Search Results (201)

A methodological framework for real estate collateral under CRR3, taking into account the International Valuation Standards (IVS) and relevant ESG factors, including physical and environmental risks, in determining prudential value. The study includes illustrative numerical applications to property resilience and physical risks. This paper examines the methodological implications of property value (PV) under Article 229 of Regulation (EU) 2024/1623, which, in implementation of the Basel III framework, amended Regulation (EU) No 575/2013 on prudential requirements for credit institutions and investment firms, for real estate collateral valuation (CRR3). It considers how current market value (MV) may be tested against the value sustainable over the life of the loan, with particular attention to property resilience, energy efficiency and materially relevant environmental and physical risks. The study combines the CRR3 framework, European Banking Autority (EBA) Guidelines and European Central Bank (ECB) Good Practices with valuation standards and a targeted critical review of recent literature. Drawing on the IVS and the Italian property valuation standard, it proposes a market-capped and sustainability-tested framework for determining property value, in which risk-adjusted market value (MVRA) is used as an analytical variable to identify residual risk not already reflected in market prices. The A_phys formulation provides a first-order analytical representation of event-based physical and environmental risk adjustments through probability, uninsured property damage, property-level loss of use, non-overlapping restoration costs, discounting, and a residual-risk coefficient intended to control double counting. The framework is then applied to three hypothetical numerical worked cases in different Italian Regions: a residential property exposed to hydraulic risk in Emilia-Romagna, an income-producing commercial property exposed to seismic risk in the Marche, and a residential property with partial seismic improvement in Sicily (Messina). The cases include structured comparable analysis, illustrative scenario parameterization, and multivariate sensitivity analysis. They illustrate the computational mechanics and internal consistency of the proposed framework but do not constitute empirical calibration, validation, or evidence of real-world predictive performance; the residual-risk parameters still require calibration using observed market, hazard, vulnerability, insurance, and loss data. The framework may affect the exposure-to-value ratio (ETV) and, depending on the applicable prudential treatment, risk-weighted exposure amounts. The broader ESG perimeter recognized by valuation standards is also acknowledged: Social and Governance variables are not numerically parameterized in the three worked cases, but, where material, they should be mapped to transparent and non-duplicative valuation channels. Full article

Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) loss, remains a major goal in chronic hepatitis B (CHB) management. HBsAg kinetics during interferon (IFN)-based therapy are associated with treatment response and prognosis, but real-world data on weekly HBsAg dynamics remain limited. This retrospective real-world study enrolled 533 CHB patients treated with IFN monotherapy or IFN plus tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), or entecavir (ETV). Weekly HBsAg levels up to week 24 were analyzed using propensity score matching (PSM), subgroup analyses, and generalized estimating equations (GEEs). HBsAg kinetics showed marked heterogeneity, with some patients exhibiting transient early increases. Lower baseline HBsAg levels and rapid early decline were strongly associated with HBsAg loss. After PSM, IFN monotherapy and combination therapy showed comparable HBsAg decline trajectories. The three NA regimens demonstrated similar overall kinetics, although subgroup differences were observed by sex, immune activity, HBV DNA status, and prior treatment. TDF showed a faster decline in females, whereas ETV declined faster in males and immune-active patients. In conclusion, HBsAg kinetics during IFN-based therapy are highly heterogeneous and mainly influenced by baseline HBsAg levels, early on-treatment decline, and host factors. Weekly HBsAg monitoring may help predict treatment response and guide individualized CHB management. Full article

