Discovery of Pathogenic Variants Associated with Idiopathic Recurrent Pregnancy Loss Using Whole-Exome Sequencing.

Idiopathic recurrent pregnancy loss (RPL) is defined as at least two pregnancy losses before 20 weeks of gestation. Approximately 5% of pregnant couples experience idiopathic RPL, which is a heterogeneous disease with various causes including hormonal, chromosomal, and intrauterine abnormalities. Although how pregnancy loss occurs is still unknown, numerous biological factors are associated with the incidence of pregnancy loss, including genetic variants. Whole-exome sequencing (WES) was conducted on blood samples from 56 Korean patients with RPL and 40 healthy controls. The WES data were aligned by means of bioinformatic analysis, and the detected variants were annotated using machine learning tools to predict the pathogenicity of protein alterations. Each indicated variant was confirmed using Sanger sequencing. A replication study was also conducted in 112 patients and 114 controls. The Variant Effect Scoring Tool, Combined Annotation Dependent Depletion tool, Sorting Intolerant from Tolerant annotation tool, and various databases detected 10 potential variants previously associated with spontaneous abortion genes in patients by means of a bioinformatic analysis of WES data. Several variants were detected in more than one patient. Interestingly, several of the detected genes were functionally clustered, including some with a secretory function (mucin 4; MUC4; rs200737893 G>A and hyaluronan-binding protein 2; HABP2; rs542838125 G>T), in which growth arrest-specific 2 Like 2 (GAS2L2; rs140842796 C>T) and dynamin 2 (DNM2; rs763894364 G>A) are functionally associated with cell protrusion and the cytoskeleton. ATP Binding Cassette Subfamily C Member 6 (ABCC6) was the only gene with two variants. HABP2 (rs542838125 G>T), MUC4 (rs200737893 G>A), and GAS2L2 (rs140842796 C>T) were detected in only the patient group in the replication study. The combination of WES and machine learning tools is a useful method to detect potential variants associated with RPL. Using bioinformatic tools, we found 10 potential variants in 9 genes. WES data from patients are needed to better understand the causes of RPL.

Implementing Point-of-Care Ultrasound for Acute Scrotal Pain in the Pediatric Emergency Department: Screening Testicular Torsion and Patient Flow Analysis.

OBJECTIVES: Testicular torsion (TT) is a pediatric surgical emergency that requires prompt treatment. This study investigated the feasibility of point-of-care ultrasound (POCUS) for diagnosing TT in the pediatric emergency department (ED). METHODS: We retrospectively reviewed the medical records of patients, aged 18 years or younger, who visited a university-affiliated hospital pediatric ED with acute scrotal pain without trauma history and underwent diagnostic ultrasounds between January 2010 and October 2022. RESULTS: This study included 731 patients (median age: 9 years), Of these, 315 (43%) were in the POCUS-performed group: 188 in the POCUS-only group, and 127 in the POCUS-and-RADUS group. The other 416 patients (56.9%) were in the RADUS-only group. In total, 45 patients (6.2%) were diagnosed with TT (19 in the POCUS-performed group and 26 in the RADUS-only group). The sensitivity, specificity, and positive and negative predictive values of POCUS for diagnosing TT were 94.7%, 92.9%, 46.2%, and 99.6%, respectively. The median time to perform POCUS was shorter than RADUS (23 versus 61 minutes, P < .001). The POCUS-performed group had a shorter ED length of stay than the RADUS-only group (93 versus 170 minutes, P < .001). Among the patients diagnosed with TT, performing POCUS first did not significantly delay the ED process, including time to operation (250 versus 205 minutes, P = .142). CONCLUSIONS: For patients with acute scrotal pain, evaluation performed by pediatric emergency physicians using POCUS performs well in screening TT, and can decrease length of stay in the ED.

Identifying commonalities in definition and governance of point-of-care ultrasound within statements from medical organizations in the United States: A scoping review for a shared understanding.

