Eiman Mahmoud Mohammed

Background: Ewing sarcoma (ES) is a rare, aggressive small round cell sarcoma (SRCS) that peaks in adolescence. Given its rarity, atypical age or site presentations increase the risk of misclassification. This study examines age-related clinicopathological patterns in molecularly confirmed canonical ES (FET::ETS-fused). Methods: Between 2016 and 2025, 90 tumors diagnosed as ES or Ewing-like SRCSs underwent targeted RNA sequencing and/or EWSR1 break-apart fluorescence in situ hybridization. Patients were stratified into three age groups: 0–18, 19–39, and ≥40 years. Clinical, anatomical, pathological, molecular, and treatment/outcome variables were compared across strata. Results: Canonical ES accounted for 84% (76/90) of SRCSs, dominated by EWSR1::FLI1 (89%). ES comprised 91% of SRCSs in children but declined to 75% in older adults. Tumors arose mainly in bone (63%), with a significant age association (p = 0.016): children and young adults were primarily skeletal (73% and 62%), whereas older adults were predominantly extraskeletal (78%). Renal ES clustered in adults ≥40 years (p = 0.003). Classic histology predominated; atypical patterns were more common in extraskeletal tumors but lacked age specificity. Ewing-like SRCSs (n = 14), with heterogeneous or absent fusions, displayed a broader age distribution—including infants and older adults—and a marked extraskeletal predominance (86%, p = 0.001). Metastatic presentation strongly predicted inferior survival (p = 0.025). Treatment was multimodal, with neoadjuvant chemotherapy more frequent in children (90%, p = 0.029). Conclusions: Age significantly influences anatomic presentation and certain treatment choices in ES, whereas histology and survival remain broadly similar across groups. Age-linked extraskeletal trends reinforce the importance of routine molecular testing, particularly in underreported Middle Eastern populations.

Multiple sclerosis (MS) is a complex autoimmune disorder of the central nervous system (CNS) with an unknown etiology and pathophysiology that is not completely understood. Although great strides have been made in developing disease-modifying therapies (DMTs) that have significantly improved the quality of life for MS patients, these treatments do not entirely prevent disease progression or relapse. Identifying the unaddressed pathophysiological aspects of MS and developing targeted therapies to fill in these gaps are essential in providing long-term relief for patients. Recent research has uncovered some aspects of MS that remain outside the scope of available DMTs, and as such, yield only limited benefits. Despite most MS pathophysiology being targeted by DMTs, many patients still experience disease progression or relapse, indicating that a more detailed understanding is necessary. Thus, this literature review seeks to explore the known aspects of MS pathophysiology, identify the gaps in present DMTs, and explain why current treatments cannot entirely arrest MS progression.

In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in the KIT/PDGFRA oncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limited treatment options. Data on the mutational landscape of GISTs and their impact on disease progression are very limited in Kuwait. Using a targeted next-generation sequencing panel, we investigated the spectrum and frequency of KIT, PDGFRA, and RAS-pathway-related mutations in 95 out of 200 GISTs diagnosed at Kuwait Cancer Center from 2005 to 2023 and assessed their correlation with clinicopathological parameters. Among the 200 tumors (median age 55 years; 15–91), 54% originated in the stomach, 33% in the small bowel, 7% in the colorectum, 1.5% in the peritoneum, and 4.5% had an unknown primary site. Of the 95 molecularly profiled cases, 88% had a mutation: KIT (61%), PDGFRA (25%), NF1 (2%), and one NTRK1 rearrangement. Ten WT-GISTs were identified (stomach = 6, small bowel = 2, and colorectum = 2). WT-GISTs tended to be smaller (median 4.0 cm; 0.5–8.0) (p = 0.018), with mitosis ≤5/5 mm², and were of lower risk (p = 0.019). KIT mutations were an adverse indicator of disease progression (p = 0.049), while wild-type status did not significantly impact progression (p = 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants.

Aims Mitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait. Methods We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations. Results Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2–17.6) and 21 adult patients (median 37 years; 18.9–89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs. Conclusion The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.

