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Clinical and laboratory characteristics of cashew nut allergy in Korean children: Findings from a tertiary hospital
No full textOBJECTIVE: Cashew nut (CN) allergy is becoming increasingly prevalent and represents a major cause of tree nut-induced anaphylaxis in Korean children. This study investigated the clinical characteristics and laboratory findings of CN allergy in Korean children. PATIENTS AND METHODS: Sixty-four children with a history of CN ingestion, who underwent serum CN-specific immunoglobulin E (CN-sIgE) measurements from January 2013 to February 2023, were enrolled through a retrospective medical record review. The demographic characteristics, clinical profiles, and laboratory findings were evaluated. RESULT: Thirty-five patients had immediate-type reactions after exposure to CN (CN-allergic group), whereas 29 showed no symptoms after ingesting CN (CN-tolerant group). Over 60% of patients in the CN-allergic group were allergic to >/= 1 other tree nuts and 17.1% had peanut allergies. In the CN-allergic group, cutaneous symptoms were most common (94.1%), followed by respiratory (35.3%), gastrointestinal (32.4%), and cardiovascular (2.9%) symptoms. Anaphylaxis due to CN exposure was observed in 51.4% of patients in the CN-allergic group. The median CN-sIgE level of the CN-allergic group was significantly higher than that of the CN-tolerant group (5.5 kUA/L vs. 0.06 kUA/L, P < 0.001). The optimal cutoff level for distinguishing the CN-allergic group from the CN-tolerant group was 0.55 kU(A)/L (sensitivity 94.29%, specificity 93.10%). CONCLUSION: Co-allergies to other tree nuts were common in children with CN allergy and more than 50% of patients with CN allergy experienced anaphylaxis. The optimal cutoff level for distinguishing between the CN-allergic and CN-tolerant groups was 0.55 kU(A)/L
Drosophila peptidyl-prolyl cis/trans isomerase-like 4 regulates circadian rhythm by supporting high-amplitude oscillations of PERIOD
No full textPeptidyl-prolyl cis/trans isomerases (PPIases) accelerate proline peptide bond isomerization, affecting substrate protein function. In this study, through RNAi-based behavioral screening of PPIases in Drosophila melanogaster, we identified CG5808, termed Drosophila peptidyl-prolyl cis/trans isomerase-like 4 (dPPIL4), as crucial for circadian rhythm regulation. Knockdown of dppil4 in clock cells lengthened the circadian rhythm period and decreased rhythmicity, accompanied by a significant reduction of core clock protein PERIOD (PER). d ppil4 knockdown downregulated per transcription and reduced phosphorylation at Ser5 in the RNA polymerase II C-terminal domain, critical for transcription elongation. In addition, dPPIL4 stabilized Cullin1 of the Skp1-Cullin1-F-box protein complex, a key regulator of PER degradation. Our findings suggest that dPPIL4 supports high-amplitude PER oscillation by enhancing both synthesis and degradation processes in a timely manner. In conclusion, our study underscores the importance of high-amplitude PER oscillations in PER for robust circadian rhythms and highlights the critical role of dPPIL4 in this process
Impact of growth hormone therapy on bone and body composition in prepubertal children with idiopathic short stature
No full textOBJECTIVES: Few studies have investigated the effect of growth hormone (GH) therapy on bone health and body composition in children with idiopathic short stature (ISS). Therefore, this study aimed to evaluate the short-term effects of GH treatment on bone mineral density (BMD) and prepubertal body composition in children with ISS. METHODS: The study included 53 prepubertal children with ISS (mean age, 6.3 +/- 1.5 years). Their BMD was compared to that of 20 healthy prepubertal children matched for chronological age. Of the 53 children with ISS, 11 received GH therapy for 1 year. Anthropometric measurements and bone age assessments were conducted, and body composition was analyzed using dual-energy X-ray absorptiometry at 6-month intervals. RESULTS: At baseline, lumbar spine and femoral neck BMD Z scores, adjusted for height, showed no significant differences between the ISS and control groups. However, bone mineral apparent density (BMAD) Z scores were significantly lower in children with ISS compared to controls. Over 12 months of GH therapy, no significant changes were observed in lumbar spine or femoral neck height-adjusted BMD Z scores. Nevertheless, GH treatment led to a significant reduction in percent body fat for chronological age and an increase in lean body mass after 1 year. CONCLUSIONS: Prepubertal children with ISS exhibited lower BMAD at the lumbar spine compared to healthy controls. Although short-term GH therapy did not significantly alter bone density, it positively impacted body composition. These findings provide valuable clinical insights into bone health and body composition in children with ISS
