Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
1.
Childs Nerv Syst ; 40(7): 2051-2059, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38526575

RESUMO

INTRODUCTION: Intraventricular hemorrhage (IVH) can ensue permanent neurologic dysfunction, morbidity, and mortality. While previous reports have identified disparities based on patient gender or weight, no prior study has assessed how race may influence in neonatal or infantile IVH patients. The aim of this study was to investigate the impact of race on adverse event (AE) rates, length of stay (LOS), and total cost of admission among newborns with IVH. METHODS: Using the 2016-2019 National Inpatient Sample database, newborns diagnosed with IVH were identified using ICD-10-CM codes. Patients were stratified based on race. Patient characteristics and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of race on extended LOS and exorbitant cost. RESULTS: Of 1435 patients, 650 were White (45.3%), 270 African American (AA) (18.8%), 300 Hispanic (20.9%), and 215 Other (15.0%). A higher percentage of AA and Other patients than Hispanic and White patients were < 28 days old (p = 0.008). Each of the cohorts had largely similar presenting comorbidities and symptoms, although AA patients did have significantly higher rates of NEC (p < 0.001). There were no observed differences in rates of AEs, rates of mortality, mean LOS, or mean total cost of admission. Similarly, on multivariate analysis, no race was identified as a significant independent predictor of extended LOS or exorbitant cost. CONCLUSIONS: Our study found that in newborns with IVH, race is not associated with proxies of poor healthcare outcomes like prolonged LOS or excessive cost. Further studies are needed to validate these findings.


Assuntos
Tempo de Internação , Humanos , Recém-Nascido , Masculino , Feminino , Tempo de Internação/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Negro ou Afro-Americano , Hemorragia Cerebral Intraventricular/epidemiologia , Hemorragia Cerebral/etnologia , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/economia , Hemorragia Cerebral/mortalidade , População Branca
2.
Childs Nerv Syst ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38955900

RESUMO

BACKGROUND: Intraventricular hemorrhage (IVH) often affects newborns of low gestational age and low birth weight, requires critical care for neonates, and is linked to long-term neurodevelopmental outcomes. Assessing regional differences in the U.S. in care for neonatal IVH and subsequent outcomes can shed light on ways to mitigate socioeconomic disparities. METHODS: Using the 2016-2019 National Inpatient Sample (NIS), patients with a primary diagnosis of IVH were identified using ICD-10-CM codes. A retrospective cohort study was conducted with patients stratified by hospital region. Demographics, comorbidities, presentation, intraoperative variables, and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as > 75th percentile of LOS), exorbitant cost (defined as > 75th percentile of cost), and mortality. RESULTS: Included in this study were 1630 newborns with IVH. A larger portion of patients in the South and Midwest were Black, compared to the Northeast and West (Northeast: 12.2% vs Midwest: 30.2% vs South: 22.8% vs West: 5.8%, p < 0.001), while a greater percentage of patients in the West and South were Hispanic (Northeast: 7.3% vs Midwest: 9.5% vs South: 22.8% vs West: 36.2%, p < 0.001). LOS was similar among all regions. Factors associated with prolonged LOS included hydrocephalus and CSF diversions. Median total cost of admission was highest in the West, while the South was associated with decreased odds of exorbitant cost. LOS was associated with exorbitant cost, and large bed-volume hospital, VLBW, and permanent CSF shunt were associated with mortality. CONCLUSIONS: Demographic variables, but not presenting or intraoperative variables, differed among regions, pointing to possible geographic health disparities. The West had the highest total cost of admission, while the South was associated with reduced odds of exorbitant admission costs.

