PARVB and HSD17B13 variants are associated with nonalcoholic fatty liver disease in children.

BACKGROUND AND AIM: The aim of this study was to investigate the comprehensive genetic effects of exploratory variants of LYPLAL1, GCKR, HSD17B13, TRIB1, APOC3, MBOAT7, and PARVB on pediatric nonalcoholic fatty liver disease in addition to the previously reported variants of TM6SF2, PNPLA3, and SAMM50 in Korean children. METHODS: A prospective case-control study was conducted involving 309 patients diagnosed using ultrasound and 339 controls. Anthropometric measurements, liver function tests, and metabolic marker analysis were conducted, and fibrosis scores were calculated. Transient elastography was performed in 69 some patients with nonalcoholic fatty liver disease. TaqMan allelic discrimination assays were used for genotyping. The genetic risk scores were calculated using significant variants, namely, HSD17B13, PARVB, PNPLA3, SAMM50, and TM6SF2, to evaluate the additive effect. RESULTS: Risk allele carriers of the PARVB variant showed significantly higher levels of aminotransferases, gamma-glutamyl transferase, alkaline phosphatase, pediatric nonalcoholic fatty liver disease fibrosis score, and aspartate aminotransferase/platelet ratio index. Individuals with a homozygous variant of HSD17B13 showed significantly lower levels of aminotransferase, gamma-glutamyl transferase, liver stiffness measurement, and aspartate aminotransferase/platelet ratio index than those with other genotypes. These parameters did not significantly differ among other variants of LYPLAL1, GCKR, TRIB1, APOC3, and MBOAT7. The genetic risk scores was identified as an independent risk factor for nonalcoholic fatty liver disease and had a positive association with severity. CONCLUSION: HSD17B13 has protective effects on the severity of pediatric nonalcoholic fatty liver disease. Variants of HSD17B13, PARVB, PNPLA3, SAMM50, and TM6SF2 had an additive effect on nonalcoholic fatty liver disease.

Biceps Rerouting Regardless of a Biceps-Labral Lesion During Rotator Cuff Repair Results in Lower Retear Rates and Comparable Clinical Outcomes to Subpectoral Biceps Tenodesis.

PURPOSE: To evaluate the radiographic and clinical outcomes when rerouting a pathologic biceps during arthroscopic rotator cuff repair by comparing it with concomitant subpectoral biceps tenodesis (SPBT). METHODS: This retrospective, historical cohort study was conducted with patients who underwent an arthroscopic repair of a full-thickness rotator cuff tear, with intraoperative confirmation of biceps pathology including partial tears, subluxation, pulley lesions, or type II SLAP lesions. Until May 2018, such patients were treated with concomitant subpectoral tenodesis (group SPBT). Afterward, biceps rerouting (BR) was done regardless of biceps pathology (group BR) without biceps or SLAP repair. Radiographic parameters, including fatty degeneration, acromiohumeral distance, Sugaya classification, and retears, were evaluated using preoperative and 1-year postoperative magnetic resonance imaging results. Clinical evaluation with a minimum 2-year follow-up included pain visual analog scale, American Shoulder and Elbow Surgeons, Simple Shoulder Test, and Constant-Murley scores. Whether individual patients exceeded these scores' minimal clinically important difference also was determined. RESULTS: A total of 64 patients (group SPBT = 32; group BR = 32) were included in the final analysis. The duration of clinical follow-up was 36.2 ± 9.3 months in group SPBT and 29.4 ± 6.9 months in the BR group (P = .002). Compared with group SPBT, group BR demonstrated a significantly lower retear rate (SPBT vs BR: 34.4% vs 12.5%, P = .039). In the BR group, 8 of 32 (25%) patients demonstrated a postoperative LHBT tear. The 4 cuff retears in group BR only took place within these patients. Other postoperative radiographic and clinical outcomes were comparable between the groups. Within each group, significant postoperative improvements were demonstrated (P < .05 for all clinical scores). CONCLUSIONS: Even in the presence of a pathologic LHBT and/or a type II SLAP lesion, augmenting the rotator cuff repair with BR significantly reduced retear rates while achieving clinical scores comparable with SPBT in a minimum 2-year follow-up. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues.

