Frailty as a Predictor of Postoperative Morbidity and Mortality in Patients Aged 80 Years and Older Undergoing Instrumented Fusion.

BACKGROUND AND OBJECTIVES: Degenerative spine disease is a leading cause of disability, with increasing prevalence in the older patients. While age has been identified as an independent predictor of outcomes, its predictive value is limited for similar older patients. Here, we aimed to determine the most predictive frailty score of adverse events in patients aged 80 and older undergoing instrumented lumbar fusion. METHODS: We proceeded with a multisite (3 tertiary academic centers) retrospective review including patients undergoing instrumented fusion aged 80 and older from January 2010 to present. A composite end point encompassing 30-day return to operating room, readmission, and mortality was created. We estimated the area under the receiver operating characteristic curve for frailty scores (Modified Frailty Index-5 [MFI-5], Modified Frailty Index-11 [MFI-11], and Charlson Comorbidity Index [CCI]) in relation to that composite score. In addition, we estimated the association between each score and the composite end point by means of logistic regression. RESULTS: A total of 153 patients with an average age of 85 years at the time of surgery were included. We observed a 30-day readmission rate of 11.1%, reoperation of 3.9%, and mortality of 0.6%. The overall rate of the composite end point at 30 days was 25 (15.1%). The AUC for MFI-5 was 0.597 (0.501-0.693), for MFI-11 was 0.620 (0.518-0.723), and for CCI was 0.564 (0.453-0.675). The association between the scores and composite end point did not reach statistical significance for MFI-5 (odds ratio [OR] = 1.45 [0.98-2.15], P = .061) and CCI (OR = 1.13 [0.97-1.31], P = .113) but was statistically significant for MFI-11 (OR = 1.46 [1.07-2.00], P = .018). CONCLUSION: This is the largest study comparing frailty index scores in octogenarians undergoing instrumented lumbar fusion. Our findings suggest that while MFI-11 score correlated with adverse events, the predictive ability of existing scores remains limited, highlighting the need for better approaches to identify select patients at age extremes.

Congenital Pediatric Hydrocephalus in the Brazilian Public Health System: The Reality of a Middle-Income Country in the Past 13 Years.

BACKGROUND: Congenital hydrocephalus is a significant challenge in neurosurgery, particularly in resource-limited settings. This study focuses on the congenital hydrocephalus in Brazil, a developing country, over the past 13 years. METHODS: This study is a retrospective analysis of congenital hydrocephalus treatment and outcomes using data records on DATASUS from January 2008 to July 2021. Demographics, cost of hospitalizations, amount paid to professionals, mortality, and mean length of stay (LOS) were analyzed. Statistical analysis was conducted to determine significant associations between these indicators and pediatric hydrocephalus. RESULTS: DATASUS recorded 8493 cases of congenital hydrocephalus in the studied period, with a prevalence of 24.28 per 100,000 newborns, mostly linked to spina bifida. Congenital hydrocephalus caused 60.83 ± 13.98 neonatal deaths per year, with the highest rate among 32-36 weeks gestational age. Acquired hydrocephalus led to 1063 infant deaths, whereas congenital hydrocephalus resulted in 3122 deaths, with no clear trend by the years. White infants had the highest mortality. A total of 33,184 shunt procedures were performed, with an average cost of $715.37 per procedure. The mortality model showed no significant effects of cost or professionals' salary, but a significant effect of LOS on hospitalization costs was observed. CONCLUSIONS: Pediatric hydrocephalus in Brazil's public health system is a significant burden. Congenital hydrocephalus prevalence and mortality emphasize the need for early diagnosis and treatment. Early diagnosis, prenatal care, and adequate resources are crucial. This study offers insights into congenital hydrocephalus, highlighting challenges and future directions for improved care.

Immunohistochemical markers predicting recurrence following resection and radiotherapy in chordoma patients: insights from a multicenter study [RETRACTED].

