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1.
Exp Mol Med ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39218979

RESUMEN

Functional variations in coding and noncoding RNAs are crucial in tumorigenesis, with cancer-specific alterations often resulting from chemical modifications and posttranscriptional processes mediated by enzymes. These RNA variations have been linked to tumor cell proliferation, growth, metastasis, and drug resistance and are valuable for identifying diagnostic or prognostic cancer biomarkers. The diversity of posttranscriptional RNA modifications, such as splicing, polyadenylation, methylation, and editing, is particularly significant due to their prevalence and impact on cancer progression. Additionally, other modifications, including RNA acetylation, circularization, miRNA isomerization, and pseudouridination, are recognized as key contributors to cancer development. Understanding the mechanisms underlying these RNA modifications in cancer can enhance our knowledge of cancer biology and facilitate the development of innovative therapeutic strategies. Targeting these RNA modifications and their regulatory enzymes may pave the way for novel RNA-based therapies, enabling tailored interventions for specific cancer subtypes. This review provides a comprehensive overview of the roles and mechanisms of various coding and noncoding RNA modifications in cancer progression and highlights recent advancements in RNA-based therapeutic applications.

2.
J Clin Med ; 13(17)2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39274527

RESUMEN

Background: We aimed to evaluate the association between androgen deprivation therapy (ADT) and newly developed dry eye syndrome (DES) in patients with prostate cancer. Methods: A nested case-control study was conducted. From the nationwide claims database of the Republic of Korea, 125,005 patients were included in the final analysis. Cases were defined as those newly diagnosed with DES during follow-up, and 12,654 patients were identified. The cases were matched with controls in a ratio of 1:4. Odds ratios (ORs) for newly developed DES associated with ADT were estimated using conditional logistic regression. Results: After matching, 7499 cases and 29,996 controls were selected. ADT was associated with a reduced risk of newly developed DES in patients with prostate cancer compared to no ADT (OR = 0.875; 95% confidence interval, 0.825-0.927; p < 0.0001). An accumulated dose of ADT < 1 year was associated with a reduced risk of incidental DES (OR = 0.811; 95% CI, 0.751-0.875; p < 0.0001), and a duration of 1-2 years was also associated with a reduced risk (OR = 0.890; 95% CI, 0.802-0.986; p = 0.026). No association was observed with an ADT duration of ≥2 years. Conclusions: The use of ADT, especially for shorter durations (<2 years), was associated with a reduced risk of newly developed DES in S. Korean patients with prostate cancer.

3.
Eur J Clin Nutr ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060541

RESUMEN

OBJECTIVE: To investigate the relationship of serum uric acid (Uacid) and derived parameters as predictors of insulin resistance (IR) and elevated liver transaminases in children and adolescents METHODS: Data of 1648 participants aged 10-18 years was analyzed using nationwide survey. Logistic regression analysis was performed with IR and elevated liver transaminases as dependent variables, and odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles 2 and 3 of each parameter in comparison to tertile 1, which served as the reference. Receiver operating characteristic (ROC) curves were generated to assess predictability of the parameters for IR and elevated liver transaminases. RESULTS: Hyperuricemia, IR, and elevated liver transaminases were significantly associated with each other. All Uacid and derived markers showed continuous increase in ORs and 95% CIs for IR and elevated liver transaminases across the tertiles of several biochemical and metabolic variables of interest (all p < 0.001), and were also significantly predictive in ROC curve. Overall, Uacid combined with obesity indices showed higher ORs and area under the curve (AUC) compared to Uacid alone. Uacid-body mass index (BMI) standard deviation score presented the largest AUC for IR. For elevated liver transaminases, Uacid-BMI and Uacid-waist-to-height ratio showed the largest AUC. CONCLUSIONS: Uacid combined with obesity indices are robust markers for prediction of IR and elevated liver transaminases in children and adolescents. Uacid and derived markers have potential as simple markers which do not require fasting for screening of IR and elevated liver transaminases in children and adolescents.

