Wnt1 inducible signaling pathway protein-3 regulation and microsatellite structure in arthritis

OBJECTIVE: Rheumatoid arthritis (RA) synovial tissue expresses several embryonic gene families, including wingless (wnt) and their receptors, frizzled (fz). The Wnt proteins, including Wnt-1, activate the Wnt inducible signaling pathway proteins (WISP), which are members of the CCN family that regulate cell growth and differentiation. WISP3 is of particular interest because it contains a microsatellite region in its coding region that is susceptible to frameshift mutations and leads to a truncated protein. To investigate the contribution of WISP3 to synovial inflammation, we evaluated its expression and regulation in arthritis. METHODS: mRNA and protein expression of WISP3 were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. For mutation analysis, PCR product amplified from genomic DNA of synovial tissue and cultured fibroblast-like synoviocytes (FLS) was subcloned and sequenced. RESULTS: WISP3 mRNA is expressed in synovial tissue, but is 11-fold higher in RA than osteoarthritis (OA) or normal samples. Surprisingly, WISP3 protein levels are similar in RA, OA, and normal synovium samples. Immunohistochemistry of synovial tissue reveals that WISP3 protein is located primarily in the synovial intimal lining. WISP3 mRNA expression is also 6-fold higher in RA FLS compared with OA FLS and 50-fold higher in RA than in normal FLS. When RA FLS are stimulated with interleukin 1 or tumor necrosis factor-a, WISP3 mRNA is significantly increased. The cytokines also increase WISP3 mRNA in OA FLS, but the maximal level in stimulated OA FLS is still less than medium-treated RA FLS. Mutation analysis in the coding region microsatellite of the WISP3 gene in RA and OA synovium and FLS shows a limited number of insertion and deletion mutations. CONCLUSION: WISP3 gene expression is higher in RA synovium and FLS compared with OA and normal synovial tissue and is further induced by proinflammatory cytokines in vitro. Protein levels are not increased, indicating discoordinate regulation of WISP3 protein and mRNA. Although functionally relevant mutations were observed in genomic DNA, they were noted in both OA and RA samples.     

Does Magnifying Narrow-Band Imaging or Magnifying Chromoendoscopy Help Experienced Endoscopists Assess Invasion Depth of Large Sessile and Flat Polyps?

Background

Distinguishing deep submucosa (SM) from superficial SM cancer in large sessile and flat colorectal polyps (>2 cm) is crucial in making the most appropriate therapeutic decision. We evaluated the additional role of magnifying narrow-band imaging (NBI) and magnifying chromoendoscopy (MCE) in assessing the depth of invasion in large sessile and flat polyps in comparison to morphological evaluation performed by experienced endoscopists.

Methods

From May 2011 to December 2011, a total of 85 large sessile and flat polyps were analyzed. Endoscopic features of the polyps were independently evaluated by experienced endoscopists. Subsequently, the polyps were observed using magnifying NBI and MCE.

Results

A total of 58 intramucosal lesions and 27 SM cancers (five superficial and 22 deep) were identified. The diagnostic accuracy of the experienced endoscopists, NBI, and MCE were 92.9, 90.6, and 89.4 %, respectively, for deep SM cancer. In combination with NBI or MCE, the diagnostic accuracy of the experienced endoscopists did not change significantly for deep SM cancer, with an accuracy of 95.3 % for both NBI and MCE.

Conclusions

Conventional colonoscopy can differentiate superficial from deep SM cancers with an accuracy of as high as 92.9 % in large sessile and flat polyps. Further diagnostic strategies are required in order to precisely assess the depth of invasion, especially in large colorectal polyps.     

Effect of Follow-Up Endoscopy on the Outcomes of Patients with Inflammatory Bowel Disease

Background

Little is known about the role of follow-up endoscopy in patients with inflammatory bowel disease (IBD).

Aim

The present study aimed to evaluate whether repeated endoscopies would be beneficial in improving outcomes of patients with IBD.

