Everolimus exerts anticancer effects through inhibiting the interaction of matrix metalloproteinase-7 with syndecan-2 in colon cancer cells.

Previous work showed that matrix metalloproteinase-7 (MMP-7) regulates colon cancer activities through an interaction with syndecan-2 (SDC-2) and SDC-2-derived peptide that disrupts this interaction and exhibits anticancer activity in colon cancer. Here, to identify potential anticancer agents, a library of 1,379 Food and Drug Administration (FDA)-approved drugs that interact with the MMP-7 prodomain were virtually screened by protein-ligand docking score analysis using the GalaxyDock3 program. Among five candidates selected based on their structures and total energy values for interacting with the MMP-7 prodomain, the known mechanistic target of rapamycin kinase (mTOR) inhibitor, everolimus, showed the highest binding affinity and the strongest ability to disrupt the interaction of the MMP-7 prodomain with the SDC-2 extracellular domain in vitro. Everolimus treatment of the HCT116 human colon cancer cell line did not affect the mRNA expression levels of MMP-7 and SDC-2 but reduced the adhesion of cells to MMP-7 prodomain-coated plates and the cell-surface localization of MMP-7. Thus, everolimus appears to inhibit the interaction between MMP-7 and SDC-2. Everolimus treatment of HCT116 cells also reduced their gelatin-degradation activity and anticancer activities, including colony formation. Interestingly, cells treated with sirolimus, another mTOR inhibitor, triggered less gelatin-degradation activity, suggesting that this inhibitory effect of everolimus was not due to inhibition of the mTOR pathway. Consistently, everolimus inhibited the colony-forming ability of mTOR-resistant HT29 cells. Together, these data suggest that, in addition to inhibiting mTOR signaling, everolimus exerts anticancer activity by interfering with the interaction of MMP-7 and SDC-2, and could be a useful therapeutic anticancer drug for colon cancer.NEW & NOTEWORTHY The utility of cancer therapeutics targeting the proteolytic activities of MMPs is limited because MMPs are widely distributed throughout the body and involved in many different aspects of cell functions. This work specifically targets the activation of MMP-7 through its interaction with syndecan-2. Notably, everolimus, a known mTOR inhibitor, blocked this interaction, demonstrating a novel role for everolimus in inhibiting mTOR signaling and impairing the interaction of MMP-7 with syndecan-2 in colon cancer.

Urinary tract dilation classification system for predicting surgical management and urinary tract infection in neonates and young infants: a systematic review and meta-analysis.

BACKGROUND: The urinary tract dilation classification system has recently been developed to ensure a unified approach to describe urinary tract dilation in neonates and young infants. However, the predictive value of this system for surgical intervention or urinary tract infection (UTI) has not yet been evaluated in a meta-analysis. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the utility of a postnatal urinary tract dilation classification system for predicting surgical management or a UTI occurrence. MATERIALS AND METHODS: As the urinary tract dilation classification system was introduced in 2014, we searched Embase and PubMed databases for studies published between January 2014 and December 2022. Original articles that reported surgical interventions or UTI episodes according to postnatal urinary tract dilation grades were included. The pooled odds ratio (OR) was calculated, using either the fixed-effects or random-effects model, given the lower urinary tract dilation grades as the base category. The quality of the included studies was evaluated using the Newcastle-Ottawa scale. RESULTS: Of the 285 articles reviewed, eight (comprising 2,165 children) were included in the analysis. The studies were of medium-to-high quality. Pooled analysis demonstrated that urinary tract dilation P3 (combined OR, 21.41; 95% confidence interval [CI], 15.72-29.17) and urinary tract dilation P2-P3 (combined OR, 65.17; 95% CI, 33.08-128.38) were associated with surgical intervention. The urinary tract dilation P3 (combined OR, 2.11; 95% CI, 1.56-2.85) and urinary tract dilation P2-P3 (combined OR, 3.36; 95% CI, 2.43-4.63) were associated with UTI episodes. CONCLUSION: The postnatal urinary tract dilation classification system is useful for predicting the need for surgical management and UTI episodes in infants with hydronephrosis.