4.
Biomedicines ; 12(7)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39062161

RESUMEN

PURPOSE: To investigate whether preoperative ultrasonographic (US) features of the index cancer and metastatic lymph nodes (LNs) are associated with level II LN metastasis in N1b papillary rmfthyroid carcinoma (PTC) patients. MATERIALS AND METHODS: We enrolled 517 patients (mean age, 42 [range, 6-80] years) who underwent total thyroidectomy and lateral compartment LN dissection between January 2009 and December 2015. We reviewed the clinicopathologic and US features of the index cancer and metastatic LNs in the lateral neck. Logistic regression analysis was performed to analyze features associated with level II LN metastasis. RESULTS: Among the patients, 196 (37.9%) had level II metastasis on final pathology. In the preoperative model, larger tumor size (odds ratios [ORs], 1.031; 95% confidence interval [CI]: 1.011-1.051, p = 0.002), nonparallel tumor shape (OR, 1.963; 95% CI: 1.322-2.915, p = 0.001), multilevel LN involvement (OR, 1.906; 95% CI: 1.242-2.925, p = 0.003), and level III involvement (OR, 1.867; 95% CI: 1.223-2.850, p = 0.004), were independently associated with level II LN metastasis. In the postoperative model, non-conventional pathology remained a significant predictor for level II LN metastasis (OR, 1.951; 95% CI: 1.121-3.396; p = 0.018), alongside the presence of extrathyroidal extension (OR, 1.867; 95% CI: 1.060-3.331; p = 0.031), and higher LN ratio (OR, 1.057; 95% CI: 1.039-1.076; p < 0.001). CONCLUSIONS: Preoperative US features of the index tumor and LN may be helpful in guiding surgery in N1b PTC. These findings could enhance preoperative planning and decision-making, potentially reducing surgical morbidities by identifying those at higher risk of level II LN metastasis and tailoring surgical approaches accordingly.

5.
Cancer Epidemiol Biomarkers Prev ; 33(9): 1248-1252, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38904462

RESUMEN

BACKGROUND: Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results. METHODS: We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software. RESULTS: None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni P-value of 5 × 10-6 and less-stringent P-value of 3.5 × 10-5 accounting for the number of "independent" SNPs). None of the 10 top (nonsignificant) SNPs and corresponding genes overlapped across ancestry groups. CONCLUSIONS: This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups. IMPACT: Genetic variants in the folate pathway alone do not appear to substantially influence childhood acute lymphoblastic leukemia risk. Other mechanisms such as gene-folate interaction, DNA methylation, or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.


Asunto(s)
Ácido Fólico , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Ácido Fólico/metabolismo , Ácido Fólico/administración & dosificación , Niño , Estudios de Casos y Controles , Femenino , Masculino , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Predisposición Genética a la Enfermedad , Preescolar
6.
Proc Natl Acad Sci U S A ; 121(26): e2319322121, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38900789

RESUMEN

Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.


Asunto(s)
COVID-19 , Receptor para Productos Finales de Glicación Avanzada , SARS-CoV-2 , Humanos , Receptor para Productos Finales de Glicación Avanzada/metabolismo , COVID-19/inmunología , COVID-19/metabolismo , COVID-19/patología , COVID-19/complicaciones , COVID-19/virología , Animales , Ratones , Inflamación/metabolismo , Inflamación/patología , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/virología , Lesión Pulmonar/inmunología , Lesión Pulmonar/metabolismo , Lesión Pulmonar/patología , Proteínas del Grupo de Alta Movilidad/metabolismo , Proteínas del Grupo de Alta Movilidad/genética , Masculino , Pulmón/patología , Pulmón/metabolismo , Pulmón/inmunología , Femenino
7.
Int J Stroke ; : 17474930241265652, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38907672

