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1.
Anaesthesia ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775305

RESUMEN

BACKGROUND: Understanding how patients' frailty and the physiological stress of surgical procedures affect postoperative outcomes may inform risk stratification of older patients undergoing surgery. The objective of the study was to examine the association of peri-operative frailty with mortality, 30-day readmission and days at home after non-cardiac surgical procedures of different physiological stress. METHODS: This retrospective study used Medicare claims data from a 7.125% random sample of Medicare fee-for-service beneficiaries from 2015 to 2019 who were aged ≥ 65 years and underwent non-cardiac surgical procedure listed in the Operative Stress Score categories. The exposure of the study was claims-based frailty index (robust, < 0.15; pre-frail, 0.15 to < 0.25; mildly frail, 0.25 to < 0.35; and moderate-to-severely frail, ≥ 0.35) with Operative Stress Score categories being 1, very low stress to 5, very high stress. The primary outcome was all-cause mortality at 30 days and 365 days after the surgical procedure. RESULTS: In total, 1,019,938 patients (mean (SD) age of 76.1 (7.3) years; 52.3% female; 16.8% frail) were included. The cumulative incidence of mortality generally increased with Operative Stress Score category, ranging from 5.0% (Operative Stress Score 2) to 24.9% (Operative Stress Score 4) at 365 days. Within each category, increasing frailty was associated with mortality at 30 days (hazard ratio comparing moderate-to-severe frailty vs. robust ranged from 1.59-3.91) and at 365 days (hazard ratio 1.30-4.04). The variation in postoperative outcomes by patients' frailty level was much greater than the variation by the operative stress category. CONCLUSIONS: These results emphasise routine frailty screening before major and minor non-cardiac procedures and the need for greater clinician awareness of postoperative outcomes beyond 30 days in shared decision-making with older adults with frailty.

2.
Ann Geriatr Med Res ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757259

RESUMEN

Medication is a potential factor influencing frailty. However, the relationship between pharmaceutical treatments and frailty remains unclear. Therefore, we conducted the present systematic review to summarize the association between drug therapy and the risk of incident frailty in older adults. We systematically searched the MEDLINE electronic database for articles indexed between January 1, 2000, and December 31, 2021, for randomized controlled trials (RCTs) and cohort studies reporting frailty changes associated with drug therapy. A total of 6 RCTs and 13 cohort studies involving 211,948 participants were identified, and their treatments were categorized into six medication classes: analgesics, cardiometabolic medication, chemotherapy, central nervous system (CNS)-active medication, hormonal therapy, and nutritional supplements. While the analysis revealed that only CNS-active medications were associated with an elevated risk of frailty, other medication classes also affected frailty; however, this is not conclusively attributable to a class-wide effect.

3.
Oncologist ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716777

RESUMEN

BACKGROUND: Frailty is a dynamic syndrome characterized by reduced physiological reserve to maintain homeostasis. Prospective studies have reported frailty worsening in women with breast cancer during chemotherapy, with improvements following treatment. We evaluated whether the Faurot frailty index, a validated claims-based frailty measure, could identify changes in frailty during chemotherapy treatment and identified predictors of trajectory patterns. METHODS: We included women (65+ years) with stage I-III breast cancer undergoing adjuvant chemotherapy in the SEER-Medicare database (2003-2019). We estimated the Faurot frailty index (range: 0-1; higher scores indicate greater frailty) at chemotherapy initiation, 4 months postinitiation, and 10 months postinitiation. Changes in frailty were compared to a matched noncancer comparator cohort. We identified patterns of frailty trajectories during the year following chemotherapy initiation using K-means clustering. RESULTS: Twenty-one thousand five hundred and ninety-nine women initiated adjuvant chemotherapy. Mean claims-based frailty increased from 0.037 at initiation to 0.055 4 months postchemotherapy initiation and fell to 0.049 10 months postinitiation. Noncancer comparators experienced a small increase in claims-based frailty over time (0.055-0.062). We identified 6 trajectory patterns: a robust group (78%), 2 resilient groups (16%), and 3 nonresilient groups (6%). Black women and women with claims for home hospital beds, wheelchairs, and Parkinson's disease were more likely to experience nonresilient trajectories. CONCLUSIONS: We observed changes in a claims-based frailty index during chemotherapy that are consistent with prior studies using clinical measures of frailty and identified predictors of nonresilient frailty trajectories. Our study demonstrates the feasibility of using claims-based frailty indices to assess changes in frailty during cancer treatment.

