Background/Aims: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Methods: Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Results: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05). Conclusions This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

Background: We aimed to investigate the predictive values of plasma C-peptide levels and the continuous glucose monitoring (CGM)-defined coefficient of variation (CV) in risk prediction for hypoglycemia in Korean people with diabetes with normal and impaired kidney function. Methods: We analyzed data from 1,185 participants diagnosed with type 1 and type 2 diabetes who underwent blinded professional CGM between January 2009 and May 2021 at outpatient clinics. We explored correlations among CGM-defined CV, plasma C-peptide levels, and time below range at <70 and 54 mg/dL across different kidney function categories. Results: In patients with chronic kidney disease (CKD) stages 1–2 (n=934), 89.3% who had a random plasma C-peptide level higher than 600 pmol/L exhibited a CV of ≤36%. Among those in CKD stage 3 (n=161) with a random plasma C-peptide level exceeding 600 pmol/L, 66.7% showed a CV of ≤36%. In stages 4–5 of CKD (n=90), the correlation between random C-peptide levels and CV was not significant (r=–0.05, P=0.640), including cases with a CV greater than 36% despite very high random plasma C-peptide levels. Random plasma C-peptide levels and CGM-assessed CV significantly predicted hypoglycemia in CKD stages 1–2 and 1–5, respectively. Conclusion The established C-peptide criteria in Western populations are applicable to Korean people with diabetes for hypoglycemic risk prediction, unless kidney function is impaired equivalent to CKD stage 3–5. The CGM-defined CV is informative for hypoglycemic risk prediction regardless of kidney function.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Background: Tinnitus is a multifactorial condition with no universally accepted assessment guidelines. The Korean Tinnitus Study Group previously established consensus statements on the definition, classification, and diagnostic tests for tinnitus. As a continuation of this effort, this study aims to establish expert consensus on tinnitus assessment and treatment outcome evaluation, specifically tailored to the Korean clinical context. Methods: A modified Delphi method involving 26 otology experts from across Korea was used. A two-round Delphi survey was conducted to evaluate statements related to tinnitus assessment before and after treatment. Statements were rated on a scale of 1 to 9 for the level of agreement. Consensus was defined as ≥ 70% agreement (score of 7–9) and ≤ 15% disagreement (score of 1–3). Statistical measures such as content validity ratio and Kendall’s coefficient of concordance (W) were calculated to assess agreement levels. Results: Of the 46 assessment-related statements, 17 (37%) reached consensus, though overall pre-treatment assessments showed weak agreement (Kendall’s W = 0.319). Key areas of agreement included the use of the visual analogue scale, numeric rating scale, and validated questionnaires for pre-treatment evaluation. Five statements, such as the use of computed tomography, magnetic resonance imaging, and angiography for diagnosing pulsatile tinnitus, achieved over 90% agreement. For treatment outcome measurements, 8 of 12 statements (67%) reached a consensus, with moderate agreement (Kendall’s W = 0.513). Validated questionnaires and psychoacoustic tests were recommended for evaluating treatment effects within 12 weeks. While standardized imaging for pulsatile tinnitus and additional clinical tests were strongly recommended, full consensus was not achieved across all imaging modalities. Conclusion This study provides actionable recommendations for tinnitus assessment and treatment evaluation, emphasizing the use of standardized tools and individualized approaches based on patient needs. These findings offer a practical framework to enhance consistency and effectiveness in tinnitus management within Korean clinical settings.

Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

Background: Although total intravenous anesthesia (TIVA) with propofol and remifentanil is frequently used to optimize intraoperative neurophysiological monitoring (IONM), the exact effect of remimazolam on IONM remains unknown. Here, we compared the effects of propofol and remimazolam along with remifentanil on IONM during TIVA. Methods: In this prospective, double-blind, randomized controlled trial, 64 patients requiring IONM during cervical spine surgery were administered either propofol (Group P) or remimazolam (Group R). The preoperative latencies of the somatosensory-evoked potentials (SEP; N20 for the median nerve and P37 for the tibial nerve) were measured. SEP latencies and amplitudes and motor-evoked potential (MEP) amplitudes were measured 30 min after anesthetic induction (T1), 30 min after surgical incision (T2), after laminectomy or discectomy (T3), immediately after plate insertion or pedicle screw fixation (T4), and before surgical wound closure (T5). The primary outcome was the between-group difference in the N20 latency changes measured at T1 and preoperatively. Results: The change in SEP latencies including N20 and P37 at T1 compared with preoperative time was not significantly different between Groups P and R. Except for the amplitude of the right abductor brevis, there was no significant group-by-time interaction effect for intraoperative MEP amplitudes or SEP latencies and amplitudes. Conclusions TIVA with remimazolam and remifentanil for cervical spine surgery yielded stable IONM, comparable to those observed with conventional TIVA with propofol and remifentanil. Further clinical trials are needed in other surgical contexts and with more diverse patient populations to determine the effects of remimazolam on IONM.