Background: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. Methods: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping.The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trioWGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. Results: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants.There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. Conclusion This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.

Cerebellar hemorrhage in full-term infants is a rare condition recently recognized in high-risk newborns requiring intensive care with the availability of advanced neuroimaging techniques. Several aspects such as the incidence, pathophysiology, clinical features, and prognosis of cerebellar hemorrhage in full-term infants remain unknown. We present a case of cerebellar hemorrhage with subdural hemorrhage in a patient hospitalized for jaundice after birth without a history of traumatic delivery, such as breech presentation, prolonged labor or forceps delivery. A full-term female infant weighing 3,100 g at birth, with no complications during delivery, developed jaundice within 48 hours of birth and was admitted for intensive phototherapy in the first 3 days of life with a transcutaneous total bilirubin level of 18.1 mg/dL. Magnetic resonance imaging revealed cerebellar brain lesions with a subdural hemorrhage. At the age of 3 months, the infant exhibited leg rigidity and was referred for rehabilitation. The patient showed signs of improvement during treatment and was generally catching up well with her peers at the age of 9 months. Long-term follow-ups are required to evaluate the consequences on cognitive development, behavior, and motor performance subsequently in life.

Purpose: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. Materials and Methods: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. Results: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). Conclusion Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.

Purpose: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are frequently employed to counteract the detrimental effects of proteinuria on glomerular diseases. However, the effects of ARBs remain poorly examined in pediatric patients with immunoglobulin A (IgA) nephropathy. Herein, we evaluated the efficacy and safety of losartan, an ARB, in pediatric IgA nephropathy with proteinuria. Methods: This prospective, single-arm, multicenter study included children with IgA nephropathy exhibiting proteinuria. Changes in proteinuria, blood pressure, and kidney function were prospectively evaluated before and 4 and 24 weeks after losartan administration. The primary endpoint was the difference in proteinuria between baseline and 24 weeks. Results: In total, 29 patients were enrolled and received losartan treatment. The full analysis set included 28 patients who received losartan at least once and had pre- and post-urinary protein to creatinine ratio measurements (n=28). The per-protocol analysis group included 22 patients who completed all scheduled visits without any serious violations during the study period. In both groups, the mean log (urine protein to creatinine ratio) value decreased significantly at 6 months. After 24 weeks, the urinary protein to creatinine ratio decreased by more than 50% in approximately 40% of the patients. The glomerular filtration rate was not significantly altered during the observation period. Conclusions Losartan decreased proteinuria without decreasing kidney function in patients with IgA nephropathy over 24 weeks. Losartan could be safely employed to reduce proteinuria in this patient population. ClinicalTrials.gov trial registration (NCT0223277)

Objectives: Recent epidemiological data reported that young adults in their 20 ~ 30s are a vulnerable population with unhealthy dietary practices and a few signs of deteriorated health indicators. However, there are no dietary guidelines that are specifically developed for the young adult population. This study introduces some data collection tools that are mostly used in the service design field, and demonstrates how these tools can be used in nutrition research for developing dietary guidelines for specific target groups. Methods: To understand the context of food choices among young people, 39 people were enrolled to complete a probes booklet. Thematic analysis and word cloud were performed to capture the main themes from the probes and a persona was developed based on the findings. Results: Data from the probes enabled us to grasp the various contextual meanings of eating practices among young people. Most participants understand what a healthy diet is and often have a willingness to practice it. However, there were very few participants who were following the practices. We created four types of persona for developing dietary guidelines: healthy eating, emotional eating, convenient eating, and trendy eating. Conclusions Probes and persona were used in order to understand the lives of young adults and develop targeted messages. We hope that this introduction will be helpful to researchers who are looking for new ways of understanding their target population in the field of community nutrition.

Purpose: For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1). Materials and Methods: We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS. Results: The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes. Conclusion Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.

Pericardial effusion (PCE) in neonates has various clinical presentations depending on the amount and speed of fluid accumulation and can cause cardiac tamponade (CT). We report a case of rapidly accumulating PCE and near-fatal CT with an umbilical venous catheter successfully resolved by emergent echo-guided pericardiocentesis in a term infant who had been hospitalized with meconium aspiration syndrome and persistent pulmonary hypertension. This case report suggests that if a patient with an intracardiac umbilical catheter shows sudden cardiopulmonary instability, the possibility of PCE and CT should be considered. Furthermore, if necessary, emergency drainage of the PCE and removal of the umbilical catheter should be immediately performed.