4.
J Am Heart Assoc ; 13(10): e033611, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38761083

RESUMEN

BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. CONCLUSIONS: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.


Asunto(s)
Aspirina , Clopidogrel , Terapia Antiplaquetaria Doble , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Sistema de Registros , Humanos , Clopidogrel/uso terapéutico , Aspirina/uso terapéutico , Masculino , Anciano , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/prevención & control , Terapia Antiplaquetaria Doble/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Anciano de 80 o más Años , Factores de Tiempo , Japón/epidemiología , Prevención Secundaria/métodos , Prevención Secundaria/tendencias , Quimioterapia Combinada , Factores de Riesgo
5.
JACC Adv ; 3(4)2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38694996

RESUMEN

Calcific aortic stenosis can be considered a model for geriatric cardiovascular conditions due to a confluence of factors. The remarkable technological development of transcatheter aortic valve replacement was studied initially on older adult populations with prohibitive or high-risk for surgical valve replacement. Through these trials, the cardiovascular community has recognized that stratification of these chronologically older adults can be improved incrementally by invoking the concept of frailty and other geriatric risks. Given the complexity of the aging process, stratification by chronological age should only be the initial step but is no longer sufficient to optimally quantify cardiovascular and noncardiovascular risk. In this review, we employ a geriatric cardiology lens to focus on the diagnosis and the comprehensive management of aortic stenosis in older adults to enhance shared decision-making with patients and their families and optimize patient-centered outcomes. Finally, we highlight knowledge gaps that are critical for future areas of study.

6.
Investig Clin Urol ; 65(3): 279-285, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38714518

RESUMEN

PURPOSE: To investigate the relationship between urine cytology results after overnight continuous saline irrigation (OCSI) following transurethral resection of bladder tumor (TURBT) and bladder tumor recurrence in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A retrospective study was conducted on patients diagnosed with NMIBC between 2016 and 2020 after undergoing TURBT at our hospital. All patients received OCSI following TURBT and had urine cytology test at postoperative 1 day. Urine cytology was classified into three groups: Negative, low-grade urothelial neoplasm (LGUN)+atypical urothelial cells (AUC), and suspicious for high-grade urothelial carcinoma (SHGUC)+high-grade urothelial carcinoma (HGUC). Recurrence-free survival (RFS) in each group was compared using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to evaluate independent prognostic factors. RESULTS: A total of 172 patients were included in this study. Based on urine cytology group (after OCSI), RFS did not reach the median value in the Negative group. In the LGUN+AUC group, the median RFS was 615.00 days. In the SHGUC+HGUC group, the median RFS was 377.00 days. In survival analysis, the Negative group had a longer RFS than the SHGUC+HGUC group (p=0.013). However, Cox regression analysis showed that SHGUC+HGUC was not an independent prognostic factor for recurrence. CONCLUSIONS: Urine cytology results after OCSI following TURBT in NMIBC were associated with bladder tumor recurrence. Specifically, SHGUC or HGUC in urine cytology after OCSI showed earlier recurrence than negative cases. However, further research is needed to accurately determine whether it is an independent prognostic factor.


Asunto(s)
Recurrencia Local de Neoplasia , Solución Salina , Irrigación Terapéutica , Neoplasias de la Vejiga Urinaria , Orina , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina , Neoplasias de la Vejiga Urinaria/cirugía , Recurrencia Local de Neoplasia/orina , Estudios Retrospectivos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Orina/citología , Solución Salina/administración & dosificación , Cistectomía/métodos , Factores de Tiempo , Uretra/patología , Urinálisis , Resección Transuretral de la Vejiga , Citología
7.
J Gen Intern Med ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38592606

