Enhancing gadoxetic acid-enhanced liver MRI: a synergistic approach with deep learning CAIPIRINHA-VIBE and optimized fat suppression techniques.

OBJECTIVE: To investigate whether a deep learning (DL) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE) technique can improve image quality, lesion conspicuity, and lesion detection compared to a standard CAIPIRINHA-VIBE technique in gadoxetic acid-enhanced liver MRI. METHODS: This retrospective single-center study included 168 patients who underwent gadoxetic acid-enhanced liver MRI at 3 T using both standard CAIPIRINHA-VIBE and DL CAIPIRINHA-VIBE techniques on pre-contrast and hepatobiliary phase (HBP) images. Additionally, high-resolution (HR) DL CAIPIRINHA-VIBE was obtained with 1-mm slice thickness on the HBP. Three abdominal radiologists independently assessed the image quality and lesion conspicuity of pre-contrast and HBP images. Statistical analyses involved the Wilcoxon signed-rank test for image quality assessment and the generalized estimation equation for lesion conspicuity and detection evaluation. RESULTS: DL and HR-DL CAIPIRINHA-VIBE demonstrated significantly improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE (p < 0.001), with a shorter acquisition time (DL vs standard, 11 s vs 17 s). However, the former presented a more synthetic appearance (both p < 0.05). HR-DL CAIPIRINHA-VIBE showed superior lesion conspicuity to standard and DL CAIPIRINHA-VIBE on HBP images (p < 0.001). Moreover, HR-DL CAIPIRINHA-VIBE exhibited a significantly higher detection rate of small (< 2 cm) solid focal liver lesions (FLLs) on HBP images compared to standard CAIPIRINHA-VIBE (92.5% vs 87.4%; odds ratio = 1.83; p = 0.036). CONCLUSION: DL and HR-DL CAIPIRINHA-VIBE achieved superior image quality compared to standard CAIPIRINHA-VIBE. Additionally, HR-DL CAIPIRINHA-VIBE improved the lesion conspicuity and detection of small solid FLLs. DL and HR-DL CAIPIRINHA-VIBE hold the potential clinical utility for gadoxetic acid-enhanced liver MRI. CLINICAL RELEVANCE STATEMENT: DL and HR-DL CAIPIRINHA-VIBE hold promise as potential alternatives to standard CAIPIRINHA-VIBE in routine clinical liver MRI, improving the image quality and lesion conspicuity, enhancing the detection of small (< 2 cm) solid focal liver lesions, and reducing the acquisition time. KEY POINTS: • DL and HR-DL CAIPIRINHA-VIBE demonstrated improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE, in addition to a shorter acquisition time. • DL and HR-DL CAIPIRINHA-VIBE yielded a more synthetic appearance than standard CAIPIRINHA-VIBE. • HR-DL CAIPIRINHA-VIBE showed improved lesion conspicuity than standard CAIPIRINHA-VIBE on HBP images, with a higher detection of small (< 2 cm) solid focal liver lesions.

Clinical Experiences and Selection of Accessory Devices for Pediatric Endoscopic Foreign Body Removal: A Retrospective Multicenter Study in Korea.

BACKGROUND: Swallowing of foreign bodies (FBs) is the most common indication of therapeutic endoscopy in children. Endoscopic removal may be necessary depending on the type of FB, age of the child, and location of the FB. We attempted to analyze the characteristics of each device used for the endoscopic removal of FBs in children. METHODS: Medical records of the patient's age, sex, weight, type, location, size, shape, type of device used for endoscopic removal, and endoscopic time were retrospectively collected. RESULTS: A total of 424 FB removal procedures were analyzed. The average age of the patients at the time of FB removal was 4.1 ± 3.7 years. Coins were the most common FBs (192, 45.3%). The most common locations of the FBs were the esophagus (45.7%) and the stomach (48.3%), respectively. For a total of 371 cases, forceps were used in 96 cases (25.9%) for esophageal FBs and in 25 cases for gastric FBs (6.7%), while nets were used in 250 cases (67.4%) for gastric FBs retrieval; the average durations of the procedures were 7.2 ± 7.4 minutes, 8.5 ± 7.2 minutes, and 5.7 ± 7.3 minutes, respectively (P = 0.003). The procedure time was significantly shorter, in the group of patients with low body weights, when nets were used than when forceps were used to remove gastric FBs (P = 0.001). CONCLUSION: The endoscopic procedure duration, in low-weight children, was shorter when retrieval nets were used than that with forceps.

