Recurrence pattern of glioblastoma treated with intensity-modulated radiation therapy versus three-dimensional conformal radiation therapy.

PURPOSE: To evaluate recurrence patterns of and survival outcomes in glioblastoma treated with intensity-modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3D-CRT). MATERIALS AND METHODS: We retrospectively examined 91 patients with glioblastoma treated with either IMRT (n = 60) or 3D-CRT (n = 31) between January 2013 and December 2019. Magnetic resonance imaging showing tumor recurrence and planning computed tomography scans were fused for analyzing recurrence patterns categorized as in-field, marginal, and out-of-field based on their relation to the initial radiation field. RESULTS: The median overall survival (OS) was 18.9 months, with no significant difference between the groups. The median progression-free survival (PFS) was 9.4 months, with no significant difference between the groups. Patients who underwent gross total resection (GTR) had higher OS and PFS than those who underwent less extensive surgery. Among 78 relapse cases, 67 were of in-field; 5, marginal; and 19, out-of-field recurrence. Among 3D-CRT-treated cases, 24 were of in-field; 1, marginal; and 9, out-of-field recurrence. Among IMRT-treated cases, 43 were of in-field; 4, marginal; and 10, out-of-field recurrence. In partial tumor removal or biopsy cases, out-of-field recurrence was less frequent in the IMRT (16.2%) than in the 3D-CRT (36.3%) group, with marginal significance (p = 0.079). CONCLUSION: IMRT and 3D-CRT effectively managed glioblastoma with no significant differences in OS and PFS. The survival benefit with GTR underscored the importance of maximal surgical resection. The reduced rate of out-of-field recurrence in IMRT-treated patients with partial resection highlights its potential utility in cases with unfeasible complete tumor removal.

Fixed-Bearing and Higher Postoperative Knee Flexion Angle as Predictors of Satisfaction in Asian Patients Undergoing Posterior-Stabilized Total Knee Arthroplasty.

Background: Patient-reported satisfaction following total knee arthroplasty (TKA) can be affected by various factors. This study aimed to assess patient satisfaction rates and identify factors related to patients, surgery, and postoperative knee motion associated with satisfaction in posterior-stabilized TKA among Asian patients. Methods: A retrospective cross-sectional study was conducted in patients with primary osteoarthritis who underwent TKA and had a follow-up period of over 2 years. Patient satisfaction was measured using a 5-point Likert scale, and the patients were divided into satisfied and dissatisfied groups. The factors potentially affecting satisfaction were collected, including demographics, comorbidities, surgical options, and knee motion. Univariate and multivariate regression analyses were performed. Results: Of the 858 patients included, 784 (91.4%) were satisfied and 74 (8.6%) were dissatisfied. Fixed-bearing implants and higher postoperative knee flexion angles were associated with satisfaction (odds ratio [OR], 2.366; p = 0.001 and OR, 1.045; p < 0.001, respectively), whereas cerebrovascular disease was related to dissatisfaction (OR, 0.403; p = 0.005). The regression model demonstrated moderate predictability (R 2 = 0.112). Conclusions: Fixed-bearing implants and higher postoperative knee flexion angles were associated with patient satisfaction following TKA, whereas cerebrovascular disease was associated with dissatisfaction. The identification of these factors could help improve surgical outcomes and patient satisfaction following TKA.

TACE vs. TARE for HCC ≥ 8 cm: A propensity score analysis.

OBJECTIVE: This study aimed to compare transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) as first-line treatments for unresectable HCC > 8 cm. METHODS: This retrospective study analyzed 129 HCC patients with tumor diameters greater than 8 cm from January 2010 to December 2021, including 40 patients who received TARE, and 89 patients treated with TACE as primary treatment. Following Propensity Score Matching (PSM), 40 patients from each group were harmonized for baseline characteristics. Tumor responses were evaluated using mRECIST criteria, and survival outcomes were compared between treatment groups using Kaplan-Meier curves and the Log-rank test. RESULTS: There was no significant difference in the objective response rate (ORR) and disease control rate (DCR) at 3, 6, and 12 months between the two groups; ORR and DCR were 72.6%, 83.1% in TACE group vs. 72.5%. 87.5% in TARE group for best tumor response (p-values: 0.625 and 0.981, respectively). Overall survival (OS) and progression-free survival (PFS) between the two groups were comparable pre- and post-PSM. After PSM, the OS was 33.2 months (20.0-58.6) in TACE group and 38.1 months (13.8-98.1) in TARE group (p = 0.53), while PFS was 11.5 months (7.7-18.4) and 9.1 months (5.2-23.8) respectively. After PSM, post-embolization syndrome developed more in TACE group (100% vs. 75%, p = 0.002). Major adverse events were 72% in TACE group vs. 5% in TARE group (p < 0.001). CONCLUSIONS: TARE and TACE offer comparable efficacy in managing large HCC, with TARE providing a safer profile, suggesting its consideration as a preferable initial therapeutic approach for unresectable HCC patients with tumors larger than 8 cm.

