Peptide-based therapeutics targeting genetic disorders.

Genetic disorders (GDs) are challenging to treat owing to a lack of optimal treatment regimens and intricate and often difficult-to-understand underlying biological processes. Limited therapeutic approaches, which mostly provide symptomatic relief, are available. To date, a limited number of peptide-based drugs for the treatment of GDs are available, and several candidates are under clinical study. This review provides mechanistic insights into GDs and potential target areas where peptide-based drugs are beneficial. In addition, it emphasizes the usefulness of peptides as carriers for gene delivery, biomarkers for mutation detection and peptide-based vaccines for treating GDs.

Chemical Complementarity of Blood-Sourced, Breast Cancer-Related TCR CDR3s and the CMV UL29 and IE1 Antigens is Associated with Worse Overall Survival.

Cytomegalovirus (CMV) infection is common and becomes a particular concern in immunocompromised patients. Understanding the potential role CMV plays in breast cancer patients' disease progression is important for providing more patient-specific treatments. In this study, we analyzed whether a breast cancer patient's blood-sourced T-cell receptor (TCR) complementarity determining-3 (CDR3) amino acid (AA) sequences could provide an indication of the impact of a systemic CMV infection. Specifically, we assessed the chemical complementarity of patient TCR CDR3 AAs and CMV antigens to determine whether patients with greater complementarity also represented different survival probabilities. Initially, we examined five distinct CMV antigens, of which two, IE1 and UL29, represented TCR (TRA+ RB)-CDR3-CMV antigen complementarity scores (CSs) whereby cases representing the upper 50th percentile of CSs had a worse overall survival (log-rank p = 5.034E-3, for IE1). Then, an analysis of CSs representing previously identified, TCR IE1 epitopes indicated that greater TRB CDR3-IE1 epitope complementarities represented a worse OS (log-rank p = 0.0111). These results raise the question of whether a systemic, anti-CMV response leads to increased systemic inflammation, which is either directly or indirectly supportive of tumor growth; or are patients succumbing to a direct impact of CMV functions on tumor growth or metastasis?

Detection of anti-EBV TCR CDR3s associated with better outcomes for EBV-positive, Ugandan cases of Burkitt lymphoma.

Burkitt lymphoma (BL) has a tight association with Epstein-Barr virus (EBV), especially in sub-Saharan Africa. While the relationship between BL and EBV is well documented, the relationship between the anti-EBV adaptive immune response, particularly in sub-Saharan African cases, and disease course, has not been substantially investigated. An analysis of T-cell receptor (TCR) complementarity determining region-3 (CDR3) sequences, reported here, from EBV-positive, Ugandan BL tumor samples revealed a correlation between the presence of anti-EBV CDR3s and improved overall survival probabilities. Furthermore, chemical complementarity assessments demonstrated higher complementarity for TCR CDR3s and EBV epitopes in the cases where there had been a detection of the anti-EBV CDR3 AA sequence matches in the BL tumor samples. Overall, the results reported here raise the question of whether EBV targeted immunotherapy would lead to better BL outcomes?

SAMA: A Self-and-Mutual Attention Network for Accurate Recurrence Prediction of Non-Small Cell Lung Cancer Using Genetic and CT Data.

Accurate preoperative recurrence prediction for non-small cell lung cancer (NSCLC) is a challenging issue in the medical field. Existing studies primarily conduct image and molecular analyses independently or directly fuse multimodal information through radiomics and genomics, which fail to fully exploit and effectively utilize the highly heterogeneous cross-modal information at different levels and model the complex relationships between modalities, resulting in poor fusion performance and becoming the bottleneck of precise recurrence prediction. To address these limitations, we propose a novel unified framework, the Self-and-Mutual Attention (SAMA) Network, designed to efficiently fuse and utilize macroscopic CT images and microscopic gene data for precise NSCLC recurrence prediction, integrating handcrafted features, deep features, and gene features. Specifically, we design a Self-and-Mutual Attention Module that performs three-stage fusion: the self-enhancement stage enhances modality-specific features; the gene-guided and CT-guided cross-modality fusion stages perform bidirectional cross-guidance on the self-enhanced features, complementing and refining each modality, enhancing heterogeneous feature expression; and the optimized feature aggregation stage ensures the refined interactive features for precise prediction. Extensive experiments on both publicly available datasets from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) demonstrate that our method achieves state-of-the-art performance and exhibits broad applicability to various cancers.