RESUMEN

BACKGROUND: The effect of clinical interventions may vary by patients' frailty status. Understanding treatment effect heterogeneity by frailty could lead to frailty-guided treatment strategies and reduce overtreatment and undertreatment. This systematic review aimed to examine the effect modification by frailty in randomized controlled trials (RCTs) that evaluate pharmacological, non-pharmacological, and multicomponent interventions. METHODS: We searched PubMed, Web of Science, EMBASE, and ClinicalTrial.gov, from their inception to 8 December 2023. Two reviewers independently extracted trial data and examined the study quality with senior authors. RESULTS: Sixty-one RCTs that evaluated the interaction between frailty and treatment effects in older adults were included. Frailty was evaluated using different tools such as the deficit accumulation frailty index, frailty phenotype, and other methods. The effect of several pharmacological interventions (e.g., edoxaban, sacubitril/valsartan, prasugrel, and chemotherapy) varied according to the degree of frailty, whereas other treatments (e.g., antihypertensives, vaccinations, osteoporosis medications, and androgen medications) demonstrated consistent benefits across different frailty levels. Some non-pharmacological interventions had greater benefits in patients with higher (e.g., chair yoga, functional walking, physical rehabilitation, and higher dose exercise program) or lower (e.g., intensive lifestyle intervention, psychosocial intervention) levels of frailty, while others (e.g., resistance-type exercise training, moderate-intensive physical activity, walking and nutrition or walking) produced similar intervention effects. Specific combined interventions (e.g., hospital-based disease management programs) demonstrated inconsistent effects across different frailty levels. DISCUSSION: The efficacy of clinical interventions often varied by frailty levels, suggesting that frailty is an important factor to consider in recommending clinical interventions in older adults. REGISTRATION: PROSPERO registration number CRD42021283051.

9.
Animals (Basel) ; 14(7)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38612332

RESUMEN

Sinus venosus atrial septal defects (SVASDs), concurrent with partial anomalous pulmonary venous connections (PAPVCs), are a rare congenital heart disease in dogs. Surgical correction is essential when clinical signs or significant hemodynamic changes are present. We aimed to report on the successful surgical correction of an SVASD with PAPVCs, using a computed tomography (CT)-based customized 3D cardiac model. A 10-month-old male poodle was referred for corrective surgery for an ASD. Echocardiography confirmed a hemodynamically significant left-to-right shunting flow through an interatrial septal defect and severe right-sided heart volume overload. For a comprehensive diagnosis, a CT scan was performed, which confirmed an SVASD with PAPVCs. A customized 3D cardiac model was used for preoperative decision-making and surgical rehearsal. The defect was repaired using an autologous pericardial patch under a cardiopulmonary bypass (CPB). Temporary pacing was applied for sinus bradycardia and third-degree atrioventricular block. The patient recovered from the anesthesia without further complications. The pacemaker was removed during hospitalization and the patient was discharged without complications 2 weeks post-surgery. At the three-month follow-up, there was no shunting flow in the interatrial septum and the right-sided volume overload had been resolved. The cardiac medications were discontinued, and there were no complications. This report indicates the validity of surgical correction under CPB for an SVASD with PAPVCs, and the advantages of utilizing a CT-based 3D cardiac model for preoperative planning to increase the surgical success rate.

10.
Clin Epidemiol ; 16: 267-279, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645475

RESUMEN

Background: High risk of intracranial hemorrhage (ICH) is a leading reason for withholding anticoagulation in patients with atrial fibrillation (AF). We aimed to develop a claims-based ICH risk prediction model in older adults with AF initiating oral anticoagulation (OAC). Methods: We used US Medicare claims data to identify new users of OAC aged ≥65 years with AF in 2010-2017. We used regularized Cox regression to select predictors of ICH. We compared our AF ICH risk score with the HAS-BLED bleed risk and Homer fall risk scores by area under the receiver operating characteristic curve (AUC) and assessed net reclassification improvement (NRI) when predicting 1-year risk of ICH. Results: Our study cohort comprised 840,020 patients (mean [SD] age 77.5 [7.4] years and female 52.2%) split geographically into training (3963 ICH events [0.6%] in 629,804 patients) and validation (1397 ICH events [0.7%] in 210,216 patients) sets. Our AF ICH risk score, including 50 predictors, had superior AUCs of 0.653 and 0.650 in the training and validation sets than the HAS-BLED score of 0.580 and 0.567 (p<0.001) and the Homer score of 0.624 and 0.623 (p<0.001). In the validation set, our AF ICH risk score reclassified 57.8%, 42.5%, and 43.9% of low, intermediate, and high-risk patients, respectively, by HAS-BLED score (NRI: 15.3%, p<0.001). Similarly, it reclassified 0.0, 44.1, and 19.4% of low, intermediate, and high-risk patients, respectively, by the Homer score (NRI: 21.9%, p<0.001). Conclusion: Our novel claims-based ICH risk prediction model outperformed the standard HAS-BLED score and can inform OAC prescribing decisions.