This scoping review analyzed statements from 22 medical organizations in the United States to identify commonalities in the definition and governance of point-of-care ultrasound (POCUS). A total of 41 statements were included. The review found that the most commonly used elements in defining POCUS were "focused," "bedside," and "patient care." In terms of governance, consistent requirements included specific training programs, documentation in medical records, continuous quality assurance, and standards for credentialing and privileging. These findings suggest the existence of essential commonalities that could facilitate communication and the development of standardized POCUS programs in the future.

Association of Thymidylate Synthase (TS) Gene Polymorphisms with Incidence and Prognosis of Coronary Artery Disease.

Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. While distinct features of CAD have been reported, the association between genetic factors and CAD in terms of biomarkers was insufficient. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase (TS) gene, a gene involved in DNA synthesis and one-carbon metabolism. TS plays a critical role in maintaining the deoxythymidine monophosphate (dTMP) pool, which is essential for DNA replication and repair. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact TS gene expression and lead to dysfunction. Our findings strongly associate the TS 1100T>C and 1170A>G genotypes with CAD susceptibility. We observed that TS 1100T>C polymorphisms increased disease susceptibility in several groups, while the TS 1170A>G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the TS 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the TS gene had the possibility of clinically useful biomarkers for the prevention, prognosis, and management of CAD in the Korean population.

Association between PAI-1 Polymorphisms and Ischemic Stroke in a South Korean Case-Control Cohort.

Stroke is the second leading cause of death in the world. Approximately 80% of strokes are ischemic in origin. Many risk factors have been linked to stroke, including an increased level of plasminogen activator inhibitor-1 (PAI-1). PAI-1 levels increase and remain elevated in blood during the acute phase of ischemic stroke, which can impair fibrinolytic activity, leading to coronary artery disease and arterial thrombotic disorders. Here, we present a case-control study of 574 stroke patients and 425 controls seen for routine health examination or treatment for nonspecific dizziness, nonorganic headache, or anxiety for positive family history of stroke at the Bundang Medical Center in South Korea. Polymorphisms in PAI-1 were identified by polymerase chain reaction/restriction fragment length polymorphism analysis using genomic DNA. Specifically, three variations (-675 4G>5G, 10692T>C, and 12068G>A) were linked to a higher overall prevalence of stroke as well as a higher prevalence of certain stroke subtypes. Haplotype analyses also revealed combinations of these variations (-844G>A, -675 4G>5G, 43G>A, 9785A>G, 10692T>C, 11053T>G, and 12068G>A) that were significantly associated with a higher prevalence of ischemic stroke. To the best of our knowledge, this is the first strong evidence that polymorphic sites in PAI-1 promoter and 3'-UTR regions are associated with higher ischemic stroke risk. Furthermore, the PAI-1 genotypes and haplotypes identified here have potential as clinical biomarkers of ischemic stroke and could improve the prognosis and future management of stroke patients.

Genetic Correlation of miRNA Polymorphisms and STAT3 Signaling Pathway with Recurrent Implantation Failure in the Korean Population.

The growing prevalence of in vitro fertilization-embryo transfer procedures has resulted in an increased incidence of recurrent implantation failure (RIF), necessitating focused research in this area. STAT3, a key factor in maternal endometrial remodeling and stromal proliferation, is crucial for successful embryo implantation. While the relationship between STAT3 and RIF has been studied, the impact of single nucleotide polymorphisms (SNPs) in miRNAs, well-characterized gene expression modulators, on STAT3 in RIF cases remains uncharacterized. Here, we investigated 161 RIF patients and 268 healthy control subjects in the Korean population, analyzing the statistical association between miRNA genetic variants and RIF risk. We aimed to determine whether SNPs in specific miRNAs, namely miR-218-2 rs11134527 G>A, miR-34a rs2666433 G>A, miR-34a rs6577555 C>A, and miR-130a rs731384 G>A, were significantly associated with RIF risk. We identified a significant association between miR-34a rs6577555 C>A and RIF prevalence (implantation failure [IF] ≥ 2: adjusted odds ratio [AOR] = 2.264, 95% CI = 1.007-5.092, p = 0.048). These findings suggest that miR-34a rs6577555 C>A may contribute to an increased susceptibility to RIF. However, further investigations are necessary to elucidate the precise mechanisms underlying the role of miR-34a rs6577555 C>A in RIF. This study sheds light on the genetic and molecular factors underlying RIF, offering new avenues for research and potential advancements in the diagnosis and treatment of this complex condition.

