1.Network meta-analysis and validation study of expanded liver transplantation criteria for hepatocellular carcinoma: Significant role of alpha-fetoprotein
Dongman YU ; Yeongseok HWANG ; Jin-Sung JU ; Subin HEO ; Seon-Ok KIM ; Sang Hyun CHOI ; Gi-Won SONG ; Jihyun AN ; Ju Hyun SHIM
Clinical and Molecular Hepatology 2026;32(2):751-771
Background/Aims:
Various expanded criteria (EC) for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) have been proposed to avoid the narrow nature of the Milan criteria (MC). To investigate which EC predicts more favorable outcomes in terms of overall survival (OS) and recurrence-free survival (RFS), we conducted a network meta-analysis (NMA).
Methods:
A database search was conducted on PubMed, Embase, and the Cochrane Library, to identify studies comparing OS and RFS between patients within the MC and those exceeding the MC but within the EC. Hazard ratios (HRs) were pooled using a random-effects NMA and validated in an in-house cohort of 1,008 LT recipients.
Results:
Among 22,466 articles identified, 35 studies with 45 pairwise comparisons were included in the NMA along with 8 different EC. The University of California San Francisco (HR, 1.43; 95% CI, 1.19–1.71), Up-to-Seven (HR, 1.50; 95% CI, 1.15–1.97), and Hangzhou criteria (HR, 1.69; 95% CI, 1.11–2.57) showed inferior OS to the MC. The MC ranked highest for both OS and RFS, followed by Metroticket 2.0 for OS and the Asan criteria for RFS. In the validation cohort, both Metroticket 2.0 and AFP model yielded more favorable HCC-specific mortality than other EC.
Conclusions
Several EC, of which those of Metroticket 2.0 were the best, yielded comparable outcomes to the MC. AFP-based EC such as Metroticket 2.0 and AFP model appeared to be useful in both the NMA and the validation cohort, suggesting a potential role in identifying selected low-risk patients beyond the MC.
2.Establishing a rabbit sham model of cervical esophageal surgery for circumferential esophageal transplantation
Ji Hyun KIM ; Yu Jin KIM ; Hee Yeon JEON ; Young Shin JOO ; Jae Hee CHUNG
Clinical Transplantation and Research 2026;40(1):96-103
Background:
This study was performed to establish a rabbit model for esophageal surgery in the treatment of cervical esophageal diseases. The necessary steps for postoperative treatment and esophageal examination were detailed.
Methods:
This study aimed to confirm the feasibility of the surgical procedure in rabbits and develop a postoperative management protocol. Six New Zealand White rabbits underwent esophagectomy and end-to-end anastomosis of the cervical esophagus under general anesthesia. Postoperatively, the rabbits were fed a specially formulated therapeutic liquid diet for 3 to 7 days. Recovery was monitored for 8 weeks, after which the rabbits were euthanized. Esophagography and endoscopy were conducted during the first postoperative week to assess healing.
Results:
Of the six rabbits that underwent surgery, two died from nonsurgical complications within 7 days after the operation. Of the remaining rabbits, two were diagnosed with esophageal stricture via esophagography and underwent endoscopy after the first postoperative week. The final two rabbits completed the 8-week postoperative period without complications.
Conclusions
Esophageal surgery and postoperative treatment in rabbits require careful attention. We anticipate that this study will provide valuable and practical information for researchers conducting esophageal studies using rabbits.
4.Unexpected Cancellation of Radioactive Iodine Treatment after Thyroid Hormone Withdrawal: Lessons from a Case Series
Hye-Seon OH ; Won Gu KIM ; Won Bae KIM ; Jin-Sook RYU ; Min Ji JEON ; Tae Yong KIM
Endocrinology and Metabolism 2026;41(2):300-307
Background:
Radioactive iodine treatment (RAIT) is an essential therapy for differentiated thyroid cancer. However, unforeseen complications arising during thyroid hormone withdrawal (THW) can lead to Cancellation of the scheduled treatment. This study aimed to identify cases in which THW-RAIT was discontinued due to THW-related complications and to explore potentially preventable causes to improve patient management.
Methods:
Among 4,174 patients who underwent THW-RAIT between 2012 and 2024, 39 did not complete the planned treatment. After excluding Cancellations unrelated to THW, 11 (0.26%) patients with unexpected THW-related medical issues were analyzed.
Results:
The median age of the included patients was 61 years (range, 23 to 70), and 10 were male. The reasons for THW-RAIT Cancellation were hyponatremia (n=1), abnormal liver function (n=1), renal dysfunction (n=3), and combined liver and renal dysfunction (n=6). The patient with hyponatremia was taking a thiazide diuretic. Most cases of liver dysfunction were associated with prior use of herbal medications, whereas renal dysfunction was linked to diuretic or nonsteroidal anti-inflammatory drug use, pre-existing conditions such as single kidney or diabetic nephropathy, or inadequate oral intake during low-iodine preparation. Two cases of concurrent liver and renal dysfunction were attributed to rhabdomyolysis following intense exercise or heavy physical labor.