3.
J Craniofac Surg ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38752737

RESUMO

OBJECTIVE: The objective of this study was to assess whether race and ethnicity are independent predictors of inferior postoperative clinical outcomes, including increased complication rates, extended length of stay (LOS), and unplanned 30-day readmission following cranial vault repair for craniosynostosis. METHODS: A retrospective cohort study was performed using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric database. Pediatric patients under 2 years of age undergoing cranial vault repair for craniosynostosis between 2012 and 2021 were identified using the International Classification of Diseases-9/10 and Current Procedural Terminology codes. Patients were dichotomized into 4 cohorts: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and other. Only patients with available race and ethnicity data were included in this study. Patient demographics, comorbidities, surgical variables, postoperative adverse events, and hospital resource utilization were assessed. Multivariate logistic regression analysis was used to assess the impact of race on complications, extended LOS, and unplanned readmissions. RESULTS: In our cohort of 7764 patients, 72.80% were NHW, 8.44% were NHB, 15.10% were Hispanic, and 3.67% were categorized as "other." Age was significantly different between the 4 cohorts (P<0.001); NHB patients were the oldest, with an average age of 327.69±174.57 days old. Non-Hispanic White experienced the least adverse events while NHB experienced the most (P=0.01). Total operative time and hospital LOS were shorter for NHW patients (P<0.001 and P<0.001, respectively). Rates of unplanned 30-day readmission, unplanned reoperation, and 30-day mortality did not differ significantly between the 4 cohorts. On multivariate analysis, race was found to be an independent predictor of extended LOS [NHB: adjusted odds ratio: 1.30 (1.04-1.62), P=0.021; other: 2.28 (1.69-3.04), P=0.005], but not of complications or readmission. CONCLUSIONS: Our study demonstrates that racial and ethnic disparities exist among patients undergoing cranial vault reconstruction for craniosynostosis. These disparities, in part, may be due to delayed age of presentation among non-Hispanic, non-White patients. Further investigations to elucidate the underlying causes of these disparities are necessary to address gaps in access to care and provide equitable health care to at-risk populations.

4.
East Mediterr Health J ; 23(6): 404-407, 2017 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-28836652

RESUMO

The aim of this case-control study was to determine the frequency of pica and its relationship with iron deficiency in children in Zanjan. We selected 872 children and determined the frequency of pica. We selected students who did not have pica of the same age and sex, and in the same class as our cases as a control group. Both groups were evaluated for iron deficiency anaemia. Among the 57 students (6.7%) who had pica, there was no significant relationship with sex (P > 0.05). The most common types of pica were soil (62.3%) and paper (31.2%). The frequency of anaemia among cases was greater than in controls, although the difference was not statistically significant. The serum iron/total iron binding capacity ratio ≤ 0.15 did not differ significantly between the 2 groups. We did not find any association between pica and anaemia and/or iron deficiency (P > 0.05).


Assuntos
Anemia Ferropriva/epidemiologia , Ferro/sangue , Pica/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Prevalência
5.
Neurosurgery ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836613

RESUMO

BACKGROUND AND OBJECTIVES: Intracranial modulation paradigms, namely deep brain stimulation (DBS) and motor cortex stimulation (MCS), have been used to treat intractable pain disorders. However, treatment efficacy remains heterogeneous, and factors associated with pain reduction are not completely understood. METHODS: We performed an individual patient review of pain outcomes (visual analog scale, quality-of-life measures, complications, pulse generator implant rate, cessation of stimulation) after implantation of DBS or MCS devices. We evaluated 663 patients from 36 study groups and stratified outcomes by pain etiology and implantation targets. RESULTS: Included studies comprised primarily retrospective cohort studies. MCS patients had a similar externalized trial success rate compared with DBS patients (86% vs 81%; P = .16), whereas patients with peripheral pain had a higher trial success rate compared with patients with central pain (88% vs 79%; P = .004). Complication rates were similar for MCS and DBS patients (12% vs 15%; P = .79). Patients with peripheral pain had lower likelihood of device cessation compared with those with central pain (5.7% vs 10%; P = .03). Of all implanted patients, mean pain reduction at last follow-up was 45.8% (95% CI: 40.3-51.2) with a 31.2% (95% CI: 12.4-50.1) improvement in quality of life. No difference was seen between MCS patients (43.8%; 95% CI: 36.7-58.2) and DBS patients (48.6%; 95% CI: 39.2-58) or central (41.5%; 95% CI: 34.8-48.2) and peripheral (46.7%; 95% CI: 38.9-54.5) etiologies. Multivariate analysis identified the anterior cingulate cortex target to be associated with worse pain reduction, while postherpetic neuralgia was a positive prognostic factor. CONCLUSION: Both DBS and MCS have similar efficacy and complication rates in the treatment of intractable pain. Patients with central pain disorders tended to have lower trial success and higher rates of device cessation. Additional prognostic factors include anterior cingulate cortex targeting and postherpetic neuralgia diagnosis. These findings underscore intracranial neurostimulation as an important modality for treatment of intractable pain disorders.