RESUMEN

BACKGROUND: Multiple attempts of thrombectomy have been linked to a higher risk of intracerebral hemorrhage and worsened functional outcomes, potentially influenced by blood pressure (BP) management strategies. Nonetheless, the impact of intensive BP management following successful recanalization through multiple attempts remains uncertain. AIMS: This study aimed to investigate whether conventional and intensive BP managements differentially affect outcomes according to multiple-attempt recanalization (MAR) and first-attempt recanalization (FAR) groups. METHODS: In this secondary analysis of the OPTIMAL-BP trial, which was a comparison of intensive (systolic BP target: <140 mm Hg) and conventional (systolic BP target = 140-180 mm Hg) BP managements during the 24 h after successful recanalization, we included intention-to-treat population of the trial. Patients were divided into the MAR and the FAR groups. We examined a potential interaction between the number of thrombectomy attempts (MAR and FAR groups) and the effect of BP managements on clinical and safety outcomes. The primary outcome was functional independence at 3 months. Safety outcomes were symptomatic intracerebral hemorrhage within 36 h and mortality within 3 months. RESULTS: Of the 305 patients (median = 75 years), 102 (33.4%) were in the MAR group and 203 (66.6%) were in the FAR group. The intensive BP management was significantly associated with a lower rate of functional independence in the MAR group (intensive, 32.7% vs conventional, 54.9%, adjusted odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12-0.90, p = 0.03). In the FAR group, the proportion of patients with functional independence was not significantly different between the BP managements (intensive, 42.5% vs conventional, 54.2%, adjusted OR = 0.73, 95% CI = 0.38-1.40). Incidences of symptomatic intracerebral hemorrhage and mortality rates were not significantly different according to the BP managements in both MAR and FAR groups. CONCLUSIONS: Among stroke patients who received multiple attempts of thrombectomy, intensive BP management for 24 h resulted in a reduced chance of functional independence at 3 months and did not reduce symptomatic intracerebral hemorrhage following successful reperfusion.

9.
Front Endocrinol (Lausanne) ; 15: 1385002, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38883602

RESUMEN

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a growing health concern in pediatric populations due to its association with obesity and metabolic syndrome. Bioelectrical impedance analysis (BIA) offers a non-invasive and potentially effective alternative for identifying MASLD risk in youth with overweight or obesity. Therefore, this study aimed to assess the utility of BIA for screening for MASLD in the youth. Method: This retrospective, cross-sectional study included 206 children and adolescents aged <20 years who were overweight and obese. The correlations between anthropometric measurements and BIA parameters and alanine aminotransferase (ALT) levels were assessed using Pearson's correlation analysis. Logistic regression analysis was performed to examine the associations between these parameters and ALT level elevation and MASLD score. Receiver operating characteristic (ROC) curves were generated to assess the predictive ability of the parameters for MASLD. Results: Pearson's correlation analysis revealed that waist-to-hip ratio (WHR), percentage body fat (PBF), and BIA parameters combined with anthropometric measurements were correlated with ALT level. Logistic regression revealed that WHR, skeletal muscle mass/WHR, PBF-WHR, fat-free mass/WHR, and appendicular skeletal muscle mass/WHR were correlated with ALT level elevation after adjusting for age, sex, and puberty. WHR, PBF-WHR, and visceral fat area (VFA)-WHR were positively correlated with the MASLD score in the total population after adjusting for age, sex, and puberty. PBF-WHR and VFA-WHR were correlated with the MASLD score even in youth with a normal ALT level. The cutoff points and area under the ROC curves were 34.6 and 0.69 for PBF-WHR, respectively, and 86.6 and 0.79 for VFA-WHR, respectively. Discussion: This study highlights the utility of combining BIA parameters and WHR in identifying the risk of MASLD in overweight and obese youth, even in those with a normal ALT level. BIA-based screening offers a less burdensome and more efficient alternative to conventional MASLD screening methods, facilitating early detection and intervention in youth at risk of MASLD.


Asunto(s)
Impedancia Eléctrica , Sobrepeso , Relación Cintura-Cadera , Humanos , Masculino , Femenino , Niño , Estudios Transversales , Adolescente , Estudios Retrospectivos , Sobrepeso/complicaciones , Obesidad Infantil/complicaciones , Síndrome Metabólico/complicaciones , Hígado Graso/complicaciones , Composición Corporal , Índice de Masa Corporal , Pronóstico
10.
PLoS One ; 19(6): e0304362, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38857214