Predictors of failed enema reduction in children with intussusception: a systematic review and meta-analysis.

OBJECTIVE: To identify predictors of failed enema reduction in children with intussusception. METHODS: PubMed and EMBASE were searched for all studies published over a 20-year time frame, prior to March 25, 2020. Original articles that reported predictors of failed enema reduction were included. The pooled odds ratio (OR) for successful enema reduction according to various features was calculated. The combined estimates were meta-analytically pooled by random-effects modeling. The risk of bias was assessed using the National Institute of Health Quality Assessment Tool. This review was registered to the PROSPERO (CRD42020190178). RESULTS: A total of 38 studies, comprising 40,133 cases, were included. The shorter duration of symptoms (< 24 h; combined OR, 3.812; 95% CI, 2.150-6.759) and abdominal pain (combined OR, 2.098; 95% CI, 1.405-3.133) were associated with the success (all p < 0.001). Age < 1 year (combined OR, 0.385; 95% CI, 0.166-0.893; p = 0.026), fever (combined OR, 0.519; 95% CI, 0.371-0.725; p < 0.001), rectal bleeding (combined OR, 0.252; 95% CI, 0.165-0.387; p < 0.001), and vomiting (combined OR, 0.497; 95% CI, 0.372-0.664; p < 0.001) were associated with the failed reduction. The ascites (combined OR, 0.127; 95% CI, 0.044-0.368; p = 0.001), left-sided intussusception (combined OR, 0.121; 95% CI, 0.058-0.252; p < 0.001), and trapped fluid (combined OR, 0.179; 95% CI, 0.061-0.525; p = 0.017) on US were associated with the failed reduction. CONCLUSIONS: Successful predictors for intussusception reduction have been summarized. This evidence can help identify patients who are more likely to fail non-operative reduction and could be potential surgical candidates. KEY POINTS: • A shorter duration of symptoms and presence of abdominal pain were associated with increased probability of success. • Age (less than 1 year), presence of fever, rectal bleeding, vomiting, and presence of ascites, left-sided intussusception, or trapped fluid on ultrasonography were associated with decreased probability of success. • This study suggests that various clinical and ultrasonography predictors would help identify patients who are more likely to fail nonoperative reduction and identify potential preoperative candidates.

Clinical utility of procalcitonin in febrile infants younger than 3 months of age visiting a pediatric emergency room: a retrospective single-center study.

BACKGROUND: Fever in infants under 90 days of age is highly likely to be caused by a severe bacterial infection (SBI) and it accounts for a large number of patients visiting the pediatric emergency room. In order to predict the bacterial infection and reduce unnecessary treatment, the classic classification system is based on white blood cell (WBC) count, urinalysis, and x-ray, and it is modified and applied at each center by incorporating recently studied biomarkers such as c-reactive protein (CRP) or procalcitonin (PCT). This study analyzed the usefulness of PCT in predicting SBI when applied along with the existing classification system, including CRP, among infants less than 90 days old who visited with a fever at a single institution pediatric emergency center. METHODS: We retrospectively reviewed the medical records of patients younger than 3 months of age who presented with fever at the Seoul Asan Medical Center pediatric emergency room between July 2017 and October 2018. RESULTS: A total of 317 patients were analyzed, and 61 were diagnosed with SBI, among which urinary tract infection (UTI) accounted for the largest proportion (55/61, 90.2%). There were differences in WBC, neutrophil proportion, CRP, and PCT between the SBI group and the non-SBI group, and the AUC values of WBC, CRP, and PCT were 0.651, 0.804, and 0.746, respectively. When using the cut-off values of CRP and PCTs as 2.0 mg/dL and 0.3 ng/mL, respectively, the sensitivity and specificity for SBI were 49.2/89.5, and 54.1/87.5, respectively. WBC, CRP, and PCT were statistically significant for predicting SBI in multivariate analysis (odds ratios 1.066, 1.377, and 1.291, respectively). When the subjects were classified using the existing classification criteria, WBC and CRP, the positive predictive value (PPV) and negative predictive value (NPV) were 29.3 and 88.7%, respectively, and when PCT was added, the PPV and NPV were 30.7 and 92%, respectively, both increased. CONCLUSION: PCT is useful for predicting SBI in children aged 3 months or less who visit the emergency room with a fever. It is useful as a single biomarker, and when used in conjunction with classic biomarkers, its diagnostic accuracy is further increased.