Methods

Patients who had been initially confirmed to have IBD at two tertiary hospitals in Korea were regularly followed and included in this study. The clinical impact as assessed by the presence or absence of a change in management after endoscopy and cumulative hospitalization rate was compared between two groups classified according to the presence or absence of indications.

Results

A total of 188 patients with IBD were enrolled [69 patients with Crohn’s disease (CD) and 119 with ulcerative colitis (UC)]. Of these patients, 130 underwent follow-up endoscopy (48 with CD and 82 with UC). The rate of management change was significantly higher in the group with indications for follow-up endoscopy (p = 0.001 in CD and <0.001 in UC). The presence of any indications for follow-up endoscopy was found to be a significant predictor of hospitalization risk in patients with UC (p = 0.015), but not in those with CD. However, there was no significant difference in cumulative hospitalization hazard with respect to treatment change in patients without any endoscopic indications (p = 0.561 in CD and 0.423 in UC).

Conclusions

Follow-up endoscopy might not have a significant impact on the overall clinical course and outcomes in patients with IBD. However, the presence of endoscopic indications predicts a poor clinical outcome in UC.     

Primary alveolar soft part sarcoma arising from the cerebellopontine angle

Introduction

Alveolar soft part sarcoma (ASPS), a rare soft tissue malignant neoplasm, frequently metastasizes to the brain. However, primary intracranial ASPS is extremely rare. We present a case of primary intracranial ASPS arising from the cerebellopontine angle (CPA) without demonstrable systemic lesions.

Case report

An 11-year-old girl presented with a recurrent tumor in the right CPA after a partial resection and radiation therapy (RT). Near-total resection with a minimal tumor left in the jugular foramen was performed. The pathological diagnosis was ASPS. There was no evidence of primary extracranial tumors. She underwent adjuvant chemotherapy and gamma knife surgery. At 29 months after the second surgery, magnetic resonance imaging revealed multifocal enhancing lesions at the prepontine cistern, right CPA and medulla oblongata, despite intensive treatment. However, extracranial metastasis was not noted. This case suggested a poor outcome of primary intracranial ASPS, similar to extracranial ASPS.     

The Ability of Stroke Volume Variation Measured by a Noninvasive Cardiac Output Monitor to Predict Fluid Responsiveness in Mechanically Ventilated Children

Continuous noninvasive cardiac output monitoring (NICOM) is a clinically useful tool in the pediatric setting. This study compared the ability of stroke volume variation (SVV) measured by NICOM with that of respiratory variations in the velocity of aortic blood flow (△Vpeak) and central venous pressure (CVP) to predict of fluid responsiveness in mechanically ventilated children after ventricular septal defect repair. The study investigated 26 mechanically ventilated children after the completion of surgery. At 30 min after their arrival in an intensive care unit, a colloid solution of 10 ml/kg was administrated for volume expansion. Hemodynamic variables, including CVP, stroke volume, and △Vpeak in addition to cardiac output and SVV in NICOM were measured before and 10 min after volume expansion. The patients with a stroke volume increase of more than 15 % after volume expansion were defined as responders. The 26 patients in the study consisted of 13 responders and 13 nonresponders. Before volume expansion, △Vpeak and SVV were higher in the responders (both p values <0.001). The areas under the receiver operating characteristic curves of △Vpeak, SVV, and CVP were respectively 0.956 (95 % CI 0.885–1.00), 0.888 (95 % CI 0.764–1.00), and 0.331 (95 % CI 0.123–0.540). This study showed that SVV by NICOM and △Vpeak by echocardiography, but not CVP, reliably predicted fluid responsiveness during mechanical ventilation after ventricular septal defect repair in children.     

Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier

Respiratory syncytial virus (RSV) is one of the most common causes of viral deaths in infants worldwide, yet no effective vaccines are available. Here, we report an osmotically active polysaccharide-based polysorbitol transporter (PST) prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine (PEI) showing a potent, yet safe, adjuvant activity and acting as an effective delivery tool for RSV glycoprotein (RGp) antigen. PST showed no toxicity in vitro or in vivo, unlike PEI and the well-known experimental mucosal adjuvant cholera toxin (CT). PST formed nano-sized complexes with RGp by simple mixing, without affecting antigenic stability. The complexes exhibited negative surface charges that made them highly efficient in the selective activation of phagocytic cells and enhancement of phagocytic uptake. This resulted in an improved cytokine production and in the significant augmentation of RGp-specific antibody production, which persisted for over 200 days. Interestingly, PST/RGp enhanced phagocytic uptake owing to the osmotic property of PST and its negative zeta potential, suggesting that PST could selectively stimulate phagocytic cells, thereby facilitating a long-lived antigen-specific immune response, which was presumably further enhanced by the polysaccharide properties of PST.     

Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity

BackgroundAtopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea.MethodsAD patients aged 6–18 years who presented to 18 hospitals nationwide were surveyed. The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites, treatment history and quality of life were collected. The results of the patient’s allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschool-onset (2–5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups.ResultsA total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancy-onset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group.ConclusionThis study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.     

Distinct patterns of cleavage and translocation of cell cycle control proteins in CD95-induced and p53-induced apoptosis

Apoptotic cell death induced by p53 occurs at a late G1 cell cycle checkpoint termed the restriction (R) point, and it has been proposed that p53-induced apoptosis causes upregulation of CD95. However, as cells with defective in CD95 signaling pathway are still sensitive to p53-induced apoptosis, CD95 cannot be the sole factor resulting in apoptosis. In addition, unlike p53-induced apoptosis, the relationship between CD95-mediated apoptosis and the cell cycle is not clearly understood. It would therefore be worth investigating whether CD95-mediated cell death is pertinent with p53-induced apoptosis in view of cell cycle related molecules. In this report, biochemical analysis showed that etoposide-induced apoptosis caused the induction and the nuclear translocation of effector molecules involved in G1 cell cycle checkpoint. However, there was no such translocation in the case of CD95-mediated death. Thus, although both types of apoptosis involved caspase activation, the cell cycle related proteins responded differently. This argues against the idea that p53-induced apoptosis occurs through the induction of CD95/CD95L expression.     

Deep Learning-Assisted Diagnosis of Pediatric Skull Fractures on Plain Radiographs

ObjectiveTo develop and evaluate a deep learning-based artificial intelligence (AI) model for detecting skull fractures on plain radiographs in children.Materials and MethodsThis retrospective multi-center study consisted of a development dataset acquired from two hospitals (n = 149 and 264) and an external test set (n = 95) from a third hospital. Datasets included children with head trauma who underwent both skull radiography and cranial computed tomography (CT). The development dataset was split into training, tuning, and internal test sets in a ratio of 7:1:2. The reference standard for skull fracture was cranial CT. Two radiology residents, a pediatric radiologist, and two emergency physicians participated in a two-session observer study on an external test set with and without AI assistance. We obtained the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity along with their 95% confidence intervals (CIs).ResultsThe AI model showed an AUROC of 0.922 (95% CI, 0.842–0.969) in the internal test set and 0.870 (95% CI, 0.785–0.930) in the external test set. The model had a sensitivity of 81.1% (95% CI, 64.8%–92.0%) and specificity of 91.3% (95% CI, 79.2%–97.6%) for the internal test set and 78.9% (95% CI, 54.4%–93.9%) and 88.2% (95% CI, 78.7%–94.4%), respectively, for the external test set. With the model’s assistance, significant AUROC improvement was observed in radiology residents (pooled results) and emergency physicians (pooled results) with the difference from reading without AI assistance of 0.094 (95% CI, 0.020–0.168; p = 0.012) and 0.069 (95% CI, 0.002–0.136; p = 0.043), respectively, but not in the pediatric radiologist with the difference of 0.008 (95% CI, -0.074–0.090; p = 0.850).ConclusionA deep learning-based AI model improved the performance of inexperienced radiologists and emergency physicians in diagnosing pediatric skull fractures on plain radiographs.