RESUMEN

This study aimed to define real-world prescription patterns in Korea and compare the effectiveness of chronic obstructive pulmonary disease (COPD) medications. We used national claims data provided by the Health Insurance Review and Assessment Service in Korea and examined patients who were first diagnosed with COPD and started treatment between May 1, 2017, and April 30, 2018, with no change in drug regimen. Among 30,784 patients with COPD, long-acting ß2 agonist (LABA) combined with long-acting muscarinic antagonist (LAMA) (32.7%), inhaled corticosteroid-LABA (ICS-LABA) (25.6%), LAMA (18.3%), ICS (5.8%), or LABA (4.6%) were prescribed as the first-choice inhalers. The use of LABA-LAMA (hazard ratio [HR], 0.248-0.584), LAMA (HR, 0.320-0.641), ICS-LABA (HR, 0.325-0.643), and xanthine (HR, 0.563-0.828) significantly reduced the total and severe exacerbation rates compared with no use of each medication. However, the use of ICS or LABA individually did not yield such effects. The continued use of LABA-LAMA, LAMA, and ICS-LABA showed a significant effect on exacerbation rate, whereas the long-term use of ICS, LABA, and xanthine did not. Moreover, some high doses of ICS-LABA did not show significant effects. This real-world study revealed that LAMA and/or LABA could be the first choice of therapy, as recommended by recent guidelines. However, ICS, xanthine, and high-dose ICS-LABA are still being prescribed frequently as first-line drugs in Korea.


Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2 , Antagonistas Muscarínicos , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/uso terapéutico , República de Corea , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Resultado del Tratamiento , Broncodilatadores/uso terapéutico , Broncodilatadores/administración & dosificación , Prescripciones de Medicamentos/estadística & datos numéricos , Adulto
11.
J Clin Med ; 13(10)2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38792519

RESUMEN

Background/Objectives: to evaluate the association between androgen deprivation therapy (ADT) and newly developed neovascular age-related macular degeneration (AMD) in patients with prostate cancer. Methods: We identified 228,803 men from the nationwide claims database in the Republic of Korea diagnosed with prostate cancer between 1 August 2009 and 31 December 2018 and followed until April 2021. Cases were defined as those newly diagnosed with neovascular AMD during follow-up. Cases were matched with controls based on age, index date, and follow-up duration, at a case-to-control ratio of 1:4. Adjusted odds ratios (aORs) of incident neovascular AMD associated with ADT were estimated using conditional logistic regression. Results: The main analysis included 1700 cases and 6800 controls, with a median follow-up of 3.42 years. ADT was associated with a reduced risk of incident neovascular AMD in patients with prostate cancer (aOR = 0.840; 95% confidence interval [CI], 0.743-0.951; p = 0.0058) in the multivariable analysis. A cumulative ADT duration less than 1 year was associated with a reduced risk of neovascular AMD (aOR = 0.727; 95% CI, 0.610-0.866; p = 0.0004); however, no association was observed when the duration of ADT was between 1 and 2 years (aOR = 0.862; 95% CI, 0.693-1.074; p = 0.1854) or more than 2 years (aOR = 1.009; 95% CI, 0.830-1.226; p = 0.9304). Conclusions: In patients with prostate cancer, medical castration for less than a year is associated with a reduced risk of incident neovascular AMD. These results suggest that androgens are involved in the pathogenesis of neovascular AMD.

12.
J Pers Med ; 14(4)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38673009

RESUMEN

This study compared the overall postoperative recovery of patients who underwent total intravenous anesthesia with remimazolam or propofol, using the Quality of Recovery-15 questionnaire (QoR-15). Seventy-two patients who underwent spine surgery with intraoperative neurophysiological monitoring (IONM) were randomly categorized into the remimazolam group (group R) or propofol group (group P). On the first postoperative day, the QoR-15 scores for groups P and R were 114 and 112, respectively, indicating no significant difference (p = 0.691). Similarly, group-time interaction effects on QoR-15 scores were not significantly different. In the post-anesthesia care unit, the pain intensity at rest was notably higher in group P than in group R (3.0 [0.0] vs. 2.8 [0.5], respectively, p = 0.009). Although the intraoperative consumption of remifentanil was higher in group R (1452.4 µg vs. 2066.8 µg, respectively, p < 0.001), the intraoperative use of vasopressors was lower in group R (1705.6 µg vs. 286.1 µg, respectively, p < 0.001) compared to group P. Group R exhibited significantly lower variability in mean blood pressure over time compared to group P. Remimazolam was viewed as a promising intravenous agent for general anesthesia, showing potential to replace propofol in spine surgery with IONM, considering both recovery quality and intraoperative hemodynamic stability.