6.
J Neurosurg Pediatr ; : 1-9, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996393

RESUMO

OBJECTIVE: The authors evaluated the impact of the timing of epilepsy surgery on postoperative neurocognitive outcomes in a cohort of children followed in the multiinstitutional Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research Network (TACERN) study. METHODS: Twenty-seven of 159 patients in the TACERN cohort had drug-refractory epilepsy and underwent surgery. Ages at surgery ranged from 15.86 to 154.14 weeks (median 91.93 weeks). Changes in patients' first preoperative (10-58 weeks) to last postoperative (155-188 weeks) scores on three neuropsychological tests-the Mullen Scales of Early Learning (MSEL), the Vineland Adaptive Behavior Scales, 2nd edition (VABS-2), and the Preschool Language Scales, 5th edition (PLS-5)-were calculated. Pearson correlation and multivariate linear regression models were used to correlate test outcomes separately with age at surgery and duration of epilepsy prior to surgery. Analyses were separately conducted for patients whose seizure burdens decreased postoperatively (n = 21) and those whose seizure burdens did not (n = 6). Regression analysis was specifically focused on the 21 patients who achieved successful seizure control. RESULTS: Age at surgery was significantly negatively correlated with the change in the combined verbal subtests of the MSEL (R = -0.45, p = 0.039) and predicted this score in a multivariate linear regression model (ß = -0.09, p = 0.035). Similar trends were seen in the total language score of the PLS-5 (R = -0.4, p = 0.089; ß = -0.12, p = 0.014) and in analyses examining the duration of epilepsy prior to surgery as the independent variable of interest. Associations between age at surgery and duration of epilepsy prior to surgery with changes in the verbal subscores of VABS-2 were more variable (R = -0.15, p = 0.52; ß = -0.05, p = 0.482). CONCLUSIONS: Earlier surgery and shorter epilepsy duration prior to surgery were associated with greater improvement in postoperative language in patients with TSC. Prospective or comparative effectiveness clinical trials are needed to further elucidate surgical timing impacts on neurocognitive outcomes.

7.
Spine J ; 24(4): 682-691, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38101547

RESUMO

BACKGROUND CONTEXT: Type II odontoid fractures (OF) are among the most common cervical spine injuries in the geriatric population. However, there is a paucity of literature regarding their epidemiology. Additionally, the optimal management of these injuries remains controversial, and no study has evaluated the short-term outcomes of geriatric patients presenting to emergency departments (ED). PURPOSE: This study aims to document the epidemiology of geriatric patients presenting to EDs with type II OFs and determine whether surgical management was associated with early adverse outcomes such as in-hospital mortality and discharge to skilled nursing facilities (SNF). STUDY DESIGN: This is a retrospective cohort study. PATIENT SAMPLE: Data was used from the 2016-2020 Nationwide Emergency Department Sample. Patient encounters corresponding to type II OFs were identified. Patients younger than 65 at the time of presentation to the ED and those with concomitant spinal pathology were excluded. OUTCOME MEASURES: The association between the surgical management of geriatric type II OFs and outcomes such as in-hospital mortality and discharge to SNFs. METHODS: Patient, fracture, and surgical management characteristics were recorded. A propensity score matched cohort was constructed to reduce differences in age, comorbidities, and injury severity between patients undergoing operative and nonoperative management. Additionally, to develop a positive control for the analysis of geriatric patients with type II OFs and no other concomitant spinal pathology, a cohort of patients that had been excluded due to the presence of a concomitant spinal cord injury (SCI) was also constructed. Multivariate regressions were then performed on both the matched and unmatched cohorts to ascertain the associations between surgical treatment and in-hospital mortality, inpatient length of stay, encounter charges, and discharge to SNFs. RESULTS: A total of 11,325 encounters were included. The mean total charge per encounter was $60,221. 634 (5.6%) patients passed away during their encounters. In total, 1,005 (8.9%) patients were managed surgically. Surgical management of type II OFs was associated with a 316% increase in visit charge (95% CI: 291%-341%, p<.001), increased inpatient length of stay (IRR: 2.87, 95% CI: 2.62-3.12, p<.001), and increased likelihood of discharge to SNFs (OR=2.62, 95% CI: 2.26-3.05, p<.001), but decreased in-hospital mortality (OR=0.32, CI: 0.21-0.45, p<.001). The propensity score matched cohort consisted of 2,010 patients, matching each of the 1,005 that underwent surgery to 1,005 that did not. These cohorts were well balanced across age (78.24 vs 77.91 years), Elixhauser Comorbidity Index (3.68 vs 3.71), and Injury Severity Score (30.15 vs 28.93). This matching did not meaningfully alter the associations determined between surgical management and in-hospital mortality (OR=0.34, CI=0.21-0.55, p<.001) or SNF discharge (OR=2.59, CI=2.13-3.16, p<.001). Lastly, the positive control cohort of patients with concurrent SCI had higher rates of SNF discharge (50.0% vs 42.6%, p<.001), surgical management (32.3% vs 9.7%, p<.001), and in-hospital mortality (28.9% vs 5.6%, p<.001). CONCLUSIONS: This study lends insight into the epidemiology of geriatric type II OFs and quantifies risk factors influencing adverse outcomes. Patient informed consent should include a discussion of the protective association between definitive surgical management and in-hospital mortality against potential operative morbidity, increased lengths of hospital stay, and increased likelihood of discharge to SNFs. This information may impact patient treatment selection and decision making.


