Purpose: The chromodomain helicase DNA-binding (CHD) protein family comprises adenosine triphosphate-dependent chromatin remodelers that regulate chromatin structure and gene expression. Pathogenic CHD2 variants are associated with neurodevelopmental phenotypes, but these genotype–phenotype correlations remain unclear. This study aimed to delineate the clinical and genetic features of patients with CHD2-related disorders and to explore the associated genotype–phenotype relationships. Methods: Among 22 patients with pathogenic or likely pathogenic CHD2 variants identified using a customized 172-gene neurodevelopmental and epilepsy panel, 19 with sufficient clinical data were included. Demographic, clinical, neuroimaging, electroencephalographic, and genetic data were retrospectively reviewed. Results: Eighteen pathogenic or likely pathogenic variants were identified, including eight novel variants: nine nonsense (50.0%), five splice-site (27.8%), two missense (11.1%), and two exon deletions (11.1%). All patients had epilepsy, with a median age of seizure onset of 2.33 years. Comorbidities included global developmental delay (89.5%), intellectual disability (82.0%), and neuropsychiatric symptoms (47.4%). Seizure types were heterogeneous, with a predominance of generalized-onset seizures, and 13 patients (68.4%) achieved seizure freedom. Marked phenotypic variability was observed: two unrelated patients with the same truncating variant had different developmental and seizure-related profiles, a symptomatic child with an inherited exon 5 deletion contrasted with her asymptomatic father, and a patient with an exon 17–29 deletion exhibited relatively mild features. Conclusion Epilepsy was a consistent manifestation in this study and was accompanied by diverse developmental and neurobehavioral features, with substantial genotype–phenotype discordance. Further research on genotype–phenotype correlation is warranted.

Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled “Multidisciplinary guidelines for the management of rectal cancer”). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.

Background: Fusion genes are major drivers of acute leukemia. Conventional diagnostics are limited in detecting the diverse fusions included in recently updated acute leukemia classifications. We evaluated the fusion detection performance of RNA sequencing (RNAseq) compared with that of conventional diagnostics in patients with acute leukemia. Methods: We retrospectively obtained the data of 101 patients with acute leukemia who underwent conventional diagnostics (i.e., karyotyping, FISH, or multiplex reverse transcription PCR) at diagnosis at Samsung Medical Center, Seoul, Korea, between September 2022 and September 2023. Whole RNA-seq was performed using the Illumina Stranded mRNA Prep kit (Illumina, San Diego, CA, USA). The concordance, sensitivity, and specificity of RNA-seq for fusion gene detection were compared with those of conventional diagnostics. Results: RNA-seq helped identify 52 fusion genes in 51 (50.5%) of 101 patients, with detection rates of 40.7%, 70.3%, 37.5%, and 50% in acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia, respectively. RNA-seq showed 83.3% sensitivity and 80.8% concordance with conventional diagnostics; it missed eight fusions, likely because of low transcript abundance or enhancer hijacking. RNA-seq also helped clarify three previously unspecified rearrangements and detected 12 fusions (21.4%) in 56 cases that tested negative with conventional diagnostics, including four novel (KMT2A::THAP12 , RUNX1::PRPF19 , MLLT10::UBE2L6, and FUS::ZNF362) and three rare (HNRNPH1::ERG, RUNX1::USP42, and ETV6::NCOA2) fusions. Conclusions This was the first study to evaluate the performance of whole RNA-seq in fusion detection in patients with acute leukemia in Korea. Incorporating RNA-seq into diagnostic workflows may facilitate earlier and more precise therapeutic decisions and improve prognostic assessment in patients with acute leukemia.