Pediatric Sedation in the Emergency Department: Trends from a Nationwide Population-based Study in Korea, 2007-2018.

BACKGROUND: Pediatric sedation in the emergency department (ED) is widely performed in Korea; thus exploring the trends of its use is necessary. This study aimed to investigate the characteristics of patients and sedatives use in the ED and verify their changes over recent years. METHODS: A nationwide population-based retrospective study was conducted including pediatric patients aged ≤ 15 years who received sedative medication in the ED and were discharged during 2007-2018, using the Korean Health Insurance Review and Assessment Service database. Patient characteristics (age, sex, level of ED, and diagnosis) and type of sedative used were analyzed. RESULTS: Sedation was performed in total 468,221 visits during 2007-2018 (399,320 visits, at least 3.8% of overall ED visits during 2009-2018). Among these, 71.0% were children aged 1-3 years and 93.5% were sedated to support diagnosis of injury. An increase in total sedation was observed in patients aged 4-6 years during the study period (from 13.8% to 21.8%). A gradual decrease in the use of chloral hydrate (CH) compared with an increase in ketamine use was observed (CH, from 70.6% to 28.6%; ketamine, from 23.8% to 60.7%). Therefore, ketamine was the most used sedative since 2014. The most frequently used sedatives over the study period differed according to age groups (CH in <1 year and 1-3 years; ketamine in 4-6 years and 7-10 years; and midazolam in 11-15 years). CONCLUSIONS: The characteristics of patients related to sedatives use in the ED have changed over time. These changes should be considered in the development of future Korean guidelines regarding pediatric sedation in the ED.

Feasibility of Point-of-Care Ultrasound for Diagnosing Hypertrophic Pyloric Stenosis in the Emergency Department.

OBJECTIVES: This study aimed to investigate the feasibility of point-of-care ultrasound (POCUS) for diagnosing hypertrophic pyloric stenosis (HPS) in the emergency department (ED). METHODS: A retrospective study was conducted in infants aged younger than 90 days who were brought to the ED due to vomiting between January 2015 and December 2019. Of these, infants who were clinically suspected of having HPS and underwent ultrasound were included and categorized into 3 groups: POCUS only, POCUS followed by radiologist-performed ultrasound (RADUS), and RADUS only. All confirmative diagnoses of HPS were made by RADUS. The diagnostic performance of POCUS was analyzed, and the ED patient flow was compared between the POCUS-performed (POCUS only or POCUS followed by RADUS) and RADUS-only groups. RESULTS: Overall, 171 patients with a median age of 34 days were included. Of these, 79 patients (46.2%) underwent POCUS only, and none had HPS; 50 patients (29.2%) underwent POCUS followed by RADUS; and 42 patients (24.5%) underwent RADUS only. Overall, 41 patients (24.0%) were diagnosed with HPS, and POCUS showed a sensitivity of 96.6% and specificity of 94.0%. In the total cohort, length of stay in the ED (EDLOS) was shorter in the POCUS-performed group than in the RADUS-only group (2.6 vs 3.8 hours, P = 0.015). Among non-HPS patients, time to disposition (1.8 vs 2.7 hours, P = 0.005) and EDLOS (2.0 vs 3.0 hours, P = 0.004) were shorter in the POCUS-performed group than in the RADUS-only group. Performing POCUS followed by RADUS did not significantly delay the treatment among HPS patients. CONCLUSIONS: Point-of-care ultrasound is accurate and useful for diagnosing HPS and improved the ED patient flow by reducing EDLOS and door-to-disposition time in non-HPS patients.

