Emerging Outlook on Personalized Neuromodulation for Depression: Insights from Tractography-Based Targeting.

BACKGROUND: Deep brain stimulation (DBS) has shown individual promise in treating treatment resistant depression (TRD), but larger-scale trials have been less successful. Here, we create the largest meta-analysis with individual patient data (IPD) to date to explore if the use of tractography enhances the efficacy of DBS for TRD. METHODS: We systematically reviewed 1823 articles, selecting 32 that contributed data from 366 patients. We stratified the IPD based on stimulation target and use of tractography. Utilizing two-way type III Analysis of Variance (ANOVA), Welch Two Sample t-tests, and mixed-effects linear regression models, we evaluated changes in depression severity 9-15 months post-surgery (1-Y) and at last follow-up (LFU) (4 weeks - 8 years) as assessed by depression scales. RESULTS: Tractography was used for medial forebrain bundle (MFB, n=17/32), subcallosal cingulate (SCC, n=39/241), and ventral capsule/ventral striatum (VC/VS, n=3/41) targets; and 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-Y (p<0.001) and LFU (p=0.009). Within the target cohorts, tractography improved depression scores at 1-Y for both MFB and SCC, though significance was only met at the alpha = 0.1 level (SCC: ß=15.8%, p=0.09; MFB: ß=52.4%, p=0.10). Within the tractography cohort, MFB with tractography patients showed greater improvement than those with SCC with tractography (72.42±7.17% versus 54.78±4.08%) at 1-Y (p=0.044). CONCLUSIONS: Our findings underscore the promise of tractography in DBS for TRD as a methodology for personalization of therapy, supporting its inclusion in future trials.

Reduced racial disparities among newborns with intraventricular hemorrhage.

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.

Evaluating Computer Vision, Large Language, and Genome-Wide Association Models in a Limited Sized Patient Cohort for Pre-Operative Risk Stratification in Adult Spinal Deformity Surgery.

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.

Implications of Frailty on Postoperative Health Care Resource Utilization in Ankylosing Spondylitis Patients Undergoing Spine Surgery for Spinal Fractures.

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.

Type II odontoid fractures in the elderly presenting to the emergency department: an assessment of factors affecting in-hospital mortality and discharge to skilled nursing facilities.

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.

Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms.

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.

The relation between pica and iron deficiency in children in Zanjan, Islamic Republic of Iran: a case-control study.

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).