Antibody-mediated blockade for galectin-3 binding protein in tumor secretome abrogates PDAC metastasis.

The major challenges in pancreatic ductal adenocarcinoma (PDAC) management are local or distant metastasis and limited targeted therapeutics to prevent it. To identify a druggable target in tumor secretome and to explore its therapeutic intervention, we performed a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis of tumors obtained from a patient-derived xenograft model of PDAC. Galectin-3 binding protein (Gal-3BP) is identified as a highly secreted protein, and its overexpression is further validated in multiple PDAC tumors and primary cells. Knockdown and exogenous treatment of Gal-3BP showed that it is required for PDAC cell proliferation, migration, and invasion. Mechanistically, we revealed that Gal-3BP enhances galectin-3-mediated epidermal growth factor receptor signaling, leading to increased cMyc and epithelial-mesenchymal transition. To explore the clinical impact of these findings, two antibody clones were developed, and they profoundly abrogated the metastasis of PDAC cells in vivo. Altogether, our data demonstrate that Gal-3BP is an important therapeutic target in PDAC, and we propose its blockade by antibody as a therapeutic option for suppressing PDAC metastasis.

Allergic rhinitis phenotypes with distinct transcriptome profiles in children: A birth cohort.

BACKGROUND: Allergic rhinitis (AR) phenotypes in childhood are unclear. OBJECTIVES: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics. METHODS: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype. RESULTS: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response. CONCLUSIONS: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.

Association between serum total cholesterol and chronic kidney disease progression in children: results from the KNOW-PedCKD.

BACKGROUND: Dyslipidemia can cause cardiovascular disease and increase the fatality rate among children with chronic kidney disease (CKD); this makes early screening and treatment of dyslipidemia crucial. This study aimed to assess the association between the changes in serum total cholesterol levels over time and the degree of CKD progression in children. METHODS: From April 2011 to August 2021, 379 of the 432 participants enrolled in the KoreaN cohort study for Outcomes in patients With Pediatric CKD (KNOW-PedCKD) were included and divided into 4 categories based on total cholesterol levels (< 170 mg/dL, acceptable; 170-199, borderline; 200-239, high; and ≥ 240, very high). Survival analysis using conventional and time-dependent Cox proportional hazards model were performed for a composite event of CKD progression (≥ 50% decrease in estimated glomerular filtration rate from baseline, a twofold increase in creatinine, or the occurrence of dialysis or kidney transplantation). RESULT: The incidence of composite event of CKD progression was 96.3, 90.4, 87.3, and 270.6 cases per 1000 person-years in the acceptable, borderline, high, and very high categories, respectively. On using the time-dependent Cox proportional hazards model, the hazard ratio of the very high category was significantly higher than that of the acceptable category by 3.13 times as per univariate analysis and 2.37 times as per multivariate analysis. CONCLUSIONS: Very high serum total cholesterol is a significant risk factor for CKD progression in children. Lowering total cholesterol levels below the very high category in children with CKD may delay the progression of CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

De Novo Crescentic Glomerulonephritis Following COVID-19 Infection: A Pediatric Case Report.

As the global coronavirus disease 2019 (COVID-19) pandemic continues to sweep across the globe, reports of kidney involvement in adult patients infected with COVID-19 have been documented, and recently, cases in the pediatric population have also been reported. This report highlights the case of an 11-year-old boy who developed acute kidney injury presenting as gross hematuria, proteinuria, and hypertension immediately after a COVID-19 infection. A renal biopsy allowed us to diagnose the patient with post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis. Oral prednisolone and cyclophosphamide treatments were initiated after methylprednisolone pulse therapy administration. Currently, the patient is receiving medical treatment for five weeks, and his renal function is gradually recovering. Previous studies have suggested that, although quite rare, a variety of kidney complications can occur after COVID-19 infection or vaccination, and it is recommended to monitor renal function through evaluation. Herein, we report a pediatric case of post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis consistent with rapidly progressive glomerulonephritis.

Annexin A2 Stabilizes Oncogenic JAG1 Intracellular Domain by Inhibiting Proteasomal Degradation in Glioblastoma Cells.

