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Machine learning-driven prediction of brain metastasis in lung adenocarcinoma using miRNA profile and target gene pathway analysis of an mRNA dataset
No full textBackground: Brain metastasis (BM) is common in lung adenocarcinoma (LUAD) and has a poor prognosis, necessitating predictive biomarkers. MicroRNAs (MiRNAs) promote cancer cell growth, infiltration, and metastasis. However, the relationship between the miRNA expression profiles and BM occurrence in patients with LUAD remains unclear. Methods: We conducted an analysis to identify miRNAs in tissue samples that exhibited different expression levels between patients with and without BM. Using a machine learning approach, we confirmed whether the miRNA profile could be a predictive tool for BM. We performed pathway analysis of miRNA target genes using a matched mRNA dataset. Results: We selected 25 miRNAs that consistently exhibited differential expression between the two groups of 32 samples. The 25-miRNA profile demonstrated a strong predictive potential for BM in both Group 1 and Group 2 and the entire dataset (area under the curve [AUC] = 0.918, accuracy = 0.875 in Group 1; AUC = 0.867, accuracy = 0.781 in Group 2; and AUC = 0.908, accuracy = 0.875 in the entire group). Patients predicted to have BM, based on the 25-miRNA profile, had lower survival rates. Target gene analysis of miRNAs suggested that BM could be induced through the ErbB signaling pathway, proteoglycans in cancer, and the focal adhesion pathway. Furthermore, patients predicted to have BM based on the 25-miRNA profile exhibited higher expression of the epithelial-mesenchymal transition signature, TWIST, and vimentin than those not predicted to have BM. Specifically, there was a correlation between EGFR mRNA levels and BM. Conclusions: This 25-miRNA profile may serve as a biomarker for predicting BM in patients with LUAD
Association Between Individualized Versus Conventional Blood Glucose Thresholds and Acute Kidney Injury After Cardiac Surgery: A Retrospective Observational Study
No full textObjectives: This study was designed to compare individualized and conventional hyperglycemic thresholds for the risk of acute kidney injury (AKI) after cardiac surgery. Design: This was an observational study. Setting: The study took place in a single-center tertiary teaching hospital. Participants: Adult patients who underwent cardiac surgery between January 2012 and November 2021 were enrolled. Measurements and Main Results: Two blood glucose thresholds were used to define intraoperative hyperglycemia. While the conventional hyperglycemic threshold (CHT) was 180 mg/dL in all patients, the individualized hyperglycemic threshold (IHT) was calculated based on the preoperative hemoglobin A1c level. Various metrics of intraoperative hyperglycemia were calculated using both thresholds: any hyperglycemic episode, duration of hyperglycemia, and area above the thresholds. Postoperative AKI associations were compared using receiver operating characteristic curves and logistic regression analysis. Among the 2,427 patients analyzed, 823 (33.9%) developed AKI. The C-statistics of IHT-defined metrics (0.58-0.59) were significantly higher than those of the CHT-defined metrics (all C-statistics, 0.54; all p < 0.001). The duration of hyperglycemia (adjusted odds ratio, 1.09; 95% confidence interval, 1.02-1.16) and area above the IHT (1.003; 1.001-1.004) were significantly associated with the risk of AKI, except for the presence of any hyperglycemic episode. None of the CHT-defined metrics were significantly associated with the risk of AKI. Conclusions: Individually defined intraoperative hyperglycemia better predicted postcardiac surgery AKI than universally defined hyperglycemia. Intraoperative hyperglycemia was significantly associated with the risk of AKI only for the IHT. Target blood glucose levels in cardiac surgical patients may need to be individualized based on preoperative glycemic status
Development of a Risk Prediction Model for Adverse Skin Events Associated with TNF-α Inhibitors in Rheumatoid Arthritis Patients
Get PDFBackground: Rheumatoid arthritis (RA) is a chronic inflammatory disorder primarily targeting joints, significantly impacting patients’ quality of life. The introduction of tumor necrosis factor-alpha (TNF-α) inhibitors has markedly improved RA management by reducing inflammation. However, these medications are associated with adverse skin reactions, which can vary greatly among patients due to genetic differences. Objectives: This study aimed to identify risk factors associated with skin adverse events by TNF-α in RA patients. Methods: A cohort study was conducted, encompassing patients with RA who were prescribed TNF-α inhibitors. This study utilized machine learning algorithms to analyze genetic data and identify markers associated with skin-related adverse events. Various machine learning algorithms were employed to predict skin and subcutaneous tissue-related outcomes, leading to the development of a risk-scoring system. Multivariable logistic regression analysis identified independent risk factors for skin and subcutaneous tissue-related complications. Results: After adjusting for covariates, individuals with the TT genotype of rs12551103, A allele carriers of rs13265933, and C allele carriers of rs73210737 exhibited approximately 20-, 14-, and 10-fold higher incidences of skin adverse events, respectively, compared to those with the C allele, GG genotype, and TT genotype. The machine learning algorithms used for risk prediction showed excellent performance. The risk of skin adverse events among patients receiving TNF-α inhibitors varied based on the risk score: 0 points, 0.6%; 2 points, 3.6%; 3 points, 8.5%; 4 points, 18.9%; 5 points, 36.7%; 6 points, 59.2%; 8 points, 90.0%; 9 points, 95.7%; and 10 points, 98.2%. Conclusions: These findings, emerging from this preliminary study, lay the groundwork for personalized intervention strategies to prevent TNF-α inhibitor-associated skin adverse events. This approach has the potential to improve patient outcomes by minimizing the risk of adverse effects while optimizing therapeutic efficacy
Association of the dietary inflammatory index with sarcopenic obesity and frailty in older adults
Get PDFObjectives: This study examined whether a higher dietary inflammatory index (DII®) is associated with the risk of sarcopenic obesity (SO) and frailty among Korean older adults. Methods: A total of 950 participants aged 70–84 years, who completed the baseline nutrition survey of the Korean Frailty and Aging Cohort Study, were included in the analysis. The DII, quantifying the dietary inflammatory potential, was calculated using 23 foods and nutrients as assessed by a 24-h dietary recall. SO was defined as the coexistence of sarcopenia (dual-energy X-ray absorptiometry-measured appendicular skeletal muscle mass index of < 7.0 for males; <5.4 for females) and abdominal obesity (waist circumference of ≥ 90 cm for males; ≥85 cm for females). Frailty status was assessed using the Fried frailty index (range, 0–5), a simple tool for defining frailty that consists of three or more of five frailty items. Multinomial logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for confounders. Results: The prevalence of SO and frailty was 9.8% and 10.8%, respectively. The DII was significantly higher in the frail group (2.7) compared to the robust and SO groups (2.0 vs. 1.8) (P < 0.001). Among nutrients and foods included in the DII, the frail group exhibited lower vitamin E, niacin, vitamin B6, energy, and protein intakes than the robust and SO groups. Multivariable-adjusted OR (95% CI) for frailty versus robust (comparing DII tertile 3 to tertile 1) was 2.3 (1.1–4.8; P-trend = 0.02). However, no significant association was observed between the DII and SO (OR, 1.1; 95% CI, 0.5–2.1; P-trend = 0.6). Conclusions: A higher DII score was associated with increased odds of frailty but not with SO in Korean older adults, suggesting that proinflammatory diets have a greater impact on frailty than that on SO in the older population
Serum Galectin-10: A biomarker for persistent airflow limitation in adult asthmatics
Get PDFBackground: Inhaled corticosteroids (ICS) are primary anti-inflammatory medications to control eosinophilic airway inflammation, and prevent asthma exacerbation. However, persistent airflow limitation (PAL) presents in some asthmatics even on ICS treatment, leading to lung function decline. Thus, we evaluated clinical associations of serum galectin-10 (Gal10) and galectin-3 (Gal3) levels in adult asthmatics who had maintained anti-asthma medication. Methods: Sixty-seven asthmatics and 78 healthy controls (HCs) were recruited. Serum Gal10 and Gal3 levels were measured by enzyme-linked immunosorbent assay, and their clinical relevance with inflammatory and lung function parameters was evaluated. Spirometry was performed to assess PAL and small airway dysfunction (SAD). Airway epithelial cells were cocultured with eosinophils/neutrophils, and were exposed to house dust mites to assess the production of Gal10 and Gal3. Results: Serum Gal10 (not Gal3) levels were significantly higher in asthmatics than in HCs (P < 0.001), in asthmatics with PAL than in those without PAL (P = 0.005), and in those with SAD than in those without SAD (P = 0.004). The Gal10-high group had significantly higher levels of peripheral CD66+ neutrophil counts, serum periostin and Gal3, and lower values of FEV1% and MMEF% than the Gal10-low group (P < 0.050 for all). The production of Gal10 and Gal3 was increased in eosinophilic airway model, while Gal10 (not Gal3) levels were increased in neutrophilic airway model as well as house dust mite stimulation. Conclusion: Our findings suggest that serum Gal10 level may be a potential biomarker for PAL in adult asthmatics
The degree of respiratory depression according to the effect-site concentration in remimazolam target-controlled infusion : A randomised controlled trial
No full textBACKGROUND Remimazolam is not only associated with a lower incidence of respiratory depression than propofol but also in itself has the risk of respiratory depression. OBJECTIVE We investigated respiratory depression following remimazolam infusion, targeting different effect-site concentrations using target-controlled infusion. DESIGN A prospective, double-blind, randomised controlled study. SETTING Tertiary hospital, Suwon, South Korea, from April 2022 to November 2022. PARTICIPANTS One hundred and seven patients scheduled for general anaesthesia were randomised into three groups targeting remimazolam effect-site concentrations of 500 (RMZ-500) (n = 36), 1000 (RMZ-1000) (n = 35) and 1500 ng ml-1 (RMZ-1500) (n = 36). INTERVENTIONS Remimazolam was solely infused for 10 min according to target effect-site concentrations. According to the degree of SpO2 decrease, oxygen desaturations were managed with the following respiratory supports: jaw-thrust for SpO2 less than 97%, 100% oxygen delivery for SpO2 less than 93% and assisted ventilation for SpO2 less than 90%. MAIN OUTCOME MEASURES The incidence of each respiratory support, along with respiratory variables (at baseline, 5 min and 10 min after remimazolam infusion) and loss of consciousness were observed for 10 min after remimazolam target-controlled infusion. RESULTS Both RMZ-1000 and RMZ-1500 required more frequent respiratory support than RMZ-500 (both P < 0.001), with nearly identical frequencies between RMZ-1000 and RMZ-1500. In terms of respiratory support, the incidence of assisted ventilation was significantly lower in RMZ-500 (2.8%) than RMZ-1000 (48.6%) and RMZ-1500 (50%) (P < 0.001). RMZ-1000 and RMZ-1500 achieved loss of consciousness in all patients; RMZ-500 only achieved loss of consciousness in 86.1% of patients (P = 0.010). In patients who maintained spontaneous respiration, tidal volume decreased by 41 to 48% and respiratory rate increased by 118 to 158% at 5 and 10 min, significantly compared to baseline in all groups (P < 0.001). CONCLUSIONS Remimazolam infusion, like that of other benzodiazepines, led to respiratory depression, which was more prominent at higher target effect-site concentrations. Therefore, appropriate countermeasures should be developed to prevent oxygen desaturation
Nursing experiences and knowledge of paediatric delirium: Analysing knowledge-practice gaps
Get PDFBackground: Delirium commonly occurs in paediatric patients with acute critical illness and negatively affects clinical outcomes. Variations in delirium knowledge levels and its management have been noted among nurses. Aims: This study investigated nurses' experiences and knowledge levels regarding paediatric delirium. Additionally, we aimed to assess the gap between knowledge levels and practical experiences with paediatric delirium. Study Design: This cross-sectional descriptive study conveniently sampled paediatric nurses from a university hospital in South Korea between September 2022 and March 2023. Nursing experiences with paediatric delirium and delirium knowledge levels were measured using structured survey questionnaires. Delirium knowledge was scored 0 to 47, and higher scores indicated higher levels of delirium-related knowledge. Data were analysed using descriptive statistics and presented as mean, standard deviation, frequency and percentage. Results: A total of 127 paediatric nurses participated in this study; 40.2% had experience with 1–5 delirium cases in the previous year, and 86.6% (n = 110) had never used assessment tools for paediatric