Increased cow's milk protein-specific IgG4 levels after oral desensitization in 7- to 12-month-old infants.

BACKGROUND: Cow's milk protein (CMP)-specific IgG4 responses and the efficacy of oral desensitization in infants with cow's milk allergy (CMA) warrant more clarification. OBJECTIVE: To explore whether CMP-specific IgG4 responses develop during infancy and whether regular CM exposure is efficacious for inducing a CMP-specific IgG4 response accompanying CM desensitization in 7- to 12-month-old infants. METHODS: CM-specific IgE and CMP (α-lactalbumin, ß-lactoglobulin, and casein)-specific IgG4 levels were measured in 262 CM-sensitized children. Of these, 31 infants 7 to 12 months old with challenge-proved CMA were randomly assigned to oral desensitization or an elimination diet and evaluated 6 months later. RESULTS: CMP-specific IgG4 levels in 7- to 12-month-old infants were higher than in those younger than 6 months but comparable to those in children older than 12 months. CMP-specific IgG4 levels in 7- to 12-month-old infants with CMA were significantly lower than in those without CMA. Fourteen of 16 patients receiving oral desensitization could accept daily doses of 200 mL of CM, whereas all but 3 dropout patients receiving the elimination diet still showed allergic symptoms at the follow-up food challenge. In patients who became desensitized, CM-specific IgE levels were lower than at baseline, whereas CMP-specific IgG4 levels were significantly increased. In patients receiving the elimination diet, CM-specific IgE and CMP-specific IgG4 levels remained unchanged. CONCLUSION: CMP-specific IgG4 responses did not develop sufficiently in 7- to 12-month-old infants with CMA. Oral desensitization in 7- to 12-month-old infants with CMA was associated with the upregulation of CMP-specific IgG4 responses accompanying the alleviation of CMA symptoms.

Deep learning-based iodine contrast-augmenting algorithm for low-contrast-dose liver CT to assess hypovascular hepatic metastasis.

PURPOSE: To investigate the image quality and diagnostic performance of low-contrast-dose liver CT using a deep learning-based iodine contrast-augmenting algorithm (DLICA) for hypovascular hepatic metastases. METHODS: This retrospective study included 128 patients who underwent contrast-enhanced dual-energy CT for hepatic metastasis surveillance between July 2019 and June 2022 using a 30% reduced iodine contrast dose in the portal phase. Three image types were reconstructed: 50-keV virtual monoenergetic images (50-keV VMI); linearly blended images simulating 120-kVp images (120-kVp); and post-processed 120-kVp images using DLICA (DLICA 120-kVp). Three reviewers evaluated lesion conspicuity, image contrast, and subjective image noise. We also measured image noise, contrast-to-noise ratios (CNRs), and signal-to-noise ratios (SNRs). The diagnostic performance for hepatic metastases was evaluated using a jackknife alternative free-response receiver operating characteristic method with the consensus of two independent radiologists as the reference standard. RESULTS: DLICA 120-kVp demonstrated significantly higher CNR of lesions to liver (5.7 ± 3.1 vs. 3.8 ± 2.1 vs. 3.8 ± 2.1) and higher SNR compared with 50-keV VMI and 120-kVp (p < 0.001 for all). DLICA 120-kVp had significantly lower image noise than 50-kVp VMI for all regions (p < 0.001 for all). DLICA 120-kVp also exhibited superior lesion conspicuity (4.0 [3.3-4.3] vs. 3.7 [3.0-4.0] vs. 3.7 [3.0-4.0]), higher image contrast, and lower subjective image noise compared with 50-keV VMI and 120-kVp (p < 0.001 for all). Although there was no significant difference in the figure of merit for lesion diagnosis among the three methods (p = 0.11), DLICA 120-kVp had a significantly higher figure of merit for lesions with a diameter < 20 mm than 50-keV VMI (0.677 vs. 0.648, p = 0.007). On a per-lesion basis, DLICA 120-kVp also demonstrated higher sensitivity than the 50-keV VMI (81.2% vs. 72.9%, p < 0.001). The specificities per lesion were not significantly different among the three algorithms (p = 0.15). CONCLUSION: DLICA at 120-kVp provided superior lesion conspicuity and image quality and similar diagnostic performance for hypovascular hepatic metastases compared with 50-keV VMI.