Glioblastoma (GBM) is the most lethal brain cancer, causing inevitable deaths of patients owing to frequent relapses of cancer stem cells (CSCs). The significance of the NOTCH signaling pathway in CSCs has been well recognized; however, there is no NOTCH-selective treatment applicable to patients with GBM. We recently reported that Jagged1 (JAG1), a NOTCH ligand, drives a NOTCH receptor-independent signaling pathway via JAG1 intracellular domain (JICD1) as a crucial signal that renders CSC properties. Therefore, mechanisms regulating the JICD1 signaling pathway should be elucidated to further develop a selective therapeutic regimen. Here, we identified annexin A2 (ANXA2) as an essential modulator to stabilize intrinsically disordered JICD1. The binding of ANXA2 to JICD1 prevents the proteasomal degradation of JICD1 by heat shock protein-70/90 and carboxy-terminus of Hsc70 interacting protein E3 ligase. Furthermore, JICD1-driven propagation and tumor aggressiveness were inhibited by ANXA2 knockdown. Taken together, our findings show that ANXA2 maintains the function of the NOTCH receptor-independent JICD1 signaling pathway by stabilizing JICD1, and the targeted suppression of JICD1-driven CSC properties can be achieved by blocking its interaction with ANXA2.

Combined effect of hygienic and polygenic risk scores in children with allergic rhinitis.

BACKGROUND: Although the development of allergic rhinitis (AR) is associated with multiple genetic and hygienic environmental factors, previous studies have focused mostly on the effect of a single factor on the development of AR. OBJECTIVE: This study aimed to investigate the combined effect of multiple genetic and hygienic environmental risk factors on AR development in school children. METHODS: We conducted a cross-sectional study, comprising 1,797 children aged 9-12 years. Weighted environmental risk score (ERS) was calculated by using four hygienic environmental factors, including antibiotic use during infancy, cesarean section delivery, breast milk feeding, and having older siblings. Weighted polygenic risk score (PRS) was calculated by using four single nucleotide polymorphisms (SNPs), including interleukin-13 (rs20541), cluster of differentiation 14 (rs2569190), toll-like receptor 4 (rs1927911), and glutathione S-transferase P1 (rs1695). Multivariable logistic regression analysis was used. RESULTS: More than three courses of antibiotic use during infancy increased the risk of current AR (adjusted odd ratio [aOR], 2.058; 95% confidence interval [CI]: 1.290-3.284). Having older siblings, especially > 2 (aOR, 0.526; 95%Cl: 0.303-0.913) had a protective effect. High ERS ( > median; aOR, 2.079; 95%Cl: 1.466-2.947) and PRS ( > median; aOR, 1.627; 95%Cl: 1.117-2.370) increased the risk of current AR independently. Furthermore, children who had both high ERS and PRS showed a higher risk of current AR (aOR, 3.176; 95%Cl: 1.787-5.645). CONCLUSIONS: Exposure to multiple hygienic risk factors during infancy increases the risk of AR in genetically susceptible children.

An access to highly enantioenriched cis-3,5-disubstituted γ-lactones from α-bromoacetate and silyl enol ether.

A novel synthetic strategy for highly enantioenriched cis-3,5-disubstituted γ-lactones has been developed by the AgOTf-promoted nucleophilic substitution of α-bromoacetates with silyl enol ethers and subsequent reductive lactonization. The utility of this synthetic method was further demonstrated through the concise stereodivergent synthesis of cis- and trans-2,4-disubstituted tetrahydrofurans.

Emergency Department Utilization by In-hospital Healthcare Workers after COVID-19 Vaccination.

BACKGROUND: This is an observational study to analyze an emergency department (ED) utilization pattern of coronavirus disease 2019 (COVID-19) vaccinated in-hospital healthcare workers (HCWs). METHODS: We included 4,703 HCWs who were administered the first dose of the COVID-19 vaccine between March 4 and April 2, 2021, in a tertiary hospital in Korea where fast-track and post-vaccination cohort zone (PVCZ) were introduced in ED. We analyzed data of participants' age, sex, occupation, date and type of vaccination, and their clinical information using SPSS v25.0. RESULTS: The sample comprised HCWs, who received either the ChAdOx1 (n = 4,458) or the BNT162B2 (n = 245) vaccines; most participants were female (73.5%), and 81.1% were under 50 years old. Further, 153 (3.3%) visited the ED and reported experiencing fever (66.9%) and myalgia (56.1%). Additionally, 91 (59.5%) of them were in their 20s, and 106 (67.5%) were assigned to the PVCZ. Lastly, 107 (68.2%) of the patients received parenteral management. No patient required hospitalization. CONCLUSION: In conclusion, vaccinated HCWs who visited the ED with adverse events had a high incidence of fever and a low likelihood of developing serious illnesses. As the COVID-19 vaccination program for Korean citizens continues to expand, strategies to minimize unnecessary ED overcrowding should be put into effect.

