Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.

Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Introduction: Severe hypertriglyceridemia, though rare in pregnancy, is a clinically significant condition that poses substantial maternal and perinatal risks. Case: We present a case of a 42-year-old pregnant female with class I obesity and pre-existing type 2 diabetes mellitus, with a booking hemoglobin A1c 12.1%. Her poorly controlled diabetes was complicated by nephrotic syndrome, with a 24-hour urine protein 4.9 g/day. She also had bilateral diabetic retinopathies requiring multiple sessions of panretinal photocoagulation. Throughout the pregnancy, her triglycerides rose progressively, peaking at 30 mmol/L by 33 weeks. Investigations revealed normal thyroid function, urea 4.8 mmol/L, creatinine 66 umol/L, and albumin 26 g/dL. The patient was hospitalized at 33 weeks of gestation and started on an intravenous insulin infusion along with a very low-fat, low-carbohydrate diet prescribed by a dietitian. Pulmonary embolism was diagnosed during evaluation for maternal tachycardia, and subcutaneous enoxaparin was initiated. One week after admission in 35 weeks of gestation, the baby was delivered via emergency Caesarean section due to fetal distress. The baby was small for gestational age, with a birth weight of 1.9 kg, below the 10th percentile for gestational age, and required admission to the neonatal intensive care unit with oxygen support for pneumonia-related respiratory distress. Post-delivery, intravenous insulin infusion and dietary control were continued, reducing her triglyceride level to the lowest level of 8.3 mmol/L. Both mother and baby were discharged well. Lipid-lowering agents such as rosuvastatin and fenofibrate were started after breastfeeding stopped, aiming to normalize her triglyceride levels. Conclusion Hypertriglyceridemia in this patient was the result of uncontrolled diabetes mellitus with nephrotic-range proteinuria. Severe hypertriglyceridemia can cause acute pancreatitis and/or hyperviscosity syndrome, both of which are life-threatening to the mother and baby. Thus, rapid reduction of triglyceride levels is crucial. This case highlights the importance of achieving good diabetes control prior to pregnancy, with strict adherence to treatment and enhanced patient education.
Female ; Pregnancy ; Glycemic Control ; Hypertriglyceridemia

Introduction: Diabetic ketoacidosis (DKA) and thyroid storm are individually rare but potentially fatal endocrine crises in pregnancy. Each carries significant maternal and fetal morbidity, with mortality risk compounded when they occur concomitantly. Physiological and pharmacokinetic changes of pregnancy, combined with overlapping symptoms, necessitate urgent treatment strategies. Case: A 29-year-old G2P2 female at 29 weeks’ gestation, with poorly controlled type 2 diabetes mellitus (hemoglobin A1c 8.1%) on a basal–bolus insulin regimen and Graves’ disease managed with carbimazole, non-adherent to medications, presented with fever, vomiting, and dyspnea. On examination, she was tachycardic (HR 138 bpm), hypotensive (BP 94/60 mmHg), and hypoxic. Laboratory investigations revealed hyperglycemia (glucose 27.1 mmol/L), severe metabolic acidosis (pH 7.02, bicarbonate 4.9 mmol/L), and elevated serum ketones (4.6 mmol/L), consistent with DKA. Thyroid function tests showed suppressed thyroid-stimulating hormone (<0.005 mIU/L) and elevated free T4 (28.2 pmol/L), with a Burch–Wartofsky score of 70. Unfortunately, intrauterine fetal demise was confirmed upon the patient’s presentation to the emergency department. She was intubated and admitted to the intensive care unit, receiving fluid resuscitation judiciously according to the DKA regimen, with frequent assessment of volume status. Intravenous insulin and potassium supplements were commenced concurrently. Metabolic stabilization was achieved within 24 hours. Carbimazole, propranolol, Lugol’s iodine, and intravenous hydrocortisone were started for treatment of thyroid storm. A breech-assisted vaginal delivery was performed, and her postpartum course was uneventful. Conclusion The case reveals the catastrophic potential of concurrent DKA and thyroid storm in pregnancy, where rapid maternal deterioration and poor fetal outcomes can occur despite timely intervention. High clinical suspicion, early biochemical confirmation, and coordinated multidisciplinary management are vital. Precipitating factors, particularly medication non-adherence, must be addressed through intensive patient education and structured follow-up to prevent recurrence.
Female ; Pregnancy ; Diabetic Ketoacidosis ; Thyroid Crisis

Introduction: Incidental hyperparathyroidism with hypercalcemia is not uncommon. However, parathyroid carcinoma is an extremely rare endocrine malignancy, accounting for less than 1% of cases of primary hyperparathyroidism. Case: A 57-year-old Malay female with well-controlled type 2 diabetes was incidentally found to have hypercalcemia during hospitalization for pyelonephritis. She was asymptomatic, with no history of calcium supplementation or family history of endocrine disorders. Physical examination revealed no obvious neck swelling, and other systemic examinations were unremarkable. Investigations showed elevated serum calcium (2.87–3.4 mmol/L), low phosphate (0.34–0.76 mmol/L), and elevated intact parathyroid hormone (iPTH) (6.81 pmol/L). Her 25-OH vitamin D was deficient (45.58 nmol/L). Ultrasound of the neck revealed a solid lesion (1.6 × 2.0 × 2.8 cm) posterior to the right thyroid lobe with bilateral thyroid nodules, with the highest TR4, and normal cervical lymph nodes. Sestamibi scan showed multinodular goiter with cold nodules in bilateral thyroid lobes and a soft tissue lesion posterior to the right thyroid lobe. Subsequently, she underwent right hemithyroidectomy with intraoperative nerve monitoring and right inferior parathyroidectomy with intraoperative iPTH monitoring; the intraoperative iPTH level dropped appropriately from 24 to 2.4 pmol/L. Histopathological examination of the excised right parathyroid gland revealed parathyroid carcinoma, while the right thyroid lobe showed nodular hyperplasia. Postoperatively, calcium and iPTH levels normalized, and she remained well under follow-up. Conclusion Parathyroid carcinoma typically presents with markedly elevated calcium and iPTH levels, often alongside a palpable neck mass. However, in this patient, serum iPTH was only slightly above the upper limit of normal, with tumor size less than 3 cm, no lymph node or surrounding structures involvement from pre-operative evaluation imaging. This highlights the variability in both physical and biochemical presentations of parathyroid carcinoma and the challenges in distinguishing it from benign parathyroid tumors preoperatively.
Parathyroid Neoplasms

Background/Aims: We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL). Methods: We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis. Results: In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05). Conclusions While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.

Purpose: This study aimed to develop a comprehensive practical guide for enteral nutrition (EN) designed to enhance patient safety and reduce complications in Korea. Under the leadership of the Korean Society for Parenteral and Enteral Nutrition (KSPEN), the initiative sought to standardize EN procedures, improve decision-making, and promote effective multidisciplinary communication. Methods: The KSPEN EN committee identified key questions related to EN practices and organized them into seven sections such as prescribing, delivery route selection, formula preparation, administration, and quality management. Twenty-one experts, selected based on their expertise, conducted a thorough literature review to formulate evidence-based recommendations. Drafts underwent peer review both within and across disciplines, with final revisions completed by the KSPEN Guideline Committee. The guide, which will be published in three installments, addresses critical elements of EN therapy and safety protocols. Results: The practical guide recommends that EN orders include detailed elements and advocates the use of electronic medical records for communication. Standardized prescription forms and supplementary safety measures are outlined. Review frequency is adjusted according to patient condition—daily for critically ill or unstable patients and as dictated by institutional protocols for stable patients. Evidence indicates that adherence to these protocols reduces mortality, complications, and prescription errors. Conclusion The KSPEN practical guide offers a robust framework for the safe delivery of EN tailored to Korea’s healthcare context. It emphasizes standardized protocols and interdisciplinary collaboration to improve nutritional outcomes, patient safety, and operational efficiency. Rigorous implementation and monitoring of adherence are critical for its success.

Purpose: This study aimed to develop a comprehensive practical guide for enteral nutrition (EN) designed to enhance patient safety and reduce complications in Korea. Under the leadership of the Korean Society for Parenteral and Enteral Nutrition (KSPEN), the initiative sought to standardize EN procedures, improve decision-making, and promote effective multidisciplinary communication. Methods: The KSPEN EN committee identified key questions related to EN practices and organized them into seven sections such as prescribing, delivery route selection, formula preparation, administration, and quality management. Twenty-one experts, selected based on their expertise, conducted a thorough literature review to formulate evidence-based recommendations. Drafts underwent peer review both within and across disciplines, with final revisions completed by the KSPEN Guideline Committee. The guide, which will be published in three installments, addresses critical elements of EN therapy and safety protocols. Results: The practical guide recommends that EN orders include detailed elements and advocates the use of electronic medical records for communication. Standardized prescription forms and supplementary safety measures are outlined. Review frequency is adjusted according to patient condition—daily for critically ill or unstable patients and as dictated by institutional protocols for stable patients. Evidence indicates that adherence to these protocols reduces mortality, complications, and prescription errors. Conclusion The KSPEN practical guide offers a robust framework for the safe delivery of EN tailored to Korea’s healthcare context. It emphasizes standardized protocols and interdisciplinary collaboration to improve nutritional outcomes, patient safety, and operational efficiency. Rigorous implementation and monitoring of adherence are critical for its success.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.