13.
JAMA Netw Open ; 7(4): e246878, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38630474

RESUMEN

Importance: The associations between blood pressure (BP) decreases induced by medication and functional outcomes in patients with successful endovascular thrombectomy remain uncertain. Objective: To evaluate whether BP reductions induced by intravenous BP medications are associated with poor functional outcomes at 3 months. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, a comparison of intensive and conventional BP management during the 24 hours after successful recanalization from June 18, 2020, to November 28, 2022. This study included 302 patients who underwent endovascular thrombectomy, achieved successful recanalization, and exhibited elevated BP within 2 hours of successful recanalization at 19 stroke centers in South Korea. Exposure: A BP decrease was defined as at least 1 event of systolic BP less than 100 mm Hg. Patients were divided into medication-induced BP decrease (MIBD), spontaneous BP decrease (SpBD), and no BP decrease (NoBD) groups. Main Outcomes and Measures: The primary outcome was a modified Rankin scale score of 0 to 2 at 3 months, indicating functional independence. Primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and mortality due to index stroke within 3 months. Results: Of the 302 patients (median [IQR] age, 75 [66-82] years; 180 [59.6%] men), 47 (15.6%)were in the MIBD group, 39 (12.9%) were in the SpBD group, and 216 (71.5%) were in the NoBD group. After adjustment for confounders, the MIBD group exhibited a significantly smaller proportion of patients with functional independence at 3 months compared with the NoBD group (adjusted odds ratio [AOR], 0.45; 95% CI, 0.20-0.98). There was no significant difference in functional independence between the SpBD and NoBD groups (AOR, 1.41; 95% CI, 0.58-3.49). Compared with the NoBD group, the MIBD group demonstrated higher odds of mortality within 3 months (AOR, 5.15; 95% CI, 1.42-19.4). The incidence of symptomatic intracerebral hemorrhage was not significantly different among the groups (MIBD vs NoBD: AOR, 1.89; 95% CI, 0.54-5.88; SpBD vs NoBD: AOR, 2.75; 95% CI, 0.76-9.46). Conclusions and Relevance: In this cohort study of patients with successful endovascular thrombectomy after stroke, MIBD within 24 hours after successful recanalization was associated with poor outcomes at 3 months. These findings suggested lowering systolic BP to below 100 mm Hg using BP medication might be harmful.


Asunto(s)
Hipertensión , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Masculino , Presión Sanguínea , Hemorragia Cerebral , Estudios de Cohortes , Hipertensión/epidemiología , Presión , Accidente Cerebrovascular/cirugía , Anciano de 80 o más Años
14.
Cardiovasc Diabetol ; 23(1): 92, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38468265

RESUMEN

BACKGROUND: Research on identifiable risks for metabolic syndrome (MetS) is ongoing, and growing evidence suggests that bilirubin is a potent antioxidant and cytoprotective agent against MetS. However, there have been conflicting results on the association between bilirubin and MetS. Our study aimed to validate the association by separately stratifying data for men and women in a longitudinal prospective study. METHODS: Data were derived from the Korean Genome Epidemiology Study provided by the Korea Centers for Disease Control and Prevention. Data from 5,185 adults aged 40-69 years (3,089 men and 2,096 women) without MetS were analyzed. The participants were divided according to sex-specific quartiles of serum total bilirubin levels and followed up biennially for 16 years (until 2018). The log-rank test was used for obtaining the Kaplan-Meier curves of cumulative incidence of MetS according to sex-specific serum total bilirubin quartiles, and the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident metabolic syndrome were analyzed with a multiple Cox proportional hazard regression analysis model, after propensity score matching for removing differences at baseline. RESULTS: With increasing serum total bilirubin quartiles, the incidence rate per 1000 person-years proportionally decreased in both men and women. After propensity score matching and adjusting for confounding variables, the HRs (95% CIs) for MetS of the highest quartile in reference to the lowest quartile were 1.00 (0.80-1.24) for men and 0.80 (0.65-0.99) for women. Higher quartiles of serum total bilirubin showed significantly lower cumulative incidence of MetS in women (log-rank test p = 0.009), but not in men (log-rank test p = 0.285). CONCLUSION: Serum total bilirubin levels were significantly inversely associated with MetS in women, but there was no significant association observed in men. Sex differences in the effects of serum total bilirubin should be noted when predicting incident MetS by sex in clinical settings.