Ultrahigh Stability and Operation Performance in Bi-doped GeTe/Sb2Te3 Superlattices Achieved by Tailoring Bonding and Structural Properties.

Changes in bond types and the reversible switching process between metavalent and covalent bonds are related to the operating mechanism of the phase-change (PC) behavior. Thus, controlling the bonding characteristics is the key to improving the PC memory performance. In this study, we have controlled the bonding characteristics of GeTe/Sb2Te3 superlattices (SLs) via bismuth (Bi) doping. The incorporation of Bi into the GeTe sublayers tailors the metavalent bond. We observed significant improvement in device reliability, set speed, and power consumption induced upon increasing Bi incorporation. The introduction of Bi was found to suppress the change in density between the SET and RESET states, resulting in a significant increase in device reliability. The reduction in Peierls distortion, leading to a more octahedral-like atomic arrangement, intensifies electron-phonon coupling with increased bond polarizability, which are responsible for the fast set speed and low power consumption. This study demonstrates how the structural and thermodynamic changes in phase change materials alter phase change characteristics due to systematic changes of bonding and provides an important methodology for the development of PC devices.

Weisheng-tang protects against ischemic brain injury by modulating microglia activation through the P2Y12 receptor.

Background: Stroke, a leading cause of death and disability, lacks effective treatments. Post-stroke secondary damage worsens the brain microenvironment, further exacerbating brain injury. Microglia's role in responding to stroke-induced damage in peri-infarct regions is crucial. In this study, we explored Weisheng-tang's potential to enhance ischemic outcomes by targeting microglia. Methods: We induced middle cerebral artery occlusion and reperfusion in mice, followed by behavioral assessments and infarct volume analyses after 48 h, and examined the changes in microglial morphology through skeleton analysis. Results: Weisheng-tang (300 mg/kg) significantly reduced infarction volume and alleviated neurological and motor deficits. The number of activated microglia was markedly increased within the peri-infarct territory, which was significantly reversed by Weisheng-tang. Microglial morphology analysis revealed that microglial processes were retracted owing to ischemic damage but were restored in Weisheng-tang-treated mice. This restoration was accompanied by the expression of the purinergic P2Y12 receptor (P2Y12R), a key regulator of microglial process extension. Weisheng-tang increased neuronal Kv2.1 clusters while suppressing juxtaneuronal microglial activation. The P2Y12R inhibitor-ticagrelor-eliminated the tissue and functional recovery that had been observed with Weisheng-tang after ischemic damage. Discussion: Weisheng-tang improved experimental stroke outcomes by modulating microglial morphology through P2Y12R, shedding light on its neuroprotective potential in ischemic stroke.

Innovative Therapeutic Delivery of Metastasis-Associated in Colon Cancer 1-Suppressing miRNA Using High Transmembrane 4 L6 Family Member 5-Targeting Exosomes in Colorectal Cancer Mouse Models.

Elevated metastasis-associated in colon cancer 1 (MACC1) expression in colorectal cancer patients, and high transmembrane 4 L6 family member 5 (TM4SF5) protein expressed on various solid tumors' surface, are linked to aggressive cancer behavior and progression. In this study, adipose-derived stem cells (ASCs) were engineered to produce exosomes (Ex) that target the TM4SF5 protein on tumors. Moreover, MACC1-targeting microRNA was encapsulated within the Ex, resulting in TM4SF5-targeting Ex (MACC1-suppressing miRNA; miR-143). The anticancer effects of these Ex were investigated in vitro using the human colorectal cell line HCT116 and in vivo using colorectal cancer mouse xenograft models. In the in vivo assessment, administration of TM4SF5-targeting Ex[miR-143], referred to as tEx[miR-143] herein, resulted in the smallest tumor size, the lowest tumor growth rate, and the lightest excised tumors compared to other treatments (p < 0.05). It also led to the decreased expression of MACC-1 and anti-apoptotic markers MCL-1 and Bcl-xL while inducing the highest expression of pro-apoptotic markers BAX and BIM. These results were consistent with in vitro findings, where t Ex[miR-143] demonstrated the highest inhibition of HCT116 cell migration and invasion. These findings highlight the potential of tEx[miR-143] as an effective therapeutic strategy for colorectal cancer, demonstrating promising results in both targetability and anti-tumor effects in vitro and in vivo, warranting further investigation in clinical settings.

Clinical effects and safety of intra-arterial infusion chemotherapy with lipiodol versus intra-arterial infusion chemotherapy alone for treatment of advanced hepatocellular carcinoma.

Introduction This study aims to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in two groups of patients: those who receive lipiodol (referred to as the lipiodol group) and those who do not receive lipiodol (referred to as the control group). Methods From January 2016 through December 2023, 85 patients with advanced hepatocellular carcinoma were enrolled in this retrospective study. In total, 40 patients received HAIC with lipiodol, while 45 patients were given HAIC without lipiodol. The modified response evaluation criteria for solid tumors were used to evaluate the tumor response, which was assessed through an imaging study. The two groups were compared regarding their overall survival, progression-free survival, and safety. Results: The outcomes between the lipiodol group and control group demonstrated no significant difference: the objective response rates (P = 0.066) were 32.5% and 15.6%; the disease control rates (P = 0.556) were 67.5% and 73.3%; the median overall survival times (P = 0.339) were 224 days and 398 days; the median progression-free survival (P = 0.334) times were 191 days and 286 days in the lipiodol group and the control group, respectively. Adverse events also showed no significant difference between the two groups: elevation of total bilirubin (P = 0.834) rates were 40.0% and 37.8%; elevation of alanine aminotransferase (P = 0.191) percentages were 35.0% and 22.2%; and elevation of aspartate aminotransferase values (P = 0.058) were 65.0% and 44.4% in the lipiodol group and the control group, respectively. Conclusions: HAIC without lipiodol was non-inferior to HAIC with lipiodol in the clinical outcome.

Efficient data labeling strategies for automated muscle segmentation in lower leg MRIs of Charcot-Marie-Tooth disease patients.

We aimed to develop efficient data labeling strategies for ground truth segmentation in lower-leg magnetic resonance imaging (MRI) of patients with Charcot-Marie-Tooth disease (CMT) and to develop an automated muscle segmentation model using different labeling approaches. The impact of using unlabeled data on model performance was further examined. Using axial T1-weighted MRIs of 120 patients with CMT (60 each with mild and severe intramuscular fat infiltration), we compared the performance of segmentation models obtained using several different labeling strategies. The effect of leveraging unlabeled data on segmentation performance was evaluated by comparing the performances of few-supervised, semi-supervised (mean teacher model), and fully-supervised learning models. We employed a 2D U-Net architecture and assessed its performance by comparing the average Dice coefficients (ADC) using paired t-tests with Bonferroni correction. Among few-supervised models utilizing 10% labeled data, labeling three slices (the uppermost, central, and lowermost slices) per subject exhibited a significantly higher ADC (90.84±3.46%) compared with other strategies using a single image slice per subject (uppermost, 87.79±4.41%; central, 89.42±4.07%; lowermost, 89.29±4.71%, p < 0.0001) or all slices per subject (85.97±9.82%, p < 0.0001). Moreover, semi-supervised learning significantly enhanced the segmentation performance. The semi-supervised model using the three-slices strategy showed the highest segmentation performance (91.03±3.67%) among 10% labeled set models. Fully-supervised model showed an ADC of 91.39±3.76. A three-slice-based labeling strategy for ground truth segmentation is the most efficient method for developing automated muscle segmentation models of CMT lower leg MRI. Additionally, semi-supervised learning with unlabeled data significantly enhances segmentation performance.

p16 Immunohistochemical Patterns in Triple-Negative Breast Cancer: Clinical and Genomic Similarities of the p16 Diffuse Pattern to pRB Deficiency.