Persistent hyperparathyroidism after kidney transplantation in children
No full textBACKGROUND: Persistent hyperparathyroidism after kidney transplantation (KT) has been reported in up to 50% of adult recipients, but pediatric data remain limited. We evaluated the prevalence, skeletal manifestations, and risk factors for persistent hyperparathyroidism in children following KT. METHODS: In this retrospective cohort study, 107 pediatric KT recipients (58% male; median age 10.3 years) transplanted between 2004 and 2019 were analyzed. Persistent hyperparathyroidism was defined as a median parathyroid hormone (PTH) > 65 pg/mL between 3 and 12 months post-KT. Risk factors for persistent hyperparathyroidism, post KT clinical features, and treatment status were analyzed. RESULTS: Thirty-six patients (33.6%) had persistent hyperparathyroidism after KT. On univariable analysis, dialysis duration of 24 months or longer (p = 0.028) and pretransplant hyperphosphatemia (p = 0.026) were significantly associated with persistent hyperparathyroidism. The multivariable model identified pretransplant hyperphosphatemia as an independent predictor (OR 2.70, 95% CI 1.10-6.87; p = 0.030). There was no significant difference in height Z score change between patients with and without persistent hyperparathyroidism (p = 0.97). However, persistent hyperparathyroidism was associated with poorer graft survival (log-rank p = 0.049). Six patients received cinacalcet and one underwent subtotal parathyroidectomy for refractory hypercalcemia. CONCLUSIONS: Persistent hyperparathyroidism is relatively common in pediatric KT recipients, affecting one-third of patients by one-year post-transplant. Prolonged dialysis and pre-existing hyperphosphatemia before KT may be risk factors. These findings underscore the importance of optimizing chronic kidney disease-mineral bone disease management and routine PTH monitoring before and after transplant in children
Comparison of treatment strategies for submucosal tumors originating from the muscularis propria at esophagogastric junction or cardia
No full textBACKGROUND: The spectrum of gastric submucosal tumors (SMTs) in the upper gastrointestinal system ranges from non-neoplastic to malignant lesions, with gastrointestinal stromal tumors exhibiting inherent malignant potential. However, the diagnosis of SMTs remains challenging, and treatment methods, especially for tumors located at the cardia or esophagogastric junction (EGJ), are not well established. Minimally invasive techniques - such as endoscopic submucosal dissection (ESD), submucosal tunneling endoscopic resection (STER), and laparoscopic wedge resection (LWR) - have been developed for these lesions. However, comparative data on their feasibility, safety, and clinical outcomes in these locations remain limited. AIM: To compare ESD, STER, and LWR for SMTs at the EGJ or cardia, focusing on procedural feasibility. METHODS: This single-center retrospective study included patients with SMTs less than 45 mm from the muscularis propria, growing intraluminally at the EGJ or cardia, and treated with ESD, STER, or LWR between July 2014 and September 2022. The primary outcome was relapse-free survival during follow-up. RESULTS: The median age (interquartile range) was 53.0 (40.0-57.5), 43.0 (39.0-57.0), and 56.0 (43.0-64.0) years for ESD, STER, and LWR, respectively. The median follow-up time (interquartile range) was 60.0 (26.5-66.5), 24.0 (13.0-38.0), and 35.0 (21.0-60.0) months. LWR had the largest tumors (30.0 mm) and the highest rate of high-risk gastrointestinal stromal tumors (68.0%, P < 0.001). Tumor recurrence occurred in one LWR patient (4.0%, P = 0.600). En bloc and macroscopic resection rates were 100% (P = 1.000), but microscopic resection rates differed (P = 0.021). Significant minor complications occurred in 5 patients (10.0%), all grade IIIa. Tumor location (cardia/fundus, P = 0.006) and prolonged procedure time (P < 0.001) were significantly associated with complications. CONCLUSION: ESD, STER, and LWR are effective for SMTs at the EGJ and cardia, with minor complications associated with tumor location and procedure time, and comparable recurrence rates