Assuntos
Processo Odontoide , Traumatismos da Medula Espinal , Fraturas da Coluna Vertebral , Humanos , Idoso , Fraturas da Coluna Vertebral/epidemiologia , Estudos Retrospectivos , Processo Odontoide/cirurgia , Processo Odontoide/lesões , Instituições de Cuidados Especializados de Enfermagem , Alta do Paciente , Mortalidade Hospitalar , Traumatismos da Medula Espinal/complicações , Serviço Hospitalar de Emergência
8.
World Neurosurg ; 182: e16-e28, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37925147

RESUMO

OBJECTIVE: The rise of spinal surgery for ankylosing spondylitis (AS) necessitates balancing health care costs with quality patient care. Frailty has been independently associated with adverse outcomes and increased costs. This study investigates whether frailty is an independent predictor of poor outcomes after elective surgery for AS. METHODS: Using the National Inpatient Sample (NIS) database, a retrospective study was conducted on adult patients with AS who underwent posterior spinal fusion for fracture between 2016 and 2019. Each patient was assigned a modified frailty index (mFI) score and categorized as prefrail (mFI = 0 or 1), moderately frail (mFI = 2), and highly frail (mFI≥3). Multivariate logistic regression analyses were used to identify independent predictors of extended length of stay, non-routine discharge (NRD), and exorbitant admission costs. RESULTS: Of the 1910 patients, 35.3% were prefrail, 31.2% moderately frail, and 33.5% highly frail. Age was significantly different across groups (P < 0.001), and frailty was associated with increased comorbidities (P < 0.001). Mean length of stay (P = 0.007), NRD rate (P < 0.001), and mean cost of admission (P = 0.002) all significantly increased with increasing frailty. However, frailty was not an independent predictor of extended hospital stay, NRD, or higher costs on multivariate analysis. Instead, predictors included multiple adverse events, number of comorbidities, and race. CONCLUSIONS: While frailty in patients with AS is associated with older age, greater comorbidities, and increased adverse events, it was not an independent predictor of extended hospital stay, NRD, or higher hospital costs. Further research is required to understand the full impact of frailty on surgical outcomes and develop effective interventions.