Antifungal Activity of Bulgarian Rose Damascena Oil against Vaginitis-Causing Opportunistic Fungi.

Since Bulgarian rose damascena oil is known for its anti-inflammatory, antioxidant, and antimicrobial properties, we investigated its antifungal activity against the species of Candida, which are among the most common opportunistic fungal pathogens. Our disk-diffusion assay revealed that Bulgarian rose damascena oil effectively inhibited the growth of Candida albicans along with various bacteria. The minimum inhibitory and fungicidal concentrations against Candida albicans and Candida glabrata were all 0.25%. Under our experimental conditions, Bulgarian rose damascena oil showed better inhibitory effects on Candida glabrata and Candida albicans than several popular essential oils reported to have antifungal activity other than Origanum vulgare oil. Interestingly, Bulgarian rose damascena oil showed better antifungal activity against Candida species at acidic pH and induced cell death of Candida species in the culture medium, with cell death seen in 25-35% of the cells exposed to 0.05% Bulgarian rose damascena oil. Furthermore, Bulgarian rose damascena oil inhibited the hyphal growth of Candida albicans cultured in the RPMI medium with fetal bovine serum. These findings collectively suggest that Bulgarian rose damascena oil has antifungal activity against Candida species and thus could potentially be developed in novel therapies for vaginitis-causing pathogenic fungi.

Bone Age Assessment Using Artificial Intelligence in Korean Pediatric Population: A Comparison of Deep-Learning Models Trained With Healthy Chronological and Greulich-Pyle Ages as Labels.

OBJECTIVE: To develop a deep-learning-based bone age prediction model optimized for Korean children and adolescents and evaluate its feasibility by comparing it with a Greulich-Pyle-based deep-learning model. MATERIALS AND METHODS: A convolutional neural network was trained to predict age according to the bone development shown on a hand radiograph (bone age) using 21036 hand radiographs of Korean children and adolescents without known bone development-affecting diseases/conditions obtained between 1998 and 2019 (median age [interquartile range {IQR}], 9 [7-12] years; male:female, 11794:9242) and their chronological ages as labels (Korean model). We constructed 2 separate external datasets consisting of Korean children and adolescents with healthy bone development (Institution 1: n = 343; median age [IQR], 10 [4-15] years; male: female, 183:160; Institution 2: n = 321; median age [IQR], 9 [5-14] years; male: female, 164:157) to test the model performance. The mean absolute error (MAE), root mean square error (RMSE), and proportions of bone age predictions within 6, 12, 18, and 24 months of the reference age (chronological age) were compared between the Korean model and a commercial model (VUNO Med-BoneAge version 1.1; VUNO) trained with Greulich-Pyle-based age as the label (GP-based model). RESULTS: Compared with the GP-based model, the Korean model showed a lower RMSE (11.2 vs. 13.8 months; P = 0.004) and MAE (8.2 vs. 10.5 months; P = 0.002), a higher proportion of bone age predictions within 18 months of chronological age (88.3% vs. 82.2%; P = 0.031) for Institution 1, and a lower MAE (9.5 vs. 11.0 months; P = 0.022) and higher proportion of bone age predictions within 6 months (44.5% vs. 36.4%; P = 0.044) for Institution 2. CONCLUSION: The Korean model trained using the chronological ages of Korean children and adolescents without known bone development-affecting diseases/conditions as labels performed better in bone age assessment than the GP-based model in the Korean pediatric population. Further validation is required to confirm its accuracy.

Synergistic Anti-Inflammatory Effects of Ethanol Extracts from Chrysanthemum zawadskii Flower and Cudrania tricuspidata Fruit Occur via Inhibition of the NF-κB Signaling Pathway.