ADAR1 Suppresses Interferon Signaling in Gastric Cancer Cells by MicroRNA-302a-Mediated IRF9/STAT1 Regulation.

ADAR (adenosine deaminase acting on RNA) catalyzes the deamination of adenosine to generate inosine, through its binding to double-stranded RNA (dsRNA), a phenomenon known as RNA editing. One of the functions of ADAR1 is suppressing the type I interferon (IFN) response, but its mechanism in gastric cancer is not clearly understood. We analyzed changes in RNA editing and IFN signaling in ADAR1-depleted gastric cancer cells, to clarify how ADAR1 regulates IFN signaling. Interestingly, we observed a dramatic increase in the protein level of signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 9 (IRF9) upon ADAR1 knockdown, in the absence of type I or type II IFN treatment. However, there were no changes in protein expression or localization of the mitochondrial antiviral signaling protein (MAVS) and interferon alpha and beta-receptor subunit 2 (IFNAR2), the two known mediators of IFN production. Instead, we found that miR-302a-3p binds to the untranslated region (UTR) of IRF9 and regulate its expression. The treatment of ADAR1-depleted AGS cells with an miR-302a mimic successfully restored IRF9 as well as STAT1 protein level. Hence, our results suggest that ADAR1 regulates IFN signaling in gastric cancer through the suppression of STAT1 and IRF9 via miR-302a, which is independent from the RNA editing of known IFN production pathway.

Tumor-Stroma Crosstalk Enhances REG3A Expressions that Drive the Progression of Hepatocellular Carcinoma.

BACKGROUND: Crosstalk between tumors and their microenvironment plays a crucial role in the progression of hepatocellular carcinoma (HCC). However, there is little existing information about the key signaling molecule that modulates tumor-stroma crosstalk. METHODS: Complementary DNA (cDNA) microarray analysis was performed to identify the key molecule in tumor-stroma crosstalk. Subcutaneous xenograft in vivo murine model, immunoblotting, immunofluorescence, and real-time polymerase chain reaction using HCC cells and tissues were performed. RESULTS: The key molecule, regenerating gene protein-3A (REG3A), was most significantly enhanced when coculturing HCC cells and activated human hepatic stellate cells (HSCs) (+8.2 log) compared with monoculturing HCC cells using cDNA microarray analysis. Downregulation of REG3A using small interfering RNA significantly decreased the proliferation of HSC-cocultured HCC cells in vitro and in vivo, and enhanced deoxycholic acid-induced HCC cell apoptosis. Crosstalk-induced REG3A upregulation was modulated by platelet-derived growth factor ßß (PDGF-ßß) in p42/44-dependent manner. REG3A mRNA levels in human HCC tissues were upregulated 1.8-fold compared with non-tumor tissues and positively correlated with PDGF-ßß levels. CONCLUSIONS: REG3A/p42/44 pathway/PDGF-ßß signaling plays a significant role in hepatocarcinogenesis via tumor-stroma crosstalk. Targeting REG3A is a potential novel therapeutic target for the management of HCCs by inhibiting crosstalk between HCC cells and HSCs.

Niacin and Selenium Attenuate Brain Injury After Cardiac Arrest in Rats by Up-Regulating DJ-1-Akt Signaling.