Initial Characteristics and Clinical Severity of Hemophagocytic Lymphohistiocytosis in Pediatric Patients Admitted in the Emergency Department.

OBJECTIVES: The diagnosis and management of children with hemophagocytic lymphohistiocytosis (HLH) admitted in the emergency department (ED) are challenging. The present study aimed at describing the initial characteristics of pediatric patients with HLH upon admission in the ED. Moreover, the clinical severity of the condition was assessed. METHODS: We performed a retrospective study of patients who visited the pediatric ED and were newly diagnosed with HLH during hospitalization between February 2012 and January 2017. The patients were classified in the clinically unstable group if at least 1 of the following conditions was observed upon admission in the ED: hypoxia requiring oxygen supplementation, hypotension requiring inotropic support, coagulopathy with prothrombin time (international normalized ratio, ≥1.5), and seizures or altered consciousness. RESULTS: We enrolled 31 pediatric patients with HLH, with a median age of 6.53 years (interquartile range, 1.35-13.24 years). Abdominal discomfort along with fever (74.2%) was the most common presenting symptom in patients admitted in the ED. Based on the HLH-2004 diagnostic criteria, fever (96.8%), hyperferritinemia (96.8%), splenomegaly (74.2%), hypertriglyceridemia and/or hypofibrinogenemia (67.7%), and bicytopenia (41.9%) were observed in the patients. However, only 8 patients (25.8%) met the criteria. Nineteen patients (61.3%) were included in the clinically unstable group. This group had lower albumin (2.3 vs 3.3 g/dL, P = 0.002) and fibrinogen levels and higher ferritin level and neutrophil count than the clinically stable group. Meanwhile, the number of clinical findings that met the diagnostic criteria was not different between the 2 groups. Lower albumin level was a significant risk factor in the clinically unstable group (odds ratio, 0.040; P = 0.004). CONCLUSIONS: Pediatric patients with HLH often have clinically unstable conditions upon admission in the ED. However, only few patients meet the HLH-2004 diagnostic criteria. Lower albumin level may be useful in assessing clinically unstable patients and preparing for possible deterioration.

Association between HOX Transcript Antisense RNA Single-Nucleotide Variants and Recurrent Implantation Failure.

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization-embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.

Associations between microRNA (miR-25, miR-32, miR-125, and miR-222) polymorphisms and recurrent implantation failure in Korean women.

BACKGROUND: Recurrent implantation failure (RIF) is the failure of embryos to implant more than two times in a given individual. There is debate about a precise definition for RIF, but we consider more than two implantation failures for individuals who undergo in vitro fertilization-embryo transfer (IVF-ET) to constitute RIF. There are many potential reasons for RIF, including embryonic factors, immunological factors, uterine factors, coagulate factors, and genetic factors. Genetic variation has been suggested as one of the contributing factors leading to RIF, and a number of single-nucleotide polymorphisms (SNPs) have been reported to be associated with RIF. The recent elucidation of miRNA functions has provided new insight into the regulation of gene expression. METHODS: We investigated associations between polymorphisms in four miRNAs and RIF in 346 Korean women: 118 patients with RIF and 228 controls. We determined the genotypes of the miRNAs in the study participants by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. We analyzed the effects of genotypes, allele combinations, and environmental and clinical factors on the risk of RIF. RESULTS: The miR-25 T/miR-125aT/miR-222G (odds ratio (OR), 0.528; 95% confidence interval (CI), 0.282-0.990; P = 0.044) and miR-25 T/miR-125aT allele combinations were associated with a reduced risk of RIF. The miR-25 T/miR-32C/miR-125aC/miR-222 T allele combination was associated with an increased risk of RIF. The miR-222GT+TT genotypes interacted with high prothrombin time (≥ 12 s) to increase the risk of RIF. CONCLUSIONS: MicroRNA polymorphisms are significantly different between patients that experience RIF and healthy controls. Combinations of microRNA polymorphisms were associated with the risk of RIF. Interactions between environmental factors and genotypes increased the risk of RIF in Korean women.