Automated interpretation of cardiotocography using deep learning in a nationwide multicenter study
No full textTimely detection of abnormal cardiotocography (CTG) during labor plays a crucial role in enhancing fetal prognosis. Recent research has explored the use of deep learning for CTG interpretation, most studies rely on small, localized datasets or focus on outcomes less relevant to clinical practice. To address these limitations, we developed a clinically applicable model using a large-scale, nationwide CTG dataset with reliable annotations provided by a board-certified obstetrician. Our study utilized 22,522 deliveries from 14 hospitals, each including cardiotocography (CTG) recordings of up to 75 min in length. The CTG signals were segmented into 5-minute intervals, resulting in a total of 519,800 person-minutes of analyzed data. We trained and validated a deep learning model based on CTG segments for classifying normal and abnormal CTGs. In the independent test dataset, the model achieved an AUC (area under the receiver operating characteristic curve) of 0.880 and PRC (area under the precision-recall curve) of 0.625 in internal tests. External tests across three datasets achieved AUCs of 0.862, 0.895, and 0.862 and PRCs of 0.553, 0.615, and 0.601. Our study results show the potential of the deep learning for automated CTG interpretation. We will evaluate this model in future prospective studies to assess the model's clinical applicability
Decreased frequency and inflammatory change of FoxP3+ regulatory T cells in immunopathogenesis of human acute graft-versus-host disease
No full textBACKGROUND/AIMS: Acute graft-versus-host disease (GvHD) is a severe complication of allogeneic stem cell transplantation, characterized by immune-mediated tissue damage primarily affecting the skin, liver, and gastrointestinal tract. Regulatory T (Treg) cells play a critical role in maintaining immune homeostasis. However, the pathogenic roles of changes in Treg cell number and function on acute GvHD remain poorly understood. This study aimed to investigate the quantitative and qualitative changes in Treg cells and their clinical and pathogenic implication of acute GvHD. METHODS: A total of 62 patients who underwent allogeneic stem cell transplantation at a tertiary institution from 2019 to 2024 were enrolled. Peripheral blood mononuclear cells were isolated and analyzed by multicolor flow cytometry. Treg cell subsets and cytokine production were assessed after T-cell receptor stimulation. Serum levels of inflammatory cytokines were measured using cytometric bead array, and Treg cell suppressive function was evaluated through co-culture experiments. RESULTS: Patients with acute GvHD showed a decreased frequency of circulating Treg cells, with a notable increase in the CD45RA-FoxP3lo pro-inflammatory subset. Treg cells produced inflammatory cytokines including TNF-alpha upon stimulation and exhibited reduced suppressive activity. The frequency of TNF-alpha+ Treg cells correlated with the clinical severity of acute GvHD. Elevated serum levels of IL-6 and IL-21 were associated with the inflammatory conversion of Treg cells. CONCLUSION: During human acute GvHD, frequencies of circulating Treg cells are significantly decreased. Inflammatory change of Treg cells, represented by TNF-alpha production and reduced suppressive capacity, contributes to the immunopathogenesis of acute GvHD
EnsemPred-ACP: Combining machine and deep learning to improve anticancer peptide prediction
No full textAnticancer peptide (ACP) has emerged as potent therapeutic agents owing to its ability to selectively target cancer cells while minimising toxicity to healthy cells. However, the accurate computational prediction of ACP remains challenging because of the complex molecular mechanisms underlying cancer. In this study, we introduce EnsemPred-ACP, an innovative ensemble framework that combines machine learning (ML) and deep learning (DL) approaches to enhance ACP prediction. Our primary innovation is the introduction of binary profile features (BPF) to augment pre-trained protein embeddings, thereby capturing position-specific patterns crucial for ACP identification. The framework used a dual-pipeline architecture; ML models processed handcrafted sequence features and embeddings, whereas DL models handled BPF-enhanced embeddings. Upon evaluation with independent datasets, EnsemPred-ACP achieved an accuracy of 0.863, sensitivity of 0.897, and specificity of 0.830, notably outperforming existing methods. The model demonstrated a strong generalisation performance, achieving an area under the receiver operating characteristic curve of 0.93. Ablation studies on independent datasets further highlighted the substantial impact of BPF, enhancing the prediction accuracy by 2.5 % and 11.1 % when integrated with ESM2 and ProtT5 embeddings, respectively. These results demonstrate the effectiveness of our integrated approach in accurately identifying potential therapeutic peptides, thereby contributing to the advancement of peptide-based cancer therapeutics