Synthesis and mechanistic study of Aß42 C-terminus domain derived tetrapeptides that inhibit Alzheimer's Aß-aggregation-induced neurotoxicity.

Amyloid plaque formation in the brain is mainly responsible for the onset of Alzheimer's disease (AD). Structure-based peptides have gained importance in recent years, and rational design of the peptide sequences for the prevention of Aß-aggregation and related toxicity is imperative. In this study, we investigate the structural modification of tetrapeptides derived from the hydrophobic C-terminal region of Aß42 "VVIA-NH2" and its retro-sequence "AIVV-NH2." A preliminary screening of synthesized peptides through an MTT cell viability assay followed by a ThT fluorescence assay revealed a peptide 13 (Ala-Ile-Aib-Val-NH2) that showed protection against Aß-aggregation and associated neurotoxicity. The presence of the α-helix inducer "Aib" in peptide 13 manifested the conformational transition from cross-ß-sheets to α-helical content in Aß42. The absence of fibrils in electron microscopic analysis suggested the inhibitory potential of peptide 13. The HRMS, DLS, and ANS studies further confirmed the inhibitory activity of 13, and no cytotoxicity was observed. The structure-based peptide described herein is a promising amyloid-ß inhibitor and provides a new lead for the development of AD therapeutics.

Patterns of Antibiotic Resistance in Urinary Tract Infections: A Retrospective Observational Study.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections, and antibiotic resistance complicates empiric treatment. This study aimed to describe recent resistance patterns among uropathogens in a tertiary-care teaching hospital to optimize empiric UTI management. METHODS: This retrospective observational study included 280 patients diagnosed with UTIs at the Dr. Patnam Mahender Reddy Institute of Medical Sciences, Hyderabad, over a six-month period from June 2023 to November 2023. Urine culture and antibiotic susceptibility data were collected from electronic medical records. Patient demographics, including age, sex, and comorbid diabetes, were recorded. Causative uropathogens and their resistance rates to commonly prescribed UTI antibiotics were analyzed. Empiric antibiotic treatment patterns and outcomes were talked about. These included clinical cure, recurrence, susceptibility match, and microbiologic eradication. RESULTS:  The mean age of patients was 43.5 years, with 196 (70%) being female and 70 (25%) having diabetes. Escherichia coli caused 210 (75%) of UTIs, Klebsiella pneumoniae 42 (15%), Proteus mirabilis 14 (5%), Enterococcus faecalis 8 (3%), and Staphylococcus saprophyticus 6 (2%). E. coli resistance rates were 48% for ampicillin, 25% for ciprofloxacin, 18% for trimethoprim/sulfamethoxazole (TMP/SMX), and 5% for nitrofurantoin. K. pneumoniae resistance rates were 89% for ampicillin, 67% for ciprofloxacin, 44% for TMP/SMX, and 22% for nitrofurantoin. The most frequently prescribed antibiotic was nitrofurantoin (45%), then ciprofloxacin (35%). Clinical cure was achieved in 75% of cases. Recurrent UTIs within four weeks occurred in 25% of cases. Treatment matched urine culture susceptibility in 82% of patients. CONCLUSION:  The rising fluoroquinolone resistance highlights the need for current local data to guide empiric UTI treatment. Nitrofurantoin had low resistance rates and was an effective first-line therapy. Ongoing monitoring of resistance patterns in UTIs is essential to optimize antibiotic selection.

Optimizing outcomes in multicompartmental brain tumor surgery: A comparative study of integrated endoscopic and microsurgical techniques versus endoscope-assisted microsurgery.

BACKGROUND: Multicompartmental lesions within the central nervous system are challenging due to their complex anatomy. This study evaluates the efficacy, safety, and utility of hybrid endoscopic and microsurgery versus endoscope-assisted microsurgery(EAM) for excising these lesions. METHODS: A retrospective comparative analysis was conducted on patients who underwent multicompartmental brain tumor surgery, utilizing either hybrid endoscopic and microsurgical techniques with the Endocameleon Hopkins telescope featuring a rotating lens system and knob (Karl Storz GmbH & Co., Tuttlingen, Germany), alternately used with a microscope (ZEISS PENTERO 800 S) (Group 1, n = 69), or endoscope-assisted microsurgery employing a fully high-definition, 45° angled endoscopic tool, QEVO®, integrated into the digital surgical microscope KINEVO 900 (Carl Zeiss Meditec, Oberkochen, Germany) as a plug-in feature (Group 2, n = 63), from July 2018 to March 2024. Data on demographics, clinical presentation, lesion characteristics, surgical details, and outcomes were meticulously collected and analyzed using rigorous statistical methods, including t-tests and chi-square tests. RESULTS: Compared to Group 2, Group 1 had better ease of dissection and visualization of bleeders (p = 0.01) and fewer postoperative hematomas (p = 0.04). Surgical times were similar (p = 0.134). Postoperative follow-up revealed fewer recurrences in Group 1, though not statistically significant (p = 0.33). Group 1 patients reported higher cosmetic satisfaction and shorter hospital stays (p = 0.002). Logistic regression identified tumor vascularity(p = 0.001) and ease of dissection(p = 0.008) as significant factors for recurrence. CONCLUSIONS: Hybrid endoscopic and microsurgery demonstrated superior intraoperative visualization, ease of dissection, and postoperative outcomes compared to endoscope-assisted microsurgery with the Quevo device. These findings suggest that the integrated approach may offer better outcomes for multicompartmental lesion excision regarding safety, efficacy, and patient satisfaction.

"Pediatric Spontaneous Intracranial Dissecting Aneurysms: Impact of Ischemic and Hemorrhagic Manifestations on Endovascular Treatment Strategies - Insights from a Developing World Setting".

BACKGROUND: Pediatric spontaneous intracranial dissecting aneurysms are rare, but systematic studies comparing hemorrhagic and ischemic presentations are lacking. This study addresses gaps in understanding their epidemiology, clinical presentation, management, and outcome. METHODS: A retrospective analysis of 23 pediatric patients with nontraumatic intracranial dissecting aneurysms treated between July 2018 and December 2023 was conducted. Patients were divided into 2 groups based on presentation: hemorrhagic (n = 16) and ischemic (n = 7). Clinical data were analyzed, including demographics, radiologic findings, treatment modalities, and outcomes. RESULTS: Clinical presentations varied, with limb weakness being more prevalent in hemorrhagic cases (P = 0.014), while headache and seizures were more common in ischemic cases. Angiographic analysis revealed distinct patterns, with hemorrhagic cases showing more distal involvement on vessel segments with stenosis and dilatation (pearl string sign). At the same time, the ischemic group exhibited the double-lumen sign. Various treatments, including microsurgery and endovascular techniques, were utilized, with perioperative complications observed, including one mortality in a hemorrhagic case. Multiple regression analysis identified significant risk factors for perioperative complications, namely, the configuration of the dissecting aneurysm (P = 0.016) and the type of presentation (P = 0.0006). Long-term Glasgow Outcome Scores were comparable, but patients with hemorrhagic manifestations experienced prolonged hospital and ICU stays (P = 0.001). CONCLUSIONS: Pediatric intracranial dissecting aneurysms, particularly hemorrhagic cases, are associated with severe neurologic deficits and higher perioperative complications. Despite similar long-term outcomes, hemorrhagic cases require prolonged hospitalization, increasing treatment costs. Optimizing management strategies for pediatric intracranial dissecting aneurysms, especially those with hemorrhagic features, is essential to improve outcomes and reduce healthcare expenditures.

Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving docetaxel: Pooled data analysis.

OBJECTIVES: Limited data are available on central nervous system (CNS) efficacy with standard-of-care therapies for KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC treated with docetaxel using pooled data from historical clinical trials. MATERIALS AND METHODS: Data from phase 2/3 trials of docetaxel-containing regimens in advanced NSCLC were sourced from the Medidata platform. Analysis was restricted to stage IIIB-IV KRASmut NSCLC with disease progression after ≥ 1 systemic anticancer therapy. Participants with asymptomatic, treated, and stable brain metastases were included. Endpoints included 12-month CNS disease control rate (CNS-DCR) and CNS progression per Response Evaluation Criteria in Solid Tumors; progression-free survival (PFS); and overall survival (OS). Data were pooled and analyses stratified by baseline brain metastases status. RESULTS: A total of 595 participants were included in the analysis (62 [10%] with baseline brain metastases and 533 [90 %] without). Among participants with brain metastases, 17 (27.4 %) had CNS progression during docetaxel treatment and 12-month CNS-DCR was 75.8 %; 45 (8.4 %) participants without baseline brain metastases developed brain metastases during treatment. In an analysis restricted to patients with metastatic disease, outcomes with and without baseline brain metastases included: median PFS, 3.3 and 4.9 months (p < 0.005); 12-month PFS, 5 % and 16 %; median OS, 6.9 and 10.4 months (p < 0.005); and 12-month OS, 20 % and 44 %, respectively. CONCLUSION: These findings establish CNS progression rates with docetaxel in previously treated KRASmut advanced NSCLC and facilitate interpretation of data from ongoing randomized clinical trials of novel KRAS-targeted therapeutic strategies vs. docetaxel.