OBJECTIVE: To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice. METHODS: The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5'-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis. RESULTS: HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone I, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology. CONCLUSION: C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM.

A Report on a Nationwide Surveillance System for Pediatric Acute Hepatitis of Unknown Etiology in Korea.

BACKGROUND: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. METHODS: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. RESULTS: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. CONCLUSION: The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

Is the Direct Fixation of Displaced Quadrilateral Plates in Acetabular Fractures Necessary?

Quadrilateral plate fractures represent a heterogeneous group of acetabular fractures. Accurate reduction is required to prevent post-traumatic arthritis. The purpose of this study is to determine the reduction effect of the direct fixation of quadrilateral plates in acetabular fractures, and to evaluate the strength of direct fixation compared to indirect fixation. Between 2005 and 2021, 49 patients underwent surgery for open reduction and internal fixation in acetabular fractures with severely displaced quadrilateral plates. Twenty-nine patients comprised the indirect fixation group, and twenty patients comprised the direct fixation group. In a comparison of primary outcome between two groups, 10 out of 29 indirect-group patients and 1 out of 20 direct-group patients developed post-traumatic osteoarthritis, wherein the difference between the two groups is statistically significant. In the assessment of postoperative Matta's radiological reduction status, 19 out of 20 patients in the direct group had achieved anatomical and congruent reduction. The treatment using a direct reduction and internal fixation improved the reduction quality of articular displacement and offered a better survivorship of the affected hip joint.

The Validation of Two-Dimensional and Three-Dimensional Radiographic Measurements of Host Bone Coverage in Total Hip Arthroplasty for Hip Dysplasia: A Comparison with Intra-Operative Measurements.

Several methods have been introduced to measure the host bone coverage of the acetabular component after total hip arthroplasty (THA). The aims of this study were (1) to validate two-dimensional- and three-dimensional-based host bone coverage measurements by comparing intra-operative measurements, and (2) to determine the minimum host bone coverage for achieving stable cup fixation after THA in hip dysplasia. The clinical outcomes of each patient were evaluated during their final follow-up period using the Harris Hip score (HHS). The coverage of the host bone was analyzed by comparing 2D-based, 3D-based, and intraoperative assessments. The mean HHS was increased significantly from 60.84 ± 14.21 pre-operatively to 93.13 ± 4.59 (p < 0.0001). The host bone coverage ratio measured intraoperatively was 83.67 ± 3.40%, while the ratio measured by 3D CT reconstruction was 82.72 ± 3.59%. There was a strong positive correlation between the intra-operative host bone coverage and the 3D-based one (r = 0.826, p < 0.0001). It is recommended that 3D-based measurements are used to evaluate the host bone coverage after THA in patients with hip dysplasia. In addition, achieving a minimum host bone coverage of 75% is recommended for the attainment of stable cup fixation.

Cadaveric Biomechanical Study of Partial Glenoid Arthroplasty Versus the Latarjet Procedure for Anterior Glenoid Bone Loss.

BACKGROUND: For severe anterior glenoid bone loss due to recurrent shoulder instability, the Latarjet procedure offers a dynamic sling effect in addition to bone augmentation. Yet, it heavily alters the surrounding anatomy, while fixation and graft union issues are also common. PURPOSE/HYPOTHESIS: The purpose of this study was to compare a novel printed 3-dimensional (3D) partial glenoid arthroplasty (PGA) implant with the classic Latarjet procedure. It was hypothesized that by replicating the original glenoid geometry and preserving soft tissue anatomy, PGA may better reproduce normal joint kinematics. In addition, the locking screw construct may offer stronger fixation. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 14 matched cadaveric shoulders were tested. The PGA implant was 3D printed in titanium based on preoperative computed tomography. The intact, 25% anterior glenoid bone loss, and postoperative states were tested in the scapular and coronal planes. The following parameters were measured: articular surface area and stepoff, rotational range of motion and the humeral head apex position during rotation, and load and linear stiffness at 25% anterior translation and at 2-mm construct displacement. RESULTS: The baseline dimensions of the glenoid articular surface were comparable between the groups. The articular surface area after PGA was significantly larger (P = .006) with less articular stepoff (P = .030). PGA better approximated the intact state's external (P = .006) and total (P = .019) rotational range of motion in the scapular plane. The course of the humeral head apex after PGA better followed that of the intact state (P < .001). Resistance against anterior translation after PGA was not significantly different compared with after the Latarjet procedure. Greater linear stiffness (P = .031) and loading (P = .002) at 2-mm construct displacement were demonstrated in the PGA group. CONCLUSION: In addressing anterior glenoid bone loss, PGA better approximated intact glenohumeral joint kinematics compared with the Latarjet procedure with less articular stepoff in a cadaveric model. PGA was comparable in resisting anterior translation while being significantly stronger against loading at 2-mm construct displacement. Further clinical studies are warranted to validate this novel procedure. CLINICAL RELEVANCE: A 3D-printed PGA implant may offer an alternative treatment option for severe glenoid bone loss due to shoulder instability, overcoming the previous drawbacks of the Latarjet procedure, including altered kinematics, fixation failure, and hardware issues.

Spontaneous Deltoid Tear in Cuff Tear Arthropathy and Its Effect on the Outcome of Reverse Total Shoulder Arthroplasty: A Comparison Using Propensity Score Matching.

Background: Deltoid function critically influences the results of reverse total shoulder arthroplasty (RTSA), and spontaneous deltoid attrition tears are frequently detected in cuff tear arthropathy (CTA) patients; however, the clinical impacts of these tears on RTSA outcomes are undetermined. Our aim was to determine the effect of spontaneous deltoid attrition tears on postoperative outcomes after RTSA without an additional deltoid procedure. Methods: Seventy-two patients who underwent RTSA for CTA with preoperative magnetic resonance imaging (MRI) and a minimum clinical follow-up of 1 year (mean, 32 months) were retrospectively reviewed in the study. Patients with a history of previous shoulder surgery or injury were excluded. The presence and location of deltoid attrition tears were determined in preoperative MRI. Propensity score matching (1:1) was performed to construct tear and no-tear groups. Finally, 21 patients, matched with respect to age, sex, hand dominance, symptom duration, medical comorbidity (obesity, diabetes mellitus, and coronary artery disease), Hamada grade, and implant type, were assigned to each group. Clinical outcomes (functional scores, isometric power, and range of motion) in the two groups were compared. Results: Deltoid attrition tears were detected in 21 of the 72 enrolled cases (29.1%). Anterolateral deltoid was the most frequent location and no tear was detected in the posterior deltoid. The tear rate increased with disease severity (Hamada G2, 4.8%; G3, 23.8%; > G4, 71.4%). No pre- or postoperative clinical variables differed significantly between the tear and no tear groups. Conclusions: Deltoid attrition tears were detected in 29% of CTA patients who underwent RTSA. The most common site was the anterolateral region and tear prevalence tended to increase with CTA progression. However, RTSA was found to provide satisfactory outcomes regardless of the presence of a deltoid attrition tear.

Who Hurt You at Work? Results From a Nationwide Survey of Association Between Absenteeism and Workplace Violence, Stratified by Perpetrator.

OBJECTIVE: This study aimed to determine the association between workplace violence and sickness absenteeism. METHODS: We analyzed the data from the fifth and sixth waves of the Korean Working Conditions Surveys. Individuals younger than 18 years and self-employed or unpaid family workers were excluded. Descriptive statistics, χ 2 tests, and multiple logistic regression analysis were conducted. RESULTS: After adjusting for sociodemographic, occupational, and job-related characteristics, we found that the workers who had experienced workplace violence had higher rates of sickness absenteeism, especially when the perpetrator of violence was a coworker. CONCLUSIONS: Daily contact with the perpetrator at the workplace can cause distress and recollection of painful memories; thus, the aftermath of being harassed inside the workplace can be even more devastating than the event itself. A sensitive approach to recognizing the perpetrators of violence is needed.

The effect of teriparatide on fracture healing after atypical femoral fracture: A systematic review and meta-analysis.

This meta-analysis demonstrated that a greater prevalence of delayed union and nonunion and a longer time to fracture healing in the group that did not receive TPTD treatment after AFFs than in the group that received TPTD treatment. PURPOSE: To date, there is no hard evidence for medical management after atypical femoral fracture (AFF), even though weak data indicate faster healing with teriparatide (TPTD). Herein, we aimed to investigate the effect of postfracture TPTD treatment on AFF healing using a pairwise meta-analysis focusing on delayed union, nonunion, and fracture healing time. METHODS: A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies investigating the effect of TPTD after AFF up to October 11, 2022. We compared the incidence of delayed union and nonunion and the time of fracture healing between the TPTD ( +) and TPTD (-) groups. RESULTS: The 6 studies analyzed a total of 214 AFF patients, including 93 who received TPTD therapy after AFF and 121 who did not. The pooled analysis showed a significantly higher rate of delayed union in the TPTD (-) group than in the TPTD ( +) group (OR, 0.24; 95% CI, 0.11-0.52; P < 0.01; I2 = 0%), and a higher nonunion rate was observed in the TPTD (-) group than in the TPTD ( +) group with low heterogeneity (OR, 0.21; 95% CI, 0.06-0.78; P = 0.02; I2 = 0%). The TPTD (-) group required 1.69 months longer to achieve fracture union than the TPTD ( +) group, with statistical significance (MD = - 1.69, 95% CI: - 2.44 to - 0.95, P < 0.01; I2 = 13%). Subgroup analysis for patients with complete AFF showed that the TPTD (-) group had a higher rate of delayed union with low heterogeneity (OR, 0.22; 95% CI, 0.10-0.51; P < 0.01; I2 = 0%), but there was no significant difference in the nonunion rate between TPTD ( +) and TPTD (-) groups (OR, 0.35; 95% CI, 0.06-2.21; P = 0.25; I2 = 0%). Fracture healing took significantly longer in the TPTD (-) group (MD = - 1.81, 95% CI: - 2.55 to - 1.08; P < 0.01; I2 = 48%). The reoperation rate showed no significant difference between the two groups (OR, 0.29; 95% CI, 0.07-1.20; P = 0.09; I2 = 0%). CONCLUSIONS: The current meta-analysis supported the hypothesis that TPTD treatment following AFF might benefit fracture healing, lowering the rate of delayed union and nonunion and shortening the fracture healing time.

A Nationwide Survey on Gastrointestinal Endoscopy Practice Patterns among Pediatric Endoscopists in South Korea.

Purpose: Gastrointestinal (GI) endoscopy is an important tool for diagnosing and treating GI diseases in children. This study aimed to analyze the current GI endoscopy practice patterns among South Korean pediatric endoscopists. Methods: Twelve members of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition developed a questionnaire. The questionnaire was emailed to pediatric gastroenterologists attending general and tertiary hospitals in South Korea. Results: The response rate was 86.7% (52/60), and 49 of the respondents (94.2%) were currently performing endoscopy. All respondents were performing esophagogastroduodenoscopy, and 43 (87.8%) were performing colonoscopy. Relatively rare procedures for children, such as double-balloon enteroscopy (DBE) (4.1%), endoscopic retrograde cholangiopancreatography (ERCP) (2.0%), and endoscopic ultrasound (EUS) (2.0%), were only performed by pediatric gastroenterologists at very few centers, but were performed by adult endoscopists in most of the centers; of all the respondents, 83.7% (41/49) performed emergency endoscopy. In most centers, the majority of the endoscopies were performed under sedation, with midazolam (100.0%) and ketamine (67.3%) as the most frequently used sedatives. Conclusion: While most pediatric GI endoscopists perform common GI endoscopic procedures, rare procedures, such as DBE, ERCP, and EUS, are only performed by pediatric gastroenterologists at very few centers, and by adult GI endoscopists at most of the centers. For such rare procedures, close communication and cooperation with adult GI endoscopists are required.

Fecal Calprotectin Levels Significantly Correlate with Polyp Size in Children and Adolescents with Juvenile Colorectal Polyps.