11.
Front Vet Sci ; 11: 1270819, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650855

RESUMEN

Two intact male dogs were evaluated for symptoms, including hematuria, prostatomegaly, anuria, lethargy, and abdominal mass. Presurgical evaluations, including complete physical examinations, blood examinations, abdominal radiography with contrast (only in Case 2), ultrasonography, and computed tomography and magnetic resonance imaging (only in Case 1), were performed. A paraprostatic cyst was diagnosed initially, and laparoscopic exploration and surgery were performed. Complete resection was performed in case 1, whereas partial resection with omentalization was performed in case 2. Histopathological examination of the tissue samples confirmed the presence of paraprostatic pseudocysts in both cases, with no evidence of an epithelial lining. These two cases represent the first documented instances of laparoscopic treatment for extraparenchymal prostatic cysts. The laparoscopic treatment proved feasible even in the case of a giant cyst causing anuria (Case 2). Paraprostatic cysts should be considered a potential differential diagnosis for abnormal urination accompanied by an abdominal mass, and long-term postoperative follow-up is necessary.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38557604

RESUMEN

BACKGROUND: The relationship of claims-based frailty index (CFI), a validated measure to identify frail individuals using Medicare data, and frailty measures used in clinical practice has not yet been fully explored. METHODS: We identified community-dwelling participants of the 2015 National Health and Aging Trends Study (NHATS) whose CFI scores could be calculated using linked Medicare claims. We calculated 9 commonly used clinical frailty measures from NHATS in-person examination: Study of Osteoporotic Fracture Index (SOF), FRAIL Scale, Frailty Phenotype, Clinical Frailty Scale (CFS), Vulnerable Elder Survey-13 (VES-13), Tilburg Frailty Indicator (TFI), Groningen Frailty Indicator (GFI), Edmonton Frail Scale (EFS), and 40-item Frailty Index (FI). Using equipercentile method, CFI scores were linked to clinical frailty measures. Then, C-statistics and test characteristics of CFI to identify frailty defined by each clinical frailty measure were calculated. RESULTS: Of the 3,963 older adults, 44.5% were ≥75 years, 59.4% were female, and 82.3% were non-Hispanic White. A CFI of 0.25 was equipercentile to the following clinical frailty measures scores: SOF 1.4, FRAIL 1.8, Phenotype 1.8, CFS 5.4, VES-13 5.7, TFI 4.6, GFI 5.0, EFS 6.0, and FI 0.26. The C-statistics of using CFI to identify frailty defined by each clinical measure were above ≥0.70 except for CFS and VES-13. The optimal CFI cutpoints to identify frailty per clinical frailty measure ranged from 0.212 to 0.242, with sensitivity and specificity of 0.37-0.83 and 0.66-0.84, respectively. CONCLUSION: Understanding the relationship of CFI and commonly used clinical frailty measures can enhance the interpretability and potential utility of CFI.

15.
Med Care ; 62(5): 305-313, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38498870

RESUMEN

BACKGROUND: Frailty is an aging-related syndrome of reduced physiological reserve to maintain homeostasis. The Faurot frailty index has been validated as a Medicare claims-based proxy for predicting frailty using billing information from a user-specified ascertainment window. OBJECTIVES: We assessed the validity of the Faurot frailty index as a predictor of the frailty phenotype and 1-year mortality using varying frailty ascertainment windows. RESEARCH DESIGN: We identified older adults (66+ y) in Round 5 (2015) of the National Health and Aging Trends Study with Medicare claims linkage. Gold standard frailty was assessed using the frailty phenotype. We calculated the Faurot frailty index using 3, 6, 8, and 12 months of claims prior to the survey or all-available lookback. Model performance for each window in predicting the frailty phenotype was assessed by quantifying calibration and discrimination. Predictive performance for 1-year mortality was assessed by estimating risk differences across claims-based frailty strata. RESULTS: Among 4253 older adults, the 6 and 8-month windows had the best frailty phenotype calibration (calibration slopes: 0.88 and 0.87). All-available lookback had the best discrimination (C-statistic=0.780), but poor calibration. Mortality associations were strongest using a 3-month window and monotonically decreased with longer windows. Subgroup analyses revealed worse performance in Black and Hispanic individuals than counterparts. CONCLUSIONS: The optimal ascertainment window for the Faurot frailty index may depend on the clinical context, and researchers should consider tradeoffs between discrimination, calibration, and mortality. Sensitivity analyses using different durations can enhance the robustness of inferences. Research is needed to improve prediction across racial and ethnic groups.