INTRODUCTION: Triple-negative breast cancer (TNBC) is associated with alterations in the retinoblastoma pathway. As a consequence of retinoblastoma protein (pRB) loss, compensatory upregulation of p16 occurs due to the loss of phosphorylated pRB-mediated negative feedback on p16 expression. The aim of this study is to investigate the clinicopathologic and genomic characteristics associated with the diffuse pattern of p16 immunohistochemistry (IHC) in TNBC. METHODS: The study analyzed surgically resected TNBC for whole-exome sequencing in 113 cases and for cDNA microarray in 144 cases. The p16 IHC results were classified into two patterns: diffuse and negative/mosaic. RESULTS: In the entire cohort (n = 257), the diffuse pattern of p16 IHC was observed in 123 (47.9%) patients and the negative/mosaic pattern in 134 (52.1%). Bi-allelic RB1 inactivation was observed in 14.3% of patients with the diffuse pattern. The diffuse pattern of p16 IHC showed more frequent RB1 alterations and cell cycle progression signatures, a higher Ki-67 labeling index, more frequent chromosome segment copy number changes, a higher frequency of homologous recombination deficiency high, and immune-related signatures. PIK3CA mutations were more frequent in the negative/mosaic pattern. CCND1 amplification was identified in five cases, all with the negative/mosaic pattern Conclusion: In TNBC, the diffuse p16 pattern shows clinical and genomic similarities to pRB-deficient tumors, suggesting shared characteristics. This suggests that p16 IHC testing may provide new therapeutic approaches, underscoring its potential clinical importance.

Recurrent and De Novo Focal Segmental Glomerulosclerosis After Kidney Transplantation: Comparison of Clinical Features and Transplant Outcomes.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a notable subtype of glomerulonephritis in kidney transplantation, often resulting in graft failure. Yet, research comparing transplant outcomes between de novo and recurrent FSGS is scarce. This study aims to compare clinical features and transplant outcomes between these two categories. METHODS: This retrospective study enrolled 773 kidney transplant recipients from two centers between January 2008 and October 2021. Patients diagnosed with FSGS through graft kidney biopsy were included. They were categorized into two groups based on the time of FSGS occurrence and results of native kidney biopsy: the recurrent FSGS group and the de novo FSGS group. RESULTS: Of 773 kidney transplant patients, 24 had primary FSGS-causing end-stage renal disease. During a median 65-month follow-up, 5 of these patients developed recurrent FSGS (incidence: 26.3%). Among 749 patients with other kidney diseases causing end-stage renal disease, 9 had de novo FSGS (incidence: 1.2%). In the recurrent FSGS group, 2 out of 5 patients experienced graft failure, with no deaths or acute rejections. Similarly, in the de novo FSGS group, 3 out of 9 patients experienced graft failure, with no deaths or acute rejections. Kaplan-Meier analysis showed slower graft loss in de novo FSGS, resulting in a higher graft survival rate compared to recurrent FSGS (probability of graft survival, 60% vs 33.3%, P = .036). CONCLUSIONS: Graft loss progresses more slowly in de novo FSGS compared to recurrent FSGS, resulting in a higher long-term graft survival rate in de novo FSGS than in recurrent FSGS.

Experience from 100 consecutive pancreas transplants amidst low national transplant activity: a retrospective study at a single center in Korea.

Background: Since 1992, over 800 pancreas transplants have been performed in Korea. However, this number is significantly lower compared to the number of kidney or liver transplants. Methods: Between 2015 and July 2023, Pusan National University Yangsan Hospital conducted 100 pancreas transplants, accounting for about 20% of all transplants performed in Korea during this period. The study comprised 27 simultaneous pancreas and kidney (SPK) transplants, 23 pancreas after kidney (PAK) transplants, and 50 pancreas transplant alone (PTA) cases. Duodenoduodenostomy was the primary surgical technique employed for exocrine drainage, along with various modifications of the venous outflow anastomosis. Results: The availability of brain-dead donors for kidney transplants was lower compared to isolated pancreas transplants. Patients undergoing SPK transplants faced significantly longer waiting times than those receiving PTA or PAK transplants. The rate of surgical complications was acceptable, with a notably low thrombotic graft failure rate of 1.0%. In the PTA group, acute rejection of the graft pancreas occurred frequently (18.0%), though this was not statistically significant (P=0.328). The pancreas transplantation survival rates were 91.0%, 78.5%, and 75.4% at 1, 5, and 9 years, respectively. The PTA group exhibited a lower graft survival rate than the SPK and PAK groups, with marginal statistical significance (P=0.059). Conclusions: Graft survival rates have improved over time due to advancements in surgical techniques and immunosuppressant strategies. By sharing our experiences, we aim to enhance the activity and success of pancreas transplantation in Korea.

Performance of ChatGPT on Solving Orthopedic Board-Style Questions: A Comparative Analysis of ChatGPT 3.5 and ChatGPT 4.

Background: The application of artificial intelligence and large language models in the medical field requires an evaluation of their accuracy in providing medical information. This study aimed to assess the performance of Chat Generative Pre-trained Transformer (ChatGPT) models 3.5 and 4 in solving orthopedic board-style questions. Methods: A total of 160 text-only questions from the Orthopedic Surgery Department at Seoul National University Hospital, conforming to the format of the Korean Orthopedic Association board certification examinations, were input into the ChatGPT 3.5 and ChatGPT 4 programs. The questions were divided into 11 subcategories. The accuracy rates of the initial answers provided by Chat GPT 3.5 and ChatGPT 4 were analyzed. In addition, inconsistency rates of answers were evaluated by regenerating the responses. Results: ChatGPT 3.5 answered 37.5% of the questions correctly, while ChatGPT 4 showed an accuracy rate of 60.0% (p < 0.001). ChatGPT 4 demonstrated superior performance across most subcategories, except for the tumor-related questions. The rates of inconsistency in answers were 47.5% for ChatGPT 3.5 and 9.4% for ChatGPT 4. Conclusions: ChatGPT 4 showed the ability to pass orthopedic board-style examinations, outperforming ChatGPT 3.5 in accuracy rate. However, inconsistencies in response generation and instances of incorrect answers with misleading explanations require caution when applying ChatGPT in clinical settings or for educational purposes.

Isolated Polyethylene Insert Exchange for Instability after Total Knee Arthroplasty: Comparable Survival Rates and Range of Motion and Improved Clinical Scores Regardless of Hyperextension.

Background: Isolated polyethylene insert exchange (IPIE) has not been established as a treatment option for hyperextension instability after primary total knee arthroplasty (TKA). The purpose of the study was to evaluate the survival rate and clinical outcomes of IPIE for the treatment of instability with or without hyperextension after TKA. Methods: This study retrospectively reviewed 46 patients who underwent IPIE for symptomatic prosthetic knee instability by dividing them into 2 groups based on the presence of hyperextension (without for group I and with for group IH). Patient demographics, clinical scores, radiographic data, range of motion (ROM), and surgical information were collected. Clinical failure was defined as a subsequent surgery following IPIE for any reason. The survival rate of IPIE and differences in demographics, clinical scores, and ROM were compared. Results: There were 46 patients (91% were women) with an average age of 70.1 years and a mean follow-up of 44.8 months. The average time between primary TKA and IPIE surgery was 6.5 ± 4.2 years, and during IPIE, 2 out of the 8 cruciate-retaining inserts were converted to "deep-dish" ultracongruent inserts while the insert thickness increased from 11.9 ± 1.8 mm to 17.1 ± 3.1 mm. After IPIE surgery, a significantly thicker tibial insert was used in the group with hyperextension (15.39 ± 2.4 mm for group I, 18.3 ± 2.9 mm for group IH; p < 0.001 by independent t-test), and no significant differences were observed in the ROM and clinical scores before and after IPIE between the 2 groups. The overall survival rate for IPIE was 83% at 5 years and 57% at 10 years, and there were no statistically significant differences between the groups using the Cox proportional hazards regression model. Conclusions: IPIE demonstrated an overall survival rate of 83% at 5 years with no difference in the recurrence of instability regardless of hyperextension. This study highlighted the effectiveness of using thicker inserts to resolve instability without significant differences in the ROM or clinical scores between the groups, suggesting its potential as a decision-making reference for surgeons.

Cement Filling Technique to Prevent Greater Trochanter Displacement in Hip Arthroplasty for Femoral Intertrochanteric Fracture: A Technical Note.