Impact of robotic surgery proportion among minimally invasive gastrectomy on surgical complications
No full textOBJECTIVE: The Safety of robotic gastrectomy (RG) compared to laparoscopic gastrectomy (LG) for gastric cancer remains uncertain on a national scale, with limited comparative studies across institutions. This study aims to compare the morbidity rates between RG and LG using data from a nationwide survey. METHODS: We utilized data from the Korean Gastric Cancer Association's 2019 nationwide survey. The proportion of robotic surgeries in minimally invasive surgery at each institution was classified using a cut-off value of 10%, and defined as high robotic proportion cohort and low robotic proportion cohort. We analyzed surgical outcomes between robotic and laparoscopic gastrectomy in each cohort using propensity score matching (PSM). To account for potential clustering effects within hospitals, we employed Generalized Estimating Equations with hospital as the clustering variable. RESULTS: This study included 776 patients who underwent RG and 7,804 patients who underwent LG for gastric cancer. In low robotic proportion cohort, RG had a longer operation time (P<0.001) but similar blood loss (P=0.792) compared to LG. In the high robotic proportion cohort, RG showed longer operation time (P<0.001), less blood loss (P<0.001), and shorter hospital stays (P<0.001) compared to LG. Additionally, RG in the high robotic proportion cohort had shorter operative time (P<0.001) and less blood loss (P=0.024) compared with that in the low robotic proportion cohort. CONCLUSIONS: RG demonstrated comparable perioperative outcomes to LG in a nationwide PSM analysis. However, RG offers limited benefits over LG at institutions with lower frequencies of RG use
Damage control does not offer a survival advantage and increases the risk of serious complications compared with early total care in severely injured patients with femoral shaft fractures
No full textBACKGROUND: Damage control orthopedics (DCO) was proposed to minimize the second hit of extensive surgical procedures in severely injured patients when treated with early fracture fixation (early total care [ETC]). The impact of DCO and ETC on the outcomes of severely injured patients sustaining femoral shaft fractures (FSFs) is unclear. We hypothesized that DCO is associated with lower mortality and decreased incidence of complications compared with ETC. METHODS: The Trauma Quality Improvement Project database was queried from 2007 to 2021. Adult patients 14 years or older with FSF and Injury Severity Score of >15 were included. Patients were divided into ETC and DCO groups and stratified according to fracture type: open or closed. The primary outcomes included acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), severe sepsis, deep venous thrombosis (DVT), and mortality. Inverse probability treatment of weighting was used to balance the two cohorts of interest. A binomial logistic regression analysis was performed after inverse probability treatment of weighting to identify potential associations between the type of fixation procedure and the outcomes of interest. RESULTS: A total of 44,577 FSF patients were included. Mortality was 2.1%. No survival advantage was observed in the DCO group (odds ratio [OR], 0.92). However, significant associations between DCO and the risk of ARDS (OR, 1.64), AKI (OR, 1.57), severe sepsis (OR, 1.64), and DVT (OR, 1.64) were identified. Damage control orthopedics was not associated with decreased mortality after stratifying patients according to the fracture type and the type of operation. CONCLUSION: Damage control orthopedics is not associated with improved survival of severely injured patients with FSF. Damage control orthopedics is associated with an increased risk of ARDS, AKI, severe sepsis, and DVT compared with ETC. These findings persisted after analyzing the type of fracture. These results are significant for clinical practice, as more patients could be treated by ETC when compensated physiologically, independent of the fracture type. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV