Purpose: Some patients with respiratory failure fail initial weaning attempts and need prolonged mechanical ventilation (MV). Prolonged MV is associated with many complications and consumption of heathcare resources. Objective weaning indices help staffs to identify high-potential patients for weaning from the MV. Traditional weaning indices are not reliable in clinical practice. Transitional percentage of minute volume (TMV%) is a new index of the work of breathing. This study aimed to investigate the utility of TMV% in the prediction of weaning potential. Methods: This study was prospectively performed including all patients with prolonged MV. Researchers recorded their demographics, TMV%, respiratory parameters, Acute Physiology and Chronic Health Evaluation II score, and laboratory data upon arrival at the respiratory care center. The factors associated with successful weaning were analyzed. Results: Out of the 120 patients included, 84 (70.0%) were successfully weaned from MV. Traditional weaning indices such as rapid shallow breathing index could not predict the weaning outcome. TMV% was a valuable parameter as patients with a lower TMV%, higher tidal volume, higher hemoglobin, lower blood urea nitrogen, and lower Acute Physiology and Chronic Health Evaluation II scores had a higher rate of successful weaning. TMV%, tidal volume, and HCO3- levels were independent predictors of successful weaning, and the area under the curve was .79 in the logistic regression model. Conclusion TMV% is a novel and effective predictor of successful weaning. Patients with lower TMV% had a higher MV weaning outcome. Once patients with a high potential for successful weaning are identified, they should be aggressively weaned from MV as soon as possible.

Purpose: Some patients with respiratory failure fail initial weaning attempts and need prolonged mechanical ventilation (MV). Prolonged MV is associated with many complications and consumption of heathcare resources. Objective weaning indices help staffs to identify high-potential patients for weaning from the MV. Traditional weaning indices are not reliable in clinical practice. Transitional percentage of minute volume (TMV%) is a new index of the work of breathing. This study aimed to investigate the utility of TMV% in the prediction of weaning potential. Methods: This study was prospectively performed including all patients with prolonged MV. Researchers recorded their demographics, TMV%, respiratory parameters, Acute Physiology and Chronic Health Evaluation II score, and laboratory data upon arrival at the respiratory care center. The factors associated with successful weaning were analyzed. Results: Out of the 120 patients included, 84 (70.0%) were successfully weaned from MV. Traditional weaning indices such as rapid shallow breathing index could not predict the weaning outcome. TMV% was a valuable parameter as patients with a lower TMV%, higher tidal volume, higher hemoglobin, lower blood urea nitrogen, and lower Acute Physiology and Chronic Health Evaluation II scores had a higher rate of successful weaning. TMV%, tidal volume, and HCO3- levels were independent predictors of successful weaning, and the area under the curve was .79 in the logistic regression model. Conclusion TMV% is a novel and effective predictor of successful weaning. Patients with lower TMV% had a higher MV weaning outcome. Once patients with a high potential for successful weaning are identified, they should be aggressively weaned from MV as soon as possible.

OBJECTIVES: The aims of this study were to compare the performance of machine learning methods for the prediction of the medical costs associated with spinal fusion in terms of profit or loss in Taiwan Diagnosis-Related Groups (Tw-DRGs) and to apply these methods to explore the important factors associated with the medical costs of spinal fusion. METHODS: A data set was obtained from a regional hospital in Taoyuan city in Taiwan, which contained data from 2010 to 2013 on patients of Tw-DRG49702 (posterior and other spinal fusion without complications or comorbidities). Naïve-Bayesian, support vector machines, logistic regression, C4.5 decision tree, and random forest methods were employed for prediction using WEKA 3.8.1. RESULTS: Five hundred thirty-two cases were categorized as belonging to the Tw-DRG49702 group. The mean medical cost was US $4,549.7, and the mean age of the patients was 62.4 years. The mean length of stay was 9.3 days. The length of stay was an important variable in terms of determining medical costs for patients undergoing spinal fusion. The random forest method had the best predictive performance in comparison to the other methods, achieving an accuracy of 84.30%, a sensitivity of 71.4%, a specificity of 92.2%, and an AUC of 0.904. CONCLUSIONS: Our study demonstrated that the random forest model can be employed to predict the medical costs of Tw-DRG49702, and could inform hospital strategy in terms of increasing the financial management efficiency of this operation.
Area Under Curve ; Costs and Cost Analysis ; Dataset ; Decision Trees ; Diagnosis-Related Groups ; Financial Management ; Forests ; Humans ; Length of Stay ; Logistic Models ; Machine Learning ; Methods ; Sensitivity and Specificity ; Spinal Fusion ; Support Vector Machine ; Taiwan

Background: and Purpose Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. Methods: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. Results: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. Conclusions This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.

OBJECTIVE: Postoperative delirium (POD) is a highly prevalent complex neuropsychiatric syndrome in elderly patients. However, its pathophysiology is currently unknown. Early detection and prevention of POD is important; therefore, the aim of this study was to investigate the link between preoperative insulin growth factor 1 (IGF-1) levels in the serum and POD in the Chinese elderly patients. METHODS: One hundred and three patients who were undergoing an orthopedic operation took part in the study. Preoperative serum IGF-1 levels were measured. POD was determined daily using the Confusion Assessment Method (CAM) and DSM-IV TR. Baseline serum IGF-1 levels were compared between patients who did and did not develop POD. Correlation coefficients were calculated to evaluate relationship between baseline characteristics and serum IGF-1 levels. The relationship between baseline biomarkers and delirium status was investigated using logistic regression analysis, adjusting for potential confounding variables. RESULTS: Twenty-three patients developed POD. The POD group had lower MMSE scores and higher CCI scores and proportions of acute admission. Preoperative serum IGF-1 levels were correlated with MMSE scores and age (MMSE: r=0.230, p<0.05; age: r=-0.419, p<0.001). Baseline serum IGF-1 levels did not differ between patients who did and did not develop POD, even after adjusting for potential confounding factors, MMSE score, and age. CONCLUSION: No association was found between preoperative IGF-1 levels and POD, suggesting that they are not direct biomarkers of the incidence of POD among the Chinese elderly population. Further research with larger sample sizes is warranted to clarify the relationship.
Aged* ; Asian Continental Ancestry Group* ; Biomarkers ; Confounding Factors (Epidemiology) ; Delirium* ; Diagnostic and Statistical Manual of Mental Disorders ; Humans ; Incidence ; Insulin ; Insulin-Like Growth Factor I ; Logistic Models ; Orthopedics ; Sample Size

The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b+ macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.
ATP-Binding Cassette Transporters/metabolism ; Age Factors ; Animals ; Blood Chemical Analysis ; Cholesterol/metabolism ; Diabetes Mellitus, Type 2/*drug therapy/genetics ; Dyslipidemias/drug therapy/genetics ; Female ; Hyperglycemia/drug therapy/genetics ; Hypoglycemic Agents/*therapeutic use ; Injections, Intraperitoneal ; *Lipid Metabolism/drug effects ; Listeria monocytogenes/*drug effects/immunology ; Listeriosis/*drug therapy/immunology/microbiology ; Macrophages/drug effects/*metabolism ; Mice ; Obesity/drug therapy/genetics ; Peptides/*therapeutic use ; Phagocytosis/drug effects ; Venoms/*therapeutic use

OBJECTIVE: To study the metabolic characteristics of 5-bromo-2-fluorobenzonitrile in vitro and compare the differences between rats and human,and for the purpose of providing data for poison effect research and extrapolating poison effect of 5-bromo-2-fluorobenzonitrile from animals to human being. METHODS: Equilibrium dialysis method was used to analyze the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the plasma of rats and humans in the groups of low dose,medium dose and high dose which were treated with mass concentration of 5-bromo-2-fluorobenzonitrile at 500,5 000 and 50 000 μg / L respectively. Metabolic incubation systems of SD rat microsomes and human liver microsomes were established in vitro. When the mass concentration of 5-bromo-2-fluorobenzonitrile in the systems was 800 μg / L,the concentration of liver microsome was 0. 5 g / L; after being incubated for 0,10,30,60 and 90 min with the involvement of the regeneration system of nicotinamide-adenine dinucleotide phosphate in the incubation systems,the metabolic reaction was stoped. The residual amounts of 5-bromo-2-fluorobenzonitrile were analyzed and metabolic half-life of 5-bromo-2-fluorobenzonitrile incubating with liver microsomes in vitro was figured out. RESULTS: Protein binding ratio of 5-bromo-2-fluorobenzonitrile in the groups of low dose,medium dose and high dose were( 83. 5 ± 0. 9) %,( 88. 8 ± 0. 3) % and( 88. 6 ± 0. 3) % in rats plasma,and( 85. 2 ± 0. 1) %,( 89. 0 ± 0. 1) % and( 91. 1 ± 0. 4) % in human plasma. Both in rat plasma and human plasma,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the groups of medium dose and high dose were significantly increased than that in the low-dose group( P < 0. 01). In human plasma,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in the high-dose group significantly increased than that in the medium-dose group( P < 0. 01). In the groups of low dose and high dose,the protein binding ratio of 5-bromo-2-fluorobenzonitrile in human plasma significantly increased than that in rats plasma( P < 0. 01). Absolute differences in protein binding ratio of 5-bromo-2-fluorobenzonitrile between the rat plasma and the human plasma were no more than 2. 5% in the same dose groups. Metabolic half-life of 5-bromo-2-fluorobenzonitrile incubating with rats and human liver microsomes and control solution in vitro were respectively( 58. 6 ± 1. 6),( 59. 2 ± 1. 5) and( 65. 0 ± 6. 3) min,which shows no significant differences( P < 0. 05). CONCLUSION: The potein binding ratio and metabolism of 5-bromo-2-fluorobenzonitrile in liver microsomes in rat plasma is similar to those in human plasma. Both in the plasmas of rats and humans,5-bromo-2-fluorobenzonitrile has high protein binding ratio,and 5-bromo-2-fluorobenzonitrile is not metabolized in liver microsomes of either rats or humans.

Purpose: The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. Materials and Methods: From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. Results: A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). Conclusion Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

Objective: aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. Methods: aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. Results: aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. Conclusion aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.