Correction: A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

[This corrects the article DOI: 10.1371/journal.ppat.1010092.].

A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

The development of safe and effective vaccines to prevent SARS-CoV-2 infections remains an urgent priority worldwide. We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 vaccine candidate. We have constructed VSV genomes carrying exogenous genes resulting in the production of avirulent rVSV carrying the full-length spike protein (SF), the S1 subunit, or the receptor-binding domain (RBD) plus envelope (E) protein of SARS-CoV-2. Adding the honeybee melittin signal peptide (msp) to the N-terminus enhanced the protein expression, and adding the VSV G protein transmembrane domain and the cytoplasmic tail (Gtc) enhanced protein incorporation into pseudotype VSV. All rVSVs expressed three different forms of SARS-CoV-2 spike proteins, but chimeras with VSV-Gtc demonstrated the highest rVSV-associated expression. In immunized mice, rVSV with chimeric S protein-Gtc derivatives induced the highest level of potent neutralizing antibodies and T cell responses, and rVSV harboring the full-length msp-SF-Gtc proved to be the superior immunogen. More importantly, rVSV-msp-SF-Gtc vaccinated animals were completely protected from a subsequent SARS-CoV-2 challenge. Overall, we have developed an efficient strategy to induce a protective response in SARS-CoV-2 challenged immunized mice. Vaccination with our rVSV-based vector may be an effective solution in the global fight against COVID-19.

Novel MRI signs of ruptured disc in the cervical spine with intraoperative comparisons.

OBJECTIVES: To evaluate the diagnostic performance of two novel MRI signs for extruded disc (ED) and uncontained ED (ruptured disc, RD) in the cervical spine using intraoperative findings as reference. METHODS: This retrospective study included patients who underwent cervical spine MRI and surgery for disc pathology with intraoperative confirmation of RD from September 1, 2016, to January 31, 2021. Two radiologists determined whether the disc was extruded or ruptured with and without the aid of two novel MRI signs suggesting RD (sign 1: blurred margin of the disc; sign 2: mushroom-shaped disc). The diagnostic performance was analyzed using surgical findings as reference. Intra- and interobserver agreements were measured for each MRI sign. RESULTS: A total of 91 patients totaling 131 discs were enrolled (mean age: 56.02 ± 12.93; range: 26-88; 62 men and 29 women), of whom 62 were surgically confirmed with RD. When the diagnosis was based exclusively on existing ED definitions, ED was diagnosed with 62.9-79.0% sensitivity and 80.2% accuracy, whereas RD was diagnosed with 35.5-45.2% sensitivity and 67.9-71.0% accuracy. However, when the two novel MRI signs were used as an aid in the diagnosis, ED was diagnosed with 95.2-96.8% sensitivity and 84.0-88.5% accuracy, while RD was diagnosed with 95.2-96.8% sensitivity and 84.0-89.3% accuracy. Intra- and interobserver agreement was substantial (k = 00.77-0.86, 0.69-0.79, respectively, p < 0.001). CONCLUSIONS: The detection of two novel MRI signs on preoperative MRI can lead to a more accurate RD diagnosis. KEY POINTS: • The diagnostic sensitivity of MRI for cervical ruptured disc is very low (about 35-45 %) using the standardized definition of lumbar disc nomenclature. • Two novel MRI signs can lead to a more accurate diagnosis of the surgically confirmed ruptured disc in the cervical spine. • These two novel MRI signs showed substantial intra-and interobserver reliabilities.

Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea.

Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.

Pharmaceutical and Immunological Evaluation of Cholera Toxin A1 Subunit as an Adjuvant of Hepatitis B Vaccine Microneedles.