Point-of-care ultrasound may be useful for detecting pediatric intussusception at an early stage.

BACKGROUND: This study aimed to verify the usefulness of point-of-care ultrasound (POCUS) performed by pediatric emergency physicians for detecting intussusception at an early stage. METHODS: This retrospective study included 1-month- to 6-year-old children with clinically suspected intussusception, who underwent POCUS in the pediatric emergency department between December 2016 and February 2018. The criteria for performing POCUS were set to broader standards: presenting any one of intermittent abdominal pain/irritability or bloody stool, or ≥ 2 symptoms among nonspecific abdominal pain/irritability, abdominal mass/distension, vomiting, or lethargy. POCUS results were interpreted and categorized as "negative" or "suspicious," and a radiologist performed confirmatory ultrasound in "suspicious" cases. RESULTS: We analyzed 575 POCUS scans from 549 patients (mean age, 25.5 months). Among the 92 "suspicious" cases (16.0%), 70 (12.2%) were confirmed to have intussusception. POCUS showed 100% sensitivity, 95.6% specificity, and 97.8% accuracy. Patients with confirmed intussusception were mainly diagnosed in the early stages, with a mean symptom duration of 11.7 h, and most patients (97.1%) were treated successfully via air enema reduction. Compared to the non-intussusception group, the intussusception group had more intermittent abdominal pain (P < 0.001), but less vomiting (P = 0.001); the other clinical features showed no intergroup differences. CONCLUSION: POCUS performed using the criteria set to broader standards by pediatric emergency physicians may be useful for detecting intussusception at an early stage, which may present with obscure clinical symptoms.

Lactic acid level as an outcome predictor in pediatric patients with intussusception in the emergency department.

BACKGROUND: Intussusception decreases blood flow to the bowel, and tissue hypoperfusion results in increased lactic acid levels. We aimed to determine whether lactic acid levels are associated with pediatric intussusception outcomes. METHODS: The electronic medical records of our emergency department pediatric patients diagnosed with intussusception, between January 2015 and October 2018, were reviewed. An outcome was considered poor when intussusception recurred within 48 h of reduction or when surgical reduction was required due to air enema failure. RESULTS: A total of 249 patients were included in the study, including 39 who experienced intussusception recurrence and 11 who required surgical reductions; hence, 50 patients were included in the poor outcome group. The poor and good outcome groups showed significant differences in their respective blood gas analyses for pH (7.39 vs. 7.41, P = .001), lactic acid (1.70 vs. 1.30 mmol/L, P < .001), and bicarbonate (20.70 vs. 21.80 mmol/L, P = .036). Multivariable logistic regression analyses showed that pH and lactic acid levels were the two factors significantly associated with poor outcomes. When the lactic acid level cutoff values were ≥ 1.5, ≥2.0, ≥2.5, and ≥ 3.0 mmol/L, the positive predictive values for poor outcomes were 30.0, 34.6, 50.0, and 88.9%, respectively. CONCLUSION: Lactic acid levels affect outcomes in pediatric patients with intussusception; higher lactic acid levels are associated with higher positive predictive values for poor outcomes.

Point-of-Care Ultrasound Could Streamline the Emergency Department Workflow of Clinically Nonspecific Intussusception.