Early Postoperative Fever and Atelectasis in Patients Undergoing Upper Abdominal Surgery.

BACKGROUND: Atelectasis is a common complication after upper abdominal surgery and considered as a cause of early postoperative fever (EPF) within 48 hours after surgery. However, the pathophysiologic mechanism of how atelectasis causes fever remains unclear. STUDY DESIGN: Data for adult patients who underwent elective major upper abdominal surgery under general anesthesia at Seoul National University Hospital between January and December of 2021 were retrospectively analyzed. The primary outcome was the association between fever and atelectasis within 2 days after surgery. RESULTS: Of 1,624 patients, 810 patients (49.9%) developed EPF. The incidence of atelectasis was similar between the fever group and the no-fever group (51.6% vs 53.9%, p = 0.348). Multivariate analysis showed no significant association between atelectasis and EPF. Culture tests (21.7% vs 8.8%, p < 0.001) and prolonged use of antibiotics (25.9% vs 13.9%, p < 0.001) were more frequent in the fever group compared to the no-fever group. However, the frequency of bacterial growth on culture tests and postoperative pulmonary complications within 7 days were similar between the two groups. CONCLUSIONS: EPF after major upper abdominal surgery was not associated with radiologically detected atelectasis. EPF also was not associated with the increased risk of postoperative pulmonary complications, bacterial growth on culture studies, or prolonged length of hospital stay.

Development of a Universal Cloning System for Reverse Genetics of Human Enteroviruses.

Enteroviruses (EVs) have been associated with several human diseases. Due to their continuous emergence and divergence, EV species have generated more than 100 types and recombinant strains, increasing the public health threat caused by them. Hence, an efficient and universal cloning system for reverse genetics (RG) of highly divergent viruses is needed to understand the molecular mechanisms of viral pathology and evolution. In this study, we generated a versatile human EV whole-genome cDNA template by enhancing the template-switching method and designing universal primers capable of simultaneous cloning and rapid amplification of cDNA ends (RACE)-PCR of EVs. Moreover, by devising strategies to overcome limitations of previous cloning methods, we simplified significant cloning steps to be completed within a day. Of note, we successfully verified our efficient universal cloning system enabling RG of a broad range of human EVs, including EV-A (EV-A71), EV-B (CV-B5, ECHO6, and ECHO30), EV-C (CV-A24), and EV-D (EV-D68), with viral titers and phenotypes comparable to those of their wild types. This rapid and straightforward universal EV cloning strategy will help us elucidate molecular characteristics, pathogenesis, and applications of a broad range of EV serotypes for further development of genetic vaccines and delivery tools using various replication systems. IMPORTANCE Due to the broad spread, incidence, and genetic divergence of enteroviruses (EVs), it has been challenging to deal with this virus that causes severe human diseases, including aseptic meningitis, myocarditis, encephalitis, and poliomyelitis. Therefore, an efficient and universal cloning system for the reverse genetics of highly divergent EVs contributes to an understanding of the viral pathology and molecular mechanisms of evolution. We have simplified the important cloning steps, hereby enhancing the template-switching method and designing universal primers, which enable the important cloning steps to be completed in a day. We have also successfully demonstrated recovery of a broad range of human EVs, including EV-A to -D types, using this advanced universal cloning system. This rapid and robust universal EV cloning strategy will aid in elucidating the molecular characteristics, pathogenesis, and applications of a wide range of EVs for further development of genetic vaccines and antiviral screening using various replication systems.

Ultrasound-guided transient elastography and two-dimensional shear wave elastography for assessment of liver fibrosis: emphasis on technical success and reliable measurements.

