≤20 as an endpoint, were 86.3% (95% CI 76.8-95.7%) at 20 years and 65.6% (95% CI 52.3-79.0%) at 30 years. Only older age at osteotomy was the significantly poor prognostic factor for conversion to THA, with a hazard ratio of 1.11/year, 95% CI 1.06 to 1.18, (p < 0.01). CONCLUSION: Chiari pelvic osteotomy may still be a good alternative to bony reconstructive surgery for acetabular dysplasia especially in young patients. Only older age at the osteotomy was related to the poor prognosis of preserving hip function.

Polymerization Properties of n-Butyl Cyanoacrylate Mixed with Ethiodized Oil in the Lymphatic System: In Vivo Investigation in a Rabbit Model.

PURPOSE: To evaluate the polymerization properties of a mixture of n-butyl cyanoacrylate (nBCA) and ethiodized oil in the lymphatic system using an animal model. MATERIALS AND METHODS: Nineteen male Japanese White rabbits underwent 28 lymphatic embolization procedures under fluoroscopic guidance using manually injected mixtures of nBCA and ethiodized oil at ratios of 1:2 (nBCA density of 33%), 1:4 (20%), 1:6 (14%), and 1:8 (11%) via the popliteal lymph node. The time required for polymerization and the distance traveled by the mixture were evaluated and compared among the groups using the Kruskal-Wallis test. Histopathologic intergroup comparisons and time-course changes were also evaluated using embolized lymph nodes. RESULTS: Among 23 successful procedures, the mean polymerization times were 14 ± 3, 88 ± 93, 331 ± 292, and 932 seconds ± 540 and the mean distances traveled were 13 ± 10, 31 ± 44, 85 ± 89, and 108 mm ± 35 in the 33% (n = 5), 20% (n = 6), 14% (n = 6), and 11% (n = 6) groups, respectively. The 11% group demonstrated a significantly longer polymerization time than the 33%, 20%, and 14% groups and distance traveled than the 33% group. Pathologically, the embolized lymph nodes showed inflammatory changes and massive necrosis regardless of the nBCA density. CONCLUSIONS: Polymerization times and distances traveled were increased when nBCA was diluted with increasing quantitites of ethiodized oil in this rabbit model of lymphatic embolization. These relationships should be considered when dilution is prescribed for clinical use.

Separation Properties of Plasmid DNA Using a Two-Stage Particle Adsorption-Microfiltration Process.

Plasmid DNA is used as a vector for gene therapy and DNA vaccination; therefore, the establishment of a mass production method is required. Membrane filtration is widely employed as a separation method suitable for the mass production of plasmid DNA. Furthermore, the separation of plasmid DNA using microfiltration and ultrafiltration membranes is being investigated. Because plasmid DNA has a circular structure, it undergoes significant deformation during filtration and easily permeates the membrane, hindering the selection of separation membranes based on molecular weight. In this study, we applied affinity microfiltration to plasmid DNA purification. α-Fe2O3 with an isoelectric point of approximately 8 and a particle size of 0.5 µm was selected as the ligand for two-stage affinity microfiltration of plasmid DNA. In the first stage of microfiltration, the experiment was conducted at a pH of 5, and a cake of α-Fe2O3 with bound plasmid DNA was obtained. Next, liquid permeation (pH 9 and 10) through the cake was performed to elute the bound plasmid DNA. Plasmid DNA was eluted during the early phase of liquid permeation at pH 10. Furthermore, agarose gel analysis confirmed the usefulness of the two-stage affinity microfiltration method with adsorption and desorption for plasmid DNA purification.

Real-world safety and effectiveness of omalizumab in Japanese patients with chronic spontaneous urticaria: A post-marketing surveillance study.

BACKGROUND: The safety and efficacy of omalizumab in chronic spontaneous urticaria (CSU) patients has been established, but real-world long-term data remain scarce, especially in Japan. METHODS: 52-week, open-label, single-arm, observational study evaluated the safety and effectiveness of first-time omalizumab in Japanese CSU patients responding inadequately to conventional therapies. RESULTS: Overall, 235 of 280 patients completed the study. Most patients were aged ≥ 18 and < 65 years; adolescents (≥ 12 and ≤ 18 years) accounted for 9.6% of the total population. The mean ± standard deviation (SD) duration of CSU at baseline was 1.6 ± 3.1 years; 46.1% of patients had had CSU for < 6 months. At baseline, the mean ± SD of Urticaria Control Test (UCT) score, Weekly Urticaria Activity Score (UAS7), and Dermatology Life Quality Index (DLQI) were 5.1 ± 3.2, 25.2 ± 11.9, and 8.4 ± 5.9, respectively. The mean ± SD duration of the observation period was 330.3 ± 86.2 days. Relapse was reported in 65 patients, 51, 9, and 5 of whom required retreatment with omalizumab 1, 2, and ≥ 3 times, respectively. The incidence of adverse events (AEs), serious AEs, and adverse drug reactions (ADRs) was reported in 11.8%, 1.4%, and 3.9% of patients, respectively. The most common AEs were urticaria (1.8%) and eczema (1.1%). No adolescents experienced ADRs. A cumulative of 92.8% of patients responded in the Physician's Global Impression of Change, with 81.3%, 75.0%, and 95.1% of patients achieving UCT ≥ 12, UAS7 ≤ 6, and DLQI ≤ 5 up to Week 52, respectively. CONCLUSIONS: This study supports the safety and effectiveness of omalizumab in CSU patients who responded inadequately to conventional therapies in real-world clinical practice in Japan.

Optimal threshold score of aortic valve calcification for identification of significant aortic stenosis on non-electrocardiographic-gated computed tomography.

OBJECTIVES: This study evaluated the association between aortic valve calcification (AVC) and aortic stenosis (AS) by scoring the AVC to determine the threshold scores for significant AS on non-electrocardiographic (ECG)-gated computed tomography (CT). METHODS: We retrospectively analyzed the AVC scores of 5385 patients on non-contrast non-ECG-gated CT, who underwent transthoracic echocardiography (TTE) from March 1, 2013, to December 26, 2019, at our institution. Multivariable logistic regression models were used to identify potential risk factors for significant AS. The thresholds for significant AS were computed using receiver operator characteristic (ROC) curves, based on the AVC scores after propensity score matching. RESULTS: A significant association was found between AS and age (p < 0.001; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.06), female sex (p < 0.001; OR, 4.5; 95% CI, 2.75-7.36), bicuspid aortic valve (p < 0.001; OR, 23.2; 95% CI, 7.35-72.9), and AVC score (AVC score/100) (p < 0.001; OR, 1.82; 95% CI, 1.71-1.95). All sex-specific AVC thresholds for significant AS (moderate and over AS severity, moderate and over AS severity without discordance, discordant severe AS, and concordant severe AS) showed high sensitivity and specificity (AUC, 0.939-0.968; sensitivity, 84.6-96%; specificity, 84.2-97.1%). CONCLUSIONS: We determined the optimal AVC threshold scores for significant AS, which may aid in diagnosing significant asymptomatic AS on incidental detection of AVC through non-ECG-gated CT for non-cardiac indications. KEY POINTS: • Increased frequency of non-electrocardiographic (ECG)-gated computed tomography (CT) for non-cardiac indications has led to the increased incidental identification of aortic valve calcification (AVC). • It is important to identify patients with significant aortic stenosis (AS) who require additional echocardiographic assessment on incidental detection of AVC via non-ECG-gated CT. • We determined the AVC thresholds with high sensitivity and specificity to identify significant AS on non-ECG-gated CT, which could lead to early diagnosis of asymptomatic significant AS and improved prognosis.