Chrysanthemum zawadskii (CZ) and Cudrania tricuspidata (CT) are both traditional Korea herbal medicines, which is widely used to treat fever, cough, gastritis, and women's diseases that may be linked to inflammatory response. Although it has been used to treat diseases related to inflammation, there has been no case of the synergistic anti-inflammatory properties of both extracts. Our data revealed that ethanol extracts of dried whole CZ exhibited free radical-scavenging capacity in vitro, reduced LPS-induced intracellular reactive oxygen species, and decreased the LPS-induced upregulations of the mRNAs encoding iNOS, COX-2, and IL-6 in RAW 264.7 cells, without significant cytotoxicity. This anti-inflammatory effect was most evident from flower extracts: ethanol extracts from flowers significantly reduced the LPS-induced upregulations of iNOS and COX-2 at a concentration of 100 µg/ml. An ethanol extract of the fruit from CT also exerted a radical scavenging capacity and suppressed LPS-induced proinflammatory gene expression: 5.5 µg/ml of the ethanol extract significantly reduced the ability of LPS to induce the mRNA expression levels of iNOS and IL-6 without apparent cytotoxicity. Furthermore, as little as 1.0 µg/ml of the combined ethanol extracts of CZ flower and CT fruit reduced the LPS-induced changes monitored herein, decreasing the upregulations of iNOS and IL-6, and decreasing the nuclear localization of NF-κB p65. These results suggest that the observed synergistic anti-inflammatory effects may be mediated via inhibition of NF-κB signaling. Taken together, these data suggest that ethanol extracts from CZ flowers and CT fruits have synergistic anti-inflammatory effects and that a combination of the two extracts could prove useful for the treatment of inflammation-related diseases.

Robot versus human barista: Comparison of volatile compounds and consumers' acceptance, sensory profile, and emotional response of brewed coffee.

The increasing trend of integrating robots into the food industry has sparked debates regarding their potential influence on consumer attitudes toward food technology. This study investigated volatile compound profiles via gas chromatography-mass spectrometry (GC-MS), consumer acceptability, sensory profiling, and emotional responses of consumers toward coffee samples brewed by robot and human baristas. Moreover, the effect of the robot experience on food technology neophobia (FTN) was investigated. The principal component analysis of the volatile compound profiles revealed that the samples by the robot barista exhibited a higher degree of similarity compared to those prepared by the human barista. The range of relative standard deviations of volatile compounds from the robot barista brewed coffee was 1.4-83.1% and the variation was smaller than that of the human barista, which was 5.0-118.3%. Participants had a significant decrease in FTN scores after evaluating the robot-brewed coffee (p < 0.05), but there was no significant difference in FTN scores before and after evaluating the coffee brewed by the human barista (p > 0.05). Sensory evaluation studies revealed no significant differences in acceptability ratings and purchase intentions between the two groups (p > 0.05). However, emotional responses to the coffee samples significantly varied, with the robot-brewed coffee inducing more dynamic and positive emotions and the human-brewed coffee inducing more static and positive emotions (p < 0.05). Overall, this study provides valuable insights into consumer attitudes toward food robot service to humans and indicates that consumer's experience with food robots may significantly reduce FTN (p < 0.001).

Current diagnosis and image-guided reduction for intussusception in children.

Intussusception involves an invagination of the proximal bowel into the distal bowel, with ileocolic intussusception being the most common type. However, a diagnostic delay can lead to intestinal ischemia, bowel infarction, or even death; therefore, its early diagnosis and management are important. The primary role of abdominal radiography is to detect pneumoperitoneum or high-grade bowel obstruction in cases of suspected intussusception, and ultrasonography is the modality of choice for its diagnosis. Nonoperative enema reduction, the treatment of choice for childhood intussusception in cases without signs of perforation or peritonitis, can be safely performed with a success rate of 82%. Enema reduction can be performed in various ways according to image guidance method (fluoroscopy or ultrasonography) and reduction medium (liquid or air). Successful enema reduction is less likely to be achieved in children with a longer symptom duration, younger age, lethargy, fever, bloody diarrhea, unfavorable radiologic findings (small bowel obstruction, trapped fluid, ascites, absence of flow in the intussusception, intussusception in the left-sided colon), and pathological lead points. This review highlights the current concepts of intussusception diagnosis, nonsurgical enema reduction, success rates, predictors of failed enema reduction, complications, and recurrence to guide general pediatricians in the management of childhood intussusception.