PURPOSE: For successful delivery of a solid vaccine formulation into the skin using microneedles, the solubility of an adjuvant should be considered because the decrease in the dissolution rate by the addition of adjuvant decreases the delivery efficiency of the vaccine. METHODS: In this study, cholera toxin A subunit 1 (CTA1) was examined as an adjuvant to Hepatitis B vaccine (HBV) microneedles because of its good water solubility, improved safety, and positive effect as shown in intramuscular administration of a liquid vaccine. RESULTS: All solid formulations with CTA 1 dissolved in in vivo mouse skin within 30 min, and they were successfully delivered into the skin. In experiments with mice, the addition of CTA1 led to improved IgG immune response compared to the use of an aluminum hydroxide-based formulation and intramuscular administration of HBV. In addition, CTA1 induced CD8 + T cell response as much as in which the aluminum hydroxide-based formulation induced. CONCLUSIONS: CTA1 is an adjuvant that satisfies both the delivery efficiency and the immunological characteristics required for vaccine microneedles. CTA1 will be used as a potential adjuvant through vaccine microneedles.

Utility of Preoperative Shear-Wave Elastography of the Supraspinatus Muscle for Predicting Successful Rotator Cuff Repair: A Prospective Observational Study With MRI Correlation.

BACKGROUND. After rotator cuff tear, properties of the torn muscle predict failed surgical repair. OBJECTIVE. The purpose of our study was to explore the utility of preoperative shear-wave elastography (SWE) measurements of the supraspinatus muscle to predict successful rotator cuff repair, including comparison with MRI-based measures. METHODS. This prospective study included 74 patients (37 men, 37 women; mean age, 63.9 ± 10.0 [SD] years) who underwent rotator cuff repair between May 2019 and January 2021. Patients underwent preoperative clinical shoulder MRI and investigational shoulder ultrasound including SWE using shear modulus. The mean elasticity values of the supraspinatus and trapezius muscles were measured, and the elasticity ratio (i.e., ratio of mean elasticity of supraspinatus muscle to mean elasticity of trapezius muscle) was calculated. The muscular fatty infiltration score (1-3 scale) was recorded on gray-scale ultrasound. On MRI, muscular fatty infiltration was assessed by Goutallier grade (0-4 scale), and muscular atrophy was assessed by the occupation ratio (ratio of cross-sectional areas of supraspinatus muscle and supraspinatus fossa) and by the muscle atrophy grade (0-3 scale). After rotator cuff repair, the surgeon classified procedures as achieving sufficient (n = 60) or insufficient (n = 14) repair. RESULTS. Patients with insufficient repair, versus those with sufficient repair, more commonly exhibited a large (3-5 cm) tear (100.0% vs 50.0%). Patients with insufficient, versus sufficient, repair exhibited higher mean Goutallier grade (3.8 ± 0.4 vs 1.9 ± 1.1), mean muscle atrophy grade (2.0 ± 0.8 vs 0.5 ± 0.7), mean supraspinatus elasticity (44.15 ± 8.06 vs 30.84 ± 7.89 kPa), mean elasticity ratio (3.66 ± 0.66 vs 1.83 ± 0.58), and mean gray-scale fatty infiltration grade (2.86 ± 0.36 vs 1.63 ± 0.66) and showed lower mean occupation ratio (0.3 ± 0.1 vs 0.6 ± 0.1) (all, p < .001). AUC for predicting insufficient repair was 0.945 for Goutallier grade, 0.961 for occupation ratio, 0.900 for muscle atrophy grade, 0.874 for mean elasticity, 0.971 for elasticity ratio, and 0.912 for gray-scale fatty infiltration grade. Elasticity ratio (cutoff ≥ 2.51) achieved sensitivity of 100.0% and specificity of 90.0% for insufficient repair. At multivariable analysis including tear size, the three MRI measures, elasticity ratio, and gray-scale fatty infiltration grade, the only independent predictors of insufficient repair were muscle atrophy grade of 2-3 (odds ratio [OR] = 9.3) and elasticity ratio (OR = 15.7). CONCLUSION. SWE-derived elasticity is higher in patients with insufficient rotator cuff repair; the elasticity ratio predicts insufficient repair independent of tear size and muscle characteristics. CLINICAL IMPACT. Preoperative SWE may serve as a prognostic marker in patients with rotator cuff tear.