Purpose: We aimed to investigate factors that correlate with fecal calprotectin (FC) levels in children and adolescents with colorectal polyps. Methods: Pediatric patients aged <19 years who underwent colonoscopic polypectomy for a juvenile polyps (JPs) and FC tests were simultaneously conducted in a multicenter, retrospective study. Baseline demographics, colonoscopic and histological findings, and laboratory tests, including FC levels, were investigated. Correlations between the factors were investigated, and linear regression analysis revealed factors that correlated with FC levels. FC levels measured after polypectomies were investigated and the FC levels pre- and post-polypectomies were compared. Results: A total of 33 patients were included in the study. According to Pearson correlation analysis, the polyp size was the only factor that showed a statistically significant correlation with FC levels (r=0.75, p<0.001). Furthermore, according to the multivariate linear regression analysis, polyp size was the only factor that showed a statistically significant correlation with FC levels (adjusted R2 =0.5718, ß=73.62, p<0.001). The median FC level was 400 mg/kg (interquartile range [IQR], 141.6-1,000 mg/kg), and the median polyp size was 14 mm (IQR, 9-20 mm). Nineteen patients underwent post-polypectomy FC tests. FC levels showed a significant decrease after polypectomy from a median of 445.2 mg/kg (IQR, 225-1,000) to 26.5 mg/kg (11.5-51) (p<0.001). Conclusion: FC levels significantly correlated with polyp size in children and adolescents with JPs.

Associations of Polyp Characteristics in Children and Adolescents Presenting with Less Than Five Colorectal Polyps: A Full Colonoscopy Is Still Required.

Background/Aims: A full colonoscopy is currently required in children and adolescents with colorectal polyps, because of their potential of neoplastic transformation and complications such as intussusception. We aimed to analyze the associations of polyp characteristics in children and adolescents with colorectal polyps. Based on these findings, we also aimed to reevaluate the necessity of conducting a full colonoscopy. Methods: Pediatric patients <18 years of age who had undergone a colonoscopic polypectomy and those with <5 colorectal polyps were included in this multicenter, retrospective study. Baseline clinicodemographics, colonoscopic and histologic findings were investigated. Results: A total of 91 patients were included. Multivariate logistic regression analysis showed that polyp size was the only factor associated with the presence of any polyps located proximal to the splenic flexure (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.28 to 4.28; p=0.007). Furthermore, polyp location proximal to the splenic flexure and sessile morphology were associated with the presence of any adenomatous polyp (OR, 8.51; 95% CI, 1.43 to 68.65; p=0.023; OR, 18.41; 95% CI, 3.45 to 173.81; p=0.002, respectively). Conclusions: In children and adolescents presenting with <5 colorectal polyps, polyp size and the presence of any adenomatous polyp were positively associated with polyp location proximal to the splenic flexure. This finding supports the necessity of a full colonoscopic exam in pediatric patients with colorectal polyps for the detection of polyps before the occurrence of complications such as intussusception or neoplastic transformation.

Association between receiving work communications outside of work hours via telecommunication devices and work-related headaches and eyestrain: a cross-sectional analysis of the 6th Korean Working Conditions Survey.

Background: The rise in telecommuting or non-face-to-face work owing to the coronavirus disease 2019 pandemic has fueled conversations regarding the "right to disconnect." Although evidence suggests that receiving work-related communications through telecommunication devices outside of work hours may lead to various symptoms and illnesses, limited research has been undertaken on these symptoms. This study therefore aims to investigate the correlation between receiving work communications through telecommunication devices after work hours and the occurrence of work-related headaches and eyestrain in full-time, non-shift white-collar workers. Methods: This study used data from the 6th Korean Working Conditions Survey. The frequency of using telecommunication devices for work purposes outside of working hours was divided into five categories: "Every day," "Several times a week," "Several times a month," "Rarely," and "Never." Work-related headaches and eyestrain were categorized based on a "yes" or "no" response to the survey questions. Descriptive statistics, χ2 tests, and multiple logistic regression analyses were performed using SPSS 27.0. Results: After adjusting for sex, age, income level, education, occupation, workplace size, work hours, and sleep disorders, the odds ratio (OR) of work-related headaches and eyestrain based on frequency of telecommunication device usage were as follows: "rarely" (OR: 1.292; 95% confidence interval [CI]: 1.111-1.503), "several times a month" (OR: 1.551; 95% CI: 1.249-1.926), "several times a week" (OR: 1.474; 95% CI: 1.217-1.784), and "every day" (OR: 1.548; 95% CI: 1.321-1.813). Conclusions: Employees who use telecommunication devices for work after regular hours are more susceptible to experiencing work-related headaches and eyestrain compared to those who do not. However, there is a dearth of research examining the physical and mental health impacts of using telecommunication devices for after-hours work. Furthermore, the existing preventative measures in Korea are insufficient. Consequently, it is imperative to develop effective measures and conduct additional research to address this issue.

Ex Vivo Treatment with Allogenic Mesenchymal Stem Cells of a Healthy Donor on Peripheral Blood Mononuclear Cells of Patients with Severe Alopecia Areata: Targeting Dysregulated T Cells and the Acquisition of Immunotolerance.

Alopecia areata (AA) is an autoimmune condition related to the collapse of the immune privilege of hair follicles. Certain AA populations present severe clinical manifestations, such as total scalp hair or body hair loss and a treatment refractory property. The aim of this study was to assess the effects of allogenic human mesenchymal stem cells (hMSCs) from healthy donors on the peripheral blood mononuclear cells (PBMCs) of severe AA patients, with a focus on the change in the cell fraction of Th1, Th17, and Treg cells and immunomodulatory functions. PBMCs of 10 AA patients and eight healthy controls were collected. Levels of Th17, Th1, and Treg subsets were determined via flow cytometry at baseline, activation status, and after co-culturing with hMSCs. All participants were severe AA patients with SALT > 50 and with a long disease duration. While the baseline Th1 and Treg levels of AA patients were comparable to those of healthy controls, their Th17 levels were significantly lower than those of the controls. When stimulated, the levels of CD4+IFN-γ+ T cells of the AA patients rose sharply compared to the baseline, which was not the case in those of healthy controls. The cell fraction of CD4+Foxp3+ regulatory T cells also abruptly increased in AA patients only. Co-culturing with allogenic hMSCs in activated AA PBMCs slightly suppressed the activation levels of CD4+INF-γ+ T cells, whereas it significantly induced the differentiation of CD4+Foxp3+ regulatory T cells. However, these changes were not prominent in the PBMCs of health controls. To examine the pathomechanisms, PBMCs of healthy donors were treated with IFN-γ to induce AA-like environment and then treated with allogenic grants and compared with ruxolitinib as a positive treatment control. hMSC treatment was shown to significantly inhibit the mRNA levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-1α, IL-2R, IL-15, and IL-18, and chemokines, such as CCR7 and CCR10, in IFN-treated PBMCs. Interestingly, hMSCs suppressed the activation of JAK/STAT signaling by IFN in PBMCs with an effect that was comparable to that of ruxolitinib. Furthermore, the hMSC treatment showed stronger efficacy in inducing Foxp3, IL-10, and TGF-ß mRNA transcription than ruxolitinib in IFN-treated PBMCs. This study suggests that allogenic hMSC treatments have therapeutic potential to induce immune tolerance and anti-inflammatory effects in severe AA patients.

Three-dimensional morphologic features of Asian atypical femur and clinical implications of cephalomedullary nail fixation: Computational measurement at actual size.

PURPOSE: (1) To analyze three-dimensional (3D) morphologic features of atypical femur fracture at actual size without projection error; and (2) to provide clinical implications of cephalomedullary nail (CMN) fixation by separating the medullary canal and the cortex. MATERIALS AND METHODS: Fifty-nine atypical femurs (opposite non-fractured femurs) were reconstructed as 3D models with medullary canal by importing CT data into Mimics® software. A reference line was drawn from the tip of the greater trochanter to the center of the intercondylar notch and used for classifying bowing grade according to the centerline of medulla. Proximal and distal straight lines (length of 60 mm, diameter of 1 mm) were placed in the centerline of medulla. Acute angles between the two straight lines were measured as lateral and anterior bowing. The acute angle by straight line and reference line was measured as proximal and distal bowing in both AP and lateral view. The diameter of curve (DOC) of medulla along the posterior border was measured. RESULTS: The anterior bowing of all femur on lateral view was an average of 13.82° (range, 6.2°-31.1°, SD 3.91), and the values of proximal and distal anterior bowing were an average of 7.82° (range, 2.7°-14.3°, SD 2.23) and 6.0° (range, 2.2°-16.8°, SD 2.31), respectively. The lateral bowing of all femur on AP view was an average of 5.49° (range, 0.1°-17.3°, SD 4.48), and the values of proximal and distal anterior bowing were an average of 3.64° (range, 0.1°-11.3°, SD 2.70) and 2.48° (range, 0-7.4°, SD 1.98), respectively. The medullary canal was changed to be straightened and more bowed anteriorly. Concerning the lateral bowing grade of entire diaphysis, it was grade -I for 15 femurs, grade 0 for 21 femurs, grade I for nine femurs, grade II for five femurs, and grade III for nine femurs. Regarding anterior bowing grade, it was grade II for 14 femurs and grade III for 45 femurs. The average diameter of medullary canal was 1276.3 ± 232.25 mm. CONCLUSION: Asian atypical femur had three morphologic features: (1) straightened medullary canal, (2) positive values of lateral bowing, and (3) significantly increased ante-curvature of medullary canal. Considering that conventional CMN had about 4° of mediolateral angle, the disparity between implant and medullary canal might be clear. Thus, new nail design for Asian atypical femur that could increase the radius of curve (ROC) but decrease the mediolateral angle needs to be introduced.

The Changes in Trends of Lower Gastrointestinal Endoscopy Conducted in Children and Adolescents after the COVID-19 Outbreak in Korea.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has affected medical practice in diverse ways. We aimed to investigate the change in trends of lower gastrointestinal (LGI) endoscopy conducted in children and adolescents after the COVID-19 outbreak in Korea. Material and Methods: This was a multicenter, retrospective study conducted in Korea. We included children and adolescents aged <19 years who had undergone their first LGI endoscopy between 2016 and 2020. We compared clinicodemographic and endoscopic factors between groups divided according to the pre- and postCOVID-19 era in Korea. Results: We included 1307 patients in this study. Colonoscopies, instead of sigmoidoscopies, were conducted in most patients in the postCOVID-19 era compared to those in the preCOVID-19 era (86.9% vs. 78.5%, p = 0.007). The diagnosis of inflammatory bowel disease (IBD) was also significantly higher in the postCOVID-19 era compared to the preCOVID-19 era (47.2% vs. 28.5%, p < 0.001). According to multivariate logistic regression analysis, age at LGI endoscopy, LGI bleeding indication, and IBD diagnosis were independently associated with the use of a colonoscopy over a sigmoidoscopy (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.12−1.27, p < 0.001; OR 0.56, 95% CI 0.37−0.83, p = 0.005; OR 1.80, 95% CI 1.20−2.77, p = 0.006, respectively). Conclusions: The COVID-19 pandemic has changed LGI endoscopy practice trends of pediatric gastroenterologists in Korea, who tended to perform lesser LGI endoscopies compared to previous years while conducting significantly more colonoscopies than sigmoidoscopies in the postCOVID-19 era. Furthermore, these colonoscopies were significantly associated with the diagnosis of IBD, as well as a significant increase in IBD diagnosis in the postCOVID-19 era.

Pathomechanism of Triangular Fibrocartilage Complex Injuries in Patients with Distal-Radius Fractures: A Magnetic-Resonance Imaging Study.

Injury to the triangular fibrocartilage complex (TFCC) is one of the most common complications following a fracture of the distal radius. In this study, an examination of TFCC injuries in patients with distal-radius fractures was conducted using magnetic-resonance imaging (MRI); the aim of the study was to analyze the prevalence of TFCC injury as well as to suggest acceptable radiologic parameters for use in prediction of the injury pattern. Fifty-eight patients with distal-radius fractures who underwent MRI prior to undergoing open-reduction surgery between April 2020 and July 2021 were included in this study. An analysis of various radiologic parameters, the fracture type, and the MRI classification of TFCC injuries was performed. Radiologic parameters were used in the evaluation of distal radioulnar joint (DRUJ), radial shortening, and the dorsal angularity of the fracture. All of the patients in this study had definite traumatic TFCC injuries. A statistical relationship was observed between the radial length gap between the intact wrist and the injured wrist, which represents relative radial shortening, and the pattern of TFCC injury. In conclusion, the shortening of the distal radius, causing peripheral soft tissue of the ulnar side to become tauter, is highly relevant with regard to the pattern of TFCC injury. However, because no data on the clinical outcome were utilized in this study, it is lacking in clinical perspective. The conduct of further studies on patients' clinical outcome will be necessary.

Association of Metabolic Signatures with Nonalcoholic Fatty Liver Disease in Pediatric Population.

Several adult omics studies have been conducted to understand the pathophysiology of nonalcoholic fatty liver disease (NAFLD). However, the histological features of children are different from those of adults, and the onset and progression of pediatric NAFLD are not fully understood. In this study, we aimed to evaluate the metabolome profile and metabolic pathway changes associated with pediatric NAFLD to elucidate its pathophysiology and to develop machine learning-based NAFLD diagnostic models. We analyzed the metabolic profiles of healthy control, lean NAFLD, overweight control, and overweight NAFLD groups of children and adolescent participants (N = 165) by assessing plasma samples. Additionally, we constructed diagnostic models by applying three machine learning methods (ElasticNet, random forest, and XGBoost) and multiple logistic regression by using NAFLD-specific metabolic features, genetic variants, and clinical data. We identified 18 NAFLD-specific metabolic features and metabolic changes in lipid, glutathione-related amino acid, and branched-chain amino acid metabolism by comparing the control and NAFLD groups in the overweight pediatric population. Additionally, we successfully developed and cross-validated diagnostic models that showed excellent diagnostic performance (ElasticNet and random forest model: area under the receiver operating characteristic curve, 0.95). Metabolome changes in the plasma of pediatric patients with NAFLD are associated with the pathophysiology of the disease and can be utilized as a less-invasive approach to diagnosing the disease.

Cardiac Complications Associated with Eating Disorders in Children: A Multicenter Retrospective Study.

Purpose: Eating disorders often result in somatic complications, including cardiac abnormalities. Cardiac abnormalities may involve any part of the heart, including the cardiac conduction system, and can lead to sudden cardiac death. The current study aimed to evaluate the incidence of cardiac complications in pediatric patients with eating disorders and their associated factors. Methods: We retrospectively analyzed patients aged 10-18 years who were diagnosed with DSM-V (Diagnostic and Statistical Manual of Mental Disorder-V) eating disorders and underwent electrocardiography (ECG) and/or echocardiography between January 2015 and May 2020. Results: In total, 127 patients were included, of whom 113 (89.0%) were female. The median body mass index (BMI) was 15.05±3.69 kg/m2. Overall, 74 patients (58.3%) had ECG abnormalities, with sinus bradycardia being the most common abnormality (91.9%). Patients with ECG abnormalities had significantly lower BMI (14.35±2.78 kg/m2 vs. 16.06± 4.55 kg/m2, p<0.001) than patients without ECG abnormalities, as well as lower phosphorus and higher cholesterol levels. Among the 46 patients who underwent echocardiographic evaluation, 23 (50.0%) had echocardiographic abnormalities, with pericardial effusion being the most common (60.9%). The median left ventricular mass (LVM) and ejection fraction were 67.97±21.25 g and 66.91±28.76%, respectively. LVM and BMI showed a positive correlation (r=0.604, p<0.001). After weight gain, the amount of pericardial effusion was reduced in 3 patients, and 30 patients presented with normal ECG findings. Conclusion: Cardiac abnormalities are relatively frequent in patients with eating disorders. Physicians should focus on this somatic complication and careful monitoring is required.