Background: Accurate identification of pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients at increased risk of relapse remains a major clinical challenge, as relapse occurs in 10–20% of cases, including patients initially classified as low- or intermediate-risk. This study aimed to identify clinical, genomic, and measurable residual disease (MRD) related predictors of relapse in pediatric B-ALL. Methods: 51 pediatric patients with B-ALL were included and followed for a median of 30.5 months (IQR, 16–45.5). Patients were stratified according to relapse status. At diagnosis, all cases underwent comprehensive genomic characterization based on the 2022 WHO and ICC classifications, including SNP-array analysis to identify copy number alterations (CNA) involving recurrent B-ALL genes (IKZF1, CDKN2A/B, PAX5, ETV6, BTG1, EBF1, ERG, RB1, and PAR1) and to determine IKZF1^plus status. Clinical variables, including white blood cell count, cytogenetic risk, and MRD assessed by flow cytometry at day 15, day 33, and at the end of induction, were analyzed. Kaplan–Meier and Firth-penalized Cox regression analyses were performed to identify independent predictors of relapse. Results: 86.3% of patients were classified according to the 2022 WHO/ICC classifications, with high hyperdiploidy being the most frequent subtype. During follow-up, 11 patients relapsed. Relapse was significantly associated with high cytogenetic risk (p = 0.007) and showed a trend toward association with an adverse CNA profile (p = 0.075). Patients with >25% bone marrow blasts at day 15 (p < 0.001) and those with positive MRD at the end of induction (p = 0.017) had a significantly higher risk of relapse. In multivariable analysis, high genetic risk and positive end-of-induction MRD remained independent predictors of relapse, with hazard ratios (HRs) of 9.31 (95% CI, 1.55–56.1), p = 0.010, and 10.9 (95% CI, 2.39–49.9), p = 0.002, respectively. Conclusions: An integrated diagnostic strategy including SNP-array provides a high diagnostic yield. High-risk cytogenetic abnormalities and positive end-of-induction MRD are independent predictors of relapse in pediatric B-ALL. Their combined assessment at diagnosis and early treatment may improve risk stratification and may support personalized therapeutic approaches. Full article

Background: Tenofovir alafenamide (TAF) and entecavir (ETV) are recommended alternatives to tenofovir disoproxil fumarate (TDF) for patients with chronic hepatitis B (CHB) at increased risk of kidney injury. However, data from direct head-to-head comparisons of their long-term renal safety and antiviral efficacy after switching from TDF are lacking. We aimed to compare these outcomes between TAF and ETV. Methods: This multicenter retrospective cohort study included consecutive CHB patients who switched from TDF to either TAF or ETV between January 2012 and December 2021. Inverse probability of treatment weighting using the propensity score was applied to balance the baseline characteristics. Changes in estimated glomerular filtration rate (eGFR) were assessed using a linear mixed-effects model. Renal dysfunction was defined as a decline of at least one GFR category. Results: A total of 235 patients were included (TAF, n = 168; ETV, n = 67). After adjustment for key risk factors, the mean eGFR decline over 36 months was not significantly different between the TAF and ETV groups (−3.21 mL/min/1.73 m² [95% CI, −4.98 to −1.44] vs. −3.49 mL/min/1.73 m² [95% CI, −9.49 to −2.50]; p = 0.856). The 3-year cumulative incidence of renal dysfunction was also not significantly different between groups (16.6% [95% CI, 10.5–23.3] vs. 7.8% [95% CI, 2.7–16.2]; p = 0.135). Alanine aminotransferase normalization rates (83.0% vs. 78.8%; p = 0.575) and virological suppression rates (97.8% vs. 97.1%; p = 1.000) were similarly high in both groups. Conclusions: TAF and ETV demonstrated similar long-term renal safety and antiviral efficacy, supporting both agents as reasonable switch options for CHB patients requiring TDF discontinuation because of renal safety concerns. Full article

Soft tissue sarcomas (STSs) are a heterogeneous group of rare mesenchymal malignancies with overlapping morphological and immunohistochemical features, often making definitive diagnosis challenging. Recent advances in next-generation sequencing (NGS) have enabled the identification of recurrent molecular alterations that contribute to tumor classification, prognostic stratification, and precision oncology approaches. This retrospective study aimed to evaluate the diagnostic and clinical impact of molecular profiling in pediatric soft tissue sarcomas using the Oncomine Childhood Cancer Research Assay (OCCRA) panel. Fifty-five frozen tumor samples representing 24 distinct soft tissue sarcoma subtypes were obtained from the Pediatric Oncology Institute -IOP/GRAACC/UNIFESP Biobank (B-053). Molecular analysis was performed using NGS to identify gene fusions, single nucleotide variants (SNVs), copy number variations (CNVs), and insertions/deletions (InDels). Clinically relevant molecular alterations were identified in 70% (37/55) of cases, including 18 fusion transcripts, 13 SNVs, 8 CNVs, and 6 InDels. Recurrent and diagnostically relevant alterations included BCOR::CCNB3, ASPSCR1::TFE3, NFR1::BRAF, FUS::DDIT3, EML4::NTRK3, ETV6::NTRK3, CIC::DUX4, NAB2::STAT6 and SS18::SSX1/2 fusions, as well as amplifications involving PDGFRA, FGFR1, GLI1, CDK4, ERBB3, and KIT. Pathogenic variants affecting genes involved in tumor suppression and chromatin remodeling, including TP53, NF1, DICER1, SMARCA4, PTEN, and PIK3CA, were also detected. Importantly, molecular profiling had significant diagnostic impact in several histologically ambiguous tumors, enabling molecular reclassification and refinement of previously inconclusive or inaccurate pathological diagnoses. In multiple cases, NGS transformed descriptive histopathological interpretations into genetically defined sarcoma entities, including NTRK-rearranged spindle cell neoplasms, CIC-rearranged sarcomas, synovial sarcoma, low-grade fibromyxoid sarcoma, and clear cell sarcoma. Furthermore, the identification of actionable alterations highlighted potential opportunities for targeted therapies and precision medicine approaches. Our findings demonstrate that comprehensive molecular profiling significantly enhances diagnostic accuracy in pediatric soft tissue sarcomas, particularly in morphologically challenging cases. The integration of NGS into routine sarcoma diagnostics enables biologically informed tumor classification and supports personalized therapeutic strategies. Full article