Asunto(s)
Síndrome Metabólico , Adulto , Humanos , Femenino , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Factores de Riesgo , Estudios Prospectivos , Caracteres Sexuales , Vida Independiente , Puntaje de Propensión , Bilirrubina , Incidencia , República de Corea/epidemiología
15.
Cell Genom ; 4(4): 100526, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38537633

RESUMEN

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children.


Asunto(s)
Predisposición Genética a la Enfermedad , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Niño , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Factores de Transcripción/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Hispánicos o Latinos/genética , Factor de Transcripción Ikaros/genética
16.
Dig Liver Dis ; 56(9): 1529-1536, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38336494

RESUMEN

BACKGROUNDS: Dietary components and the development of metabolic dysfunction-associated liver disease (MASLD) are closely linked, but large-scale studies on dietary patterns and MASLD are scarce, most previous studies having focused on individual nutrients or foods rather than overall dietary patterns. Therefore, we aimed to investigate the association between dietary patterns and MASLD in Koreans. METHODS: A total of 6,052 participants from the Korean Genome and Epidemiology Study. Dietary intake was assessed using a validated Korean semiquantitative food frequency questionnaire comprising 106 food items. Principal component analysis was used to determine the major dietary patterns. Cox proportional hazard regression analysis was performed to assess the association between the incidence of MASLD and dietary patterns. RESULTS: Four major dietary patterns, namely carnivore, plant-based, dairy-rich, and starch-rich diet patterns, were identified. The carnivore, plant-based, and starch-rich diet patterns showed no significant association with incident MASLD, while the dairy-rich diet pattern was associated with a lower risk of MASLD, also showing significantly lower cumulative incidence of MASLD in the higher adherence to dairy-rich diet pattern. CONCLUSION: The dairy-rich diet pattern was significantly associated with a lower risk of MASLD in Koreans. Appropriate dietary guidance based on dietary patterns is crucial for preventing MASLD.


Asunto(s)
Productos Lácteos , Dieta , Humanos , República de Corea/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Dieta/efectos adversos , Incidencia , Modelos de Riesgos Proporcionales , Factores de Riesgo , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/etiología , Conducta Alimentaria , Patrones Dietéticos
17.
Clin Exp Emerg Med ; 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38286505

RESUMEN

Object: Effective triage of febrile patients in the emergency department is crucial during times of overcrowding to prioritize care and allocate resources, especially during pandemics. However, available triage tools often require laboratory data and lack accuracy. We aimed to develop a simple and accurate triage tool for febrile patients by modifying the qSOFA score. Methods: We retrospectively analyzed data from 7,303 febrile patients and created modified versions of qSOFA using factors identified through multivariable analysis. The performance of these modified qSOFAs in predicting in hospital mortality and intensive care unit (ICU) admission was compared using the area under the receiver operating characteristic curve (AUROC). Results: Through multivariable analysis, the identified factors were age (A), male sex (M), SpO2 (S), and lactate levels (L). The AUROCs of ASqSOFA (for in-hospital mortality: 0.812; 95% CI: 0.789-0.835, for ICU admission: 0.794; 95% CI: 0.771-0.817), which included age and SpO2 with qSOFA, were simple and not inferior to other more complex models (e.g., ASMqSOFA, ASLqSOFA, and ASMLqSOFA). ASqSOFA also displayed significantly higher AUROC than other triage scales, such as the modified early warning score and Korean triage and acuity scale. The optimal cut-off score of ASqSOFA for the outcome was 2 and the score for redistribution to a lower-level emergency department was 0. Conclusion: We demonstrated that ASqSOFA can be employed as a simple and efficient triage tool for emergency febrile patients to aid in resource distribution during overcrowding. It may also be applicable in pre-hospital settings for febrile patient triage.

19.
Prostate ; 84(4): 403-413, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38149792

RESUMEN

BACKGROUND: It is uncertain how long combination therapy should be continued in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). We investigated the withdrawal effects of α1-adrenergic receptor blocker (AB) or 5α-reductase inhibitor (5ARI) following successful combination therapy. METHODS: This prospective, randomized, open-label, parallel trial enrolled 222 patients with BPH/LUTS who showed at least a seven-point improvement in International Prostate Symptom Score-total (IPSS-T) and a ≥ 20% reduction in prostate volume (PV) following the initiation of combination therapy. Patients were randomized in a 1:1:1 ratio into continued-combination, AB-withdrawal, and 5ARI-withdrawal groups. IPSS, overactive bladder symptom score, EuroQol-five-dimensional questionnaire (EQ-5D-5L), EuroQol-visual analog scale (EQ-VAS), prostate volume (PV), maximal flow rate, postvoid residual urine (PVR), and prostate-specific antigen level were assessed every 6 months for 24 months. The predictors of IPSS-T deterioration were evaluated. RESULTS: At Month 24, IPSS-T deterioration (≥2 point) was observed in 20/72 (27.8%) and 19/72 (26.4%) patients in the AB- and 5ARI-withdrawal groups, respectively. Among them, 4/72 (5.6%) and 4/70 (5.7%) patients required readdition of the withdrawn drug (p = 0.868). In the continued combination group, EQ-VAS improved at Month 24 compared to baseline (p = 0.028). At Month 24, the AB-withdrawal group showed improvements in EQ-5D-5L, EQ-VAS, and PVR (all p < 0.005), while the 5ARI-withdrawal group showed improvement in IPSS-S (p = 0.011). Diabetes mellitus was associated with IPSS-T deterioration at Month 24 (p = 0.020). CONCLUSIONS: In patients with BPH/LUTS who are reluctant to continue combination therapy, AB or 5ARI withdrawal may be offered in men with improvement in IPSS-T by at least seven points and reduction in PV by at least 20%.


Asunto(s)
Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Retención Urinaria , Masculino , Humanos , Hiperplasia Prostática/tratamiento farmacológico , Estudios Prospectivos , Quimioterapia Combinada , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Antagonistas Adrenérgicos alfa/uso terapéutico , Síntomas del Sistema Urinario Inferior/etiología , Retención Urinaria/etiología , Oxidorreductasas/uso terapéutico , Resultado del Tratamiento
20.
Biomedicines ; 11(12)2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-38137474

RESUMEN

Surgical stress can compromise the immune system of patients with cancer, affecting susceptibility to perioperative infections, tumor progression, treatment responses, and postoperative recovery. Perioperatively reducing inflammatory responses could improve outcomes. We determined the impact of intraoperative dexmedetomidine administration on the inflammatory response and postoperative recovery in patients undergoing elective laparoscopy-assisted gastrectomy. These patients were randomly assigned to the dexmedetomidine or control group (n = 42 each). The primary endpoint was the C-reactive protein (CRP) level on postoperative day 1. The secondary endpoints included the perioperative interleukin (IL)-6 levels, postoperative numerical rating scale (NRS) scores, and rescue analgesic doses. There were no significant between-group differences in terms of CRP levels. The IL-6 levels at the end of the surgery, NRS scores in the post-anesthesia care unit, and rescue pethidine requirements within the first hour postoperatively were significantly lower in the dexmedetomidine group than in the control group. The bolus deliveries-to-attempts ratio (via patient-controlled analgesia) at 2 h differed significantly between the two groups. However, IL-6 reduction was confined to a single timepoint, and the postoperative analgesic effects lasted for the first 2 h postoperatively. Low-dose dexmedetomidine infusion (0.4 µg kg-1 h-1) during laparoscopy-assisted gastrectomy exerts minimal anti-inflammatory effects.

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