Induction of protective immune responses against a lethal Zika virus challenge post-vaccination with a dual serotype of recombinant vesicular stomatitis virus carrying the genetically modified Zika virus E protein gene.

The development of a vaccine to prevent Zika virus (ZIKV) infection has been one of the priorities in infectious disease research in recent years. There have been numerous attempts to develop an effective vaccine against ZIKV. It is imperative to choose the safest and the most effective ZIKV vaccine from all candidate vaccines to control this infection globally. We have employed a dual serotype of prime-boost recombinant vesicular stomatitis virus (VSV) vaccine strategy, to develop a ZIKV vaccine candidate, using a type 1 IFN-receptor knock-out (Ifnar-/-) mouse model for challenge studies. Prime vaccination with an attenuated recombinant VSV Indiana serotype (rVSVInd) carrying a genetically modified ZIKV envelope (E) protein gene followed by boost vaccination with attenuated recombinant VSV New Jersey serotype (rVSVNJ) carrying the same E gene induced robust adaptive immune responses. In particular, rVSV carrying the ZIKV E gene with the honeybee melittin signal peptide (msp) at the N terminus and VSV G protein transmembrane domain and cytoplasmic tail (Gtc) at the C terminus of the E gene induced strong protective immune responses. This vaccine regimen induced highly potent neutralizing antibodies and T cell responses in the absence of an adjuvant and protected Ifnar-/- mice from a lethal dose of the ZIKV challenge.

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.

Cross-Protection against MERS-CoV by Prime-Boost Vaccination Using Viral Spike DNA and Protein.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness and has a high mortality of ∼34%. However, since its discovery in 2012, an effective vaccine has not been developed for it. To develop a vaccine against multiple strains of MERS-CoV, we targeted spike glycoprotein (S) using prime-boost vaccination with DNA and insect cell-expressed recombinant proteins for the receptor-binding domain (RBD), S1, S2, SΔTM, or SΔER. Our S subunits were generated using an S sequence derived from the MERS-CoV EMC/2012 strain. We examined humoral and cellular immune responses of various combinations with DNA plasmids and recombinant proteins in mice. Mouse sera immunized with SΔER DNA priming/SΔTM protein boosting showed cross-neutralization against 15 variants of S-pseudovirions and the wild-type KOR/KNIH/002 strain. In addition, these immunizations provided full protection against the KOR/KNIH/002 strain challenge in human DPP4 knock-in mice. These findings suggest that vaccination with the S subunits derived from one viral strain can provide cross-protection against variant MERS-CoV strains with mutations in S. DNA priming/protein boosting increased gamma interferon production, while protein-alone immunization did not. The RBD subunit alone was insufficient to induce neutralizing antibodies, suggesting the importance of structural conformation. In conclusion, heterologous DNA priming with protein boosting is an effective way to induce both neutralizing antibodies and cell-mediated immune responses for MERS-CoV vaccine development. This study suggests a strategy for selecting a suitable platform for developing vaccines against MERS-CoV or other emerging coronaviruses.IMPORTANCE Coronavirus is an RNA virus with a higher mutation rate than DNA viruses. Therefore, a mutation in S-protein, which mediates viral infection by binding to a human cellular receptor, is expected to cause difficulties in vaccine development. Given that DNA-protein vaccines promote stronger cell-mediated immune responses than protein-only vaccination, we immunized mice with various combinations of DNA priming and protein boosting using the S-subunit sequences of the MERS-CoV EMC/2012 strain. We demonstrated a cross-protective effect against wild-type KOR/KNIH/002, a strain with two mutations in the S amino acids, including one in its RBD. The vaccine also provided cross-neutralization against 15 different S-pseudotyped viruses. These suggested that a vaccine targeting one variant of S can provide cross-protection against multiple viral strains with mutations in S. The regimen of DNA priming/Protein boosting can be applied to the development of other coronavirus vaccines.

Subscapularis (SSC) tendon tears: diagnostic performance and reliability of magnetic resonance arthrography (MRA) with arthroscopic correlation and comparison with clinical tests.