Purpose: Hereditary spastic paraplegia (HSP) refers to a group of genetic neurodegenerative diseases marked by gradually worsening spasticity and hyperreflexia in the lower extremities. This study aimed to describe the clinical and genetic characteristics of Korean patients with spastic paraplegia. Materials and Methods: We retrospectively reviewed medical records of 69 patients with spastic paraplegia from 54 unrelated families between 2002 and 2024. Genetic, clinical, electrophysiological, and radiological features were comprehensively analyzed. Results: Causative genes were identified in 34 (63%) of 54 unrelated families; SPAST, detected in 26 families, was the most prevalent. Seven novel pathogenic variants were identified. Clinically, the median age of symptom onset was 25 years [14.0–37.0]. Out of 69 patients with spastic paraplegia, 51 (74%) presented with the pure form of spastic paraplegia, which included all patients with SPG4. Spastic gait was a universal feature in all patients. Urinary dysfunction was present in 42 (61%) patients. Additional neurologic manifestations included peripheral neuropathy 9 (13%), cognitive impairment 5 (7%), upper limb weakness 4 (6%), dysarthria 4 (6%), dysphagia 3 (4%), ataxia 3 (4%), and scoliosis 1 (3%). Brain MRI findings demonstrated a thin corpus callosum in two patients with SPG11; all patients with SPG4 had normal findings. Spine MRI revealed spinal cord atrophy in 16 (27%) patients, including 6 (21%) patients with SPG4. Conclusion The study comprehensively reviewed genetic and clinical spectra of spastic paraplegia in Korean patients, emphasizing the predominance of SPAST as the causative gene and underscoring the genetic and phenotypic heterogeneity of spastic paraplegia.

Objective: This study compared clinical and cosmetic outcomes of cranioplasty using customized three-dimensional (3-D) printed implants versus autologous bone in patients with aneurysmal subarachnoid hemorrhage (aSAH) after decompressive craniectomy (DC). Methods: We retrospectively reviewed 50 patients who underwent cranioplasty after DC for aSAH between July 2018 and December 2023. Patients were divided into the three-dimensional cranioplasty(3-DC, n=26) and autologous bone cranioplasty (AC, n=24) groups. Demographics, aneurysm characteristics, surgical parameters, morphometric analysis of defect coverage, complications, and functional outcomes assessed by the modified Rankin Scale (mRS) were compared. Results: A total of 54 hemispheres underwent cranioplasty. Compared with AC, the 3-DC group had larger defects but achieved higher coverage (96.7% vs. 93.4%, p=0.044) and smaller residual defects (338.7±274.2 mm² vs. 528.5±331.3 mm², p=0.049). Complication rates were lower in 3-DC (9 cases) than AC (15 cases, p=0.0994). Wound dehiscence and fluid collection were more frequent with 3-DC, while bone flap resorption and epidural abscess occurred only with AC. Revision surgery was required in six patients, five initially treated with autologous bone. Neurological outcomes (mRS) were maintained or improved in both groups. Conclusions In aSAH patients undergoing cranioplasty after DC, customized 3-D printed implants achieved significantly better anatomical restoration and showed a numerical trend toward fewer complications compared with autologous bone. While AC remains feasible, its risks of resorption and infection often necessitate revision. 3-D printed implants may be considered a reasonable alternative, particularly in aSAH patients at higher risk of complications.

Olanzapine is a second-generation antipsychotic drug associated with the development of type 2 diabetes. However, the development and remission of diabetes with glutamic acid decarboxylase (GAD) antibody (Ab) positivity related to olanzapine treatment have not been reported. Here, we present the case of a 33-year-old man taking olanzapine who was diagnosed with diabetes with GAD Ab positivity complicated by diabetic ketoacidosis (DKA). After discontinuation of the drug and tight glycemic control, his diabetes remitted, and the GAD Ab became negative spontaneously after 18 months. The classification of diabetes is challenging because of overlapping autoimmune and metabolic features. Olanzapine may have contributed to pancreatic β-cell apoptosis, which could potentially trigger autoimmunity and the development of type 1 diabetes-like features (DKA as the initial presentation, a low C-peptide level, and GAD Ab positivity). The rapid amelioration of hyperglycemia and weight reduction may be responsible for the remission of diabetes after the discontinuation of olanzapine.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Purpose: Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era. Materials and Methods: A retrospective analysis of 35 CML patients aged < 40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age < 20 years at HSCT (group 1, n=15) and 20-40 years at HSCT (group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan-Meier method. Results: The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003), and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11). Conclusion When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.