Assuntos
Fragilidade , Fraturas da Coluna Vertebral , Espondilite Anquilosante , Adulto , Humanos , Fragilidade/complicações , Fraturas da Coluna Vertebral/cirurgia , Estudos Retrospectivos , Espondilite Anquilosante/complicações , Espondilite Anquilosante/cirurgia , Fatores de Risco , Aceitação pelo Paciente de Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia
9.
J Clin Med ; 13(12)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38930084

RESUMO

Background: Anterior lumbar interbody fusion (ALIF) and posterior spinal fusion (PSF) play pivotal roles in restoring lumbar lordosis in spinal surgery. There is an ongoing debate between combined single-position surgery and traditional prone-position PSF for optimizing segmental lumbar lordosis. Methods: This retrospective study analyzed 59 patients who underwent ALIF in the supine position followed by PSF in the prone position at a single institution. Cobb angles were measured preoperatively, post-ALIF, and post-PSF using X-ray imaging. One-way repeated measures ANOVA and post-hoc analyses with Bonferroni adjustment were employed to compare mean Cobb angles at different time points. Cohen's d effect sizes were calculated to assess the magnitude of changes. Sample size calculations were performed to ensure statistical power. Results: The mean segmental Cobb angle significantly increased from preoperative (32.2 ± 13.8 degrees) to post-ALIF (42.2 ± 14.3 degrees, Cohen's d: -0.71, p < 0.0001) and post-PSF (43.6 ± 14.6 degrees, Cohen's d: -0.80, p < 0.0001). There was no significant difference between Cobb angles after ALIF and after PSF (Cohen's d: -0.10, p = 0.14). The findings remained consistent when Cobb angles were analyzed separately for single-screw and double-screw ALIF constructs. Conclusions: Both supine ALIF and prone PSF significantly increased segmental lumbar lordosis compared to preoperative measurements. The negligible difference between post-ALIF and post-PSF lordosis suggests that supine ALIF followed by prone PSF can be an effective approach, providing flexibility in surgical positioning without compromising lordosis improvement.

10.
World Neurosurg ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815926

RESUMO

BACKGROUND: Within the field of pediatric neurosurgery, insurance status has been shown to be associated with surgical delay, longer time to referral, and longer hospitalization in epilepsy treatment, myelomeningocele repair, and spasticity surgery.1,2 The aim of this study was to investigate the association of insurance status with inpatient adverse events (AEs), length of stay (LOS), and costs for newborns diagnosed with intraventricular hemorrhage (IVH). METHODS: A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. Patients with a primary diagnosis of intraventricular hemorrhage were identified using ICD-10-CM diagnostic and procedural codes. Patients were categorized based on insurance status: Medicaid or Private Insurance (PI). Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as >75th percentile of LOS) and exorbitant cost (defined as >75th percentile of cost). RESULTS: Demographics differed significantly between groups, with the majority of newborns in the PI cohort being White (Medicaid: 35.8% vs. PI: 60.3%, P < 0.001) and the majority of Medicaid patients being in the 0-25th quartile of household income (Medicaid: 40.9% vs. PI: 12.9%, P < 0.001). While insurance status was not independently associated with increased odds of extended LOS or exorbitant cost, Medicaid patients had a greater mean LOS and total cost of admission than PI patients. CONCLUSIONS: Demographic characteristics, mean LOS, and mean total cost differed significantly between Medicaid and PI patients, indicating potential disparities based on insurance status. However, insurance status was not independently associated with increased healthcare utilization, necessitating further research in this area of study.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38679323

RESUMO

BACKGROUND: Deep brain stimulation has shown promise in treating individual patients with treatment-resistant depression, but larger-scale trials have been less successful. Here, we created what is, to our knowledge, the largest meta-analysis with individual patient data to date to explore whether the use of tractography enhances the efficacy of deep brain stimulation for treatment-resistant depression. METHODS: We systematically reviewed 1823 articles, selecting 32 that contributed data from 366 patients. We stratified the individual patient data based on stimulation target and use of tractography. Using 2-way type III analysis of variance, Welch's 2-sample t tests, and mixed-effects linear regression models, we evaluated changes in depression severity 1 year (9-15 months) postoperatively and at last follow-up (4 weeks to 8 years) as assessed by depression scales. RESULTS: Tractography was used for medial forebrain bundle (MFB) (n = 17 tractography/32 total), subcallosal cingulate (SCC) (n = 39 tractography/241 total), and ventral capsule/ventral striatum (n = 3 tractography/41 total) targets; it was not used for bed nucleus of stria terminalis (n = 11), lateral habenula (n = 10), and inferior thalamic peduncle (n = 1). Across all patients, tractography significantly improved mean depression scores at 1 year (p < .001) and last follow-up (p = .009). Within the target cohorts, tractography improved depression scores at 1 year for both MFB and SCC, though significance was met only at the α = 0.1 level (SCC: ß = 15.8%, p = .09; MFB: ß = 52.4%, p = .10). Within the tractography cohort, patients with MFB tractography showed greater improvement than patients with SCC tractography (72.42 ± 7.17% vs. 54.78 ± 4.08%) at 1 year (p = .044). CONCLUSIONS: Our findings underscore the promise of tractography in deep brain stimulation for treatment-resistant depression as a method for personalization of therapy, supporting its inclusion in future trials.