With the increasing use of primary hip arthroplasty for management of intertrochanteric fractures, firm fixation and union of the greater trochanteric (GT) fragment are required during hip arthroplasty for management of intertrochanteric fractures. Various methods have been suggested to address this issue. However, displacement of the GT is a frequent occurrence. We have introduced a cement-filling technique for performance of hip arthroplasty of the proximal femur for achievement of immediate firm fixation of the GT. Cement filling during performance of hip arthroplasty for management of femoral intertrochanteric fractures is a valuable technique for preventing displacement of the GT and to encourage early mobilization.

Blood culture bottles meet the operating room: enhancing the diagnostic accuracy of infectious spondylitis through open microsurgical biopsy and intraoperative inoculation.

PURPOSE: Infectious spondylitis is caused by hematogenous seeding or adjacent soft tissue infection. No study has provided evidence that incubating biopsy specimens in blood culture bottles could enhance detection rates, nor has any study compared this method with conventional culture techniques. We aimed to assess the diagnostic yield of open microsurgical biopsies for infectious spondylitis and the efficacy of various culture media in the presence and absence of pre-biopsy antibiotic therapy. METHODS: This retrospective study, which was conducted at a university-affiliated teaching hospital in Korea, enrolled 165 adult patients with suspected infectious spondylitis between February 2014 and September 2020. The diagnostic yield of open biopsy was compared among three culture media, namely, blood culture bottles, swab culture using transport media, and tissue culture using plain tubes, while considering preoperative antibiotic exposure. RESULTS: Causative bacteria were identified in 84.2% of all cases. Blood culture bottles had the highest positivity rate (83.5%), followed by swab cultures (64.4%) and tissue cultures (44.9%). The differences in positivity rates were significant (P < 0.001). Preoperative antibiotic therapy reduced detection rates across all media, particularly in tissue cultures. CONCLUSIONS: We established the high diagnostic yield of open microsurgical biopsy using blood culture bottles, suggesting that pre-biopsy antibiotic therapy significantly affects bacterial detection, thereby underscoring the importance of culture medium selection in the diagnosis of infectious spondylitis.

Adenovirus expressing nc886, an anti-interferon and anti-apoptotic non-coding RNA, is an improved gene delivery vector.

Recombinant adenovirus (rAdV) vector is the most promising vehicle to deliver an exogenous gene into target cells and is preferred for gene therapy. Exogenous gene expression from rAdV is often too inefficient to induce phenotypic changes and the amount of administered rAdV must be very high to achieve a therapeutic dose. However, it is often hampered because a high dose of rAdV is likely to induce cytotoxicity by activating immune responses. nc886, a 102-nucleotide non-coding RNA that is transcribed by RNA polymerase III, acts as an immune suppressor and a facilitator of AdV entry into the nucleus. Therefore, in this study, we have constructed an rAdV expressing nc886 (AdV:nc886) to explore whether AdV:nc886 overcomes the aforementioned drawbacks of conventional rAdV vectors. When infected into mouse cell lines and mice, AdV:nc886 expresses a sufficient amount of nc886, which suppresses the induction of interferon-stimulated genes and apoptotic pathways triggered by AdV infection. As a result, AdV:nc886 is less cytotoxic and produces more rAdV-delivered gene products, compared with the parental rAdV vector lacking nc886. In conclusion, this study demonstrates that the nc886-expressing rAdV could become a superior gene delivery vehicle with greater safety and higher efficiency for in vivo gene therapy.

Nationwide Birth Prevalence of Crucial Congenital Heart Defects From 2014 to 2018 in Korea.

BACKGROUND AND OBJECTIVES: A comprehensive survey of congenital heart disease (CHD) prevalence has not yet been conducted in South Korea. This study aimed to investigate the prevalence of CHDs in Korean children and lay the foundation for national CHD epidemiology. METHODS: Target patients were infantile crucial CHDs, which include critical CHDs (requiring urgent procedures after birth with common hypoxemic defects) and diverse categorical defects excluding simple shunt defects. Data were obtained from the National Health Insurance Service over a 5-year period (2014-2018). Birth prevalence (new cases per 1,000 live births) of CHDs in Korea was analyzed and compared with that of other countries. RESULTS: The birth prevalences of right heart obstructive defects (pulmonary valve stenosis and pulmonary atresia), conus anomalies (tetralogy of Fallot and double outlet right ventricle), and total anomalous pulmonary venous return showed significant increases in the East Asian group (P < 0.001), whereas those of left heart obstructive defects (coarctation of aorta, aortic stenosis, and hypoplastic left heart syndrome), truncus anomalies (D-transposition of great artery and persistent truncus arteriosus), atrioventricular septal defect, and hypoplastic right heart syndrome were significantly decreased in the East Asian group (P < 0.001). CONCLUSIONS: The overall birth prevalence of crucial CHDs in Korea was similar to that of critical CHDs in previous studies from other countries. Some subtypes of right heart obstructive defects, left heart obstructive defects, and conotruncal anomalies showed significant differences between East Asian and Western populations. This study contributes to a foundation for national CHD epidemiology in Korean children.