Asunto(s)
Fragilidad , Humanos , Anciano , Estados Unidos/epidemiología , Anciano Frágil , Medicare , Evaluación Geriátrica , Encuestas y Cuestionarios
16.
J Ginseng Res ; 48(2): 149-162, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38465223

RESUMEN

Ginseng, the roots of Panax species, is an important medicinal herb used as a tonic. As ginsenosides are key bioactive components of ginseng, holistic chemical profiling of them has provided many insights into understanding ginseng. Mass spectrometry has been a major methodology for profiling, which has been applied to realize numerous goals in ginseng research, such as the discrimination of different species, geographical origins, and ages, and the monitoring of processing and biotransformation. This review summarizes the various applications of ginsenoside profiling in ginseng research over the last three decades that have contributed to expanding our understanding of ginseng. However, we also note that most of the studies overlooked a crucial factor that influences the levels of ginsenosides: genetic variation. To highlight the effects of genetic variation on the chemical contents, we present our results of untargeted and targeted ginsenoside profiling of different genotypes cultivated under identical conditions, in addition to data regarding genome-level genetic diversity. Additionally, we analyze the other limitations of previous studies, such as imperfect variable control, deficient metadata, and lack of additional effort to validate causation. We conclude that the values of ginsenoside profiling studies can be enhanced by overcoming such limitations, as well as by integrating with other -omics techniques.

17.
Investig Clin Urol ; 65(2): 148-156, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38454824

RESUMEN

PURPOSE: This study aimed to assess the clinical outcome and safety of holmium laser enucleation of the prostate (HoLEP) following transrectal ultrasound-guided prostate biopsy (TR biopsy) in the treatment of benign prostate hyperplasia. MATERIALS AND METHODS: We retrospectively analyzed data from 556 patients who underwent HoLEP between 2014 and 2021. The patients were categorized into six groups: Group 1-A (n=45) underwent HoLEP within four months post TR biopsy. Group 1-B (n=94) underwent HoLEP more than four months post TR biopsy. Group 1-C (n=120) underwent HoLEP after a single TR biopsy. Group 1-D (n=19) underwent HoLEP after two or more TR biopsies. Group 1-total (n=139, group 1-A+group 1-B or group 1-C+group 1-D) underwent HoLEP post TR biopsy. Group 2 (control group, n=417) underwent HoLEP without prior TR biopsy. We examined perioperative parameters, safety, and functional outcomes. RESULTS: The age, body mass index, International Prostate Symptom Score (IPSS), uroflowmetry, and comorbid diseases between group 1-total and group 2 were comparable. However, group 1-total exhibited significantly elevated prostate-specific antigen levels and larger prostate volumes (p<0.01). Perioperative factors like enucleation time, enucleation weight, and catheterization duration were notably higher in group 1-total (p<0.01). All groups showed significant improvements in IPSS, postvoid residual urine, and maximum flow rate during the 1-year postoperative period (p<0.05). The rates of postoperative complications were similar between group 1-total and group 2. CONCLUSIONS: Enucleation time and catheterization duration were significantly longer in the TR biopsy group. However, postoperative complications were not significantly different between TR biopsy and non-TR biopsy groups.


Asunto(s)
Láseres de Estado Sólido , Hiperplasia Prostática , Resección Transuretral de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/cirugía , Hiperplasia Prostática/diagnóstico por imagen , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Láseres de Estado Sólido/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Calidad de Vida , Biopsia , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía
18.
Aging (Albany NY) ; 16(5): 4095-4115, 2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38441531

RESUMEN

FoxO6, an identified factor, induces hyperlipidemia and hepatic steatosis during aging by activating hepatic lipoprotein secretion and lipogenesis leading to increased ApoC3 concentrations in the bloodstream. However, the intricate mechanisms underlying hepatic steatosis induced by elevated FoxO6 under hyperglycemic conditions remain intricate and require further elucidation. In order to delineate the regulatory pathway involving ApoC3 controlled by FoxO6 and its resultant functional impacts, we employed a spectrum of models including liver cell cultures, aged rats subjected to HFD, transgenic mice overexpressing FoxO6 (FoxO6-Tg), and FoxO6 knockout mice (FoxO6-KO). Our findings indicate that FoxO6 triggered ApoC3-driven lipid accumulation in the livers of aged rats on an HFD and in FoxO6-Tg, consequently leading to hepatic steatosis and hyperglycemia. Conversely, the absence of FoxO6 attenuated the expression of genes involved in lipogenesis, resulting in diminished hepatic lipid accumulation and mitigated hyperlipidemia in murine models. Additionally, the upregulation of FoxO6 due to elevated glucose levels led to increased ApoC3 expression, consequently instigating cellular triglyceride mediated lipid accumulation. The transcriptional activation of FoxO6 induced by both the HFD and high glucose levels resulted in hepatic steatosis by upregulating ApoC3 and genes associated with gluconeogenesis in aged rats and liver cell cultures. Our conclusions indicate that the upregulation of ApoC3 by FoxO6 promotes the development of hyperlipidemia, hyperglycemia, and hepatic steatosis in vivo, and in vitro. Taken together, our findings underscore the significance of FoxO6 in driving hyperlipidemia and hepatic steatosis specifically under hyperglycemic states by enhancing the expression of ApoC3 in aged rats.


Asunto(s)
Hígado Graso , Hipercolesterolemia , Hiperglucemia , Hiperlipidemias , Animales , Ratones , Ratas , Dieta Alta en Grasa/efectos adversos , Hígado Graso/metabolismo , Glucosa/metabolismo , Hiperglucemia/metabolismo , Hiperlipidemias/metabolismo , Hígado/metabolismo , Ratones Noqueados , Ratones Transgénicos , Factores de Transcripción/metabolismo , Triglicéridos/metabolismo , Regulación hacia Arriba , Factores de Transcripción Forkhead/metabolismo , Apolipoproteína C-III/metabolismo
19.
Reprod Toxicol ; 125: 108559, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38378073

RESUMEN

Avobenzone (AVO), an ultraviolet (UV) filter, is frequently used as an ingredient in personal cosmetics. This UV filter has been found to be easily exposed in swimming pools and beaches, and it has been detected in human urine and blood. Moreover, numerous studies have demonstrated that AVO exhibits endocrine-disrupting properties. Nevertheless, the effects of AVO on male fertility have not yet fully understood. Therefore, this study aimed to assess the effects of AVO on various sperm functions during capacitation. First, boar spermatozoa were treated with various AVO concentrations. After treatment, sperm motility and kinetic characteristics, capacitation status, intracellular adenosine triphosphate (ATP) levels, and sperm viability were evaluated. Moreover, Western blot analysis w.as conducted to evaluate protein kinase A (PKA) activity and tyrosine phosphorylation. As a result, AVO treatment significantly decreased total motility, progressive motility, and several kinetic characteristics at high concentrations (50 and 100 µM). Furthermore, the capacitation status dose-dependently decreased. Conversely, no significant differences in acrosome reaction, cell viability, and intracellular ATP levels were observed. However, the intracellular ATP level tended to decrease. In addition, AVO dose-dependently induced abnormal changes in PKA activity and tyrosine phosphorylation. Although AVO did not directly exert a toxic effect on cell viability, it ultimately negatively affected sperm functions through abnormal alterations in PKA activity and tyrosine phosphorylation. Thus, the potential implications on male fertility must be considered when contemplating the safe utilization of AVO.


Asunto(s)
Propiofenonas , Semen , Motilidad Espermática , Masculino , Porcinos , Animales , Humanos , Fosforilación , Semen/metabolismo , Espermatozoides , Tirosina/metabolismo , Adenosina Trifosfato/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Capacitación Espermática
20.
Ann Neurol ; 95(4): 788-799, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38381765

RESUMEN

OBJECTIVE: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS). METHODS: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods. RESULTS: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2. INTERPRETATION: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799.


Asunto(s)
Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Arteria Basilar , Resultado del Tratamiento , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular/etiología , Trombectomía/efectos adversos , Hemorragias Intracraneales/etiología , Sistema de Registros , Procedimientos Endovasculares/efectos adversos
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