OBJECTIVE: To evaluate the diagnostic performance and reliability of magnetic resonance of arthrography (MRA) in diagnosis of subscapularis (SSC) tendon tears between two reviewers with varying levels of experience, and compare the results with clinical tests. MATERIALS AND METHODS: SSC tendons were retrospectively evaluated in a total of 272 patients with arthroscopic confirmations. A total of 548 shoulder MRAs were evaluated by two musculoskeletal radiologists, and SSC tendon pathologies were classified into three groups: intact tendon (n = 149), partial-thickness tear (n = 92), or full-thickness tear (n = 31). Diagnostic performance was determined using arthroscopy as gold standard and compared with results of four clinical tests. Intra- and inter-observer reliabilities of two reviewers were evaluated using kappa statistics. RESULTS: For full-thickness tears, mean values of sensitivity, specificity, and accuracy of reviewer 1/reviewer 2 were 71.0%/87.1%, 97.3%/98.3%, and 94.4%/95.5%, respectively. For partial-thickness tears, mean values of sensitivity, specificity, and accuracy were 72.8%/73.4%, 78.3%/81.2%, and 76.5%/78.5%, respectively. Intra- and inter-observer reliabilities for both reviewers were good to very good (k = 0.85/0.93, p < 0.001; k = 0.74-0.89, p < 0.001). For all clinical tests, while specificity was very high, sensitivity was very low and the overall accuracy was also low. CONCLUSION: MRA showed high diagnostic performance for the diagnosis of SSC tendon tears, especially full-thickness tears, with good inter- and intra-observer reliabilities, regardless of the level of experience of the reviewer.

Vitamin D deficiency and associated factors in south Korean childbearing women: a cross-sectional study.

BACKGROUND: Adequate levels of vitamin D are important for women of childbearing age as vitamin D helps maintain the pregnancy and ensures proper maternal and fetal bone metabolism and fetal skeletal development. However, vitamin D deficiency is a health problem prevalent in women of all ages, worldwide. This study aimed to determine the current status of serum vitamin D levels and the risk factors for vitamin D deficiency among South Korean nurses of childbearing age. METHODS: Serum levels of 25-hydroxyvitamin D (25[OH]D) were measured in 1594 registered nurses aged 20 to 45 years who are participants in an ongoing prospective cohort study of the Korean Nurses' Health Study initiated in 2013. The participants completed surveys about demographic and occupational characteristics and physical and psychological health. We examined associations with vitamin D deficiency through multivariable logistic regression analysis. RESULTS: The average blood 25(OH) D concentration of the participants was 12.92 ng/mL (4.0-63.4 ng/mL), while the prevalence of vitamin D deficiency (< 20 ng/mL) was 89% (1419/1594). Multivariable logistic regression showed that significant risk factors for vitamin D deficiency included month of sampling (there was a lower level of vitamin D deficiency in winter than in spring, summer, or fall), age (women in their 20s had a lower vitamin D level than those in their 30s and 40s), and stress symptoms. Vitamin D levels were not associated with body mass index, physical activity, and depressive symptoms. CONCLUSIONS: This study showed a high prevalence of vitamin D deficiency in Korean female nurses. Serum levels of vitamin D were associated with age and season. Vitamin D deficiency should be recognized as one of the primary health concerns among young women. More proactive actions, such as vitamin D supplements and food fortification, are needed to improve vitamin D deficiency in high-risk groups.

Can Ultrasonography Be Useful in Planning Surgery for De Quervain Tenosynovitis?: A Prospective Study With Emphasis on Detection of the Superficial Radial Nerve and Dominant Pathologic Tendon.

OBJECTIVES: We performed preoperative ultrasonography (US) to detect the anatomic course of the superficial radial nerve (SRN) and dominant pathologic tendon of the first extensor compartment in de Quervain tenosynovitis. METHODS: We prospectively studied 27 patients (29 wrists) with de Quervain tenosynovitis who underwent surgical release of the first extensor compartment. Preoperatively, US was performed to evaluate the presence of the dominant pathologic tendon and the septum in the subcompartment, number of SRNs in the area of the surgical incision, and anatomic running course of the SRN. These variables were also checked intraoperatively. Cohen κ statistics were calculated to investigate agreement between US and surgical field findings. RESULTS: There were 7 men and 20 women (mean age, 47.8 years; range, 26-67 years). For the dominant pathologic tendon, there were 2 cases (6.9%) of an abductor pollicis longus, 11 cases (37.9%) of an extensor pollicis brevis, and 16 cases (55.2 %) of a nondominant tendon (κ = 0.94). For the subcompartment, there were 10 cases (34.5%) without a septum, 8 (27.6%) with an incomplete septum, and 11 (37.9%) with a complete septum (κ = 0.95). Most SRNs crossed over the first extensor compartment (κ = 0.78). CONCLUSIONS: Preoperative US can be useful in detecting the anatomic running course of the SRN and dominant pathologic tendon before surgery for de Quervain tenosynovitis. Classifying the anatomic course of the SRN could be essential to planning surgery, and it could be helpful to prevent injury of the SRN during surgery.

Paraspinal back muscles in asymptomatic volunteers: quantitative and qualitative analysis using computed tomography (CT) and magnetic resonance imaging (MRI).

BACKGROUND: To evaluate paraspinal back muscles of asymptomatic subjects using qualitative and quantitative analysis on CT and MRI and correlate the results with demographic data. METHODS: Twenty-nine asymptomatic subjects were enrolled prospectively (age: mean 34.31, range 23-50; 14 men, 15 women) from August 2016 to April 2017. Qualitative analysis of muscles was done using Goutallier's system on CT and MRI. Quantitative analysis entailed cross sectional area (CSA) on CT and MRI, Hounsfield unit (HU) on CT, fat fraction using two-point Dixon technique on MRI. Three readers independently analyzed the images; intra- and inter-observer agreements were measured. Linear regression and Spearman's analyses were used for correlation with demographic data. RESULTS: CSA values were significantly higher in men (p < 0.001). Fat fraction was higher (22.53% vs. 14.35%) and HU lower (36.00 vs. 47.43) in women (p < 0.001). Intra- and inter-observer reliabilities of the two methods were greater than 0.8, except for CSA of L5/S1 on MRI; however, regarding quantitative analysis, decreasing HU and increasing fat fraction were correlated with increasing age, female gender and lower lumbar segment (p < 0.001). CONCLUSION: MRI and CT can be reliably used for qualitative and quantitative analysis of paraspinal back muscles, regarding fat content. Fat fraction and HU showed highest reliabilities.

Threshold-based quantification of fatty degeneration in the supraspinatus muscle on MRI as an alternative method to Goutallier classification and single-voxel MR spectroscopy.

BACKGROUND: Conventional fat quantification methods for rotator cuff muscles have various limitations, such as inconsistent reliabilities of the Goutallier grades and need for advanced techniques in quantitative MRI sequences. We aimed to examine a threshold-based fat quantification method in the supraspinatus muscle on standard T1-weighted MR images and compare the threshold-based method with Goutallier grades and MR spectroscopy. METHODS: We retrospectively examined 38 symptomatic patients, who underwent T1 and T2-weighted fast spin-echo MR imaging and a single voxel spin-echo MR spectroscopy. The supraspinatus muscle and fossa were manually segmented in T1-weighted sagittal images and clustering-based thresholding was applied to quantify the fat fractions in the segmented areas using custom MATLAB software. Threshold-based fat fractions were compared with the Goutallier grades and MR spectroscopy fat/water ratios. A one-way analysis of variance and Pearson correlation were tested in the MATLAB software. RESULTS: Inter-observer reliability of threshold-based fat fractions for the supraspinatus muscle and fossa were 0.977 and 0.990 respectively, whereas the reliability of the Goutallier grading was 0.798. Threshold-based fat fractions in the supraspinatus fossa were significantly different between various Goutallier grades (one-way ANOVA, p < 0.001). Threshold-based fat fractions in the supraspinatus muscle strongly correlated with the MR spectroscopy fat/water ratio (Pearson correlation R-square = 0.83). CONCLUSIONS: Threshold-based fat quantification on standard T1-weighted MR images was highly reliable and produced comparable results to conventional Goutallier grades and MR spectroscopy fat/water ratios and could serve as an alternative method for accurate fat quantification in rotator cuff muscles.

Alterations in articular cartilage T2 star relaxation time following mechanical disorders: in vivo canine supraspinatus tendon resection models.

BACKGROUND: The role of altered joint mechanics on cartilage degeneration in in vivo models has not been studied successfully due to a lack of pre-injury information. We aimed 1) to develop an accurate in vivo canine model to measure the changes in joint loading and T2 star (T2*) relaxation time before and after unilateral supraspinatus tendon resections, and 2) to find the relationship between regional variations in articular cartilage loading patterns and T2* relaxation time distributions. METHODS: Rigid markers were implanted in the scapula and humerus of tested dogs. The movement of the shoulder bones were measured by a motion tracking system during normal gaits. In vivo cartilage contact strain was measured by aligning 3D shoulder models with the motion tracking data. Articular cartilage T2* relaxation times were measured by quantitative MRI scans. Articular cartilage contact strain and T2* relaxation time were compared in the shoulders before and 3 months after the supraspinatus tendon resections. RESULTS: Excellent accuracy and reproducibility were found in our in vivo contact strain measurements with less than 1% errors. Changes in articular cartilage contact strain exhibited similar patterns with the changes in the T2* relaxation time after resection surgeries. Regional changes in the articular cartilage T2* relaxation time exhibited positive correlations with regional contact strain variations 3 months after the supraspinatus resection surgeries. CONCLUSION: This is the first study to measure in vivo articular cartilage contact strains with high accuracy and reproducibility. Positive correlations between contact strain and T2* relaxation time suggest that the articular cartilage extracellular matrix may responds to mechanical changes in local areas.

Spinal extradural arteriovenous fistula after lumbar epidural injection: CT angiographic diagnosis using 3D-volume rendering.

Spinal extradural arteriovenous fistulas (SEDAVFs) are a rare form of spinal arteriovenous fistulas, the etiology of which has not been completely elucidated. To our knowledge, this is the first reported case of SEDAVF that may have been caused by a spinal procedure. This report describes a 50-year-old female patient who presented with an SEDAVF at the L3/4 level that developed 3 years after a transforaminal epidural block due to disc extrusion, after which she underwent no other operation or trauma. From routine spine magnetic resonance imaging, disc sequestration was considered more likely than vascular malformation. However, on lumbar CT angiography (CTA) and three-dimensional volume rendering images (3D-VRI), the lesion showed good association with arteries of the aortic branches, allowing us to confirm the exact diagnosis of the lesion as SEDAVF. A limitation of 3D-VRI reconstruction is the difficulty in separate visualization of the vertebral body and blood vessels. On follow-up CTA, 3D dual-energy computed tomography (DECT) depicted smaller vascular structures and showed their anatomical relationships to the bone. While spinal angiography has been traditionally known as the gold standard for SEDAVF diagnosis, CTA with 3D-VRI, especially obtained by DECT, allows clinicians to make an accurate diagnosis and treatment plan that are difficult to judge by routine MRI.

Glossary of terms for musculoskeletal radiology.

Members of the International Skeletal Society compiled a glossary of terms for musculoskeletal radiology. The authors also represent national radiology or pathology societies in Asia, Australia, Europe, and the USA. We provide brief descriptions of musculoskeletal structures, disease processes, and syndromes and address their imaging features. Given the abundance of musculoskeletal disorders and derangements, we chose to omit most terms relating to neoplasm, spine, intervention, and pediatrics. Consensus agreement was obtained from 19 musculoskeletal radiology societies worldwide.