Unlocking the Battle-Clipping vs. Endovascular Therapy for Shunt-Dependent Hydrocephalus After Aneurysm Rupture: An In-Depth Institutional Analysis.

AIM: To compare microsurgical clipping and endovascular therapy (EVT) for the management of shunt-dependent hydrocephalus (SDH) in patients with subarachnoid hemorrhage (SAH) and hydrocephalus. MATERIAL AND METHODS: This retrospective study was conducted from July 2018 to December 2022 and included 67 patients with SAH accompanied by acute hydrocephalus. Patients' demographic, clinical, and radiological data, such as age, sex, Glasgow Coma Scale scores, Hunt and Hess scale, Fischer grade, external ventricular drain (EVD) duration, complications, Ommaya reservoir placement, cerebrospinal fluid drainage, and outcomes, were obtained. Statistical analyses, including univariate analysis and stepwise logistic regression, revealed significant risk factors for shunt dependence. RESULTS: Of the 67 patients, 33 underwent microsurgical clipping and 34 received EVT. Spasmolysis reduced shunt dependency, whereas early EVD placement correlated with reduced shunt dependence (p=0.002). The Ommaya reservoir helped in the management of meningitis but was found to be associated with shunt dependency (p=0.04). Multiple logistic regression analysis revealed that perioperative infarct was a significant risk factor for shunt dependence (p=0.05). No significant difference in patient outcomes was observed between the two treatment groups. However, patients who received EVT had shorter intensive care unit and hospital stays. CONCLUSION: This study shows that managing clinical vasospasm with spasmolysis may reduce shunt dependency. Overall, both microsurgical clipping and EVT offer similar long-term outcomes and efficacy in preventing shunt dependence, but the latter has the advantage of shorter hospital stay. These findings provide crucial insights for clinical decision-making and patient care in SDH after SAH.

Conformation Controlled Hydrogelation of Minimalistic α, γ Hybrid Peptide.

A majority of short peptide (≤7 amino acids) hydrogels are primarily assembled via cross ß-structure formation. In contrast to the natural trend, herein, we report the formation of supramolecular hydrogel from the ultrashort hybrid folded peptide composed of canonical α-amino acid and noncanonical γ-amino acid, Fmoc-γPhe-Phe-OH. The designed hybrid peptide hydrogel is composed of entangled fibers, has viscoelastic properties, exhibits proteolytic stability, and exhibits cytocompatibility with L929 fibroblast cells. Mutating the peptide sequence by altering the position of γPhe from the N-termini to C-termini transforms the self-assembly into crystalline aggregates. Combining FTIR, 2D NMR, and DFT calculations revealed that the hydrogel-forming peptide adopts a C9 H-bonded conformation, resembling the well-known γ-turn. However, the isomeric hybrid peptide adopts an extended structure. The present study highlights the importance of secondary structure in the higher order assembly of minimalist hybrid peptides and broadens the range of secondary structures to design short peptide-based hydrogels.

Spontaneous thrombosis and calcification of giant cavernous carotid artery aneurysm: A rare case and management insights.

Background: Giant cavernous carotid artery aneurysms (>25 mm) are rare (3-5%), with some prone to spontaneous thrombosis (10-20% complete). We present a unique case of one of the largest aneurysms spontaneously thrombosing and calcifying. Case Description: A 57-year-old with persistent right-sided headaches had a substantial hyperdense mass in the right middle cranial fossa, eroding petrous bone. Magnetic resonance imaging and digital subtraction angiography revealed a giant cavernous segment fusiform aneurysm of the right internal carotid artery (ICA) with spontaneous thrombosis and distal ICA occlusion. Collateral circulation maintains the cerebral blood supply. Despite anatomical challenges, conservative management was chosen due to the patient's stability. Conclusion: This case highlights the complex interplay between thrombosed giant aneurysms and affected vessels, with unique features such as cross-flow, calcification, and bone erosion. We advocate conservative management for stable cases, supported by literature, emphasizing vigilant follow-up. This expands the spectrum of aneurysm presentations and encourages further research into their dynamics.

High-throughput quantitative assessments of the chemical complementarity of celiac disease-related IGH CDR3s and a gliadin epitope.

The long-term value of efficient antigen discovery includes gaining insights into the variety of potential cancer neoantigens, effective vaccines lacking adverse effects, and adaptive immune receptor (IR) targets for blocking adaptive IR-antigen interactions in autoimmunity. While the preceding goals have been partially addressed via big data approaches to HLA (human leukocyte antigen)-epitope binding, there has been little such progress in the big data setting for adaptive IR-epitope binding. This delay in progress for the latter is likely due to, among other things, the much more complicated adaptive IR repertoire in an individual compared to individual HLA alleles. Thus, results described here represent the application of an algorithm for efficient assessment of immunoglobulin heavy chain complementarity determining region-3 (IGH CDR3)-gliadin epitope interactions, with a focus on epitopes known to be associated with an immune response in celiac disease. The hydrophobic, chemical complementarity between celiac case IGH CDR3s and known celiac epitopes was found to be greater in comparison to the hydrophobic, chemical complementarity between the same celiac case IGH CDR3s and a series of control epitopes. Thus, the approaches indicated here likely offer guidance for the development of conveniently applied algorithms for antigen verification and discovery.

The Next Horizon of Drug Development: External Control Arms and Innovative Tools to Enrich Clinical Trial Data.

Conducting clinical trials (CTs) has become increasingly costly and complex in terms of designing and operationalizing. These challenges exist in running CTs on novel therapies, particularly in oncology and rare diseases, where CTs increasingly target narrower patient groups. In this study, we describe external control arms (ECA) and other relevant tools, such as virtualization and decentralized clinical trials (DCTs), and the ability to follow the clinical trial subjects in the real world using tokenization. ECAs are typically constructed by identifying appropriate external sources of data, then by cleaning and standardizing it to create an analysis-ready data file, and finally, by matching subjects in the external data with the subjects in the CT of interest. In addition, ECA tools also include subject-level meta-analysis and simulated subjects' data for analyses. By implementing the recent advances in digital health technologies and devices, virtualization, and DCTs, realigning of CTs from site-centric designs to virtual, decentralized, and patient-centric designs can be done, which reduces the patient burden to participate in the CTs and encourages diversity. Tokenization technology allows linking the CT data with real-world data (RWD), creating more comprehensive and longitudinal outcome measures. These tools provide robust ways to enrich the CT data for informed decision-making, reduce the burden on subjects and costs of trial operations, and augment the insights gained for the CT data.

Peptide hydrogen-bonded organic frameworks.

Hydrogen-bonded porous frameworks (HPFs) are versatile porous crystalline frameworks with diverse applications. However, designing chiral assemblies or biocompatible materials poses significant challenges. Peptide-based hydrogen-bonded porous frameworks (P-HPFs) are an exciting alternative to conventional HPFs due to their intrinsic chirality, tunability, biocompatibility, and structural diversity. Flexible, ultra-short peptide-based P-HPFs (composed of 3 or fewer amino acids) exhibit adaptable porous topologies that can accommodate a variety of guest molecules and capture hazardous greenhouse gases. Longer, folded peptides present challenges and opportunities in designing P-HPFs. This review highlights recent developments in P-HPFs using ultra-short peptides, folded peptides, and foldamers, showcasing their utility for gas storage, chiral recognition, chiral separation, and medical applications. It also addresses design challenges and future directions in the field.

OA-GAN: organ-aware generative adversarial network for synthesizing contrast-enhanced medical images.

Contrast-enhanced computed tomography (CE-CT) images are vital for clinical diagnosis of focal liver lesions (FLLs). However, the use of CE-CT images imposes a significant burden on patients due to the injection of contrast agents and extended shooting. Deep learning-based image synthesis models offer a promising solution that synthesizes CE-CT images from non-contrasted CT (NC-CT) images. Unlike natural images, medical image synthesis requires a specific focus on certain organs or localized regions to ensure accurate diagnosis. Determining how to effectively emphasize target organs poses a challenging issue in medical image synthesis. To solve this challenge, we present a novel CE-CT image synthesis model called, Organ-Aware Generative Adversarial Network (OA-GAN). The OA-GAN comprises an organ-aware (OA) network and a dual decoder-based generator. First, the OA network learns the most discriminative spatial features about the target organ (i.e. liver) by utilizing the ground truth organ mask as localization cues. Subsequently, NC-CT image and captured feature are fed into the dual decoder-based generator, which employs a local and global decoder network to simultaneously synthesize the organ and entire CECT image. Moreover, the semantic information extracted from the local decoder is transferred to the global decoder to facilitate better reconstruction of the organ in entire CE-CT image. The qualitative and quantitative evaluation on a CE-CT dataset demonstrates that the OA-GAN outperforms state-of-the-art approaches for synthesizing two types of CE-CT images such as arterial phase and portal venous phase. Additionally, subjective evaluations by expert radiologists and a deep learning-based FLLs classification also affirm that CE-CT images synthesized from the OA-GAN exhibit a remarkable resemblance to real CE-CT images.