OBJECTIVE: Chordomas are rare tumors that often recur regardless of surgery with negative margins and postoperative radiotherapy. The predictive accuracy of widely used immunohistochemical (IHC) markers in addressing the recurrence of skull base chordomas (SBCs) is yet to be determined. This study aimed to investigate IHC markers in the prediction of recurrence after SBC resection with adjuvant radiation therapy. METHODS: The authors reviewed the records of patients who had treatment for SBC between January 2017 and June 2021 across the Mayo Clinic in Minnesota, Florida, and Arizona. Exclusion criteria included patients who had no histopathology or recurrence as an outcome. Histopathological markers included cytokeratin A1/A3 only, epithelial membrane antigen (EMA), S100 protein, pan-cytokeratin, IN1, GATA3, CAM5.2, OSCAR, and chondroid. Information from patient records was abstracted, including treatment, clinical and radiological follow-up duration, demographics, and histopathological factors. Decision tree and random forest classifiers were trained and tested to predict the recurrence based on unseen data using an 80/20 split. RESULTS: A total of 38 patients with a diagnosis of SBC who underwent resection (gross-total resection: 42.1%; and subtotal resection: 57.9%) and radiation therapy were extracted from the medical records. The mean patient age was 48.2 (SD 19.6) years; most patients were male (n = 23; 60.5%) and White (n = 36; 94.7%). Pan-cytokeratin was associated with an increased risk of postoperative recurrence (OR 14.67, 95% CI 2.44-88.13; p = 0.00517) after resection and adjuvant radiotherapy. The decision tree analysis found pan-cytokeratin-positive tumors to have a 78% chance of being classified as a recurrence, with an accuracy of 75%. The distribution of minimal depth in the prediction of postoperative recurrence indicates that the most important variables were pan-cytokeratin, followed by cytokeratin A1/A3 and EMA. CONCLUSIONS: The authors' machine learning algorithm identified pan-cytokeratin as the largest contributor to recurrence among other IHC markers after SBC resection. Machine learning may facilitate the prediction of outcomes in rare tumors, such as chordomas.

Supervised machine learning to validate a novel scoring system for the prediction of disease remission of functional pituitary adenomas following transsphenoidal surgery.

Functional pituitary adenomas (FPAs) are associated with hormonal hypersecretion resulting in systemic endocrinopathies and increased mortality. The heterogenous composition of the FPA population has made modeling predictive factors of postoperative disease remission a challenge. Here, we aim to define a novel scoring system predictive of disease remission following transsphenoidal surgery (TSS) for FPAs and validate our process using supervised machine learning (SML). 392 patients with FPAs treated at one of the three Mayo Clinic campuses were retrospectively reviewed. Variables found significant on multivariate analysis were incorporated into our novel Pit-SCHEME score. The Pit-SCHEME score with a cut-off value ≥ 6 achieved a sensitivity of 86% and positive likelihood ratio of 2.88. In SML models, without the Pit-SCHEME score, the k-nearest neighbor (KNN) model achieved the highest accuracy at 75.6%. An increase in model sensitivity was achieved with inclusion of the Pit-SCHEME score with the linear discriminant analysis (LDA) model achieving an accuracy of 86.9%, which suggests the Pit-SCHEME score is the variable of most importance for prediction of postoperative disease remission. Ultimately, these results support the potential clinical utility of the Pit-SCHEME score and its prospective future for aiding in the perioperative decision making in patients with FPAs.

Immunohistochemical markers predicting long-term recurrence following clival and spinal chordoma resection: a multicenter study.

OBJECTIVE: Chordomas are rare tumors from notochordal remnants and account for 1%-4% of all primary bone malignancies, often arising from the clivus and sacrum. Despite margin-negative resection and postoperative radiotherapy, chordomas often recur. Further, immunohistochemical (IHC) markers have not been assessed as predictive of chordoma recurrence. The authors aimed to identify the IHC markers that are predictive of postoperative long-term (≥ 1 year) chordoma recurrence by using trained multiple tree-based machine learning (ML) algorithms. METHODS: The authors reviewed the records of patients who had undergone treatment for clival and spinal chordomas between January 2017 and June 2021 across the Mayo Clinic enterprise (Minnesota, Florida, and Arizona). Demographics, type of treatment, histopathology, and other relevant clinical factors were abstracted from each patient record. Decision tree and random forest classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: One hundred fifty-one patients diagnosed and treated for chordomas were identified: 58 chordomas of the clivus, 48 chordomas of the mobile spine, and 45 chordomas sacrococcygeal in origin. Patients diagnosed with cervical chordomas were the oldest among all groups (58 ± 14 years, p = 0.009). Most patients were male (n = 91, 60.3%) and White (n = 139, 92.1%). Most patients underwent resection with or without radiation therapy (n = 129, 85.4%). Subtotal resection followed by radiation therapy (n = 51, 33.8%) was the most common treatment modality, followed by gross-total resection then radiation therapy (n = 43, 28.5%). Multivariate analysis showed that S100 and pan-cytokeratin are more likely to predict the increase in the risk of postoperative recurrence (OR 3.67, 95% CI 1.09-12.42, p= 0.03; and OR 3.74, 95% CI 0.05-2.21, p = 0.02, respectively). In the decision tree analysis, a clinical follow-up > 1897 days was found in 37% of encounters and a 90% chance of being classified for recurrence (accuracy = 77%). Random forest analysis (n = 500 trees) showed that patient age, type of surgical treatment, location of tumor, S100, pan-cytokeratin, and EMA are the factors predicting long-term recurrence. CONCLUSIONS: The IHC and clinicopathological variables combined with tree-based ML tools successfully demonstrated a high capacity to identify recurrence patterns with an accuracy of 77%. S100, pan-cytokeratin, and EMA were the IHC drivers of recurrence. This shows the power of ML algorithms in analyzing and predicting outcomes of rare conditions of a small sample size.

Impact of postoperative fatigue following minimally-invasive lumbar spine surgery.

BACKGROUND: Postoperative fatigue is a distressing symptom and can have a major impact on the patient's quality of life after surgery. We investigate the extent of postoperative fatigue following minimally invasive spine surgery under general anesthesia (GA), and its impact on patients' quality of life (QOL) and activities of daily living (ADLs). METHODS: We surveyed patients that underwent minimally-invasive lumbar spine surgery under GA within the previous year. A five-point Likert scale ("very much", "quite a bit", "somewhat", "a little bit", "not at all") was used to assess the extent of fatigue during the first postoperative month, its impact on QOL, and ADLs. RESULTS: The survey was completed by 100 patients, 61% were male, mean age 64.6 ± 12.5 years, 31% underwent MIS-TLIF, 69% lumbar laminectomy. During the first postoperative month 45% of patients referred significant fatigue ("very much" or "quite a bit"); for 31% of patients fatigue significantly impacted their QOL; significantly limited their ADLs in 43% of patients. MIS-TLIF was associated with higher rate of postoperative fatigue compared to laminectomy (61.3% versus 37.7%, p = 0.02). Patients 65 years old or older had higher rates of fatigue compared to younger patients (55.6% versus 32.6%, p = 0.02). We did not observe a significant difference in postoperative fatigue between male and female patients. CONCLUSIONS: Our study revealed a substantial incidence of postoperative fatigue in patients that underwent minimally-invasive lumbar spine surgery under GA, with a significant impact on QOL and ADLs. There is a need to research new strategies to reduce fatigue after spine surgery.

Predictive factors for post operative seizures following meningioma resection in patients without preoperative seizures: a multicenter retrospective analysis.

PURPOSE: Meningiomas are the most common primary brain tumor and represent 35% of all intracranial neoplasms. However, in the early post-operative period approximate 3-5% of patients experience an acute symptomatic seizure. Establishing risk factors for postoperative seizures will identify those patients without preoperative seizures at greatest risk of postoperative seizures and may guide antiseizure medications (ASMs) management. METHODS: Adult seizure naïve patients who underwent primary resection of a World Health Organization (WHO) Grade 1-3 meningioma at the three Mayo Clinic Campuses between 2012-2022 were retrospectively reviewed. Multivariate regression analyses were used to identify radiological, surgical, and management features with the development of new-onset seizures in patients undergoing meningioma resection. RESULTS: Of 113 seizure naïve patients undergoing meningioma resection 11 (9.7%) experienced a new-onset post-operative seizure. Tumor volume ≥ 25 cm3 (Odds Ratio (OR) 5.223, 95% Confidence Interval (CI) 1.546 - 17.650, p = 0.008) and cerebral convexity meningiomas (OR 4.742, 95% CI 1.255 - 14.336, p = 0.016) were most associated with new onset postoperative seizures in multivariate analysis. ASMs and corticosteroid therapies did not display a significant difference among those with and without a new onset postoperative seizure. CONCLUSION: In the current study, a larger tumor volume (≥ 25 cm3) and/or convexity meningiomas predicted the development of new onset post-operative seizures. Those who present with these factors should be counseled for their increased risk of new onset post-operative seizures and may benefit from prophylactic ASMs therapy.

Anticancer Properties of Hexosamine Analogs Designed to Attenuate Metabolic Flux through the Hexosamine Biosynthetic Pathway.

Altered cellular metabolism is a hallmark of cancer pathogenesis and progression; for example, a near-universal feature of cancer is increased metabolic flux through the hexosamine biosynthetic pathway (HBP). This pathway produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a potent oncometabolite that drives multiple facets of cancer progression. In this study, we synthesized and evaluated peracetylated hexosamine analogs designed to reduce flux through the HBP. By screening a panel of analogs in pancreatic cancer and glioblastoma multiform (GBM) cells, we identified Ac4Glc2Bz─a benzyl-modified GlcNAc mimetic─as an antiproliferative cancer drug candidate that down-regulated oncogenic metabolites and reduced GBM cell motility at concentrations non-toxic to non-neoplastic cells. More specifically, the growth inhibitory effects of Ac4Glc2Bz were linked to reduced levels of UDP-GlcNAc and concomitant decreases in protein O-GlcNAc modification in both pancreatic cancer and GBM cells. Targeted metabolomics analysis in GBM cells showed that Ac4Glc2Bz disturbed glucose metabolism, amino acid pools, and nucleotide precursor biosynthesis, consistent with reduced proliferation and other anti-oncogenic properties of this analog. Furthermore, Ac4Glc2Bz reduced the invasion, migration, and stemness of GBM cells. Importantly, normal metabolic functions mediated by UDP-GlcNAc were not disrupted in non-neoplastic cells, including maintenance of endogenous levels of O-GlcNAcylation with no global disruption of N-glycan production. Finally, a pilot in vivo study showed that a potential therapeutic window exists where animals tolerated 5- to 10-fold higher levels of Ac4Glc2Bz than projected for in vivo efficacy. Together, these results establish GlcNAc analogs targeting the HBP through salvage mechanisms as a new therapeutic approach to safely normalize an important facet of aberrant glucose metabolism associated with cancer.

Assessment of surgeons' attitude towards awake spine surgery under spinal anesthesia.

BACKGROUND: General anesthesia (GA) and spinal anesthesia (SA) have been adopted for lumbar spine surgery (LSS), but GA is used far more widely. We conducted a survey of spine surgeons to explore their attitudes and preferences regarding awake spine surgery under SA. METHODS: A survey was emailed to 150 spine surgeons. Exposure and attitudes towards spine surgery under SA were elicited. A five-point Likert scale of agreement examined perceptions of SA, while attitudes towards SA were recorded by categorizing free text into themes. RESULTS: Seventy-five surgeons completed the survey, 50 % response rate. Only 27 % said they perform LSS under SA. Most surgeons, 83 %, would recommend GA to a healthy patient undergoing lumbar laminectomy. Only 41 % believes SA to be as safe as GA, and only 30 % believes SA is associated with better postoperative pain control. The most common reasons why SA is not favored was lack of proven benefits over GA (65 %). When asked if a randomized trial finds SA to lead to less postoperative fatigue, 50 % said they would be more likely to offer SA, a significant increase from the baseline response of 27 % (p = 0.002). CONCLUSIONS: Our survey indicates that the low adoption of SA for LSS is due to lack of surgeons' belief in the benefits of SA over GA, and that a randomized patient-centered trial has the potential of changing surgeons' perspective and increasing adoption of SA for LSS.

Melatonin Treatment Triggers Metabolic and Intracellular pH Imbalance in Glioblastoma.

Metabolic rewiring in glioblastoma (GBM) is linked to intra- and extracellular pH regulation. In this study, we sought to characterize the role of melatonin on intracellular pH modulation and metabolic consequences to identify the mechanisms of action underlying melatonin oncostatic effects on GBM tumor initiating cells. GBM tumor initiating cells were treated at different times with melatonin (1.5 and 3.0 mM). We analyzed melatonin's functional effects on GBM proliferation, cell cycle, viability, stemness, and chemo-radiosensitivity. We then assessed the effects of melatonin on GBM metabolism by analyzing the mitochondrial and glycolytic parameters. We also measured the intracellular and extracellular pH. Finally, we tested the effects of melatonin on a mouse subcutaneous xenograft model. We found that melatonin downregulated LDHA and MCT4, decreasing lactate production and inducing a decrease in intracellular pH that was associated with an increase in ROS and ATP depletion. These changes blocked cell cycle progression and induced cellular death and we observed similar results in vivo. Melatonin's cytotoxic effects on GBM were due, at least in part, to intracellular pH modulation, which has emerged as a newly identified mechanism, providing new insights into the oncostatic effect of melatonin on GBM.

Disease characteristics and patterns of familial colloid cyst of the third ventricle: An international survey of the Colloid Cyst Survivors Group.

BACKGROUND: Colloid cysts of the third ventricle are rare benign tumors, accounting for approximately 1% of all intracranial tumors. Familial colloid cysts are less common, only 25 cases have been previously reported in the literature. We aim to describe demographic and disease-specific characteristics to reduce the knowledge gap with this potentially life-threatening tumor. METHODS: We conducted a retrospective cohort study of 211 colloid cyst patients from the Colloid Cyst Survivors Group who completed a survey that included demographicandclinical data andinquired aboutfamily members diagnosed with a colloid cyst. Datawascollected from October 14th, 2021 to October 27th, 2021. We compared our data with previously published cases from the literature. RESULTS: A total of 211 responses from patients with a previous diagnosis of a colloid cyst completed our survey. 11.8 % were familial colloid cysts, of this group 60.8 % were symptomatic and 39.2 % incidental. We observed significant difference between symptom incidence between reports from the literature and our cohort: headache 75.5 % versus 49 % (p = 0.005); imbalance 13.2 % versus 31.4 % (p = 0.03); nausea 11.3 % versus 29.4 % (p = 0.02), and difficulty walking 1.9 % versus 19.6 % (p = 0.003). Additionally, we found first degree family member as the most frequent relative diagnosed with this disease. CONCLUSION: Our study involved the largestcohortof patients with familial colloid cysts. According to previous literature, siblings are the most prevalent family member affected by this disease, specifically among monozygotic twins. This suggests strong inheritance patterns and even genetic mechanism underlying the development of this disease.