PURPOSE: This study investigated whether the use of ultrasound (US) guidance in transient elastography (TE) improved the technical success and reliability of liver stiffness (LS) measurements and whether 2-dimensional (2D) shear wave elastography (SWE) provided reliable LS measurements if TE measurements failed. METHODS: In this prospective study, 292 participants (male:female, 189:103; median age, 60 years) with chronic liver disease (CLD) were enrolled. LS was measured via the consecutive use of conventional TE, 2D-SWE, and US-guided TE. The technical success rates and reliable LS measurement rates of the three elastography techniques were compared. The risk factors for TE failure were assessed through univariate and multivariate logistic regression models. RESULTS: US-guided TE was associated with a higher technical success rate (281 of 292, 96.2%) and a higher reliable measurement rate (266 of 292, 91.1%) than conventional TE (technical success: 256 of 292, 87.7%; reliable measurements: 231 of 292, 79.1%; P<0.001 for both). In participants for whom conventional TE failed, 2D-SWE provided high rates of technical success (36 of 36, 100%) and reliable measurements (30 of 36, 83.3%). TE failure was associated with female sex (odds ratio [OR], 5.85; 95% confidence interval [CI], 1.30 to 26.40), severe reverberation artifacts (OR, 8.79; 95% CI, 3.93 to 19.69), and high skin-to-liver capsule depth (OR, 1.23; 95% CI, 1.09 to 1.39). CONCLUSION: US guidance in TE improved the technical success and reliable measurement rates in the assessment of LS in patients with CLD. In participants for whom TE failed, subsequent 2D-SWE successfully delivered reliable LS measurements.

Clinical outcomes of patients with a high alpha-fetoprotein level but without evident recurrence on CT or MRI in surveillance after curative-intent treatment for hepatocellular carcinoma.

PURPOSE: Multiphasic CT or MRI and serum alpha-fetoprotein (AFP) are widely used for posttreatment surveillance of hepatocellular carcinoma (HCC). This study aimed to investigate the clinical outcomes of patients with high posttreatment AFP but without evident recurrence on CT or MRI after curative-intent treatment of HCC. METHODS: We retrospectively analyzed 121 patients presenting with high posttreatment AFP (> 20 ng/mL) without evident recurrence on multiphasic CT or MRI during surveillance after curative-intent surgical resection or radiofrequency ablation (RFA) for HCC. The time interval from the first event of high posttreatment AFP to imaging-evident recurrence (TimeAFP-Imaging recurrence) was estimated using the Kaplan-Meier method. Cox regression analyses were performed to assess the associated factors with TimeAFP-Imaging recurrence. RESULTS: The median TimeAFP-Imaging recurrence was 20.0 months (95% CI 13.0-28.0 months), and the estimated 6-month and 1-year cumulative incidences of imaging-evident recurrence were 24.4% and 40.1%, respectively. In multivariate Cox analyses, late onset of AFP elevation (> 3 months after treatment) was an independent predictor of shorter TimeAFP-Imaging recurrence (HR 2.11, P = 0.015) if using variables available at the first event of AFP elevation, while non-normalization of AFP at the next follow-up was an independent predictor of shorter TimeAFP-Imaging recurrence (HR 3.65, P < 0.001) if using variables including the follow-up data. CONCLUSION: In the surveillance setting after curative-intent treatment of HCC, patients presenting with high posttreatment AFP without evident recurrence on CT or MRI may frequently progress to imaging-evident recurrence. In high-risk patients, an extensive diagnostic workup or close monitoring is needed to detect HCC recurrence earlier.

Volumetric CT Texture Analysis of Intrahepatic Mass-Forming Cholangiocarcinoma for the Prediction of Postoperative Outcomes: Fully Automatic Tumor Segmentation Versus Semi-Automatic Segmentation.