Metal-driven folding and assembly of a minimal ß-sheet into a 3D-porous honeycomb framework.

In contrast to short helical peptides, constrained peptides, and foldamers, the design and fabrication of crystalline 3D frameworks from the ß-sheet peptides are rare because of their high self-aggregation propensity to form 1D architectures. Herein, we demonstrate the formation of a 3D porous honeycomb framework through the silver coordination of a minimal ß-sheet forming a peptide having terminal metal coordinated 4- and 3-pyridyl ligands.

Synthesis and mechanistic study of ultrashort peptides that inhibits Alzheimer's Aß-aggregation-induced neurotoxicity.

Misfolding/aggregation of ß-amyloid peptide lead to the formation of toxic oligomers or accumulation of amyloid plaques, which is a seminal step in the progression of Alzheimer's disease (AD). Despite continuous efforts in the development of therapeutic agents, the cure for AD remains a major challenge. Owing to specific binding affinity of structure-based peptides, we report the synthesis of new peptide-based inhibitors derived from the C-terminal sequences, Aß38-40 and Aß40-42. Preliminary screening using MTT cell viability assay and corroborative results from ThT fluorescence assay revealed a tripeptide showing significantly effective inhibition towards Aß1-42 aggregation and induced toxicity. Peptide 3 exhibited excellent cell viability of 94.3 % at 2 µM and of 100 % at 4 µM and 10 µM. CD study showed that peptide 3 restrict the conformation transition of Aß1-42 peptide towards cross-ß-sheet structure and electron microscopy validated the absence of Aß aggregates as indicated by the altered morphology of Aß1-42 in the presence of peptide 3. The HRMS-ESI, DLS and ANS studies were performed to gain mechanistic insights into the effect of inhibitor against Aß aggregation. This Aß-derived ultrashort motif provides impetus for the development of peptide-based anti-AD agents.

Navigating Uncharted Waters: Comparative Analysis of Clinical Progression and Outcomes in Vestibular Schwannoma Patients with Papilledema and without Hydrocephalus, Versus Those without Papilledema and Hydrocephalus: A Comprehensive Institutional Insight.

BACKGROUND: Papilledema's association with hydrocephalus (HCP)-linked larger vestibular schwannoma (VS) is established but cases lacking concurrent HCP require further investigation. METHODS: This retrospective comparative observational study, conducted from July 2018 to July 2023, examined 120 VS patients undergoing surgery. Patients were categorized into Group 1 (papilledema without HCP) and Group 2 (no papilledema or HCP), with comprehensive data analyzed. RESULTS: In this study, Group 1 (14 patients with papilledema) and Group 2 (106 patients without papilledema or HCP) were compared. Group 1 was younger (mean age 27.21 ± 11.73 years) than Group 2 (mean age 54.66 ± 11.44 years). Both groups had similar symptom durations and tumor detection times. Group 1 had increased vascularity (P = 0.001), elevated cisterna magna protein levels (P = 0.001), and a higher incidence of neurofibromatosis 2 (P = 0.003). They also experienced longer surgeries (P = 0.001) and more blood loss (P = 0.001), leading to extended postoperative complications. Group 2 showed improved postsurgery visual outcomes (P = 0.001), better Glasgow Outcome Scores (P = 0.001), enhanced facial nerve preservation (P = 0.002), and improved hearing on follow-up (P = 0.003). Logistic regression analysis highlighted prolonged surgery duration (P = 0.057) and papilledema (P = 0.0001) as significant factors influencing visual improvement. CONCLUSIONS: Patients with VS require preoperative fundoscopy evaluation due to potential visual loss and papilledema, even without HCP. Early treatment initiation enhances visual and hearing outcomes. Meticulous surgery is vital given the lesion's hypervascular nature and adherence to surrounding structures. Preoperative embolization may aid in preserving neurovascular structures. In developing countries with higher blindness rates, judicious noncontrast computed tomography brain evaluation is crucial for timely detection and treatment initiation of lesions like VS.