US Markers and Necroinflammation, Steatosis, and Fibrosis in Metabolic Dysfunction-associated Steatotic Liver Disease: The iLEAD Study.

Background Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yin in this issue.

The Effect of Oral Diet Training in Indwelling Nasogastric Tube Patients with Prolonged Dysphagia.

Background: Patients with severe dysphagia are usually fed using a nasogastric tube (NGT). Many patients who receive long-term NGT feeding are unable to obtain sufficient nutrients orally immediately after NGT removal. Thus, a transitional period involving oral diet training is required to transition from NGT feeding to exclusive oral feeding. We aimed to investigate the therapeutic effect of oral diet training in indwelling NGT patients with prolonged dysphagia. Methods: A total of 175 patients who were fed using an NGT for more than 4 weeks were enrolled. Their swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS). During the VFSS, patients received thick and thin barium while the NGT was inserted. Then, the patients underwent a VFSS without an NGT thirty minutes after NGT removal. If a patient had no aspiration with NGT inserted during the VFSS, oral diet training combined with NGT feeding was recommended. Results: Of the 49 indwelling NGT patients who were recommended to receive oral diet training, 39 (79.6%) transitioned to exclusive oral feeding. A transition period of 2-8 weeks was required for them to achieve full oral feeding. Patients who were eligible for oral feeding trials showed no significant aspiration during the VFSS with an NGT inserted and had sufficient cough function. Patients who required prolonged NGT feeding and who could not complete oral trials showed significant aspiration during the VFSS when an NGT was inserted. Conclusions: This study demonstrated that oral diet training combined with NGT feeding is safe in patients with prolonged dysphagia who have sufficient cough function and no aspiration during VFSS. We suggest that if the patient is a proper candidate for NGT removal, direct oral feeding training with an NGT inserted could be a useful therapeutic strategy during the transitional period from long-term NGT feeding to successful oral feeding.

Single-cell RNA sequencing of nc886, a non-coding RNA transcribed by RNA polymerase III, with a primer spike-in strategy.

Single-cell RNA sequencing (scRNA-seq) has emerged as a versatile tool in biology, enabling comprehensive genomic-level characterization of individual cells. Currently, most scRNA-seq methods generate barcoded cDNAs by capturing the polyA tails of mRNAs, which exclude many non-coding RNAs (ncRNAs), especially those transcribed by RNA polymerase III (Pol III). Although previously thought to be expressed constitutively, Pol III-transcribed ncRNAs are expressed variably in healthy and disease states and play important roles therein, necessitating their profiling at the single-cell level. In this study, we developed a measurement protocol for nc886 as a model case and initial step for scRNA-seq for Pol III-transcribed ncRNAs. Specifically, we spiked in an oligo-tagged nc886-specific primer during the polyA tail capture process for the 5'scRNA-seq. We then produced sequencing libraries for standard 5' gene expression and oligo-tagged nc886 separately, to accommodate different cDNA sizes and ensure undisturbed transcriptome analysis. We applied this protocol in three cell lines that express high, low, and zero levels of nc886. Our results show that the identification of oligo tags exhibited limited target specificity, and sequencing reads of nc886 enabled the correction of non-specific priming. These findings suggest that gene-specific primers (GSPs) can be employed to capture RNAs lacking a polyA tail, with subsequent sequence verification ensuring accurate gene expression counting. Moreover, we embarked on an analysis of differentially expressed genes in cell line sub-clusters with differential nc886 expression, demonstrating variations in gene expression phenotypes. Collectively, the primer spike-in strategy allows combined analysis of ncRNAs and gene expression phenotype.