delirium assessment. The mean total delirium knowledge score was 34.45 ± 5.4; the mean scores of knowledge regarding aetiology, signs and symptoms and nursing management of delirium were 8.93 ± 1.31, 13.24 ± 2.81 and 12.3 ± 2.7, respectively. Interventions associated with a lower level of delirium-related knowledge and a lower performance rate included avoiding restraint use and maintaining hydration and electrolyte levels. Interventions associated with a higher level of delirium-related knowledge but a lower rate of performance comprised providing orientation, offering emotional support, allowing participants to stay with family members and administering medications to manage delirium. Conclusions: Although nurses working in paediatric units exhibited high rate of delirium nursing care, there was the gap between their delirium-related knowledge and practice. Nurses need to be aware of the insufficient part of delirium care, and paediatric delirium education should be reinforced. Relevance to Clinical Practice: Preventing, assessing and systematically managing paediatric delirium is crucial, and considering the study results, delirium education among nurses is needed
Feasibility of Regional Lymphadenectomy for Stomach-Preserving Surgery in Early Gastric Cancer Omitting Sentinel Node Navigation: A Post Hoc Analysis of the SENORITA Trial
Get PDFBackground: Sentinel node navigation (SNN) has been known as the effective treatment for stomach-preserving surgery in early gastric cancer; however, SNN presents several technical difficulties in real practice. Objective: This study aimed to evaluate the feasibility of regional lymphadenectomy omitting SNN, using the post hoc analysis of a randomized controlled trial. Methods: Using data from the SENORITA trial that compared laparoscopic standard gastrectomy with lymphadenectomy and laparoscopic SNN, 237 patients who underwent SNN were included in this study. Tumor location was divided into longitudinal and circumferential directions. According to the location of the tumor, the presence or absence of lymph node (LN) metastases between sentinel and non-sentinel basins were analyzed. Proposed regional LN stations were defined as the closest area to the primary tumor. Sensitivities, specificities, positive predictive values, and negative predictive values (NPV) of SNN and regional lymphadenectomy were compared. Results: Metastasis to non-sentinel basins with tumor-free in sentinel basins was observed in one patient (0.4%). The rate of LN metastasis to non-regional LN stations without regional LN metastasis was 2.5% (6/237). The sensitivity and NPV of SNN were found to be significantly higher than those of regional lymphadenectomy (96.8% vs. 80.6% [p = 0.016] and 99.5% vs. 97.2% [p = 0.021], respectively). Conclusions: This study showed that regional lymphadenectomy for stomach-preserving surgery, omitting SNN, was insufficient; therefore, SNN is required in stomach-preserving surgery
2023 Korean Multidisciplinary Guidelines for Colon Cancer Management: Summary of Radiological Points
Get PDFNLRP3 Negative Regulation Mechanisms in the Resting State and Its Implications for Therapeutic Development
Get PDFThe NACHT-, leucine-rich-repeat-, and pyrin domain-containing protein 3 (NLRP3) is a critical intracellular sensor of the innate immune system that detects various pathogen- and danger-associated molecular patterns, leading to the assembly of the NLRP3 inflammasome and release of interleukin (IL) 1β and IL-18. However, the abnormal activation of the NLRP3 inflammasome has been implicated in the pathogenesis of autoinflammatory diseases such as cryopyrin-associated autoinflammatory syndromes (CAPS) and common diseases such as Alzheimer’s disease and asthma. Recent studies have revealed that pyrin functions as an indirect sensor, similar to the plant guard system, and is regulated by binding to inhibitory 14-3-3 proteins. Upon activation, pyrin transitions to its active form. NLRP3 is predicted to follow a similar regulatory mechanism and maintain its inactive form in the cage model, as it also acts as an indirect sensor. Additionally, newly developed NLRP3 inhibitors have been found to inhibit NLRP3 activity by stabilizing its inactive form. Most studies and reviews on NLRP3 have focused on the activation of the NLRP3 inflammasome. This review highlights the molecular mechanisms that regulate NLRP3 in its resting state, and discusses how targeting this inhibitory mechanism can lead to novel therapeutic strategies for NLRP3-related diseases