Citations

ABO incompatibility is frequent in haematopoietic stem cell transplantation (HSCT), yet the clinical impact of non-ABO red blood cell (RBC) alloimmunisation remains less defined. We describe the clinical course of a man in his 50s with chronic eosinophilic leukaemia who underwent a mismatched unrelated donor (MMUD) HSCT. Despite a major ABO mismatch and high-titre pre-existing anti-E antibodies against an E-antigen positive donor, the patient achieved successful trilineage engraftment without haemolysis. Six months after the transplant, he developed severe pancytopenia and a positive direct antiglobulin test (DAT) with anti-E elution. These serologic findings coincided with disease relapse rather than isolated immune-mediated haemolysis. This case illustrates that successful engraftment is possible across RhE-incompatibility and underscores the need to interpret late serologic abnormalities within the broader context of graft function and disease status.

Background Circulating tumor DNA (ctDNA) has rapidly evolved from a research tool to a clinically applicable biomarker in colorectal cancer (CRC), transforming the assessment of minimal residual disease (MRD) and recurrence risk. The growing availability of commercial assays has complicated test selection and interpretation, particularly for gastroenterologists who increasingly encounter ctDNA data in postoperative and surveillance settings. Methods We conducted a narrative review of the literature using PubMed, Embase, and Cochrane databases from January 2015 through March 2026, prioritizing randomized controlled trials, prospective cohort studies, and clinical practice guidelines relevant to ctDNA applications in CRC. The search employed predefined keyword combinations applied independently to each database. Two authors (A.S. and S.M.) independently screened titles and abstracts against the prespecified inclusion criteria, with disagreements resolved by discussion. Results Tumor-informed assays that analyze patient-specific mutations exhibit high specificity for MRD detection, with serial sampling sensitivity reaching 88% compared to 59% for tumor-agnostic approaches, based on a 2026 systematic review and diagnostic accuracy meta-analysis that pooled data across multiple platforms and settings; the authors note substantial study-level heterogeneity in platform design and patient populations, and results should be interpreted accordingly, but require tissue access and extended processing times. Tumor-agnostic tests are more rapid and accessible, incorporating genomic and epigenomic signals, though they exhibit site-specific sensitivity variations ranging from 100% for liver metastases to 40% for peritoneal recurrence and remain vulnerable to biological confounders such as clonal hematopoiesis (CH). Importantly, ctDNA interpretation is subject to additional biological limitations including tumor shedding variability by anatomical site and disease burden, the timing of sample collection relative to surgery or chemotherapy, platform-specific detection thresholds, and pre-analytical variables such as hemolysis and delayed plasma processing. Randomized evidence supports ctDNA-guided de-escalation of adjuvant therapy in stage II colon cancer, with 5-year follow-up from the DYNAMIC trial demonstrating comparable recurrence-free survival (88% vs. 87%) and overall survival (93.8% vs. 93.3%) despite reduced chemotherapy use. In stage III disease, ctDNA is strongly prognostic, but chemotherapy intensification based solely on molecular positivity has not improved outcomes. This review additionally addresses underexplored areas including ctDNA in rectal cancer and neoadjuvant therapy, the influence of microsatellite instability (MSI) status on assay performance, and disparities in ctDNA access across racial, socioeconomic, and geographic populations. Conclusions For gastroenterologists encountering ctDNA results in postoperative and surveillance settings, three principles should guide practice (i): match assay selection to clinical intent - tumor-informed platforms for MRD-directed adjuvant decisions, tumor-agnostic platforms when tissue is unavailable (ii); interpret results within biological and technical context, accounting for platform-specific sensitivity limitations, biological confounders, and quantitative VAF trajectory rather than binary thresholds; and (iii) integrate ctDNA findings into multidisciplinary pathways - de-escalation is supported by high-quality randomized evidence in stage II disease (Grade A; Level I), while chemotherapy escalation based solely on ctDNA positivity in stage III disease is not supported outside clinical trials (Grade C; Level I). Standardization of assay performance benchmarks and equitable access to testing remain critical unmet needs.

ABSTRACT HLA‐DQA1*01:67:01 is characterised by a single nucleotide substitution in codon 100 in Exon 3.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

ABSTRACT HLA‐DPA1*01:49 is characterised by a single nucleotide substitution in codon 119 in exon 3.

Abstract Background Glioblastoma (GB) exhibits marked tumor microenvironmental heterogeneity, contributing to both therapy resistance and poor survival outcomes. Intercellular adhesion molecule 1 (ICAM1) is an inflammation-associated adhesion molecule implicated in immune-stromal interactions, but its clinical and biological significance in GB remains incompletely defined. Methods We performed ICAM1 immunohistochemistry, bulk RNA sequencing, DNA methylation analysis, single-nucleus RNA sequencing, and preoperative MRI-derived morphologic feature analysis across multi-institutional cohorts of treatment-naïve IDH-wildtype GB. Results High ICAM1 expression at both transcript and protein levels is associated with shorter overall survival, particularly within the mesenchymal transcriptional subtype. ICAM1 expression is inversely associated with promoter methylation. Single-nucleus RNA-sequencing analysis shows that ICAM1-high tumors are enriched for mesenchymal, hypoxia, stress-associated, and immunosuppressive myeloid programs, suggesting that ICAM1 reflects a multicompartment inflammatory tumor ecosystem. ICAM1 expression, tumor surface irregularity, and patient age are independently prognostic and minimally correlated, capturing complementary clinical, imaging, and molecular features of GB biology. When combined, our Clinical-Imaging-Molecular (CIM) framework refines outcome prediction across independent GB cohorts using routinely available clinical data, conventional imaging, and standard immunohistochemistry. Conclusions ICAM1 characterizes an immune-remodeled, stress-adapted GB ecosystem associated with poor clinical outcomes. Integrating patient age, surface irregularity, and ICAM1 expression yields a scalable and clinically accessible prognostic framework for GB, supporting tailored outcome prediction, particularly in low- and middle-resource settings without routine access to advanced molecular profiling.

Background Congenital anomalies of the urogenital system frequently coexist with renal abnormalities due to their shared origin from the intermediate mesoderm. Skeletal anomalies may also be associated, reflecting overlapping embryological development of mesodermal derivatives. Such multisystem involvement can pose a diagnostic challenge, particularly when identified incidentally. Case Presentation We report a 15-year-old female who presented with abdominal swelling and pain, later diagnosed as an umbilical hernia. During radiological evaluation, incidental findings of right renal agenesis, scoliosis, and a bicornuate uterus were identified. The patient underwent successful surgical management of the umbilical hernia. This case highlights the importance of recognizing coexisting anomalies and adopting an integrated approach in evaluation and management. Conclusion This case highlights the need for a systematic, bidirectional evaluation when a congenital anomaly is identified, particularly involving the renal, genital, and skeletal systems. A syndromic perspective is essential to avoid missed diagnoses, facilitate appropriate follow-up, and anticipate long-term implications in such patients.