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BACKGROUND AND AIM: A large genetic effect of a novel gallstone-associated genetic variant, the hepatocyte nuclear factor 4α (HNF4A) rs1800961 polymorphism, has been identified through recent genome-wide association studies. However, this effect has not been validated in Asian populations. We investigated the association between the rs1800961 variant and gallstones among a Taiwanese population. METHODS: A total of 20 405 participants aged between 30 and 70 years voluntarily enrolled in the Taiwan Biobank. Self-report questionnaires, physical examinations, biochemical tests, and genotyping were used for analysis. The association of the HNF4A rs1800961 variant and other metabolic risks with gallstone disease was analyzed using multiple logistic regression models. RESULTS: The minor T allele of HNF4A rs1800961 was associated with an increased risk of gallstone, and the association remained significant even after adjustment for other risk factors including age, body mass index (BMI), diabetes, hyperlipidemia, hypertension, and cigarette smoking (adjusted odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.31 to 2.75) in male participants. When further stratified by BMI and age, the lithogenic effect was the most significant in male participants with obesity (adjusted OR = 3.55, 95% CI = 1.92 to 6.56) and who were younger (adjusted OR = 2.45, 95% CI = 1.49 to 4.04). CONCLUSION: The novel gallstone-associated HNF4A rs1800961 variant was associated with the risk of gallstone in the Taiwanese men. Screening for the rs1800961 polymorphism may be particularly useful in assessing the risk of gallstone formation in younger or obese men.
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Cálculos Biliares , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Cálculos Biliares/etiologia , Estudo de Associação Genômica Ampla , Fatores de Risco , Obesidade/epidemiologia , Obesidade/genética , Obesidade/complicações , Fatores Nucleares de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/genéticaRESUMO
BACKGROUND: Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. METHODS: In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. RESULTS: We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. CONCLUSIONS: Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020.
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Injúria Renal Aguda , Interleucina-18 , Adulto , Humanos , Lipocalina-2/urina , Inibidor Tecidual de Metaloproteinase-2 , Creatinina , Injúria Renal Aguda/terapia , Biomarcadores , HospitaisRESUMO
Chlorfenapyr is a new contact and stomach insecticide derived from natural pyrroles secreted by Streptomyces spp. It is a pro-insecticide and acts after metabolic transformation to its active metabolite tralopyril. Tralopyril is an uncoupler of oxidative phosphorylation in the mitochondria of the target insects and of experiment animals, leading to the disruption of adenosine triphosphate synthesis and death. Several fatal human poisonings had been reported and no blood chlorfenapyr or tralopyril measurements were available. The treatment remains supportive. A 32-year-old healthy man ingested 200 mL of 10% chlorfenapyr as a suicide attempt. Unfortunately, he succumbed at 157 h post-ingestion, shortly after having fever and seizures. His serum level of chlorfenapyr at 4 h post-exposure was 77.4 ng/mL, and was undetectable at 113 and 156 h, respectively. The serum levels of tralopyril were 723.6, 14,179, and 9654.2 ng/mL at 4, 113, and 156 h post-ingestion, respectively. The delay in the rise of serum tralopyril levels was noticeable, which seems to correlate with the patient's signs and symptoms. The information may have therapeutic implications in the management of this deadly poisoning.
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Inseticidas , Piretrinas , Animais , Masculino , Humanos , Adulto , Piretrinas/uso terapêutico , PirróisRESUMO
Renal recovery following dialysis-requiring acute kidney injury (AKI-D) is a vital clinical outcome in critical care, yet it remains an understudied area. This retrospective cohort study, conducted in a medical center in Taiwan from 2015 to 2020, enrolled patients with AKI-D during intensive care unit stays. We aimed to develop and temporally test models for predicting dialysis liberation before hospital discharge using machine learning algorithms and explore early predictors. The dataset comprised 90 routinely collected variables within the first three days of dialysis initiation. Out of 1,381 patients who received acute dialysis, 27.3% experienced renal recovery. The cohort was divided into the training group (N = 1135) and temporal testing group (N = 251). The models demonstrated good performance, with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.81-0.88) and an area under the precision-recall curve of 0.69 (95% CI, 0.62-0.76) for the XGBoost model. Key predictors included urine volume, Charlson comorbidity index, vital sign derivatives (trend of respiratory rate and SpO2), and lactate levels. We successfully developed early prediction models for renal recovery by integrating early changes in vital signs and inputs/outputs, which have the potential to aid clinical decision-making in the ICU.