OBJECTIVES: The aim of this study was to evaluate whether point-of-care ultrasound (POCUS) for intussusception screening streamlines the workflow of clinically nonspecific intussusception (CNI), an intussusception presenting with only 1 manifestation of the classic triad, and/or vomiting. METHODS: We reviewed 274 consecutive children with intussusception, aged 6 years or younger, who visited a tertiary care hospital emergency department between May 2012 and April 2016. This period was dichotomized by May 2014 (the "PRE" and "POST" groups), starting point of implementation of the POCUS protocol for intussusception screening. All children with CNI who had positive results on or forwent POCUS underwent radiologist-performed ultrasound (US). We measured and compared emergency department length of stay (EDLOS), the sum of door-to-reduction and observation times, and the frequency of POCUS and positive US results between the 2 groups. RESULTS: Of 160 children with CNI, 93 visited the emergency department since May 2014. The POST group showed a shorter median EDLOS (856 vs 630 minutes, P < 0.001), door-to-reduction time (137 vs 111 minutes, P = 0.002), and observation time (700 vs 532 minutes, P < 0.001). The POST group had a higher frequency of POCUS (12% vs 60%, P < 0.001) with positive US results (33% vs 59%, P < 0.001). The PRE group had a higher frequency of severe bowel edema (16% vs 1%, P < 0.001). No significant differences were found in the severity, recurrence, admission, and surgery. One child had a false-negative result on POCUS. CONCLUSIONS: Point-of-care ultrasound could streamline the workflow of CNI via decrease in EDLOS and unnecessary referrals for US.

Gold Binding Peptide Identified from Microfluidic Biopanning: An Experimental and Molecular Dynamics Study.

Biopanning refers to the processes of screening peptides with a high affinity to a target material. Microfluidic biopanning has advantages compared to conventional biopanning which requires large amounts of the target material and involves inefficient multiple pipetting steps to remove nonspecific or low-affinity peptides. Here, we fabricate a microfluidic biopanning system to identify a new gold-binding peptide (GBP). A polydimethylsiloxane microfluidic device is fabricated and bonded to a glass slide with a gold pattern that is deposited by electron-beam evaporation. The microfluidic biopanning system can provide high adjustability in the washing step during the biopanning process because the liquid flow rate and the resulting shear stress can be precisely controlled. The surface plasmon resonance analysis shows that the binding affinity of the identified GBP is comparable to previously reported GBPs. Moreover, molecular dynamics simulations are performed to understand its binding affinity against the gold surface in detail. Theoretical calculations suggest that the association and dissociation rates of the GBPs depend on their sequence-dependent conformations and interactions with the gold surface. These findings provide insight into designing efficient biopanning tools and peptides with a high affinity for various target materials.

High Concentration of C-Reactive Protein Is Associated With Serious Bacterial Infection in Previously Healthy Children Aged 3 to 36 Months With Fever and Extreme Leukocytosis.

OBJECTIVES: The aim of the study was to investigate the diagnostic efficacy of C-reactive protein (CRP) in predicting serious bacterial infection (SBI) in febrile children aged 3 to 36 months with extreme leukocytosis (EL), defined as a peripheral white blood cell count of 25,000 to 49,999/mm. METHODS: The presence of SBI was reviewed in previously healthy children aged 3 to 36 months with a fever of 39°C or higher and EL, who visited a tertiary care hospital emergency department between September 2010 and August 2015. We measured cutoff values of CRP with corresponding likelihood ratios (LRs) and posttest probabilities (PPs). RESULTS: Of 9989 febrile children, 4252 (42.6%) underwent assays for white blood cell and CRP. Of 233 (5.5%) children with EL, 133 (3.1%) were enrolled, of whom 43 (32.3%; 95% confidence interval [CI], 25.0%-40.7%) had SBI, including 33 pyelonephritis, 5 deep abscesses, 3 lobar pneumonia, and 2 soft tissue infections. With the cutoff of 7.8 mg/dL, the sensitivity of CRP in predicting SBI was 81.4% (95% CI, 67.4%-90.3%); the specificity, 80.0% (95% CI, 70.6%-87.0%); the positive predictive value, 66.0% (95% CI, 52.6%-77.3%); the negative predictive value, 90.0% (95% CI, 81.5%-94.9%); the positive LR, 4.1; and the PP, 66.0% (95% CI, 55.6%-75.0%). A CRP concentration of 16.1 mg/dL or higher yielded an LR of 11.2 and a PP of 84.2% (95% CI, 62.1%-94.5%). A CRP concentration of lower than 3.4 mg/dL yielded an LR of 0.05 and a PP of 2.4% (95% CI, 0.3%-14.6%). CONCLUSIONS: High concentration of CRP is strongly associated with the presence of SBI in febrile children with EL.

Requirement for Head Magnetic Resonance Imaging in Children Who Present to the Emergency Department With Acute Nontraumatic Visual Disturbance.

OBJECTIVES: This study aimed to investigate the clinical features and head magnetic resonance imaging (MRI) findings in children who presented to the emergency department with acute nontraumatic visual disturbance and to study related clinical factors for discovering positive lesions on head MRI. METHODS: We performed a retrospective study of 1-month to 15-year-old children who underwent head MRI as an evaluation for acute nontraumatic visual disturbance as a chief complaint in our pediatric emergency department between March 2010 and March 2015. The symptoms of visual disturbance were blurred vision, diplopia, loss of vision, and visual hallucination. Head MRI findings were considered positive when lesions could explain the symptoms. RESULTS: We identified 39 patients (25 with blurred vision, 9 with diplopia, 3 with loss of vision, and 2 with visual hallucination) with a mean age of 8.35 ± 4.06 years. Positive head MRI findings were identified in 13 patients (33.3%). Brain tumors were most common (53.8%), followed by optic nerve inflammations (23.1%), congenital brain lesions (15.4%), and hypertensive encephalopathy (7.7%). Compared with the negative head MRI group, the positive head MRI group showed significantly less transient visual disturbance (duration <1 hour to complete recovery) (P = 0.001), more limited eye movement (P = 0.003), and more pupillary abnormalities (P = 0.030). CONCLUSIONS: We suggest performing urgent head MRI in children with acute nontraumatic visual disturbance if the symptoms last longer than 1 hour without complete recovery and are accompanied by limited eye movement or pupillary abnormality.

Silk peptide treatment potentiates natural killer cell activity in vitro and induces natural killer cell maturation and activation in mouse splenocytes.

Context: Silk peptide from cocoons of silkworm (Bombyx mori L., Bombycidae) has been employed as a biomedical material and exhibits various bioactivities, including immune-modulating activity. Objective: We analyzed whether silk peptide exerts direct modulating effects on NK cells using an NK cell line in vitro and ex vivo splenocytes. We also attempted to delineate the mechanism underlying the modulation. Material and methods: In vitro activity of silk peptide on NK cells was determined by measurement of cytolytic activity against K562 cells at an effector-to-target ratio of 5:1 after incubation of NK-92MI cells with silk peptide (0-2000 µg/mL) for 48 and 72 h. Ex vivo activity of silk peptide on mouse splenic NK cells was determined similarly by using YAC-1 cells. Results: Treatment of NK-92MI NK cells with silk peptide (500-2000 µg/mL) significantly increased cytolytic activity on target cells by 2- to 4-fold. The same concentrations (500-2000 µg/mL) of silk peptide treatment also significantly enhanced the cytolytic activity of splenic NK cells against YAC-1 cells. Silk peptide treatment of IL-2-stimulated splenocytes induced enhanced expression of Th1, 2 and 17 cytokines including TNF-α, IFN-γ, IL-6, IL-4 and IL-17. Finally, ex vivo treatment with silk peptide on mouse splenocytes significantly enhanced the degree of NK cell maturation in a dose-dependent manner from 3.49 to 23.79%. Discussion and conclusions: These findings suggest that silk peptide stimulates NK cells, thereby influencing systemic immune functions and improving natural immunity. Thus, silk peptide could be useful as a complementary therapy in cancer patients.