Background Nearly one billion people worldwide have a mental disorder. During the last few years, the number of people suffering from psychological disorders such as depression and anxiety has increased by more than 25%. Just over 22% of multiple sclerosis (MS) patients experience anxiety. MS is an autoimmune disorder of the central nervous system (CNS) that is characterized by a complex interplay of factors, leading to inflammation, demyelination, and neurodegeneration. The disease strikes more people every year with no definitive aetiology. Many genetic, infectious, and environmental factors were confirmed as MS risk factors, but no psychological factors have been considered. Objective This review aims to explore the effect of anxiety on the manifestation of MS, the correlation between anxiety and MS symptomology, and possible connection points between anxiety and MS. Method A literature search was conducted in the NCBI PubMed database to investigate the impact of anxiety on MS symptomology and episodes, as well as any possible link between anxiety and MS. The search was conducted up to October 2022. Results Database searches retrieved a total of 1,607 articles for the phrase ‘multiple sclerosis and anxiety’ published from 1964 to 2022. Data were thoroughly reviewed to include only statistically significant associations. Several articles reported strong associations between anxiety and MS symptoms and episodes. Despite the lack of articles exploring the relationship between anxiety and MS, several pointed to the negative effect of anxiety on the immune system. The fact that MS is an autoimmune disorder of the CNS, and that anxiety dysregulates immunity, could indicate that anxiety has an effect on MS. Prospective: Further studies must be undertaken to understand the influence of anxiety on MS; meanwhile, psychological evaluation of MS patients is strongly recommended and needs to be incorporated into treatment plans.

Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS that affects millions of people worldwide. The causes of the disease remain unknown despite extensive efforts to understand it. CircRNAs are a unique class of endogenous non-coding RNA that are abundant, stable, conserved, and specifically expressed molecules, making them a promising biomarker of diseases. This review investigates the role of circRNA in MS pathogenicity and their potential as a biomarker through a comprehensive literature search conducted in 8 scientific databases. The studies found that there are differentially expressed circRNAs in MS patients compared to healthy controls (HC), and this difference is even more pronounced in different MS subtypes. Enrichment of circRNAs in linkage disequilibrium (LD) blocks that harbor MS-associated SNPs suggests that these SNPs manipulate the levels of circRNAs in the surrounding area, contributing to disease pathogenicity. While circRNA shows promise as an indicator or biomarker for MS disease pathology, further research is needed to fully explore its potential and impact on human biology.

Aims Accurate assessment of 1p/19q codeletion status in diffuse gliomas is of paramount importance for diagnostic, prognostic and predictive purposes. While targeted next generation sequencing (NGS) has been widely implemented for glioma molecular profiling, its role in detecting structural chromosomal variants is less well established, requiring supplementary informatic tools for robust detection. Herein, we evaluated a commercially available amplicon-based targeted NGS panel (Oncomine Comprehensive Assay v3) for the detection of 1p/19q losses in glioma tissues using an Ion Torrent platform and the standard built-in NGS data analysis pipeline solely. Methods Using as little as 20 ng of DNA from formalin-fixed paraffin-embedded tissues, we analysed 25 previously characterised gliomas for multi-locus copy number losses (CNLs) on 1p and 19q, including 11 oligodendrogliomas (ODG) and 14 non-oligodendroglial (non-ODG) controls. Fluorescence in-situ hybridisation (FISH) was used as a reference standard. Results The software confidently detected combined contiguous 1p/19q CNLs in 11/11 ODGs (100% sensitivity), using a copy number cut-off of ≤1.5 and a minimum of 10 amplicons covering the regions. Only partial non-specific losses were identified in non-ODGs (100% specificity). Copy number averages of ODG and non-ODG groups were significantly different (pConclusions This commercial NGS panel, along with the standard Ion Torrent algorithm, accurately detected 1p/19q losses in ODG samples, obviating the need for specialised custom-made informatic analyses. This can easily be incorporated into routine glioma workflow as an alternative to FISH.

Multiple sclerosis (MS) is a complex neurological disorder characterized by an aberrant immune system that affects patients’ quality of life. Several environmental factors have previously been proposed to associate with MS pathophysiology, including vitamin D deficiency, Epstein-Barr virus (EBV) infection, and cigarette smoking. These factors may influence cellular molecularity, interfering with cellular proliferation, differentiation, and apoptosis. This review argues that small noncoding RNA named microRNA (miRNA) influences these factors’ mode of action. Dysregulation in the miRNAs network may deeply impact cellular hemostasis, thereby possibly resulting in MS pathogenicity. This article represents a literature review and an author’s theory of how environmental factors may induce dysregulations in the miRNAs network, which could ultimately affect MS pathogenicity.

Multiple sclerosis (MS) is one of the complex diseases. Genetics, environmental and emotional factors have shown to play essential roles in evoking the disease pathology