OBJECTIVE: To determine whether volumetric CT texture analysis (CTTA) using fully automatic tumor segmentation can help predict recurrence-free survival (RFS) in patients with intrahepatic mass-forming cholangiocarcinomas (IMCCs) after surgical resection. MATERIALS AND METHODS: This retrospective study analyzed the preoperative CT scans of 89 patients with IMCCs (64 male; 25 female; mean age, 62.1 years; range, 38-78 years) who underwent surgical resection between January 2005 and December 2016. Volumetric CTTA of IMCCs was performed in late arterial phase images using both fully automatic and semi-automatic liver tumor segmentation techniques. The time spent on segmentation and texture analysis was compared, and the first-order and second-order texture parameters and shape features were extracted. The reliability of CTTA parameters between the techniques was evaluated using intraclass correlation coefficients (ICCs). Intra- and interobserver reproducibility of volumetric CTTAs were also obtained using ICCs. Cox proportional hazard regression were used to predict RFS using CTTA parameters and clinicopathological parameters. RESULTS: The time spent on fully automatic tumor segmentation and CTTA was significantly shorter than that for semi-automatic segmentation: mean ± standard deviation of 1 minutes 37 seconds ± 50 seconds vs. 10 minutes 48 seconds ± 13 minutes 44 seconds (p < 0.001). ICCs of the texture features between the two techniques ranged from 0.215 to 0.980. ICCs for the intraobserver and interobserver reproducibility using fully automatic segmentation were 0.601-0.997 and 0.177-0.984, respectively. Multivariable analysis identified lower first-order mean (hazard ratio [HR], 0.982; p = 0.010), larger pathologic tumor size (HR, 1.171; p < 0.001), and positive lymph node involvement (HR, 2.193; p = 0.014) as significant parameters for shorter RFS using fully automatic segmentation. CONCLUSION: Volumetric CTTA parameters obtained using fully automatic segmentation could be utilized as prognostic markers in patients with IMCC, with comparable reproducibility in significantly less time compared with semi-automatic segmentation.

Case report of juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome: first report in Korea with a novel mutation in the SMAD4 gene.

Juvenile polyposis/hereditary hemorrhagic telangiectasia (JPS/HHT) syndrome is a rare, autosomal dominant disorder caused by mutations in the SMAD4 gene, presenting with features of both juvenile polyposis syndrome (JPS) and HHT. Reports and studies of JPS/HHT syndrome are mostly from Western countries, while there are scarce reports from East Asian countries. We report a case of a Korean boy who had been previously diagnosed with JPS at 7 years and had first visited to our center at 15 years of age. Genetic studies of the patient and parents revealed a novel variant in the SMAD4 gene, SMAD4 c.1146_1163del; p.His382_Val387del (NM_005359.5), which had developed de novo. Numerous pedunculated and sessile polyps were observed throughout the gastrointestinal (GI) tract. Mucocutaneous telangiectases were observed on the lips, tongue, and jejunum, and arteriovenous malformations (AVMs) were observed in both lungs. This is the first case report of JPS/HHT syndrome in Korea, with a novel deletion variant in the SMAD4 gene. Patients with JPS should undergo genetic evaluation of associated genes including SMAD4, and those with genetically confirmed SMAD4 variants should undergo further evaluation for coexisting asymptomatic AVMs in order to prevent life-threatening complications of thrombotic emboli and pulmonary hemorrhage.

Using a Dual-Input Convolutional Neural Network for Automated Detection of Pediatric Supracondylar Fracture on Conventional Radiography.