Background: Aberrant DNA methylation is a hallmark of acute myeloid leukemia (AML) and contributes to leukemogenesis, treatment response, and clinical heterogeneity. While genome-wide methylation studies have identified prognostic methylation signatures, the impact of DNA methylation within pharmacologic pathways and AML-relevant disease genes remains incompletely understood. We investigated the association of DNA methylation in genes of pharmacokinetic/pharmacodynamic (PK/PD) pathways of drugs used to treat AML and in myeloid leukemia-related genes with treatment outcomes in pediatric AML. Methods: DNA methylation profiles from 924 pediatric AML patients treated on Children’s Oncology Group trials (AAML1031, AAML0531, and AAML03P1—available publicly) were analyzed as a discovery cohort. A validation cohort included 159 patients treated on the AML02 trial. A total of 2296 variable CpG sites mapping to 65 PK/PD genes and 107 AML biology/leukemia stemness genes were evaluated. Associations between CpG methylation, gene expression, event-free survival (EFS), overall survival (OS), and measurable residual disease after induction I (MRD1) were assessed using Cox proportional hazards, logistic regression, and correlation analyses. Results: Twenty-three CpG sites in PK/PD genes and forty-two CpG sites in AML-related genes were significantly associated with at least one clinical endpoint after Bonferroni correction (p < 2.17 × 10⁻⁵). Hypermethylation of drug transporters ABCA3, ABCC1, and SLC22A1, as well as pharmacologically relevant genes MPO, NOS3, and CTPS1, was associated with inferior survival and/or increased MRD1 positivity. Among AML biology genes, methylation of ETV6, NOTCH1, RUNX1, KIT, MPL, DNMT3A, and DNMT3B demonstrated consistent associations with outcomes across discovery and validation cohorts. Several genes exhibited significant inverse correlations between DNA methylation and gene expression, including MPO, KIT, MPL, SPINK2, and DNMT3B, supporting functional epigenetic regulation. Notably, hypermethylation of ABCA3, MPO, and MPL was reproducibly associated with poor OS and EFS in both cohorts. Conclusions: DNA methylation of key pharmacologic and leukemia-related genes is associated with clinical outcomes in pediatric AML. These findings identify biologically and clinically relevant epigenetic biomarkers that may improve risk stratification and support the development of precision medicine approaches incorporating DNA methylation profiling and epigenetic therapies in pediatric AML. Full article

Matrix metalloproteinase-9 (MMP9) is involved in extracellular matrix remodeling, inflammation, and metastasis, and its overexpression is associated with poor prognosis in lung cancer. However, the systems-level effects of MMP9 inhibition remain incompletely understood. We combined systems biology with experimental validation to characterize MMP9-centered signaling in non-small cell lung cancer (NSCLC) and identify downstream pharmacodynamic biomarkers. Network and pathway analyses revealed extracellular matrix- and inflammation-related interaction modules and prioritized an MMP9-associated gene panel. Synthesized compounds were evaluated using purified enzyme assays and A549 NSCLC cells. At 50 μM, compounds M34 and M33 showed the strongest inhibition of MMP9 activity (65.01% and 61.32%, respectively). Seven compounds (M1, M2, M8, M9, M10, M27, and M34) demonstrated antiproliferative activity at 72 h (IC₅₀ = 40–115 μM), suppressed migration and colony formation, induced apoptosis, and reduced MMP9 protein expression. Quantitative PCR confirmed coordinated downregulation of MMP9, VEGFA, APP, and ETV4, with upregulation of CDH1, COL5A1, COL6A2, CCL2, and CCL17. Enrichment analysis linked these changes to inflammatory signaling, immune activation, and extracellular matrix remodeling. These findings establish an experimentally supported eight-gene pharmacodynamic biomarker signature and support biomarker-guided development of MMP9-targeted strategies in NSCLC. Full article

Background: Prostate cancer remains one of the most prevalent malignancies worldwide, with high mortality in advanced and metastatic stages. Drug repurposing offers a cost-effective and time-efficient strategy to identify new therapeutic options. Objectives: This study aimed to apply physiologically based pharmacokinetic (PBPK) modeling to evaluate repurposed antiretroviral drugs efavirenz (EFV), etravirine (ETV), and saquinavir (SAQ) in prostate cancer, and to assess potential drug–drug interactions (DDIs) between EFV and ETV. Methods: PBPK models for EFV and SAQ were obtained and an ETV was developed and validated using literature and ADMET Predictor^® data. Prostate tissue models were modified to simulate malignant conditions, and population-based simulations examined the influence of age and obesity. The GastroPlus^® DDI module was applied to explore mechanistic interactions between EFV and ETV under different physiological scenarios. Results: Tumor-specific prostate tissue alterations produced minimal systemic pharmacokinetic changes but increased total drug accumulated in simulated tissue, with differences in unbound concentrations, while demographic variables such as age and weight significantly affected drug exposure, which are comorbidities in prostate cancer. Lighter individuals exhibited higher plasma concentrations across all drugs, consistent with known previously reported pharmacokinetic trends in obese individuals. DDI simulations indicated only minor changes in ETV pharmacokinetics when combined with EFV, with no clinically significant interaction detected. Conclusions: The integration of PBPK modeling, population variability, and DDI analysis highlights the potential of SAQ, EFV, and ETV as viable drugs for prostate cancer repurposing, but with a heavy focus on dosing personalization. In silico approaches provide a useful framework for early preclinical evaluation and the optimization of repurposed drugs, supporting the early evaluation of repurposed drug candidates in oncology. Full article

With advances in electric drive technology, electric tracked vehicles (ETVs) have emerged as a promising solution for high-mobility ground vehicles. However, under high-speed steering conditions, the equivalent motor load inertia varies significantly, introducing strong nonlinear and time-varying characteristics into the ETV that may induce lateral instability and even rollover. To address this issue, a novel augmented deep Koopman operator-based model predictive control (ADK-MPC) method is proposed. First, a high-order sliding-mode (HOSM) observer is designed to estimate the lumped load disturbances associated with the time-varying equivalent motor load inertia. Then, the estimated disturbances are introduced as an augmented state into the DK operator to construct a data-driven augmented model. The proposed model transforms the nonlinear dynamics into a lifted linear time-invariant representation in the augmented-state space while capturing the dominant nonlinear characteristics. Based on the ADK model, an ADK-MPC controller is developed to convert the nonlinear optimization problem into a quadratic programming problem, thereby improving steering stability and reducing computational complexity. Simulation results under steering conditions indicate that the proposed method achieves better yaw rate tracking and lower computational cost than nonlinear MPC. The yaw rate tracking error is reduced by 45.5%, while the average solving time is shortened by 11.7%. Full article

Drug repurposing presents as a promising strategy in oncology, particularly for urological prostate and bladder cancers, where resistance to current therapy remains a challenge. This study evaluated the anticancer potential of three antiretroviral drugs, namely ritonavir (RIT), saquinavir (SAQ), and rilpivirine (RPV), in PC-3 and UM-UC-5 cancer cell lines, using MTT, clonogenic, wound healing, toxicity assessment with fibroblast cells, and DCFDA assays; this last method included efavirenz (EFV) and etravirine (ETV) for intracellular reactive oxygen species (ROS) production. RIT and SAQ showed stronger antiproliferative effects than RPV, with lower concentration- and cell-line-dependent activity, while clonogenic assays confirmed a reduction in long-term proliferation, particularly for RIT in both cell lines and SAQ for UM-UC-5. In contrast, effects on cell migration were limited for all drugs. ROS production was cell-dependent, with EFV increasing ROS in PC-3 and SAQ and RIT in UM-UC-5 cells. Generally, all drugs showed minimal toxicity in non-malignant cells, with SAQ exhibiting some toxicity but only for concentrations higher than those required for anticancer activity. Overall, these findings suggest that antiretroviral, especially protease inhibitors, may cause anticancer effects, although these are concentration- and context-dependent, and further investigation is needed to understand the mechanisms involved. Full article