Intranasal Immunization With an Attenuated pep27 Mutant Provides Protection From Influenza Virus and Secondary Pneumococcal Infections.

During influenza pandemics, secondary pneumococcal infections cause excessive mortality. However, the current 13-valent pneumococcal conjugate vaccine, PCV13, provides only limited protection against secondary infection. Therefore, a more effective pneumococcal vaccine is required to protect against secondary pneumococcal infections. Here, intranasal immunization with an attenuated pneumococcal pep27 mutant provides protection from influenza virus infection, and also from secondary pneumococcal challenge. These results indicate that mucosal immunity might be an effective way to reduce the morbidity and mortality due to secondary pneumococcal infections during influenza pandemics.

A simple method for bone age assessment: the capitohamate planimetry.

OBJECTIVES: To determine if the capitohamate (CH) planimetry could be a reliable indicator of bone age, and to compare it with Greulich-Pyle (GP) method. METHODS: This retrospective study included 391 children (age, 1-180 months). Two reviewers manually measured the areas of the capitate and hamate on plain radiographs. CH planimetry was defined as the measurement of the sum of areas of the capitate and hamate. Two reviewers independently applied the CH planimetry and GP methods in 109 children whose heights were at the 50th percentile of the growth chart. RESULTS: There was a strong positive correlation between chronological age and CH planimetry measurement (right, r = 0.9702; left, r = 0.9709). There was no significant difference in accuracy between CH planimetry (84.39-84.46 %) and the GP method (85.15-87.66 %) (p ≥ 0.0867). The interobserver reproducibility of CH planimetry (precision, 4.42 %; 95 % limits of agreement [LOA], -10.5 to 13.4 months) was greater than that of the GP method (precision, 8.45 %; LOA, -29.5 to 21.1 months). CONCLUSIONS: CH planimetry may be a reliable method for bone age assessment. KEY POINTS: • Bone age assessment is important in the work-up of paediatric endocrine disorders. • Radiography of the left hand is widely used to estimate bone age. • Capitatohamate planimetry is a reliable and reproducible method for assessing bone age.

Effect of recombinant human growth hormone on rotator cuff healing after arthroscopic repair: preliminary result of a multicenter, prospective, randomized, open-label blinded end point clinical exploratory trial.

BACKGROUND: This study evaluated the effect of systemic injection of recombinant human growth hormone (rhGH) on outcomes after arthroscopic rotator cuff repair. METHODS: This multicenter, prospective, randomized, comparative trial, randomized patients who underwent arthroscopic repair of large-sized rotator cuff tears into 3 groups: rhGH 4 mg group (n = 26), rhGH 8 mg group (n = 24) , and control group (n = 26). Sustained release rhGH was injected subcutaneously once weekly for 3 months postoperatively. The healing failure rate (primary end point), fatty infiltration, and atrophy of the supraspinatus muscle, and functional scores (Constant and American Shoulder and Elbow Surgeons scores) were evaluated at 6 months. Range of motion, pain visual analog scale, and serum insulin-like growth factor-1 level were measured at each follow-up. RESULTS: The healing failure rate was similar between groups (rhGH 4 mg group, 30.8%; rhGH 8 mg group, 16.7%; and control group, 34.6%; all P > .05) The proportion of severe fatty infiltration (Goutallier grade ≥3) was 20.8% in the rhGH 8 mg group, 23.1% in the rhGH 4 mg group, and 34.6% in the control group (P > .05). Functional outcomes, range of motion, and pain visual analog scale were similar between groups (all P > .05). The rhGH 8 mg group showed more increased peak insulin-like growth factor-1 level (279.43 ng/mL) than the rhGH 4 mg group ((196.82 ng/mL) and control group (186.31 ng/mL), which was not statistically different (all P > .05). No rhGH injection-related major safety issues occurred. CONCLUSIONS: This preliminary study showed no statistically significant improvement in healing or outcomes related to the treatment of rhGH after rotator cuff repair. However, further study with more enrolled patients after resetting the rhGH dose or daily administration protocol would be mandatory.