Conclusion
Enhanced patient education, comprehensive pre-treatment assessment, and careful avoidance of high-risk medications are essential to prevent THW-related complications and minimize disruptions in RAIT.
5.Beyond Weight Loss: Skeletal Considerations in Obesity Treatment
Endocrinology and Metabolism 2026;41(2):210-221
The rapid evolution of obesity therapeutics, led by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metabolic surgery, has achieved unprecedented weight loss. However, the skeletal consequences of such substantial weight reduction are of increasing clinical concern. This review explores the relationship between obesity, weight-loss modalities, and bone health. While obesity was historically viewed as bone-protective due to mechanical loading, recent evidence highlights qualitative bone deterioration and sitespecific fracture risks. Intentional weight loss through caloric restriction or bariatric surgery consistently accelerates bone turnover and reduces bone mineral density (BMD), with surgical interventions showing the most significant impact. Emerging data on GLP-1RAs suggest modest BMD declines, largely proportional to weight loss and likely driven by mechanical unloading. Conversely, preclinical studies indicate that GLP-1 signaling may exert direct osteoanabolic and anti-resorptive effects. To preserve skeletal integrity, obesity management must shift toward a holistic body composition framework. Integrating structured resistance exercise, optimizing nutrition (calcium, vitamin D, and protein), and implementing skeletal monitoring in high-risk individuals are essential. Future obesity care should prioritize the maintenance of bone quality and lean mass alongside fat reduction to ensure long-term skeletal resilience and prevent fragility fractures.
6.Impact of Tumor Bilaterality and Multifocality in Predicting Recurrence of Papillary Thyroid Carcinoma: A Retrospective Cohort Study
Eunji KIM ; Jun Hyun PARK ; Ji-Young PARK ; Jin Hyang JUNG ; Sang-Woo LEE
Endocrinology and Metabolism 2026;41(2):288-299
Background:
This study investigated the prognostic value of bilaterality and multifocality in papillary thyroid carcinoma (PTC) recurrence, aiming to inform optimal surgical strategies.
Methods:
In this retrospective cohort, 1,966 patients who underwent total thyroidectomy for PTC (2011–2014) were categorized into four groups according to tumor multifocality and bilaterality confirmed by postoperative histopathology: group 1, unilateral solitary; group 2, unilateral multifocal; group 3, bilateral solitary; group 4, bilateral multifocal. Clinicopathologic features and clinical outcomes were compared across these groups.
Results:
Group 4 exhibited the highest prevalence of BRAFV600E positivity, nodal metastases, and recurrence. Both bilaterality and multifocality were associated with more aggressive clinicopathologic characteristics. Recurrence risk increased with the number of tumor foci, with the odds ratio (OR) significantly elevated for more than five foci. Satellite pattern was strongly linked to recurrence (OR, 19.49; P<0.001). While tumor multifocality (≥5 foci) and bilaterality were associated with recurrence in univariate analyses, these associations were not independent after adjustment. Kaplan-Meier analysis demonstrated the lowest recurrence-free survival (RFS) in group 4. Patients with bilateral disease had significantly lower RFS than those with unilateral disease (P=0.003), whereas multifocality did not significantly affect RFS compared to solitary disease (P=0.095).
Conclusion
Tumor bilaterality, multifocality (≥5 foci), and satellite pattern were associated with aggressive features and higher recurrence risk. Although not independent predictors, these factors may serve as useful surrogate markers of aggressive disease biology and help guide personalized surgical strategies in patients with PTC.
7.Acute Heart Failure Across the Ejection Fraction Spectrum: Phenotypes, Management, and Outcomes From Nationwide KorHF III Registry
Huijin LEE ; Eung Ju KIM ; Seong Woo HAN ; Seong-Mi PARK ; Hyung-Seop KIM ; Myung-Chan CHO ; Hyo-Suk AHN ; Mi-Seung SHIN ; Seok-Jae HWANG ; Jin-Ok JEONG ; Dong Heon YANG ; Junho HYUN ; Jin Oh CHOI ; Hae-Young LEE ; Byung-Su YOO ; Seok-Min KANG ; Dong-Ju CHOI ; Hyun-Jai CHO ;
International Journal of Heart Failure 2026;8(1):43-55
Background and Objectives:
Clinical characteristics and outcomes in acute heart failure (AHF) vary by phenotype. We assessed phenotype-specific features, treatment patterns, and outcomes in a nationwide Korean cohort.