OBJECTIVES: To determine neuroprotective effects and mechanism of the combination therapy of niacin and selenium in cardiac arrest rats. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Rat cortex neurons and male Sprague-Dawley rats (n = 68). INTERVENTIONS: In rat cortex neurons underwent 90 minutes of oxygen-glucose deprivation and 22.5 hours of reoxygenation, effects of the combination therapy of niacin (0.9 mM) and selenium (1.5 µM) were investigated. The role of DJ-1 was determined using DJ-1 knockdown cells. In cardiac arrest rats, posttreatment effects of the combination therapy of niacin (360 mg/kg) and selenium (60 µg/kg) were evaluated. MEASUREMENTS AND MAIN RESULTS: In oxygen-glucose deprivation and 22.5 hours of reoxygenation cells, combination therapy synergistically activated the glutathione redox cycle by a niacin-induced increase in glutathione reductase and a selenium-induced increase in glutathione peroxidase activities and reduced hydrogen peroxide level. It increased phosphorylated Akt and intranuclear Nuclear factor erythroid 2-related factor 2 expression and attenuated neuronal injury. However, these benefits were negated by DJ-1 knockdown. In cardiac arrest rats, combination therapy increased DJ-1, phosphorylated Akt, and intranuclear nuclear factor erythroid 2-related factor 2 expression, suppressed caspase 3 cleavage, and attenuated histologic injury in the brain tissues. It also improved the 7-day Neurologic Deficit Scales from 71.5 (66.0-74.0) to 77.0 (74.-80.0) (p = 0.02). CONCLUSIONS: The combination therapy of clinically relevant doses of niacin and selenium attenuated brain injury and improved neurologic outcome in cardiac arrest rats. Its benefits were associated with reactive oxygen species reduction and subsequent DJ-1-Akt signaling up-regulation.

Long-term survival of out-of-hospital cardiac arrest patients with malignancy.

BACKGROUND: The aim of this study was to investigate whether the 1-year survival rate of out-of-hospital cardiac arrest (OHCA) patients with malignancy was different from that of those without malignancy. METHODS: All adult OHCA patients were retrospectively analyzed in a single institution for 6years. The primary outcome was 1-year survival, and secondary outcomes were sustained return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge and discharge with a good neurological outcome (CPC 1 or 2). Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were performed to test the effect of malignancy. RESULTS: Among 341 OHCA patients, 59 patients had malignancy (17.3%). Sustained ROSC, survival to admission, survival to discharge and discharge with a good CPC were not different between the two groups. The 1-year survival rate was lower in patients with malignancy (1.7% vs 11.4%; P=0.026). Kaplan-Meier survival analysis revealed that patients with malignancy had a significantly lower 1-year survival rate when including all patients (n=341; P=0.028), patients with survival to admission (n=172, P=0.002), patients with discharge CPC 1 or 2 (n=18, P=0.010) and patients with discharge CPC 3 or 4 (n=57, P=0.008). Malignancy was an independent risk factor for 1-year mortality in the Cox proportional hazard regression analysis performed in patients with survival to admission and survival to discharge. CONCLUSIONS: Although survival to admission, survival to discharge and discharge with a good CPC rate were not different, the 1-year survival rate was significantly lower in OHCA patients with malignancy than in those without malignancy.

Real-time tidal volume feedback guides optimal ventilation during simulated CPR.

PURPOSE: We performed this study to investigate whether real-time tidal volume feedback increases optimal ventilation and decreases hyperventilation during manikin-simulated cardiopulmonary resuscitation (CPR). BASIC PROCEDURES: We developed a new real-time tidal volume monitoring device (TVD) which estimated tidal volume in real time using a magnetic flowmeter. The TVD was validated with a volume-controlled mechanical ventilator with various tidal volumes. We conducted a randomized, crossover, manikin-simulation study in which 14 participants were randomly divided into a control (without tidal volume feedback, n = 7) and a TVD group (with real-time tidal volume feedback, n = 7) and underwent manikin simulation. The optimal ventilation was defined as 420-490 mL of tidal volumes for a 70-kg adult manikin. After 2 weeks of the washout period, the simulation was repeated via the participants' crossover. MAIN FINDINGS: In the validation study, 97.6% and 100% of the difference ratios in tidal volumes between the mechanical ventilator and TVD were within ±1.5% and ±2.5%, respectively. During manikin-simulated CPR, TVD use increased the proportion of optimal ventilation per person. Its median values (range) of the control group and the TVD group were 37.5% (0.0-65.0) and 87.5% (65.0-100.0), respectively, P < .001). TVD use also decreased hyperventilation. The proportions of hyperventilation in the control group and the TVD group were 25.0% vs 8.9%, respectively (P < .001). PRINCIPAL CONCLUSIONS: Real-time tidal volume feedback using the new TVD guided the rescuers to provide optimal ventilation and to avoid hyperventilation during manikin-simulated CPR.

A Successful Airway Resuscitation of Life-threatening Subglottic Foreign body in an infant: A case report.