Background/Objectives: Hepatitis B core-related antigen (HBcrAg) is a surrogate marker that reflects the transcriptional activity of covalently closed circular DNA (cccDNA). However, the impact of switching nucleos(t)ide analogs on HBcrAg levels remains unclear. The current study evaluated changes in HBcrAg levels following a switch from entecavir (ETV) to tenofovir alafenamide (TAF) compared with continued ETV therapy. Methods: This retrospective study included patients with chronic hepatitis B who either switched from ETV to TAF between 2017 and 2022 (ETV–TAF group) or continued ETV therapy during the same period (ETV group). HBcrAg levels were measured annually, and longitudinal changes over 3 years were analyzed based on an index year defined for each patient. Propensity score matching for age, sex, HBcrAg levels, liver transplantation status, and ETV treatment duration yielded 10 patients per group. Results: Baseline characteristics were well balanced after matching. HBV DNA and HBsAg levels remained suppressed in both groups throughout follow-up. The ETV-TAF group showed greater declines in HBcrAg than the ETV group at year 2 (−0.20 vs. −0.10 log U/mL, p = 0.007) and year 3 (−0.30 vs. −0.10 log U/mL, p = 0.006). No virological breakthroughs occurred. Conclusions: Switching from ETV to TAF was associated with greater reductions in HBcrAg levels over 3 years than continued ETV therapy, even in patients with suppressed HBV DNA. These findings suggest that switching to TAF may be associated with further suppression of viral transcriptional activity reflected by HBcrAg reduction and support its potential clinical utility for achieving deeper viral suppression. Full article

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and genomic profiling has become increasingly vital for risk stratification. We conducted a retrospective single-center study including 96 newly diagnosed pediatric patients with ALL and mixed phenotype acute leukemia to characterize the genomic landscape using conventional and molecular cytogenetics, multiplex ligation-dependent probe amplification and targeted next-generation sequencing and to evaluate associations with treatment response and survival. Mutation co-occurrence analysis revealed a NRAS/KRAS/JAK cluster and an ETV6::RUNX1 cluster characterized by relative mutational exclusivity, with additional associations between NOTCH1–CDK4 and CDK4–CCND3 alterations. DelCDKN2A/CDKN2B alterations showed a trend toward higher day-15 minimal residual disease (MRD) levels and inferior 2-year event free survival rate (EFS). DelIKZF1-positive cases showed lower 2-year EFS. In contrast, ETV6::RUNX1 and high hyperdiploidy were associated with favorable early response and EFS. DelPAX5 did not independently influence outcome. ZNF384 positive cases showed higher early MRD levels despite excellent survival outcomes. NRAS/KRAS mutations were significantly associated with higher positive day-15 MRD (Wilcoxon, p = 0.0067) and remained independently associated after adjustment for white blood cell count and cytogenetic subgroup. Intermediate risk (IR) and high-risk groups showed comparable 2-year EFS, indicating limited discrimination by conventional risk stratification. The IR group displayed a heterogeneous genomic profile, with NRAS/KRAS, Ph-like mutations and delCDKN2A/CDKN2B among the most frequent alterations. These observations highlight the potential of integrated genomic profiling to refine risk stratification, particularly by identifying clinically relevant subgroups within the IR category. Full article