Methods:
The Korean Heart Failure III registry prospectively enrolled 7,351 AHF admissions at 47 hospitals. Among 6,777 patients with available left ventricular ejection fraction (EF), phenotypes were defined as heart failure with reduced EF (HFrEF, ≤40%), mildly reduced EF (HFmrEF,41–49%), or preserved EF (HFpEF, ≥50%). The primary endpoint was a 12-month composite of all-cause death or heart transplantation, evaluated from index admission and, among hospital survivors, from discharge. We used inverse probability weighting (multinomial generalized boosted models with stabilized, trimmed weights) and weighted Cox proportional-hazards models to estimate hazard ratios (HRs).
Results:
Phenotype distribution was 58.9% HFrEF, 13.6% HFmrEF, and 27.5% HFpEF. Crude 12-month composite rates from index admission were 13.4% (HFrEF), 12.7% (HFmrEF), and 16.8% (HFpEF). After weighting, from index admission, HFmrEF (HR, 0.892; 95% confidence interval [CI], 0.731–1.088) and HFpEF (HR, 1.101; 95% CI, 0.939–1.291) did not differ from HFrEF; from discharge, HFpEF had modestly higher risk (HR, 1.207; 95% CI, 1.008–1.445) whereas HFmrEF did not (HR, 1.039; 95% CI, 0.844–1.279). Hyponatremia and chronic kidney disease were consistent adverse markers, while angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker use at discharge was protective.
Conclusions
Across the EF spectrum, phenotypes showed distinct profiles and risk. Postdischarge risk was modestly higher in HFpEF, supporting phenotype-tailored care and systematic discharge optimization in Korean patients with AHF.
8.Awareness, Diagnostic Approaches, and Management of Heart Failure in Korea: A Nationwide Survey Comparing Primary Care Physicians and Cardiology Specialists
Sunki LEE ; Min Gyu KONG ; Mi-Hyang JUNG ; Hack-Lyoung KIM ; Jae Hyuk CHOI ; Jin Oh NA ; Yang Hyun CHO ; Dong-Ju CHOI ; Eung Ju KIM
International Journal of Heart Failure 2026;8(1):76-88
Background and Objectives:
Heart failure (HF) imposes a significant global burden, yet awareness and implementation of guideline-directed management remain suboptimal. This study evaluated HF awareness, diagnostic patterns, and therapeutic strategies among physicians in Korea.
Methods:
A nationwide online survey was conducted from July to August 2019, targeting primary care physicians (PCPs; n=8,000) and hospital-based cardiology specialists (n=1,339) across Korea. The questionnaire comprised 23 items covering baseline characteristics, perceptions of HF prognosis, diagnostic approaches, and treatment practices.
Results:
A total of 543 physicians responded (209 PCPs and 334 cardiology specialists). While the majority correctly defined HF, a substantial proportion underestimated the lifetime risk and poor prognosis. Cardiology specialists were more likely than PCPs to use objective diagnostic tools, including echocardiography (97% vs. 61%, p<0.001) and natriuretic peptide testing (90% vs. 57%, p<0.001). Among PCPs, 29% reported diagnosing HF based on symptoms and physical findings without objective testing, and 27% reported referring patients to general hospitals for diagnostic evaluation. Prescription rates for guideline-directed medical therapies, including renin-angiotensin system blockers and beta-blockers, were consistently higher among cardiology specialists.PCPs more frequently cited advanced age as a barrier to prescribing evidence-based medications.
Conclusions
Physicians’ awareness and clinical practices regarding HF in Korea remain suboptimal. Given the growing burden, high mortality, and substantial costs of HF, early detection, appropriate diagnostic evaluation, and timely referral are essential. Targeted education and system-level strategies to improve guideline implementation, particularly in primary care settings, are warranted.
9.Exosomes from Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Protect Lung Epithelium and Attenuate Fibrosis
Sangryul CHA ; Jooyeon LEE ; Jimin JANG ; Yeongcheol KIM ; Dahee HAN ; Seok-Ho HONG ; Seung-Jin KIM ; Dae-Hee LEE ; Chung Hyeun MA ; Han Pil LEE ; Se-Ran YANG
International Journal of Stem Cells 2026;19(1):66-82
Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial–mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline.This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. In vivo administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.
10.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part II. Follow-up Surveillance after Initial Treatment 2026
Eun Kyung LEE ; Seung Heon KANG ; Bon Seok KOO ; Mijin KIM ; Min Joo KIM ; Bo Hyun KIM ; Ji Won KIM ; Dong Gyu NA ; Sohyun PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Young-Ik SON ; Young Shin SONG ; Dong Yeob SHIN ; Jong-Hyuk AHN ; Hwa Young AHN ; So Won OH ; Ho-Ryun WON ; Won Sang YOO ; Min Kyoung LEE ; Sang-Woo LEE ; Jeongmin LEE ; Ji Ye LEE ; Dong-Jun LIM ; Ki-Wook CHUNG ; Ari CHONG ; Jin Hyang JUNG ; Sun Wook CHO ; Yoon Young CHO ; Chae Moon HONG ; Young Joo PARK ;
International Journal of Thyroidology 2026;19(1):1-40
In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

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