OBJECTIVES: This study aimed to develop a dual-input convolutional neural network (CNN)-based deep-learning algorithm that utilizes both anteroposterior (AP) and lateral elbow radiographs for the automated detection of pediatric supracondylar fracture in conventional radiography, and assess its feasibility and diagnostic performance. MATERIALS AND METHODS: To develop the deep-learning model, 1266 pairs of AP and lateral elbow radiographs examined between January 2013 and December 2017 at a single institution were split into a training set (1012 pairs, 79.9%) and a validation set (254 pairs, 20.1%). We performed external tests using 2 types of distinct datasets: one temporally and the other geographically separated from the model development. We used 258 pairs of radiographs examined in 2018 at the same institution as a temporal test set and 95 examined between January 2016 and December 2018 at another hospital as a geographic test set. Images underwent preprocessing, including cropping and histogram equalization, and were input into a dual-input neural network constructed by merging 2 ResNet models. An observer study was performed by radiologists on the geographic test set. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the model and human readers were calculated and compared. RESULTS: Our trained model showed an AUC of 0.976 in the validation set, 0.985 in the temporal test set, and 0.992 in the geographic test set. In AUC comparison, the model showed comparable results to the human readers in the geographic test set; the AUCs of human readers were in the range of 0.977 to 0.997 (P's > 0.05). The model had a sensitivity of 93.9%, a specificity of 92.2%, a PPV of 80.5%, and an NPV of 97.8% in the temporal test set, and a sensitivity of 100%, a specificity of 86.1%, a PPV of 69.7%, and an NPV of 100% in the geographic test set. Compared with the developed deep-learning model, all 3 human readers showed a significant difference (P's < 0.05) using the McNemar test, with lower specificity and PPV in the model. On the other hand, there was no significant difference (P's > 0.05) in sensitivity and NPV between all 3 human readers and the proposed model. CONCLUSIONS: The proposed dual-input deep-learning model that interprets both AP and lateral elbow radiographs provided an accurate diagnosis of pediatric supracondylar fracture comparable to radiologists.

Korean Children and Adolescents with Crohn's Disease Are More Likely to Present with Perianal Fistulizing Disease at Diagnosis Compared to Their European Counterparts.

PURPOSE: We aimed to investigate the disease phenotype of Korean pediatric Crohn's disease (CD) patients at diagnosis according to the Paris classification by comparison with patients from the European multicenter 5-years recruitment of children with newly developed IBD (EUROKIDS registry). METHODS: Korean children and adolescents who had been newly diagnosed with CD at the age of <18 years during 2013-2016 were included in this multicenter retrospective study. Disease phenotype at diagnosis was classified according to the Paris classification, and compared with the published data from the EUROKIDS study. RESULTS: A total of 255 patients were included. The median diagnosis age was 14.7 years (range, 0.8-17.9 years). No significant difference was observed in male-to-female ratio with EUROKIDS (1.9:1 vs. 1.45:1, p=0.062). The proportion of children aged <10 years was significantly lower in Koreans (7.1% vs. 19.6%, p<0.001). Colonic disease was less prominent (10.0% vs. 27.3%, p<0.001), while upper GI involvement was more prominent in Korean children (59.3% vs. 46.2%, p<0.001). The proportion with perianal fistulizing disease at diagnosis was significantly higher in Korean patients (44.8% vs. 8.2%, p<0.001). A separate analysis of Korean patients revealed that perianal fistulizing disease at diagnosis was positively associated with male sex and body mass index z-score (odds ratio [OR]=2.12, 95% confidence interval [CI]=1.20-3.76, p=0.010; and OR=1.29, 95% CI=1.05-1.58, p=0.015, respectively). CONCLUSION: Approximately half of pediatric CD patients in Korea present with perianal fistulas and/or abscesses at diagnosis, which is a distinct feature of CD in Korean children and adolescents compared to their European counterparts. An underlying genetic difference between ethnicities may play a role in this expression of different phenotypes in pediatric CD.

Extracellular heat shock protein 90 induces interleukin-8 in vascular smooth muscle cells.

Oxidative stress results in sustained release of heat shock protein 90 (HSP90) from vascular smooth muscle cells (VSMCs). The aim of this article is to investigate whether extracellular HSP90 predisposes VSMCs to pro-inflammatory phenotype. Exposure of aortic smooth muscle cells to HSP90 elevated IL-8 release and IL-8 transcript via promoter activation. HSP90-induced IL-8 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and MyD88, but not by dominant-negative-forms of TLR-3, TLR-2, and TRIF. IL-8 up-regulation in response to HSP90 was also attenuated by IkappaB, rasveratrol, curcumin, diphenyleneiodium, N-acetylcystein, U0126, and SB202190. Mutation at the NF-kappaB- or C/EBP-binding site, but not at the AP-1-binding site, in the IL-8 promoter region suppressed the promoter activation by HSP90. This study proposes that extracellular HSP90 would contribute to IL-8 elevation in the stressed vasculature, and that TLR-4, mitogen-activated protein kinases, NF-kappaB, and reactive oxygen species are involved in that process.