Background and Objectives: Prognostic assessments in grade 4 diffuse astrocytic tumors primarily depend on clinical and molecular characteristics, with radiological attributes frequently assessed in isolation. In this study, we explored whether an integrated radiological approach combining tumor burden, anatomical spread, and mass effect could contribute to survival prediction. Materials and Methods: A total of 310 adult patients with histopathologically confirmed grade 4 diffuse astrocytic tumors, diagnosed between January 2022 and January 2025, were included in this retrospective single-center cohort. Preoperative MRI was used to assess contrast-enhancing tumor volume, edema volume, and brain volume, combined with anatomical spread and midline shift as a marker of mass effect. Tumor burden was defined as the ratio of enhancing tumor volume to brain volume (ETV/BV). Overall survival was analyzed using Kaplan–Meier and Cox regression methods. Model performance was evaluated with the C-index, bootstrap internal validation, and 12-month calibration. Results: Tumor burden was higher in IDH-wildtype tumors, which also showed higher midline shift and more frequent deep structure involvement and contralateral extension. In multivariable analysis, IDH status, age, tumor burden, midline shift, and deep structure involvement were independently associated with overall survival. A greater tumor burden was associated with reduced survival. The addition of molecular and imaging-derived variables improved discrimination, increasing the C-index from 0.69 to 0.76. Following bootstrap validation, the corrected value was 0.73. Calibration at 12 months demonstrated acceptable agreement between predicted and observed outcomes. Conclusions: An integrated radiological approach that combines tumor burden, anatomical spread, and mass effect may support prognostic assessment in addition to established clinical and molecular variables. Full article

In this study, we systematically analyzed the dynamic changes in chromatin accessibility and the transcriptional responses in the spleen of largemouth bass (Micropterus salmoides) following infection with iridovirus (LMBV) using the assay for transposase-accessible chromatin with sequencing (ATAC-seq) and transcriptome sequencing (RNA-seq). Based on post-infection survival status, largemouth bass were classified into a resistant group (SR) and a susceptible group (SS). A total of 11,317 differentially accessible regions were identified between the two groups, among which the chromatin accessibility of core promoter regions was entirely increased in the SR group, suggesting that chromatin remodeling in these regions may directly participate in the transcriptional regulation of immune-related genes. Functional enrichment analysis revealed that genes associated with differentially accessible regions were significantly enriched in immune-related pathways such as autophagy, apoptosis, Toll-like receptor signaling, and NOD-like receptor signaling. Motif analysis further identified that transcription factors significantly enriched in the SR group included CTCF and heterodimers composed of multiple members of the ETS and FOX transcription factor families. Through integrative analysis, seven transcription factors (CTCF, Spi1, ETV2::FOXI1, FOXJ2::ELF1, FOXO1::ELK1, SPIC, and FOXO1::ELF1) were found to be significantly enriched in core promoter regions. To further screen for differentially expressed genes directly regulated by chromatin accessibility changes, an overlapping analysis was performed between 629 predicted target genes and 2656 differentially expressed genes (DEGs), resulting in the identification of 71 candidate genes. Among these, three immune-related genes (irf4a, btk, and nfil3-2) belonging to the ETS and FOX families were identified. This study reveals the dynamic chromatin accessibility landscape of largemouth bass in response to LMBV infection and demonstrates that increased chromatin accessibility in core promoter regions is closely associated with the resistant phenotype. Heterodimers of ETS and FOX family transcription factors may participate in antiviral immune responses by regulating the expression of key immune genes such as irf4a, btk, and nfil3-2, providing potential epigenetic molecular markers for disease resistance breeding in fish. Full article

Background and Clinical Significance: Endoscopic third ventriculostomy (ETV) is a well-established cerebrospinal fluid (CSF) diversion technique for treating obstructive hydrocephalus. Here, the complication of post-ETV hyponatremia is rare. Separately, aqueductal web as a cause of obstructive hydrocephalus is also an uncommon occurrence. We present an unusual case of an adolescent who presented with late symptoms of obstructive hydrocephalus secondary to an aqueductal web and developed a delayed onset of post-operative hyponatremia after a successful ETV procedure. Pertinent aspects of the case are discussed in corroboration with the recent literature. Case Presentation: A previously well 14 year old presented with symptoms of raised intracranial pressure. Neuroimaging demonstrated progressively enlarging ventricles associated with an aqueductal web. She underwent an uneventful ETV and was discharged home. However, she was readmitted for symptomatic hyponatremia that was investigated and most likely attributed to Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). She was managed with fluid restriction with good clinical improvement. Conclusions: We herein report a case of delayed onset of obstructive hydrocephalus secondary to an aqueductal web, treatment challenges faced and the patient’s unexpected occurrence of hyponatremia after a technically successful ETV. This emphasizes that clinicians need to be mindful of this potential post-operative complication and the ability to discern subtle symptoms in a patient whose clinical signs may not be straightforward. Full article