Background: To evaluate how intrauterine stress affects extremely premature infants in terms of intrauterine growth restriction. We hypothesized that extremely premature infants with mildly-low ponderal index (MPI) would have better neonatal outcomes. Methods: We selected 2,721 subjects of 23 to 28 weeks of gestation between 2013 and 2015 from Korean Neonatal Network database. They were divided into 4 groups based on ponderal index (PI) percentile; PI ≤ 3rd as severely-low PI (SPI, n = 82), 3rd < PI ≤ 10th as MPI (n = 190), 10th < PI ≤ 90th as adequate PI (API, n = 2,179), and PI > 90th as high PI (HPI, n = 270). Results: The mortality in MPI and API groups was comparable (16.3% vs. 16.9%). It was significantly lower than that in the SPI and HPI groups (30.5% and 24.9%, respectively;P = 0.001). The MPI and API groups had better neonatal morbidities compared with the SPI and/or HPI groups, while the MPI group (8.2%) showed a lower incidence of severe intraventricular hemorrhage (IVH) than the other groups (SPI, 21.3%; API, 15.0%; HPI, 19.7%, respectively; P = 0.004). The MPI group had a trend of a bottom in neonatal mortality and morbidities in extremely premature infants. Conclusion The MPI and API groups had lower mortality, massive pulmonary hemorrhage, severe bronchopulmonary dysplasia or death, pulmonary hypertension and neonatal seizure rates than the SPI and/or HPI groups, while the MPI group showed a lower incidence of severe IVH than the other groups. We speculate that the lower incidence of neonatal morbidities and mortality in the MPI group indicating mild intrauterine stress might accelerate fetal maturation resulting in better outcomes in extremely premature infants.

Objective: The purpose of this study was to assess whether a deep learning (DL) algorithm could enable simultaneous noise reduction and edge sharpening in low-dose lumbar spine CT. Materials and Methods: This retrospective study included 52 patients (26 male and 26 female; median age, 60.5 years) who had undergone CT-guided lumbar bone biopsy between October 2015 and April 2020. Initial 100-mAs survey images and 50-mAs intraprocedural images were reconstructed by filtered back projection. Denoising was performed using a vendor-agnostic DL model (ClariCT.AI TM , ClariPI) for the 50-mAS images, and the 50-mAs, denoised 50-mAs, and 100-mAs CT images were compared. Noise, signal-to-noise ratio (SNR), and edge rise distance (ERD) for image sharpness were measured. The data were summarized as the mean ± standard deviation for these parameters. Two musculoskeletal radiologists assessed the visibility of the normal anatomical structures. Results: Noise was lower in the denoised 50-mAs images (36.38 ± 7.03 Hounsfield unit [HU]) than the 50-mAs (93.33 ± 25.36 HU) and 100-mAs (63.33 ± 16.09 HU) images (p < 0.001). The SNRs for the images in descending order were as follows: denoised 50-mAs (1.46 ± 0.54), 100-mAs (0.99 ± 0.34), and 50-mAs (0.58 ± 0.18) images (p < 0.001). The denoised 50-mAs images had better edge sharpness than the 100-mAs images at the vertebral body (ERD; 0.94 ± 0.2 mm vs. 1.05 ± 0.24 mm, p = 0.036) and the psoas (ERD; 0.42 ± 0.09 mm vs. 0.50 ± 0.12 mm, p = 0.002). The denoised 50-mAs images significantly improved the visualization of the normal anatomical structures (p < 0.001). Conclusion DL-based reconstruction may enable simultaneous noise reduction and improvement in image quality with the preservation of edge sharpness on low-dose lumbar spine CT. Investigations on further radiation dose reduction and the clinical applicability of this technique are warranted.

Gabriel–de Vries syndrome, caused by the mutation of YY1, is a newly defined genetic syndrome characterized by developmental delay, facial dysmorphism, and intrauterine growth retardation. A 7-month-old girl presented developmental delay and subtle facial dysmorphism including facial asymmetry, micrognathia, and low-set ears. Whole exome sequencing identified a de novo heterozygous missense variant in the YY1 (c.1220A>G; p.His407Arg) gene. Here, we examined the clinical and genetic characteristics of an infant with a novel likely pathogenic variant of YY1. This case expands the phenotypic spectrum of Gabriel–de Vries syndrome.