Subtherapeutic Infliximab Trough Levels and Complete Mucosal Healing Are Associated With Sustained Clinical Remission After Infliximab Cessation in Paediatric-onset Crohn's Disease Patients Treated With Combined Immunosuppressive Therapy.

BACKGROUND AND AIMS: We aimed to investigate the outcome in paediatric-onset Crohn's disease patients who had discontinued infliximab after maintaining clinical remission with combined immunosuppression, and to determine factors associated with clinical relapse. METHODS: We conducted a retrospective observational study of 63 paediatric-onset Crohn's disease patients who had stopped scheduled infliximab during sustained corticosteroid-free clinical remission for at least 1 year with infliximab and azathioprine, and were followed up for at least 1 year thereafter. Cumulative relapse rates and the median time to relapse were estimated statistically. Factors at cessation were also evaluated for their association with clinical relapse. RESULTS: After a median follow-up period of 4.3 years [range, 1-7.5 years], 60.3% [38/63] of patients had experienced clinical relapse. According to Kaplan-Meier survival analysis, the estimated cumulative relapse rates at 1, 4, and 6 years were 19.0%, 62.2%, and 75.2%, respectively, and the median relapse time was 3.3 years from infliximab cessation. According to multivariate Cox proportional hazard regression analysis, infliximab trough levels of ≥2.5 µg/mL and incomplete mucosal healing were associated with clinical relapse (hazard ratio [HR] = 7.199, 95% confidence interval [CI] = 1.641-31.571, p = 0.009 and HR = 3.628, 95% CI = 1.608-8.185, p = 0.002, respectively). Although re-treatment with infliximab was effective in 90.9% [30/33] of patients, 7.9% [3/38] eventually underwent surgery within 1 year of relapse. CONCLUSIONS: Considering the high cumulative relapse rates in the long term and cases of severe relapse requiring surgery, discontinuing infliximab in paediatric-onset Crohn's disease patients is currently inadvisable. However, there may be a subgroup of patients who are good candidates for infliximab withdrawal.

Characteristics of Upper Gastrointestinal Tract Involvement in Korean Pediatric Crohn's Disease: A Multicenter Study.

PURPOSE: Crohn's disease (CD) can involve any site of the gastrointestinal tract (GIT). However, the characteristics of upper GIT involvement in CD are unclear, especially in the Eastern pediatric population. This study aimed to estimate the prevalence of upper GIT involvement and identify the clinical features of Korean children with CD. METHODS: This was a retrospective multicenter cohort study that included 52 pediatric patients with CD who underwent esophagogastroduodenoscopy and biopsy. The clinical symptoms and endoscopic and histologic features of the upper GIT were identified according to the presence or absence of upper gastrointestinal symptoms. RESULTS: Among the 52 patients, upper GIT involvement was noted in 50.0% (26/52). The mean age at CD diagnosis was 14.1±2.1 years. Gastric ulcer was the most common lesion (19.2%) found on upper GIT endoscopy, followed by duodenal ulcers (15.4%). Chronic inflammation was the most common histopathologic feature (75.0%), followed by gastric erosion (17.3%). Granuloma was found in 9.6% of patients. Helicobacter pylori infection was identified in 5.8% of patients. Endoscopic and histologic findings were not significantly different, but the mean values of erythrocyte sedimentation rate (60.7±27.1 vs. 43.0±27.6 mm/h, p=0.037) and C-reactive protein (16.5±28.2 vs. 6.62±13.4 mg/dL, p=0.014) were significantly different between patients with and without upper gastrointestinal CD symptoms. CONCLUSION: Upper GIT involvement was relatively common in pediatric patients with CD irrespective of upper gastrointestinal symptoms, and H. pylori infection was relatively uncommon. The results of this study should aid the establishment of regional guidelines for upper GIT examination.

Polyunsaturated Fatty acids in children.

Polyunsaturated fatty acids (PUFAs) are the major components of brain and retina, and are the essential fatty acids with important physiologically active functions. Thus, PUFAs should be provided to children, and are very important in the brain growth and development for fetuses, newborn infants, and children. Omega-3 fatty acids decrease coronary artery disease and improve blood flow. PUFAs have been known to have anti-inflammatory action and improved the chronic inflammation such as auto-immune diseases or degenerative neurologic diseases. PUFAs are used for metabolic syndrome related with obesity or diabetes. However, there are several considerations related with intake of PUFAs. Obsession with the intake of unsaturated fatty acids could bring about the shortage of essential fatty acids that are crucial for our body, weaken the immune system, and increase the risk of heart disease, arrhythmia, and stroke. In this review, we discuss types, physiologic mechanism of action of PUFAs, intake of PUFAs for children, recommended intake of PUFAs, and considerations for the intake of PUFAs.

Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production.

The L-gulono-γ-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo (-/-) mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo (-/-) mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo (-/-) mice, 3-week ascorbic acid-insufficient Gulo (-/-) mice, and 4-week ascorbic acid-insufficient Gulo (-/-) mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo (-/-) mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo (-/-) mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo (-/-) mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo (-/-). In summary, ascorbic acid insufficiency in Gulo (-/-) mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels.

Utility of fractional exhaled nitric oxide (F(E)NO) measurements in diagnosing asthma.

BACKGROUND: To facilitate the use of fractional exhaled nitric oxide (F(E)NO) as a clinical test, F(E)NO measurements need more clarification. AIM: We sought to evaluate the yield of F(E)NO measurement for the diagnosis of asthma and identify the determinants of F(E)NO in children. METHODS: Two hundred forty five consecutive steroid-naïve patients aged 8-16 years with symptoms suggestive of asthma were included. Children were evaluated using F(E)NO measurements, questionnaires, skin prick tests, spirometries, and methacholine challenge tests. RESULTS: Asthma was diagnosed in 167 children. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of F(E)NO measurements for the diagnosis of asthma at the best cutoff value of 22 ppb were 56.9%, 87.2%, 90.5%, and 48.6%, respectively. At a cutoff value of 42 ppb, specificity and PPV were all 100% but at the cost of very low sensitivity (23.4%) and NPV (37.9%). Both atopy and asthma were identified as independent risk factors associated with high F(E)NO. The association of asthma with high F(E)NO was found only in atopic children because F(E)NO was low in non-atopic children regardless of asthma status. Although highest F(E)NO was observed in atopic asthmatic patients, 28% of these patients had F(E)NO values lower than 22 ppb. CONCLUSION: Atopic asthmatic patients with low F(E)NO values and non-atopic asthmatic patients were responsible for false-negative cases that might contribute to low sensitivity of F(E)NO measurements in diagnosing asthma. High specificity of F(E)NO measurements may help identify patients with atopic asthma among subjects with respiratory symptoms.

Roles of ERK and NF-kappaB in Interleukin-8 Expression in Response to Heat Shock Protein 22 in Vascular Smooth Muscle Cells.

Heat shock proteins (HSPs) serve as molecular chaperones and play a role in cell protection from damage in response to stress stimuli. The aim of this article is to investigate whether HSP22 affects IL-8 expression in vascular smooth muscle cells (VSMCs), and which cellular factors are involved in the HSP-mediated IL-8 induction in that cell type in terms of mitogen activated protein kinase (MAPK) and transcription element. Exposure of aortic smooth muscle cells (AoSMCs) to HSP22 not only enhanced IL-8 release but also induced IL-8 transcript via promoter activation. HSP22 activated ERK and p38 MAPK in AoSMCs. HSP22-induced IL-8 release was inhibited by U0126, but not by SB202190. A mutation in the IL-8 promoter region at the binding site of NF-kappaB, but not AP-1 or C/EBP, impaired promoter activation in response to HSP22. Delivery of IkappaB, but not dominant negative c-Jun, lowered HSP22-induced IL-8 release from AoSMCs. These results suggest that HSP22 induces IL-8 in VSMCs via ERK1/2, and that transcription factor NF-kB may be required for the HSP22-induced IL-8 up-regulation.