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Fulltext DTI Profiles for Rapid Description of Cohorts at the Clinical-Research Interface

Lock C, Kwok J, Kumar S, Ahmad-Annuar A, Narayanan V, Ng ASL, et al.

Front Med (Lausanne), 2018;5:357.
PMID: 30687707 DOI: 10.3389/fmed.2018.00357

Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.
Neural Fiber Integrity in High- Versus Low-Grade Glioma using Probabilistic Fiber Tracking

Seow P, Hernowo AT, Narayanan V, Wong JHD, Bahuri NFA, Cham CY, et al.

Acad Radiol, 2021 12;28(12):1721-1732.
PMID: 33023809 DOI: 10.1016/j.acra.2020.09.007

RATIONALE AND OBJECTIVES: Gliomatous tumors are known to affect neural fiber integrity, either by displacement or destruction. The aim of this study is to investigate the integrity and distribution of the white matter tracts within and around the glioma regions using probabilistic fiber tracking.
MATERIAL AND METHODS: Forty-two glioma patients were subjected to MRI using a standard tumor protocol with diffusion tensor imaging (DTI). The tumor and peritumor regions were delineated using snake model with reference to structural and diffusion MRI. A preprocessing pipeline of the structural MRI image, DTI data, and tumor regions was implemented. Tractography was performed to delineate the white matter (WM) tracts in the selected tumor regions via probabilistic fiber tracking. DTI indices were investigated through comparative mapping of WM tracts and tumor regions in low-grade gliomas (LGG) and high-grade gliomas (HGG).
RESULTS: Significant differences were seen in the planar tensor (Cp) in peritumor regions; mean diffusivity, axial diffusivity and pure isotropic diffusion in solid-enhancing tumor regions; and fractional anisotropy, axial diffusivity, pure anisotropic diffusion (q), total magnitude of diffusion tensor (L), relative anisotropy, Cp and spherical tensor (Cs) in solid nonenhancing tumor regions for affected WM tracts. In most cases of HGG, the WM tracts were not completely destroyed, but found intact inside the tumor.
DISCUSSION: Probabilistic fiber tracking revealed the existence and distribution of WM tracts inside tumor core for both LGG and HGG groups. There were more DTI indices in the solid nonenhancing tumor region, which showed significant differences between LGG and HGG.
High incidence of multidrug-resistant organisms and modifiable risk factors associated with surgical site infections: a cohort study in a tertiary medical center in Kuala Lumpur, Malaysia from 2020 to 2023

Muhamad AN, Teh CSJ, Draman MR, Adnan YK, Abbas AA, Khong TL, et al.

Antimicrob Resist Infect Control, 2025 Mar 13;14(1):22.
PMID: 40082971 DOI: 10.1186/s13756-025-01537-2

BACKGROUND: Surgical site infections (SSIs) are a persistent challenge in healthcare, contributing significantly to patient morbidity, mortality, and healthcare costs. Despite advancements in preventive measures, SSIs remain prevalent, especially in countries like Malaysia where rates are higher than in high-income nations.
METHODS: A prospective, cohort study was conducted at the University Malaya Medical Center (UMMC), Malaysia, from November 2020 to May 2023. Clinical and microbiological data were collected, and logistic regression were performed to identify risk factors associated with SSIs.
RESULTS: A total of 1,815 patients undergoing orthopedic, neurosurgical, and general surgical procedures were monitored for SSIs. The incidence rate of SSIs was 3.23 per 100 procedures (n = 71) with significant associations observed between SSI occurrence and prolonged surgical duration > 100 min, extended hospitalization > 5 days, trauma-to-surgery interval > 8 days, and presence of implants. Common pathogens isolated included Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Multidrug-resistant organisms (MDROs) were identified in 42.1% of the total isolates.
CONCLUSIONS: In this study, a high rate of MDRO and risk factors for SSI were identified. It emphasises the need for ongoing surveillance to guide infection prevention strategies and antimicrobial stewardship programs. Future research should prioritize evaluating the impact of targeted interventions tailored to identified risk factors to optimize surgical patient outcomes.
Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance

Saunus JM, Quinn MC, Patch AM, Pearson JV, Bailey PJ, Nones K, et al.

J Pathol, 2015 Nov;237(3):363-78.
PMID: 26172396 DOI: 10.1002/path.4583

Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2) = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting HER3, which is broadly over-expressed and activated in BMs, independent of primary site and systemic therapy.