12.
J Clin Med ; 13(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38337352

RESUMO

Background: Adult spinal deformities (ASD) are varied spinal abnormalities, often necessitating surgical intervention when associated with pain, worsening deformity, or worsening function. Predicting post-operative complications and revision surgery is critical for surgical planning and patient counseling. Due to the relatively small number of cases of ASD surgery, machine learning applications have been limited to traditional models (e.g., logistic regression or standard neural networks) and coarse clinical variables. We present the novel application of advanced models (CNN, LLM, GWAS) using complex data types (radiographs, clinical notes, genomics) for ASD outcome prediction. Methods: We developed a CNN trained on 209 ASD patients (1549 radiographs) from the Stanford Research Repository, a CNN pre-trained on VinDr-SpineXR (10,468 spine radiographs), and an LLM using free-text clinical notes from the same 209 patients, trained via Gatortron. Additionally, we conducted a GWAS using the UK Biobank, contrasting 540 surgical ASD patients with 7355 non-surgical ASD patients. Results: The LLM notably outperformed the CNN in predicting pulmonary complications (F1: 0.545 vs. 0.2881), neurological complications (F1: 0.250 vs. 0.224), and sepsis (F1: 0.382 vs. 0.132). The pre-trained CNN showed improved sepsis prediction (AUC: 0.638 vs. 0.534) but reduced performance for neurological complication prediction (AUC: 0.545 vs. 0.619). The LLM demonstrated high specificity (0.946) and positive predictive value (0.467) for neurological complications. The GWAS identified 21 significant (p < 10-5) SNPs associated with ASD surgery risk (OR: mean: 3.17, SD: 1.92, median: 2.78), with the highest odds ratio (8.06) for the LDB2 gene, which is implicated in ectoderm differentiation. Conclusions: This study exemplifies the innovative application of cutting-edge models to forecast outcomes in ASD, underscoring the utility of complex data in outcome prediction for neurosurgical conditions. It demonstrates the promise of genetic models when identifying surgical risks and supports the integration of complex machine learning tools for informed surgical decision-making in ASD.

13.
Neuron ; 106(4): 589-606.e6, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32169171

RESUMO

ACOX1 (acyl-CoA oxidase 1) encodes the first and rate-limiting enzyme of the very-long-chain fatty acid (VLCFA) ß-oxidation pathway in peroxisomes and leads to H2O2 production. Unexpectedly, Drosophila (d) ACOX1 is mostly expressed and required in glia, and loss of ACOX1 leads to developmental delay, pupal death, reduced lifespan, impaired synaptic transmission, and glial and axonal loss. Patients who carry a previously unidentified, de novo, dominant variant in ACOX1 (p.N237S) also exhibit glial loss. However, this mutation causes increased levels of ACOX1 protein and function resulting in elevated levels of reactive oxygen species in glia in flies and murine Schwann cells. ACOX1 (p.N237S) patients exhibit a severe loss of Schwann cells and neurons. However, treatment of flies and primary Schwann cells with an antioxidant suppressed the p.N237S-induced neurodegeneration. In summary, both loss and gain of ACOX1 lead to glial and neuronal loss, but different mechanisms are at play and require different treatments.


Assuntos
Acil-CoA Oxidase/genética , Axônios/enzimologia , Degeneração Neural/genética , Neuroglia/enzimologia , Animais , Axônios/patologia , Drosophila , Humanos , Camundongos , Mutação , Degeneração Neural/enzimologia , Neuroglia/patologia , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA