Introduction Researchers have attempted to predict hearing preservation for vestibular schwannoma (VS) patients, with preoperative hearing scores and tumor size identified as useful predictors for hearing preservation. However, prior studies have not directly included magnetic resonance (MR) images in their predictive models, instead using secondary imaging measurements and other clinical features. Here, we created a deep learning model that directly incorporates preoperative images to predict VS patients' hearing preservation. Methods Using 97 patients who underwent VS hearing preservation surgery at our institution, we modeled hearing preservation with clinical and image feature-based logistic regression (LR) and an image-based convolutional neural network (CNN) model, with or without clinical features added. Results LR models that included tumor size and preoperative hearing provided good hearing preservation discrimination (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] AUC = 0.79; Word Recognition Score [WRS] Area under curve (AUC) = 0.77). Two-channel MRI inputs were used for a 3D CNN, ResNet50, and a hybrid ResNet50 including tumor size and preoperative hearing. The hybrid model was our most accurate and was comparable with existing models (four-fold mean receiver operating characteristic [ROC] = 0.71; best ROC = 0.85). Previously described MRI features were not significantly correlated with hearing outcomes. Conclusion We confirm that the first deep learning model to directly incorporate preoperative images and clinical features for VS patients can help predict hearing preservation. This type of model may help risk-stratify VS patients during surgical planning, with the goal of ultimately improving surgical outcomes for patients.

Background:Body dysmorphic disorder (BDD) is classified under obsessive-compulsive and related disorders. BDD is characterized by intense preoccupation with the perception of deficits or flaws in appearance, with repetitive behaviors manifested by altered self-perception. These symptoms bring about significant distress, making normal functioning difficult. Patients tend to respond to a combination of cognitive and pharmacologic therapies, similar to the treatment responses of patients with other obsessive-compulsive spectrum disorders. However, in severe cases of intractable BDD when multiple modalities of therapy have failed, other treatments such as deep brain stimulation (DBS) could be considered. Case Description:A 23-year-old Caucasian male presents with a 5-year history of worsening BDD, OCD, and social phobia. A combination of cognitive behavioral therapy and standard pharmacological treatment was attempted, but symptoms progressed, leading to suicidal ideation. Ultimately, the patient elected to undergo placement of a DBS device bilaterally targeting the region bound by the ventral striatum, nucleus accumbens, and subgenual cingulate. The patient was evaluated using both the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist and the Hamilton Rating Scale for Depression, both pre and postoperatively over the course of 21.5 months. Conclusion:Following DBS treatment, this patient demonstrated marked improvements in BDD-associated symptoms previously resistant to both cognitive behavioral and pharmacological therapy. This case highlights how DBS treatment can effectively improve symptoms in treatment-refractory BDD when first-line modalities have been exhausted and thus may be a potential consideration for clinical use.

Abstract Background: Glioblastoma (GBM) is the most common aggressive primary brain tumor, with a median overall survival (OS) of ≈15-18 months despite standard of care (SOC). Aging is a major negative prognostic factor, with older adults showing worse OS. Senescent cells accumulate with age and contribute to poorer outcomes. Senolytics clear senescent cells and may improve responses in older hosts. While tumor-intrinsic molecular features appear age-independent, the aging brain microenvironment impact on GBM progression and immunity remains unclear. Objective: To define age-associated senescence patterns in tumor core and peritumoral (PT) brain in GBM patients and mouse models and assess whether senolytic enhance treatment responses in aged syngeneic and humanized GBM models. Methods: MRI-guided tumor core and PT biopsies from GBM patients (<65 vs. ≥65) underwent transcriptomic and single-cell analyses to assess age-related neuro-immune and senescence changes. Senescence across tumor regions was examined in young (7-9 weeks) and aged (97-104 weeks) C57BL/6 and INK-ATTAC mice with intracranial SB28 tumors (n=5/group). Flow cytometry quantified β-gal+ senescent populations among neurons, astrocytes, oligodendrocytes, microglia, and immune infiltrates from tumor core and extratumoral brain. Mice received brain radiation, anti-PD-1, and IDO enzyme inhibition, alone ± senolytics (dasatinib+quercetin) or AP compound-induced clearance p16INK4A+ senescent cells. A human GBM aging model was developed by depleting CD4+, CD8+, CD19+, and NK1.1+ cells in young and aged C57BL/6 mice, prior to patient-derived GBM43 (PDX) intracranial engraftment, followed by SOC radiotherapy + temozolomide ± senolytics. Results: Transcriptomic profiling showed minimal age-related changes in tumor core but marked alterations in older PT tissues. Aged PT microglia exhibited a senescent phenotype with an upregulation of senescence-associated secretory phenotype (SASP) genes. Senolytics or AP compound significantly reduced extratumoral β-gal+ microglia and synergized with radio-immunotherapy to extend OS in aged mice (p<0.05). In the humanized immunodepleted GBM43 PDX model, young and aged mice developed tumors, with faster mortality in older hosts. Therapeutic responses to SOC ± senolytics are ongoing. Conclusions: The PT brain is a key site of age-dependent immune dysfunction in GBM. Senescent microglia may create an immunosuppressive niche that limits the immunotherapy efficacy in older adults. Senolytics may restore treatment efficacy and improve outcomes in older GBM hosts. We developed a novel immunodepleted GBM PDX model to mechanistically evaluate the role of aging in human tumor progression and therapy resistance. Keywords: glioblastoma, peritumoral brain, aging, immunotherapy, senescence, microglia Citation Format: Manon Penco-Campillo, Olaya de Dios, Megan Callender, Kristen L. Lauing, Oluwatomilayo Odum, Taylor Koch, Lijie Zhai, Vikram C. Prabhu, Douglas E. Anderson, Anand V. Germanwala, Jigisha P. Thakkar, Prashant Bommi, Pilar Sanchez-Gomez, Frederick Varn, Derek Wainwright. Age-dependent neuro-immune changes in glioblastoma shape therapeutic response and reveal senescent microglia as a targetable vulnerability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6826.

BACKGROUND:While most literature on the history of neurosurgery departments feature only celebratory accounts of achievements, this article represents an instrument for genuine reflection on the rich and complex medical past of the Loyola University Chicago Department of Neurosurgery over the 20th and 21st centuries. METHODS:Through conducting faculty interviews and reviewing institutional archives and past departmental publications and records, this culmination examines the evolution of Loyola University Medical Center, a quaternary-care academic hospital centered on its 61-acre campus in Maywood, Illinois. RESULTS:Initially established as a division shortly after the hospital's founding, the Department of Neurological Surgery formalized its residency program in 1977, marking a pivotal step in its academic development. Since that time, Loyola Neurosurgery has evolved into a comprehensive program distinguished by innovation, high clinical volume, research, and education. Faculty contributions include advances in microsurgical, cerebrovascular, and endoscopic endonasal techniques, early work in extracranial-intracranial (EC-IC) bypass, participation in the MISTIE III trial, and the development of novel operative approaches such as ventral pontine trigeminal tractotomy. The department has also produced one of the largest single-center experiences in vestibular schwannoma surgery in the Midwest. Loyola Neurosurgery maintains active participation in multicenter clinical trials, alongside a growing portfolio of NIH-funded research and translational collaborations. Residency graduates receive prestigious fellowships and neurosurgical positions within academia and the community. CONCLUSION:From its inception to the current day, the Loyola Department of Neurosurgery has demonstrated an emphasis on multidisciplinary patient care with clinical innovation, pursuing research investigation, and training residents and medical students, fulfilling the tripartite academic mission of university medical centers.

This study aimed to determine how age and IDO1 interact to affect the gut microbiome, microbial metabolite levels, and survival outcomes in subjects undergoing IDO1-targeted immunotherapy against glioblastoma (GBM). Serum and colon contents from younger 16-20- or older 92-118-week-old wild-type (WT), IDO1 knockout (IDO1-KO), and IDO1 enzyme null (IDO1-H350A) mice were analyzed for 16S rRNA gut microbiome composition and microbial-derived aromatic amino acid metabolites via LC/MS/MS. Fecal samples from younger 7-8 or older 81-85 week-old WT mice with intracranial syngeneic GL261 GBM cells treated with or without brain radiation (RT) and PD-1 mAb were also analyzed. Fecal and plasma samples from 12 newly diagnosed IDHwt/MGMT promoter unmethylated GBM patients who received RT plus PD-1 mAb and IDO enzyme inhibitor were also analyzed. Young and old IDO1-KO and IDO1-H350A mice demonstrated a unique gut microbiome signature with an elevated abundance of Bifidobacterium and Helicobacter (p<0.05) and a reduced abundance of Ventriosum and Sireaum compared to WT mice (p<0.001). Prevotellaceae, Muribaculum, Alistipes, Enterohabdus, Clostridia, and Akkermansia were different in IDO1-KO and IDO1-H350A mice compared to WT - but only in older mice. Serum microbiome-derived aryl-lactates phenyllactate (PLA), indolelactate (ILA), and 4-hydroxyphenyllactate (4HPLA) were increased in IDO1-KO mice compared to WT and IDO1-H350A mice (p<0.001) - but only in older mice. Older WT mice with GL261 GBM showed lower fecal aryl-lactates (PLA, 4HPLA, and ILA) compared to younger counterparts. Treatment with RT + PD-1 mAb also showed decreased serum indole propionic acid (IPA) levels in young but not old mice with GL261 GBM (p<0.05). Analyses from GBM patient baseline fecal samples revealed that higher abundance of Massilioclostridium coli, GGB3819-SGB5184, Dysosmobacter welbionis, and Phocaeicola plebeius was associated with longer survival (p<0.004), while higher levels of fecal ILA and lower levels of plasma IPA also correlated with elongated survival (p<0.04 and p<0.01 respectively). Combined treatment of RT + PD-1 mAb + IDO1 inhibitor decreased plasma IPA when compared to baseline (p<0.01). IDO1 possesses both enzyme- and non-enzyme-dependent effects that change gut microbiota composition and bioactive microbial aromatic amino acid metabolite levels, which is also influenced by aging. Certain gut microbiota species and metabolites may serve as prognostic markers for predicting outcomes to immunotherapy for GBM. These findings warrant further investigation into how IDO1 interacts with age to affect immunotherapeutic efficacy in subjects with GBM. Lijie Zhai, Akriti Shrestha, Kristen L. Lauing, Manon Penco-Campillo, Oluwatomilayo Odum, Prashant Bommi, Taylor Koch, Robert H. McCusker, Douglas E. Anderson, Anand Germanwala, Vikram C. Prabhu, Jigisha P. Thakkar, Jacob M. Allen, Rimas V. Lukas, Derek A. Wainwright. Age and indoleamine 2,3-dioxygenase 1 (IDO1) interact to affect gut microbiome homeostasis in subjects with glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2215.

Glioblastoma (GBM; IDHwt) is primarily diagnosed at ≥65 years of age with a peak incidence between 70-79 years old. Increased age is a strong detrimental factor. Older patients have significantly poorer treatment outcomes for both immune-based- and standard of care (SOC)-therapies. In addition to treatment response, maladaptive age-dependent effects have been attributed to decreased physical resilience, immune system alterations, and lack of tolerance to therapies. Yet, there is insufficient research investigating age-dependent prognostic factors in electronic health record (EHR) patient data, particularly in the diverse cohort of patients that Loyola University Medical Center (LUMC) serves. Patients were identified through ICD-9/10 definitions for brain cancer and 192 IDHwt GBM patients were chart reviewed and confirmed. Demographic, co-morbid, mutational, and treatment data was compiled. Analysis of overall survival (OS) was performed using the survminer package in R 4.0.2. Data were stratified by patient age and used to construct univariate and multivariate Cox proportional-hazard models with statistical significance assessed using log-rank tests. GBM patients ≥65 years old (n=103, median OS=221 days) experienced worse OS (p<0.001) compared to those<65 years of age (n=89, median OS=464 days). Older patients declined treatment more frequently (p=0.002) (OR=2.95) and had higher Charlson Comorbidity Index (CCI) scores (p<0.001). After removing patients who declined treatment (n=143), this age-influenced outcome disparity persisted (p=0.019). After further restricting to only patients who completed a full course of SOC radio-chemotherapy (n=125) (young: n=71, median OS=543 days) (old: n=54, median OS=495 days), OS differences between age groups lost significance (p=0.061). Among patients in this cohort, MGMT methylation (p=0.027) and initial tumor resection (p<0.001) was associated with increased OS. The development of neurocognitive symptoms within 6 months of diagnosis (p<0.001), higher initial CCI (p=0.019), and initial KPS under 80 (p=0.002) were independently associated with poorer OS. When accounting for initial KPS and resection status, OS differences between age groups were significant (p=0.01). Unlike the older cohort, younger patients had a significant association between increased body mass index and improved OS (p=0.017) while cachexia/significant weight loss was associated with worse OS (p=0.015). Though the statistical significance is missing in the completed treatment cohort, likely due to sample size, clinical trends show younger patients have better survival outcomes. The older cohort’s decreased physical resilience, as evidenced by the increased pre-existing comorbidities and higher CCI scores, could be driving their decreased participation and may suggest additional biological etiologies for the discrepancies in OS. James Fahey, Manon Penco, Emma Federico, Erica Power, Michael Egozi, Dayna Sloane, Isaac Ng, Kayeromi Gomez, Kristen L. Lauing, Ishan Roy, Theresa Walunas, Kevin P. Barton, Douglas E. Anderson, Anand V. Germanwala, Vikram C. Prabhu, Jigisha Thakkar, Derek A. Wainwright. The dual influence of treatment and age on survival in patients with glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7373.

Abstract MGMT methylated glioblastomas respond well to standard of care with temozolomide, have a longer survival as well as increased risk of pseudo-progression as compared to unmethylated patients. Shorter survival in these patients despite effective treatments is due to misdiagnosis of true progression (in cases with pseudo-progression) that leads to overtreatment or discontinuation of effective treatments. There are limited non-invasive diagnostic tools to distinguish true progression from pseudo-progression. Knowing the expected time to first true progression will aid with interpretation of MRI changes and serve as an additional tool to distinguish true from pseudo-progression. OBJECTIVE We sought to define the time to first progression in MGMT methylated glioblastoma patients who were treated with standard of care/Stupp protocol (this has not been previously defined). METHODS We conducted a retrospective analysis of an IRB-approved database at our institution from 2019 to 2022 of all MGMT methylated glioblastoma patients who completed Stupp protocol. Time to first progression (time from initial surgery to first true progression) was determined by treating multidisciplinary team based on radiographic review +/- pathology. Eligible MGMT methylated glioblastoma patients had IDH status determined by NGS and completed standard Stupp protocol after surgery. RESULTS Approximately 30% (27) patients with IDH wild-type glioblastoma were MGMT methylated. 10 patients met eligibility criteria. 50% of MGMT methylated GBM patients had multifocal disease at presentation. Median time to first progression in MGMT methylated GBM who received standard of care was 28 months. 20% patients have not had first progression 3 years after initial surgery. CONCLUSION MRI changes on surveillance scans should be carefully interpreted in the first 28 months. Knowing time to first true progression will aid with management decisions and decrease unnecessary early aggressive interventions in MGMT methylated glioblastoma patients. We will validate these findings in a larger patient population at our institution.

Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median overall survival (OS) of 15-18 months. The median age of a GBM diagnosis is 68-70 years old, and, increased subject age at the time of diagnosis is inversely associated with GBM patient OS such that older adults have significantly worse survival outcomes compared to similarly treated younger counterparts. Senescent cells accumulate in the body during progressive aging and contribute to worse outcomes in older adult mice with GBM. Senolytics are pharmacological compounds that cause senescent cells to undergo cell death. To comprehensively profile the treatment effect of senolytics combined with or without radio-immuno-therapy in mice with GBM across the lifespan. Young 7-9- and older adult 97-104-week-old wild-type (WT; C57BL/6) and 110-130-week-old INK-ATTAC (C57BL/6) mice with or without intracranial SB28 cells were treated with or without brain radiotherapy, PD-1 mAb, and an IDO enzyme inhibitor with the senolytics, dasatinib + quercetin, or the AP compound that induces p16INK4A+ senescent cell death in INK-ATTAC mice. Flow cytometric quantification of cells that are positive for beta-galactosidase, a marker for senescent cells, by flow cytometry was performed on brain-resident neurons, astrocytes, oligodendrocytes, as well as microglia in the tumor and non-bulk tumor mass brain parenchyma and correlated with overall survival. Immunofluorescence analysis of CD8+/granzyme A+ lymphocytes, CD68+/CD206+ macrophages, as well as endomucin+ endothelial cells was conducted across treatments and age groups. The treatment with senolytics or AP compound decreases beta-galactosidase+ microglia in the older adult brain with GBM (p<0.05). Older adult mice with a brain tumor show a significant decrease of endomucin staining as compared to younger counterparts (p<0.05). Strikingly, treatment with senolytics reversed this effect in older adults. Combining radio-immuno-therapy with senolytics improved overall survival of older adult mice with intracranial GBM (p<0.05). Our ongoing work aims to understand how senescent microglia affect neuronal health and function in older adults with GBM, as well as how senolytic treatment-induced vascular remodeling is associated with enhanced immunotherapeutic efficacy. Manon Penco-Campillo, Lijie Zhai, Prashant Bommi, Patience Oluwatomilayo Odum, Kristen L. Lauing, Robert Ladd, Olaya de Dios, Irene Gómez-Soria, M Angeles Ramírez-González, Douglas E. Anderson, Anand V. Anand Germanwala, Vikram C. Prabhu, Jigisha P. Thakkar, Pilar Sanchez-Gomez, Derek A. Wainwright. Senolytics decrease senescent microglia, remodel the vasculature, and improve survival in older adults with glioblastoma during co-treatment with immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6434.

Tourette syndrome (TS) is a common neurological disorder characterized by frequent and disabling motor or vocal tics. There has been widely reported variation in patient responses to deep brain stimulation (DBS) for TS treatment. However, the potentially synergistic effects of multifocal DBS placements have not been extensively explored in younger patient populations. Our patient is a 19-year-old male with a medical history significant for TS and comorbid psychological disorders. Despite medical treatment, the patient's violent tics progressed from simple back extension motor tics to vigorous and aggressive behaviors. He received multiple opinions and trialed numerous pharmacological therapies without success. He was ultimately referred for neurosurgical evaluation for placement of DBS with selected targets of the bilateral nucleus accumbens (NAcc) and bilateral centromedian thalamus for lead implantation. The Yale Global Tic Severity Scale rated by the attending surgeon demonstrated a significant improvement in the patient's baseline tics and overall quality of life from preoperatively to 56 months postoperatively. With multifocal DBS leads in place, the patient's tics are well controlled on a low-moderate dosage of haloperidol. His emotional lability is now reported as less volatile and less extreme. He has become considerably more sociable and talkative. Following DBS placement, the patient experienced substantial improvement from his preoperative violent behavior and mood lability. This case provides evidence that dual electrode DBS, in conjunction with appropriate medical management, is a safe and effective way to improve life quality in individuals struggling with debilitating TS symptoms.

Abstract BACKGROUND Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a poor median survival rate. Despite the aggressive standard of care treatment combining surgical resection, chemo-, and radio-therapy, the median overall survival (OS) is only ~15-18 months. Progressively increasing subject age is inversely associated with GBM patient OS such that older adults tend to have significantly worse survival outcomes compared to younger counterparts. Senescent cells accumulate in the body during progressive aging and contribute to worse outcomes in older adult mice with GBM. Senolytics are pharmacologics that cause senescent cells to undergo cell death. OBJECTIVE To comprehensively profile the treatment effect of senolytics combined with or without immunotherapy in mice with GBM across the lifespan. METHODS Young 7-9- and older adult 97-104-week-old wild-type (WT; C57BL/6) and 110-130-week-old INK-ATTAC mice with or without intracranial SB28 cells were treated with or without brain radiation (RT), PD-1 mAb, and an IDO enzyme inhibitor with the senolytics, dasatinib + quercetin, or the AP compound that induces p16INK4A+ senescent cell death in INK-ATTAC mice (n=5/group). The quantification of beta-galactosidase positive cells by flow cytometry was performed on brain-resident neurons, astrocytes, oligodendrocytes, microglia, as well as dendritic cells, macrophages, neutrophils, T cells in the tumor and non-tumor bulk mass. Overall survival was also evaluated. RESULTS Senolytics or AP compound treatment both decrease beta-galactosidase positive microglia in the older adult brain with GBM (p<0.05). Combining radio- and immuno-therapy with senolytics improves overall survival of older adult mice with intracranial GBM (p<0.05). CONCLUSIONS Our ongoing work aims to understand how senescent microglia affect neuronal health and function in the older adult brain with GBM. KEYWORDS Glioma, senescence, senolytic.

OBJECTIVE:Advancements in microsurgical technique and technology continue to improve outcomes in patients with skull base tumor. The primary cranial nerve eight monitoring systems used in hearing preservation surgery for vestibular schwannomas (VSs) are direct cranial nerve eight monitoring (DCNEM) and auditory brainstem response (ABR), although current guidelines are unable to definitively recommend one over the other due to limited literature on the topic. Thus, further research is needed to determine the utility of DCNEM and ABR. The authors performed a retrospective cohort study and created an interactive model that compares hearing preservation outcomes based on tumor size in patients receiving ABR+DCNEM and ABR-only monitoring. METHODS:Twenty-eight patients received ABR+DCNEM and 72 patients received ABR-only monitoring during VS hearing preservation surgery at a single tertiary academic medical center between January 2008 and November 2022. Inclusion criteria consisted of adult patients with a preoperative American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification of A or B. Tumor size was measured as the maximal medial to lateral length, including the internal auditory canal component. RESULTS:Overall hearing preservation (word recognition score [WRS] > 0%) was achieved in 31 patients with ABR-only monitoring (43.1%) and in 18 patients with ABR+DCNEM (64.3%). Serviceable hearing preservation (AAO-HNS class A or B) was attained in 19 patients with ABR-only monitoring (26.4%) and in 11 patients with ABR+DCNEM (39.3%). There was no difference in overall hearing preservation between the two groups (p = 0.13). Change in tumor size was not associated with the odds of serviceable hearing preservation for the ABR-only group (p = 0.89); however, for ABR+DCNEM, there was some indication of an interaction between tumor size and the association of ABR+DCNEM versus ABR-only monitoring, with the odds of serviceable hearing preservation at p = 0.089. Furthermore, with ABR+DCNEM, every 0.5-cm increase in tumor size was associated with a decreased odds of serviceable hearing preservation on multivariable analysis (p = 0.05). For both overall and serviceable hearing preservation, a worse preoperative AAO-HNS classification was associated with a decreased odds of preservation (OR 0.43, 95% CI 0.19-0.97, p = 0.042; OR 0.17, 95% CI 0.053-0.55, p = 0.0031, respectively). CONCLUSIONS:The result of this interactive model study proposes that there may be a higher chance of hearing preservation when using ABR+DCNEM rather than ABR alone for smaller tumors, with that relationship reversing as tumor size increases.

Background: Increased age is a strong and unfavorable prognostic factor for patients with glioblastoma (GBM). However, the relationships between stratified patient age, comorbidities, and medications have yet to be explored in GBM patient survival analyses. Objective: To evaluate co-morbid conditions, tumor-related symptoms, medication prescriptions, and subject age for patients with GBM and to establish potential targets for prospective studies. Methods: Electronic health records for 565 patients with IDHwt GBM were evaluated at a single center between January 1, 2000 and August 9, 2021 were retrospectively assessed. Data were stratified by MGMT promoter methylation status when available and were used to construct multivariable time-dependent cox models and intra-cohort hazards. Results: Younger (<65 years of age) but not older (>= 65 years) GBM patients demonstrated a worse prognosis with movement related disabilities (P < 0.0001), gait/balance difficulty (P = 0.04) and weakness (P = 0.007), as well as psychiatric conditions, mental health disorders (P = 0.002) and anxiety (P = 0.001). In contrast, older but not younger GBM patients demonstrated a worse prognosis with epilepsy (P = 0.039). Both groups had worse survival with confusion/altered mental status (P = 0.023 vs < 0.000) and an improved survival with a Temozolomide prescription. Older but not younger GBM patients experienced an improved hazard with a prescription of ace-inhibitor medications (P = 0.048). Conclusion: Age-dependent novel associations between clinical symptoms and medications prescribed for comorbid conditions were demonstrated in patients with GBM. The results of the current work support future mechanistic studies that investigate the negative relationship(s) between increased age, comorbidities, and drug therapies for differential clinical decision-making across the lifespan of patients with GBM.

Objective The evolution of acoustic neuroma (AN) care continues to shift focus on balancing optimized tumor resection and control with preservation of neurological function. Prior learning curve analyses of AN resection have demonstrated a plateau between 20 and 100 surgeries. In this study of 860 consecutive AN surgeries, we investigate the presence of an extended learning curve tail for AN resection.Methods A retrospective cohort study of AN resections by a single interdisciplinary team between 1988 and 2018 was performed. Proportional odds models and restricted cubic splines were used to determine the association between the timing of surgery and odds of improved postoperative outcomes.Results The likelihood of improved postoperative House-Brackmann (HB) scores increased in the first 400 procedures, with HB 1 at 36% in 1988 compared with 79% in 2004. While the probability of a better HB score increased over time, there was a temporary decrease in slope of the cubic spline between 2005 and 2009. The last 400 cases continued to see improvement in optimal HB outcomes: adjusted odds of HB 1 score were twofold higher in both 2005 to 2009 (adjusted odds ratio [aOR]: 2.11, 95% confidence interval [CI]: 1.38-3.22, p < 0.001) and 2010 to 2018 (aOR: 2.18, 95% CI: 1.49-3.19, p < 0.001).Conclusion In contrast to prior studies, our study demonstrates the steepest growth for learning, as measured by rates of preservation of facial function outcomes (HB 1), occurs in the first 400 AN resections. Additionally, improvements in patient outcomes continued even 30 years into practice, underlining the importance of lifelong learning.

Pig-to-human xenotransplantation is rapidly approaching the clinical arena; however, it is unclear which immunomodulatory regimens will effectively control human immune responses to pig xenografts. We transplanted a gene-edited pig kidney into a brain-dead human recipient on pharmacologic immunosuppression and studied the human immune response to the xenograft using spatial transcriptomics and single-cell RNA sequencing. Human immune cells were uncommon in the porcine kidney cortex early after xenotransplantation and consisted of primarily myeloid cells. Both the porcine resident macrophages and human infiltrating macrophages expressed genes consistent with an alternatively activated, anti-inflammatory phenotype. No significant infiltration of human B or T cells into the porcine kidney xenograft was detected. Altogether, these findings provide proof of concept that conventional pharmacologic immunosuppression is sufficient to restrict infiltration of human immune cells into the xenograft early after compatible pig-to-human kidney xenotransplantation.

Objective:This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplantation with non-hepatocellular carcinoma (HCC) model for end-stage liver disease (MELD) exceptions.Summary and Background:Prior work has demonstrated regional variability in the appropriateness of MELD exceptions for diagnoses other than HCC.Methods:Adults listed at a single center for first-time liver-only transplantation without HCC after June 18, 2013 in the Scientific Registry of Transplant Recipients database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplantation were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control's Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health.Results:There were 49,494 candidates in the cohort, of whom 4337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n = 78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 versus 0.53 in nonadvantaged HRRs (P = 0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI versus 40.7% of nonadvantaged HRRs, whereas 44.6% of advantaged HRRs were in spatial clusters of low SVI versus 38.0% of nonadvantaged HRRs (P = 0.037).Conclusions:An advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity.

Abstract OBJECTIVE This study aimed to determine how IDO and subject age impact the gut microbiome and microbial metabolites during immunotherapy for glioblastoma (GBM). METHODS Serum and colon contents were collected from young 16-20- or older adult 92-118-week-old wild-type (WT; C57BL/6), IDO knockout (IDOKO), and IDO enzyme null (H350A) mice analyzed for 16S rRNA gut microbiome composition and microbial-derived aromatic amino acid metabolites via LC/MS/MS. Fecal samples from young 7-8 or older adult 81-85 week-old WT mice with intracranial GL261 brain tumors treated with or without brain radiation (RT) and PD-1 mAb were also analyzed. RESULTS Young and old IDOKO and H350A mice demonstrated a unique gut microbiome signature with an elevated abundance of Bifidobacterium and Helicobacter (p<0.05) and a reduced abundance of Ventriosum and Sireaum compared to WT mice (p<0.001). Prevotellaceae, Muribaculum, Alistipes, Enterohabdus, Clostridia, and Akkermansia were different in IDOKO and H350A mice compared to WT - but only in old mice. Serum aryl-lactates including phenyllactate, indolelacatate, and 4-hydroxyphenyllactate were increased in IDOKO mice compared to WT and H350A mice (p<0.001) – again, only in old mice. Older adult WT mice with GL261 showed lower fecal aryl-lactates compared to younger counterparts. Treatment with RT + PD-1 mAb decreased phenyllactate levels in old but not young mice with GL261 (p<0.05). CONCLUSIONS There are IDO enzyme- and non-enzyme-dependent effects on gut microbiota composition and bioactive microbial aromatic amino acid metabolites. These data warrant further investigation into how microbial metabolism affects immunotherapy efficacy and brain tumor survival across the lifespan.

BACKGROUND/OBJECTIVE: Endoscopic endonasal transsphenoidal surgery (EETS) is a common treatment for sellar and suprasellar tumors. While endoscopic training has improved over the years and formal fellowship training is now broadly available, the operative nuances of EETS conjectures the existence a learning curve as a neurosurgeon matures with experience. We aim to evaluate operative outcomes of 3 different experience levels of neurosurgeons over time at a single institution. METHODS: We reviewed all adult patients who underwent EETS at Loyola University Medical Center by 3 early career, 1 midcareer, and 2 late career neurosurgeons from 2007 to 2023. A comparative assessment of patient demographics, tumor features, and surgical outcomes was done using metrics such as length of surgery, rates of gross total resection (GTR) and symptomatic improvement, new postoperative steroid dependence, and development of diabetes insipidus (DI). T-tests and c 2 were used to statistically evaluate the study cohorts. RESULTS: A total of 297 patients underwent EETS. One hundred three (35%) were operated on by an early career, 122 (41%) by a mid-career, and 72 (24%) by a late career neurosurgeon. Late-career surgeons had shorter operation times (144 vs. 180 minutes with early and mid-career, P = 0.029) and increased GTR rates (P P = 0.008). There were no significant differences between the symptomatic improvement rates amongst various surgeon experience levels. Although not statistically significant, early-career neurosurgeons had lower rates of new postoperative steroid dependence. Patients of early career surgeons experienced significantly less DI (15% vs. 40%, P = 0.004). CONCLUSIONS: Late-career neurosurgeons had shorter operation lengths, achieved higher rates of GTR, and their patients experienced significantly higher rates of DI. Overall outcomes remained stable throughout the course of 16 years between different surgeon experience levels.

Objective: We sought to determine if genetically modified porcine kidneys used for xenotransplantation had sufficient tissue integrity to support long-term function in a human recipient. Background: Kidney transplantation remains the best available treatment for patients with end-stage kidney disease. However, a shortage of available donor human kidneys prevents many patients from achieving the benefits of transplantation. Xenotransplantation is a potential solution to this shortage. Recent pre-clinical human studies have demonstrated kidneys from genetically modified pig donors can be transplanted without hyperacute rejection and are capable of providing creatinine and other solute clearance. It is unknown whether the porcine kidneys would tolerate the relatively higher resting blood pressure in an adult human recipient compared with the pig donor or non-human primate (NHP) recipients used in translational studies. Furthermore, previous experience in NHPs raised concerns about the tissue integrity of the porcine ureter and post-xenotransplant growth of the porcine kidney. Methods: Kidneys recovered from porcine donors with 10 gene edits were transplanted into decedent brain-dead recipients who were not eligible for organ donation. Decedents underwent bilateral native nephrectomy before transplant and were followed for 3 to 7 days. Standard induction and maintenance immunosuppression was used as previously reported. Vital signs, including blood pressure, were recorded frequently. Kidney xenografts were assessed daily, serially biopsied, and were measured at implantation and study completion. Results: Three decedents underwent successful xenotransplantation. Subcapsular hematomas developed, requiring incision of the xenograft capsules to prevent Page kidney. Blood pressures were maintained in a physiologic range for adult humans (median arterial pressures (MAP) 108.5 mm Hg (Interquartile Range (IQR): 97-114 mm Hg), 74 mm Hg (IQR: 71-78 mm Hg), and 95 mm Hg (IQR: 88-99 mm Hg, respectively) and no bleeding complications or aneurysm formation was observed. Serial biopsies were taken from the xenografts without apparent loss of tissue integrity despite the lack of a capsule. Ureteroneocystotomies remained intact without evidence of urine leak. Xenograft growth was observed, but plateaued, in 1 decedent with increased volume of the left and right xenografts by 25% and 26%, respectively, and in the context of human growth hormone levels consistently less <0.1 ng/ml and insulin-like growth factor 1 levels ranging from 34-50 ng/ml. Conclusions: The findings of this study suggest kidneys from 10-gene edited porcine donors have sufficient tissue integrity to tolerate xenotransplantation into a living human recipient. There was no evidence of anastomotic complications, and the xenografts tolerated needle biopsy without issue. Xenograft growth occurred but plateaued by the study end; further observation and investigation will be required to confirm this finding and elucidate underlying mechanisms.