Application of the postnatal urinary tract dilation classification system to predict the need for surgical intervention among neonates and young infants.

PURPOSE: The aim of this study was to validate the postnatal urinary tract dilation (UTD) classification system by correlating it with the need for surgical intervention. METHODS: Young infants who underwent ultrasound (US) examinations for prenatal hydronephrosis were retrospectively identified. The kidney units (KUs; right, left, or bilateral) were graded from UTD P0 (very low risk) to P3 (high risk) based on seven US criteria from the UTD system. Surgery-free survival curves were constructed using the Kaplan-Meier method. Univariable and multivariable Cox proportional-hazards regression analysis clustered by patients was performed. Interobserver agreement was analyzed using the weighted kappa coefficient. RESULTS: In total, 504 KUs from 336 patients (mean age, 18.3±15.9 days; range, 1 to 94 days; males, n=276) were included, with a median follow-up of 24.2 months. Fifty-eight KUs underwent surgical intervention. Significant differences were observed among the Kaplan-Meier curves stratified into UTD groups (P<0.001). The presence of anterior-posterior renal pelvic diameter ≥15 mm (hazard ratio [HR], 8.602; 95% confidence interval [CI], 1.558 to 43.065), peripheral calyceal dilation (HR, 8.190; 95% CI, 1.558 to 43.065), ureteral dilation (HR, 2.619; 95% CI, 1.274 to 5.380), parenchymal thickness abnormality (HR, 3.371; 95% CI, 1.574 to 7.223), bladder abnormality (HR, 12.209; 95% CI, 3.616 to 41.225) were significantly associated with the occurrence of surgery. The interobserver agreement was moderate to almost perfect agreement for US features (κ=0.564-0.898) and substantial for final UTD grades (κ=0.716). CONCLUSION: The UTD classification system is reliable and appropriately stratifies the risk of surgical intervention.

[Postoperative Imaging Findings of Biliary Atresia]. / 담도폐쇄증의 ìˆ˜ìˆ í›„ 영상 소견.

The Kasai portoenterostomy is the first-line treatment for the restoration of the flow of bile to the small intestine in patients with biliary atresia. Various complications can occur after Kasai portoenterostomy, including ascending cholangitis, biliary cirrhosis, and portal hypertension. Of these potential complications, ascending cholangitis in the most common. In cases of patients having uncontrolled complications due to progressive liver cirrhosis, portal hypertension, or progressive hyperbilirubinemia, liver transplantation is the indicated as treatment plan. Lifelong follow-up, particularly involving imaging studies, is important for the identification of various complications arising from biliary atresia after Kasai portoenterostomy. Additionally, imaging studies play a crucial role in the evaluation of potential liver donors and recipients. US is a key imaging modality utilized in the management of patients who undergo Kasai portoenterostomy, while CT and MRI are imperative to obtaining an accurate diagnosis.

Substituted Syndecan-2-Derived Mimetic Peptides Show Improved Antitumor Activity over the Parent Syndecan-2-Derived Peptide.

We previously showed that a synthetic peptide (S2-P) corresponding to a portion of the human syndecan-2 (SDC2) sequence can bind to the pro-domain of matrix metalloproteinase-7 (MMP-7) to inhibit colon cancer activities. Since S2-P had a relatively weak binding affinity for the MMP-7 pro-domain, we herein modified the amino acid sequence of S2-P to improve the anticancer potential. On the basis of the interaction structure of S2-P and MMP-7, four peptides were generated by replacing amino acids near Tyr 51, which is critical for the interaction. The SDC2-mimetic peptides harboring an Ala-to-Asp substitution at the C-terminal side of Tyr 51 (S2-D) or with an Ala-to-Phe substitution at the N-terminal side of Tyr 51 and an Ala-to-Asp substitution at the C-terminal side of Tyr 51 (S2-FE) showed improved interaction affinities for the MMP-7 pro-domain. Compared to S2-P, S2-FE was better able to inhibit the SDC2-MMP-7 interaction, the cell surface localization of MMP-7, the gelatin degradation activity of MMP-7, and the cancer activities (cell migration, invasion, and colony-forming activity) of human HCT116 colon cancer cells in vitro. In vivo, S2-FE inhibited the primary tumor growth and lung metastasis of CT26 mouse colon cancer cells in a xenograft mouse model. Together, these data suggest that S2-FE could be useful therapeutic anticancer peptides for colon cancer.

Re-Assessment of Applicability of Greulich and Pyle-Based Bone Age to Korean Children Using Manual and Deep Learning-Based Automated Method.

PURPOSE: To evaluate the applicability of Greulich-Pyle (GP) standards to bone age (BA) assessment in healthy Korean children using manual and deep learning-based methods. MATERIALS AND METHODS: We collected 485 hand radiographs of healthy children aged 2-17 years (262 boys) between 2008 and 2017. Based on GP method, BA was assessed manually by two radiologists and automatically by two deep learning-based BA assessment (DLBAA), which estimated GP-assigned (original model) and optimal (modified model) BAs. Estimated BA was compared to chronological age (CA) using intraclass correlation (ICC), Bland-Altman analysis, linear regression, mean absolute error, and root mean square error. The proportion of children showing a difference >12 months between the estimated BA and CA was calculated. RESULTS: CA and all estimated BA showed excellent agreement (ICC ≥0.978, p<0.001) and significant positive linear correlations (R²≥0.935, p<0.001). The estimated BA of all methods showed systematic bias and tended to be lower than CA in younger patients, and higher than CA in older patients (regression slopes ≤-0.11, p<0.001). The mean absolute error of radiologist 1, radiologist 2, original, and modified DLBAA models were 13.09, 13.12, 11.52, and 11.31 months, respectively. The difference between estimated BA and CA was >12 months in 44.3%, 44.5%, 39.2%, and 36.1% for radiologist 1, radiologist 2, original, and modified DLBAA models, respectively. CONCLUSION: Contemporary healthy Korean children showed different rates of skeletal development than GP standard-BA, and systemic bias should be considered when determining children's skeletal maturation.

Ingredient and Salinity Variations in Doenjang Stews Sold in a College Town and Consumer Acceptance of Doenjang Stews among Korean College Students.

This study determined the ingredient and salinity variations in Doenjang stew sold near a college campus and determined its consumer acceptance with varying salinity levels. Doenjang stews from four restaurants near a college campus were collected around lunchtime for 3 days. The salinity and weight of each ingredient included in Doenjang stews were recorded. Consumer acceptance testing on the stews was also conducted (n=98). Overall, variations in Doenjang stew recipes, including salinity values and the weight of each ingredient, between and within restaurants were also observed (P<0.05). The salinity of Doenjang stews collected from different restaurants ranged between 1.2% and 1.7%, higher than that recommended by the Korean government. Doenjang stew with a salinity of greater than 1.3% was most liked by consumers, whereas a salinity of 1.2% was least liked. At the same salinity value, a high stock amount of Doenjang stew was preferred to a greater extent than that with a high number of ingredients in Doenjang stew, suggesting that various ingredients included in the recipe do not necessarily increase consumer acceptance of stew.

A simplified ultrasound approach to diagnose testicular torsion and predict unsalvageable testis.

AIMS: To develop a decision tree model using US features to differentiate testicular torsion and other conditions of acute scrotum and to investigate predictive parameters of unsalvageable testis in testicular torsion. MATERIALS AND METHODS: Scrotal US was reviewed in patients aged <30 years who presented with acute scrotum from 2014 to 2020. US findings of whirlpool sign, testicular volume ratio, heterogeneous echotexture, testicular vascularity, epididymis enlargement and/or hyperemia, and avascular nodule were evaluated and compared. A decision tree model was created using the conditional inference tree analysis and the accuracy was calculated. Univariate logistic regression analysis was performed to find out the predictive US features of unsalvageable testes. RESULTS: Total of 381 patients (13.2±7.2 years old; range, 1 day-30 years) were included. Thirty-four patients were diagnosed with testicular torsion, and the others with orchitis or epididymo-orchitis (n=59), epididymitis (n=264), and appendage torsion (n=24). In the conditional inference tree analysis, whirlpool sign, avascular nodule, and increased testicular vascularity were the most significant discriminators (p<0.001), and the whirlpool sign was the first discriminator. The overall accuracy of the conditional inference tree was 91.1% (95% confidence interval [CI], 87.8-93.7%). Heterogeneous echotexture (odds ratio [OR], 74.99; 95% CI, 2.75-2046.26; p=0.01) and symptom-to-operation time >24 h (OR, 49.28; 95% CI, 1.92-1262.03; p=0.02) were significant predictors of unsalvageable testis. CONCLUSIONS: Conditional inference tree analysis showed that the whirlpool sign of the spermatic cord, avascular nodule, and altered testicular vascularity were significant discriminators. Heterogeneous echotexture and symptom-to-operation delay were important prognostic factors for unsalvageable testis.

Emerging role of syndecans in maintaining homeostasis of colon epithelium during inflammation.

The syndecans are a family of transmembrane proteoglycans that are widespread in mammalian tissues. Located at the cell surface membrane, they contribute to modulating the composition of the extracellular matrix via glycosaminoglycan chains (GAGs) attached to their extracellular domains. Syndecans can interact with a variety of extracellular ligands through their core proteins and GAGs, and may also transmit signals through their transmembrane domain to regulate intracellular functions. These properties enable syndecan to modulate glycocalyx formation, epithelial cell-to-cell connections for cell barrier formation, and epithelial cell-lamina propria interactions in the colon epithelium, all of which are crucial for the homeostasis of this tissue. Inflammation induces structural alterations of the colon epithelium, and accumulating evidence suggests that syndecan expression might play important regulatory functions during inflammation. This review summarizes the possible roles of syndecans in maintaining tissue homeostasis in the colon epithelium, especially under inflammation.

Shed syndecan-2 enhances colon cancer progression by increasing cooperative angiogenesis in the tumor microenvironment.

Although shed syndecan-2 potentiated the tumorigenic activities of colon cancer cells, how shed syndecan-2 increases this tumorigenic potential remains unclear. Using an orthotopic mouse model of colon cancer, we show that shed syndecan-2 increases colon cancer progression by cooperatively promoting angiogenesis. Co-administration with a synthetic peptide of shed syndecan-2 (S2LQ) enhanced the survival and tumor engraftment of luciferase-expressing CT26 colon adenocarcinoma cells orthotopically implanted into the cecum of BALB/c mice. Intravenous injection of S2LQ further enhanced the growth of orthotopic tumors in the cecum, with increases in the tissue infiltration of macrophages and the formation of blood vessels, mainly in peripheral layers of the tumor facing the stroma. Furthermore, S2LQ stabilized HIF1α and enhanced the VEGF expression in human colon cancer cell lines, and increased the migration of RAW 264.7 murine macrophage cells and bone marrow-derived macrophages. Finally, S2LQ increased the tube formation of vascular endothelial cells in vitro. Together, these data demonstrate that shed syndecan-2 enhances tumorigenic activity by increasing the crosstalk of cancer cells with tumor-associated macrophages and endothelial cells to enhance angiogenesis for colon cancer progression in the tumor microenvironment.

Efficacy and Safety of Selumetinib in Pediatric Patients With Neurofibromatosis Type 1: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Although the recent approval of selumetinib is expected to transform the management of children with neurofibromatosis type 1 (NF1), particularly those with symptomatic and inoperable plexiform neurofibromas, no systematic review has summarized its efficacy and safety based on the latest studies. This study was conducted to systematically evaluate the efficacy and safety of selumetinib in children with NF1. METHODS: Original articles reporting the efficacy and safety of selumetinib in patients with NF1 were identified in PubMed and EMBASE up to January 28, 2021. The pooled objective response rates (ORRs) and disease control rates (DCRs) were calculated using the DerSimonian-Laird method based on random-effects modeling. The pooled proportion of adverse events (AEs) was also calculated. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system. RESULTS: Five studies involving 126 patients were included in our analysis. The studies had a very low to moderate quality of the evidence. The pooled ORR was 73.8% (95% CI 57.3%-85.5%) and the DCR was 92.5% (95% CI 66.5%-98.7%). The 2 most common AEs were diarrhea, which had a pooled rate of 63.8% (95% CI 52.9%-73.4%), and an increase in creatine kinase levels, which had a pooled rate of 63.3% (95% CI 35.6%-84.3%). DISCUSSION: Our results indicate that selumetinib is an effective and safe treatment for pediatric patients with symptomatic, inoperable plexiform neurofibromas. Further larger-scale randomized controlled studies are needed to confirm the long-term outcome of patients treated with this drug.

Lateral Capsular Stabilization in Lateral Meniscal Allograft Transplantation.

BACKGROUND: Stabilization of the lateral capsule to the tibial plateau may decrease midbody extrusion after lateral meniscal allograft transplantation (MAT). However, there is a paucity of literature reporting on postoperative magnetic resonance imaging (MRI) findings after lateral capsular stabilization (LCS) at the time of lateral MAT. PURPOSE/HYPOTHESIS: The purpose was to describe MRI findings after LCS and compare postoperative extrusion between isolated lateral MAT and lateral MAT with LCS. It was hypothesized that allograft extrusion would be reduced after MAT with LCS but that the stabilized capsule would increase the risk of tears to the capsule or allograft. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Included were patients who underwent lateral MAT with 6-month follow-up MRI. Concomitant LCS was performed for patients with redundant lateral capsule displaced from the lateral tibial plateau as evident on coronal MRI or arthroscopic examination (MAT+LCS group); otherwise, patients underwent MAT only (isolated MAT group). The Lysholm score, Tegner score, and lateral joint space on radiographs were compared between the 2 groups at 2 years postoperatively, and the stabilized lateral capsule and allograft were evaluated using 6-month follow-up MRI. Extrusion, rotation, and position of the allograft bridge were compared between the 2 groups. Regression analysis was performed to identify factors predictive of degree of extrusion. RESULTS: There were 10 patients in the MAT+LCS group and 13 patients in the isolated MAT group. No significant differences were found between groups in preoperative patient characteristics or postoperative Lysholm score, Tegner score, lateral joint space, or MRI parameters. Postoperative extrusion was not related to obliquity angle, position of the bony bridge, or presence of LCS. In the MAT+LCS group, 1 patient showed a tear of the lateral capsule and a radial tear of the allograft, and 3 patients had a meniscocapsular separation at the midbody of the allograft. In the isolated MAT group, 1 patient had a peripheral tear at the midbody, but there was no tear of the allograft in the other patients. CONCLUSION: LCS did not decrease extrusion of lateral meniscal transplantation, but it can lead to increased risk for graft or capsule tear.

Syndecan Transmembrane Domain Specifically Regulates Downstream Signaling Events of the Transmembrane Receptor Cytoplasmic Domain.

Despite the known importance of the transmembrane domain (TMD) of syndecan receptors in cell adhesion and signaling, the molecular basis for syndecan TMD function remains unknown. Using in vivo invertebrate models, we found that mammalian syndecan-2 rescued both the guidance defects in C. elegans hermaphrodite-specific neurons and the impaired development of the midline axons of Drosophila caused by the loss of endogenous syndecan. These compensatory effects, however, were reduced significantly when syndecan-2 dimerization-defective TMD mutants were introduced. To further investigate the role of the TMD, we generated a chimera, 2eTPC, comprising the TMD of syndecan-2 linked to the cytoplasmic domain of platelet-derived growth factor receptor (PDGFR). This chimera exhibited SDS-resistant dimer formation that was lost in the corresponding dimerization-defective syndecan-2 TMD mutant, 2eT(GL)PC. Moreover, 2eTPC specifically enhanced Tyr 579 and Tyr 857 phosphorylation in the PDGFR cytoplasmic domain, while the TMD mutant failed to support such phosphorylation. Finally, 2eTPC, but not 2eT(GL)PC, induced phosphorylation of Src and PI3 kinase (known downstream effectors of Tyr 579 phosphorylation) and promoted Src-mediated migration of NIH3T3 cells. Taken together, these data suggest that the TMD of a syndecan-2 specifically regulates receptor cytoplasmic domain function and subsequent downstream signaling events controlling cell behavior.

The Incidence and Treatment Response of Double Expression of MYC and BCL2 in Patients with Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis.

MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to establish the incidence of double expressor status in patients with de novo DLBCL and identify the predictive value of this biomarker on treatment response through systematic review and meta-analysis. PubMed and Embase were searched for studies published through December 2019 that reported proportions of double expressor DLBCL. The pooled proportions of MYC and BCL2 expression, both alone and in combination, were computed using the inverse variance method for calculating weights and by the DerSimonian-Laird method. The pooled odds ratios (ORs) of complete remission (CR) rate were calculated, and meta-regression analysis was conducted to explore heterogeneity. Forty-one studies (7054 patients) were included. The pooled incidence of double expressor status in DLBCL was 23% (95% confidence interval [CI], 20-26%), with an adjusted estimate of 31% (95% CI, 27-36%). Neither MYC/BCL2 protein cutoff values, race, mean, or median age of included patients, or overall study quality was a significant factor of heterogeneity (p ≥ 0.20). Cases without double expressor status demonstrated a higher probability of CR to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment (OR, 2.69; 95% CI, 1.55-4.67). Our results reaffirm the predictive power of this important biomarker.

Outcome of staging chest CT and identification of factors associated with lung metastasis in children with hepatoblastoma.

OBJECTIVES: To evaluate the outcome of staging chest CT and to identify clinicoradiological factors predictive of lung metastasis in patients with hepatoblastoma based on the 2017 PRE-Treatment EXTent of tumor (PRETEXT) system. METHODS: This bi-center study retrospectively identified patients diagnosed with hepatoblastoma between January 1998 and September 2019 in two tertiary hospitals. The primary outcome was the proportion of the patients who had lung metastasis at staging chest CT. The diagnostic accuracy of staging chest CT was calculated based on the 2017 PRETEXT criteria. The secondary outcome was the identification of factors predictive of lung metastasis using multivariable logistic regression. RESULTS: In total, 123 patients (median age, 1 year; interquartile range, 0-4 years; 59 female) were included. Among those, 28% (35/123; 95% confidence interval [CI], 21-37%) had lung metastasis at staging chest CT. The overall accuracy of staging chest CT was 96.8%. The proportion of lung metastasis in patients with stage I, II, III, and IV was 0%, 24% (12 of 49; 95% CI, 14-38%), 23% (9 of 40; 95% CI, 12-38%), and 56% (14 of 25; 95% CI, 37-73%), respectively. Multifocality (adjusted odds ratio, 6.7; 95% CI, 2.7-17.5; p < .001) and male sex (adjusted odds ratio, 3.1; 95% CI, 1.2-8.6; p = .02) were associated with the presence of lung metastasis. CONCLUSIONS: Twenty-eight percent of the patients with hepatoblastoma had lung metastasis at staging chest CT. Multifocality and male sex were predictive factors for lung metastasis on staging chest CT. KEY POINTS: • The proportion of lung metastasis in patients with hepatoblastoma was 28%. • The overall accuracy of staging chest CT was 97% based on the 2017 PRETEXT system. • Hepatic tumor multifocality and male sex were predictors of lung metastasis.