Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Objective: The objective of this nationwide, long-term follow-up study was to explore the connection between congestive heart failure (CHF) and ossification of the posterior longitudinal ligament (OPLL) in Korea. Methods: Patient information was collected from the Health Screening cohort of the National Health Insurance Service. Individuals diagnosed with OPLL were identified using specific International Classification of Diseases, 10th revision codes (M48.8, M48.81, M48.82, and M48.83). A total of 1,289 OPLL patients and 6,445 controls were included in the study, selected through 1:5 age and sex matching. The data spanned from January 1, 2004 to July 31, 2015. To compute the incidence rate of CHF in each group, the Kaplan-Meier method was employed. Additionally, Cox proportional-hazards regression analysis was utilized to estimate the hazard ratio of CHF. Results: CHF was present in 19 patients (1.47%) in the OPLL group and 71 patients (1.10%) in the control group. After accounting for age and sex, the hazard ratio for CHF in the OPLL group was 3.164 (95% confidence interval [CI], 1.867-5.360). When additionally considering income and underlying diseases, the hazard ratio for CHF within the OPLL group was 3.355 (95% CI, 1.977-5.694). All subgroups of OPLL patients exhibited an increased risk ratio for CHF across parameters such as sex, age, diabetes, hypertension, and dyslipidemia. Conclusion According to this nationwide longitudinal study, an elevated incidence rate of CHF was associated with OPLL.

Purpose: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. Materials and Methods: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. Results: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). Conclusion Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.

Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Background/Aims: Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods: This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results: This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups. Conclusions In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.

Background: Proximal-distal mismatch has emerged as a prominent concern in Dorr type A femoral morphology, prompting the exploration of short stems as promising alternatives to conventional stems. This study aimed to evaluate clinical and radiographic outcomes of total hip arthroplasty (THA) using short femoral stems in Dorr type A proximal femoral morphology with a minimum follow-up of 5 years. Methods: Patients with short femoral stems in Dorr type A between 2011 and 2017 were included. Patients with the Short Modular Femoral (SMF) stem and Metha stem were recruited and patients with a shortened tapered stem (Tri-Lock BPS) were matched by propensity score matching based on age, sex, body mass index, calcar to canal ratio, and diagnosis. Patient-reported outcomes and the presence of thigh pain were assessed at 5 years postoperatively. Revision rate, complication rate, and radiographic outcomes were also assessed and compared. Results: Twenty-two cases (81%) in the SMF stem and 43 cases (65%) in the Metha stem had more than 5 years of follow-up data available. The SMF stem showed a higher failure rate than the other 2 groups, with 18% requiring revision surgery in the SMF stem compared to 4.6% in the Metha stem, and 2.3% in the Tri-Lock BPS. The SMF stem showed considerable complications such as stem position change and lateral cortical hypertrophy with inferior clinical outcomes than the other 2 stem groups. When the Metha stem and the Tri-Lock BPS groups were compared, more intraoperative fractures were observed in the Metha stem, whereas stress shielding and anterior thigh pain were significantly more prevalent in the Tri-Lock BPS. Conclusions The SMF stem might be less reliable than previously reported, showing a high failure rate and increased radiologic complications. Thus, its use for THA in Dorr Type A femurs needs caution. On the other hand, the Metha stem showed comparable outcomes to the shortened tapered Tri-Lock BPS.

Background: A set of criteria for severity classification is essential in alopecia areata (AA). Currently, no guidelines are universally accepted for defining AA severity. Objective: This study aimed to establish a set of consensus criteria for classifying the severity of and identifying treatment refractoriness in AA. Methods: A preliminary draft of the definition for moderate-to-severe AA was crafted based on available evidence, and members of the Korean Hair Research Society (KHRS) subsequently endorsed the recommendation through an online survey. Results: In the first Delphi round, consensus was attained on 15 questions. After refining certain items in the second round, consensus was achieved on 23 out of 26 questions. The KHRS first defined AA severity using the severity of alopecia tool (SALT). SALT ≥50 was defined as severe, 20≤ SALT <50 as moderate, and SALT <20 as mild. Moderate AA was considered severe if it meets one or more of the following criteria: dermatology life quality index >10, presence of accompanying eyebrow or eyelash loss, positive hair loss activity, or treatment-refractory AA. Conclusion These consensus criteria can help clinicians accurately diagnose AA, provide appropriate treatment, and monitor its progression.

Artificial intelligence (AI) in radiology is a rapidly developing field with several prospective clinical studies demonstrating its benefits in clinical practice. In 2022, the Korean Society of Radiology held a forum to discuss the challenges and drawbacks in AI development and implementation. Various barriers hinder the successful application and widespread adoption of AI in radiology, such as limited annotated data, data privacy and security, data heterogeneity, imbalanced data, model interpretability, overfitting, and integration with clinical workflows. In this review, some of the various possible solutions to these challenges are presented and discussed; these include training with longitudinal and multimodal datasets, dense training with multitask learning and multimodal learning, self-supervised contrastive learning, various image modifications and syntheses using generative models, explainable AI, causal learning, federated learning with large data models, and digital twins.

Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV). Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus. Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment methods and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate. Conclusion While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

Background/Aims: Although gastric neuroendocrine tumors (NETs) are uncommon neoplasms, their prevalence is increasing. The clinical importance of the World Health Organization (WHO) classification of gastric NETs, compared with NETs in other organs, has been underestimated.This study aimed to systematically evaluate the clinical and pathologic characteristics of gastric NETs based on the 2019 WHO classification and to assess the survival outcomes of patients from a single-center with a long-term follow-up. Methods: The medical records of 427 patients with gastric NETs who underwent endoscopic or surgical resection between January 2000 and March 2020 were retrospectively reviewed. All specimens were reclassified according to the 2019 WHO classification. The clinicopathologic characteristics, treatment, and oncologic outcomes of 139 gastric NETs were analyzed. Results: The patients’ median age was 53.0 years (interquartile range [IQR], 46.0 to 63.0 years). The median follow-up period was 36.0 months (IQR, 15.0 to 63.0 months). Of the patients, 92, 44, and 3 had grades 1, 2, and 3 NETs, respectively. The mean tumor size significantly increased as the tumor grade increased (p=0.025). Patients with grades 2 and 3 gastric NETs more frequently had lymphovascular invasion (29.8% vs 10.9%, p=0.005) and deeper tissue invasion (8.5% vs 0%, p=0.012) than those with grade 1 tumors. The overall disease-specific survival rate was 100%. Two patients with grades 2-3 gastric NETs experienced extragastric recurrence. Conclusions Although gastric NETs have an excellent prognosis, grade 2 or grade 3 gastric NETs are associated with a larger size, deeper invasion, and extragastric recurrence, which require active treatment.