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Injúria Renal Aguda , Unidades de Terapia Intensiva , Aprendizado de Máquina , Diálise Renal , Humanos , Feminino , Masculino , Injúria Renal Aguda/terapia , Injúria Renal Aguda/diagnóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Taiwan/epidemiologia , Curva ROC , Cuidados Críticos/métodosRESUMO
Background: Hyperuricemia and gout are risk factors of nephrolithiasis. However, it is unclear whether the ABCG2 gene contributes to the development of nephrolithiasis. We aimed to investigate the interaction between the ABCG2 rs2231142 variant and incident nephrolithiasis in the Taiwanese population. Methods: A total of 120,267 adults aged 30-70 years were enrolled from the Taiwan Biobank data-base in this retrospective case-control study and genotyped for rs2231142. The primary outcome was the prevalence of self-reported nephrolithiasis. The odds ratio (OR) of incident nephrolithiasis was analyzed by multivariable logistic regression models with adjustment for multifactorial confounding factors. Associations of the ABCG2 rs2231142 variant with serum uric acid levels, and the incident nephrolithiasis were explored. Results: The frequency of rs2231142 T allele was 53%, and 8,410 participants had nephrolithiasis. The multivariable-adjusted OR (95% confidence interval) of nephrolithiasis was 1.18 (1.09-1.28) and 1.12 (1.06-1.18) for TT and GT genotypes, respectively, compared with the GG genotype (p<0.001), specifically in the male population with hyperuricemia. Higher age, male sex, hyperlipidemia, hypertension, diabetes mellitus, hyperuricemia, smoking and overweight were independent risk factors for nephrolithiasis. In contrast, regular physical exercise is a protective factor against nephrolithiasis. Conclusions: ABCG2 genetic variation is a significant risk of nephrolithiasis, independent of serum uric acid levels. For rs2231142 T allele carriers, our result provides evidence for precision healthcare to tackle hyperuricemia, comorbidities, smoking, and overweight, and recommend regular physical exercise for the prevention of nephrolithiasis.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Hiperuricemia , Nefrolitíase , Adulto , Humanos , Masculino , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Bancos de Espécimes Biológicos , Estudos de Casos e Controles , Predisposição Genética para Doença , Hiperuricemia/epidemiologia , Hiperuricemia/genética , Proteínas de Neoplasias/genética , Nefrolitíase/epidemiologia , Nefrolitíase/genética , Sobrepeso , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Taiwan/epidemiologia , Ácido Úrico , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
Purpose: To address the contentious data sharing across hospitals, this study adopted a novel approach, federated learning (FL), to establish an aggregate model for acute kidney injury (AKI) prediction in critically ill patients in Taiwan. Methods: This study used data from the Critical Care Database of Taichung Veterans General Hospital (TCVGH) from 2015 to 2020 and electrical medical records of the intensive care units (ICUs) between 2018 and 2020 of four referral centers in different areas across Taiwan. AKI prediction models were trained and validated thereupon. An FL-based prediction model across hospitals was then established. Results: The study included 16,732 ICU admissions from the TCVGH and 38,424 ICU admissions from the other four hospitals. The complete model with 60 features and the parsimonious model with 21 features demonstrated comparable accuracies using extreme gradient boosting, neural network (NN), and random forest, with an area under the receiver-operating characteristic (AUROC) curve of approximately 0.90. The Shapley Additive Explanations plot demonstrated that the selected features were the key clinical components of AKI for critically ill patients. The AUROC curve of the established parsimonious model for external validation at the four hospitals ranged from 0.760 to 0.865. NN-based FL slightly improved the model performance at the four centers. Conclusion: A reliable prediction model for AKI in ICU patients was developed with a lead time of 24 h, and it performed better when the novel FL platform across hospitals was implemented. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00248-5.
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Introduction: Early fluid balance has been found to affect short-term mortality in critically ill patients; however, there is little knowledge regarding the association between early cumulative fluid balance (CFB) and long-term mortality. This study aims to determine the distinct association between CFB day 1-3 (CFB 1-3) and day 4-7 (CFB 4-7) and long-term mortality in critically ill patients. Patients and Methods: This study was conducted at Taichung Veterans General Hospital, a tertiary care referral center in central Taiwan, by linking the hospital critical care data warehouse 2015-2019 and death registry data of the Taiwanese National Health Research Database. The patients followed up until deceased or the end of the study on 31 December 2019. We use the log-rank test to examine the association between CFB 1-3 and CFB 4-7 with long-term mortality and multivariable Cox regression to identify independent predictors during index admission for long-term mortality in critically ill patients. Results: A total of 4,610 patients were evaluated. The mean age was 66.4 ± 16.4 years, where 63.8% were men. In patients without shock, a positive CFB 4-7, but not CFB 1-3, was associated with 1-year mortality, while a positive CFB 1-3 and CFB 4-7 had a consistent and excess hazard of 1-year mortality among critically ill patients with shock. The multivariate Cox proportional hazard regression model identified that CFB 1-3 and CFB 4-7 (with per 1-liter increment, HR: 1.047 and 1.094; 95% CI 1.037-1.058 and 1.080-1.108, respectively) were independently associated with high long-term mortality in critically ill patients after adjustment of relevant covariates, including disease severity and the presence of shock. Conclusions: We found that the fluid balance in the first week, especially on days 4-7, appears to be an early predictor for long-term mortality in critically ill patients. More studies are needed to validate our findings and elucidate underlying mechanisms.
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The elderly population is expanding rapidly, and that has become a major healthcare burden in terms of chronic kidney disease. The distribution patterns of kidney diseases in these elderly patients remain largely unclear. Here, we compared biopsy-based renal disease patterns between elderly and nonelderly patients. We performed a single-center, retrospective study (1992-2008) on biopsy-proven renal diseases to compare results between geriatric patients (ageâ ≥â 65 years; nâ =â 254) and nongeriatric patients (18â ≤â ageâ <â 65 years; nâ =â 2592). Renal pathology was interpreted by pathologists based on light microscopy, immunofluorescence, and electron microscopy. The ages of the geriatric and nongeriatric groups were 71.8â ±â 4.5 (65.1-87.3) and 39.7â ±â 17.6 (18-64.9) years, respectively, and 74% and 41% of them, respectively, were men. In the geriatric group, the most frequent diagnosis was membranous nephropathy (46.1%), followed by minimal change disease/focal segmental glomerulosclerosis (16.9%), diabetic nephropathy (8.3%), hypertensive nephrosclerosis (7.5%), and IgA nephropathy (5.9%). The geriatric group had more membranous nephropathy and less lupus nephritis and IgA nephropathy than the nongeriatric group. Furthermore, the 5-year survival rate of the geriatric group was significantly low. Our results demonstrated the different distributions of renal biopsy patterns in geriatric patients diagnosed with acute or chronic progressive kidney injury and proteinuria through renal biopsy.
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Glomerulonefrite por IGA , Glomerulonefrite Membranosa , Humanos , Idoso , Masculino , Feminino , Glomerulonefrite por IGA/epidemiologia , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranosa/patologia , Estudos Retrospectivos , Biópsia , Rim/patologiaRESUMO
Acute kidney injury and renal failure are common after heart transplantation. We retrospectively reviewed a national cohort and identified 1129 heart transplant patients. Patients receiving renal replacement therapy after heart transplantation were grouped into the dialysis cohort. The long-term survival and risk factors of dialysis were investigated. Patients who had undergone dialysis were stratified to early or late dialysis for subgroup analysis. The mean follow-up was five years, the incidence of dialysis was 28.4% (21% early dialysis and 7.4% late dialysis). The dialysis cohort had higher overall mortality compared with the non-dialysis cohort. The hazard ratios of mortality in patients with dialysis were 3.44 (95% confidence interval (CI), 2.73-4.33) for all dialysis patients, 3.58 (95% CI, 2.74-4.67) for early dialysis patients, and 3.27 (95% CI, 2.44-4.36; all p < 0.001) for late dialysis patients. Patients with diabetes mellitus, chronic kidney disease, acute kidney injury, and coronary artery disease were at higher risk of renal failure requiring dialysis. Cardiomyopathy, hepatitis B virus infection, and hyperlipidemia treated with statins were associated with a lower risk of renal dysfunction requiring early dialysis. The use of Sirolimus and Mycophenolate mofetil was associated with a lower incidence of late dialysis. Renal dysfunction requiring dialysis after heart transplantation is common in Taiwan. Early and late dialysis were both associated with an increased risk of mortality in heart transplant recipients.
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Chordoma is an uncommon malignant bone tumor that originates from the remnants of the embryonic notochord. In most of the reported cases, chordomas occur at the skull base or in the sacrococcygeal spine but rarely in the thoracic spine. In this report, we describe a case of a large thoracic chordoma with posterior mediastinal extension in a 25-year-old woman who presented with left-hand anhydrosis. The imaging studies, pathology findings, and recent advances in treatment are discussed.