Airway foreign body removal is challenging. It is a time-limited and life-saving procedure. We report a successful case of life-saving by pushing a foreign body further into the distal airway to block one lung and save the other lung. A 12-month-old boy presented in the emergency department with choking. Upon arrival, his mental status was alert. However, respiratory failure rapidly progressed and arrest occurred. We tried to push the foreign body distal by pushing the endotracheal tube as deep as possible and inserting stylet further. With this procedure, the patient was successfully resuscitated and bronchoscopic foreign body removal was performed. The patient was discharged without respiratory or neurologic sequelae. We reported this successful life-threatening subglottic airway foreign body removal case in an infant.

Genome-wide identification of histone lysine methyltransferases and their implications in the epigenetic regulation of eggshell formation-related genes in a trematode parasite Clonorchis sinensis.

Epigenetic writers including DNA and histone lysine methyltransferases (DNMT and HKMT, respectively) play an initiative role in the differentiation and development of eukaryotic organisms through the spatiotemporal regulation of functional gene expressions. However, the epigenetic mechanisms have long been suspected in helminth parasites lacking the major DNA methyltransferases DNMT1 and DNMT3a/3b. Very little information on the evolutionary status of the epigenetic tools and their role in regulating chromosomal genes is currently available in the parasitic trematodes. We previously suggested the probable role of a DNMT2-like protein (CsDNMT2) as a genuine epigenetic writer in a trematode parasite Clonorchis sinensis. Here, we analyzed the phylogeny of HKMT subfamily members in the liver fluke and other platyhelminth species. The platyhelminth genomes examined conserved genes for the most of SET domain-containing HKMT and Disruptor of Telomeric Silencing 1 subfamilies, while some genes were expanded specifically in certain platyhelminth genomes. Related to the high gene dosages for HKMT activities covering differential but somewhat overlapping substrate specificities, variously methylated histones were recognized throughout the tissues/organs of C. sinensis adults. The temporal expressions of genes involved in eggshell formation were gradually decreased to their lowest levels proportionally to aging, whereas those of some epigenetic tool genes were re-boosted in the later adult stages of the parasite. Furthermore, these expression levels were significantly affected by treatment with DNMT and HKMT inhibitors. Our data strongly suggest that methylated histones are potent epigenetic markers that modulate the spatiotemporal expressions of C. sinensis genes, especially those involved in sexual reproduction.

Research Note: Comparative evaluation of pathogenicity in SPF chicken between different subgroups of H5N6 high pathogenicity avian influenza viruses.

Since 2014, periodic outbreaks of high pathogenicity avian influenza (HPAI) caused by clade 2.3.4.4 H5 HPAI virus (HPAIV) have resulted in huge economic losses in the Korean poultry industry. During the winter season of 2016-2017, clade 2.3.4.4e H5N6 HPAIVs classified into 5 subgroups (C1-5) were introduced into South Korea. Interestingly, it was revealed that the subgroup C2 and C4 viruses were predominantly distributed throughout the country, whereas detection of the subgroup C3 viruses was confined in a specific local region. In the present study, we conducted comparative evaluation of the pathogenicity of viruses belonging to subgroups C2 and C3 (H15 and HN1 strains) in specific pathogen-free (SPF) chickens, and further compared them with previously determined pathogenicity of subgroup C4 (ES2 strain) virus. The HN1 strain showed lower viral replication in tissues, less transmissibility, and higher mean chicken lethal dose than the H15 and ES2 strains in SPF chickens. Considering that the HN1 strain has a different NS gene segment from the H15 and ES2 strains, the reassortment of the NS gene segment likely affects their infectivity and transmissibility in chickens. These findings emphasize the importance of monitoring the genetic characteristics and pathogenic features of HPAIVs to effectively control their outbreaks in the field.

Performance of ECG-Derived Digital Biomarker for Screening Coronary Occlusion in Resuscitated Out-of-Hospital Cardiac Arrest Patients: A Comparative Study between Artificial Intelligence and a Group of Experts.

Acute coronary syndrome is a significant part of cardiac etiology contributing to out-of-hospital cardiac arrest (OHCA), and immediate coronary angiography has been proposed to improve survival. This study evaluated the effectiveness of an AI algorithm in diagnosing near-total or total occlusion of coronary arteries in OHCA patients who regained spontaneous circulation. Conducted from 1 July 2019 to 30 June 2022 at a tertiary university hospital emergency department, it involved 82 OHCA patients, with 58 qualifying after exclusions. The AI used was the Quantitative ECG (QCG™) system, which provides a STEMI diagnostic score ranging from 0 to 100. The QCG score's diagnostic performance was compared to assessments by two emergency physicians and three cardiologists. Among the patients, coronary occlusion was identified in 24. The QCG score showed a significant difference between occlusion and non-occlusion groups, with the former scoring higher. The QCG biomarker had an area under the curve (AUC) of 0.770, outperforming the expert group's AUC of 0.676. It demonstrated 70.8% sensitivity and 79.4% specificity. These findings suggest that the AI-based ECG biomarker could predict coronary occlusion in resuscitated OHCA patients, and it was non-inferior to the consensus of the expert group.

Improved Intermediate Visual Function with New Monofocal Intraocular Lens in Combined Cataract and Vitrectomy Surgery for Retinal Disease.

PURPOSE: To evaluate the usefulness of a newly generated monofocal intraocular lens (IOL) in patients with various retinal diseases who underwent combined cataract and pars plana vitrectomy surgery. METHODS: This prospective observational study included 33 patients with various retinal diseases. Monocular best-corrected distance visual acuity (BCDVA), uncorrected distance visual acuity (UCDVA), uncorrected intermediate visual acuity (UCIVA), uncorrected near visual acuity (UCNVA), and contrast sensitivity were measured and compared with 40 age-matched patients in the standard monofocal IOL. RESULTS: The Eyhance IOL group demonstrated significantly better UCIVA at 6 months follow-up compared to the standard monofocal IOL group. No significant differences were observed between the two groups in contrast sensitivity, BCDVA, UCDVA, or UCNVA. The regression analysis showed a significant association between preoperative corrected distance visual acuity and improved UCIVA in the Eyhance IOL group. CONCLUSIONS: The Eyhance ICB00 IOL proved to be a valuable option for patients with retinal diseases undergoing combined cataract surgery and vitrectomy. It effectively improved intermediate vision without compromising contrast sensitivity or distance visual acuity.

Differences in the Clinical Significance of Antinuclear Antibodies According to Titers and Patterns in Children.

This study aimed to evaluate the differences in the clinical significance of antinuclear antibody (ANA) according to their titers and patterns in the diagnosis of systemic autoimmune diseases (AiD) in pediatric patients. Of the 2442 children who had undergone an ANA test, 473 (19.4%) were positive for ANA, of whom 33 (7.0%) were diagnosed with significant AiD. The positive predictive value (PPV) for significant AiD was considerably high on application of an ANA titer of ≥1:640, and the PPV of a dense fine speckled (DFS) pattern was significantly lower compared with those of speckled and homogenous patterns. The diagnostic value of ANA positivity for AiD is limited, and the clinical significance of the DFS pattern is relatively lower compared with that of other patterns, such as homogenous and speckled patterns, in children. It is necessary to approach the significance of ANA in children individually depending on titers and patterns.

Effect of donor-recipient size mismatch on long-term graft survival in pediatric kidney transplantation: a multicenter cohort study.

BACKGROUND: Donor-recipient size mismatching is commonly occurs in pediatric kidney transplantation (KT). However, its effect on graft survival remains unknown. This study aimed to determine the effect of donor-recipient size mismatch on the long-term survival rate of transplant kidneys in pediatric KT. METHODS: A total of 241 pediatric patients who received KT were enrolled. The medical records of all patients were retrospectively reviewed, and the correlation between donor-recipient size mismatch and graft function and long-term graft outcome was analyzed according to donor-recipient size mismatch. RESULTS: Recipients and donors' mean body weight at the time of KT were 34.31 ± 16.85 and 56.53 ± 16.73 kg, respectively. The mean follow-up duration was 96.49 ± 52.98 months. A significant positive correlation was observed between donor-recipient body weight ratio (DRBWR) or donor-recipient body surface area ratio (DRBSR) and graft function until 1 year after KT. However, this correlation could not be confirmed at the last follow-up. The results of long-term survival analysis using Fine and Gray's subdistribution hazard model showed no significant difference of the survival rate of the transplant kidney according to DRBWR or DRBSR. CONCLUSION: Donor-recipient size mismatch in pediatric KT is not an important factor in determining the long-term prognosis of transplant kidneys.