An overlooked source of skin dose perturbation: Commercial tattoo inks in radiotherapy

by Hongjun Park, Beechui Koo, Jungwook Shin, Byoung Hyuck Kim, James J. Sohn

Approximately one-third of US adults have tattoos, yet the dosimetric impact of intradermal tattoo pigments during radiation therapy remains uncharacterized. Commercial tattoo inks contain unregulated metallic impurities including chromium, lead, and nickel, raising concerns about dose perturbations in tattooed skin. This work quantifies radiation dose perturbations induced by high-atomic-number (Z) tattoo pigments under clinically relevant radiotherapy conditions. Monte Carlo simulations (TOPAS) modeled layered skin phantoms with a 0.3-mm intradermal tattoo layer embedded at 1.25–1.55 mm depth. Three commercial inks were evaluated: carbon-based (black) and metal-containing (Fe-rich brown, Al-containing orange) at pigment loadings of 5–100 vol% within the tattoo layer, to establish upper-bound effects. Electron (6, 18 MeV) and photon (6, 18 MV) beams were simulated with standard clinical geometry (1 × 1 cm² field, SSD = 100 cm). Photon irradiation produced pronounced, depth-localized dose enhancement, with peak dose enhancement factor (DEF) reaching 2.5 for brown ink at 18 MV, a 62% mean increase relative to non-tattooed skin driven by high-Z–mediated secondary electron production. Electron beams exhibited energy-dependent behavior: 6 MeV produced modest enhancement (peak DEF ~ 1.07), while 18 MeV unexpectedly generated dose deficits (DEF 

Tonsil-derived mesenchymal stem cells alleviate skin inflammation by modulating neutrophil extracellular trap formation and T cell migration

by Hyun Ju Kim, Kyung-Ah Cho, So-Youn Woo

Skin inflammation arises from complex interactions among immune cells, particularly T cells and neutrophils. Mesenchymal stem cells (MSCs) exhibit potent immunomodulatory properties, but the specific roles of tonsil-derived MSCs (T-MSCs) in regulating neutrophil extracellular trap (NET) formation and cell death, as well as T cell migration in inflammatory skin conditions, remain poorly defined. In this study, the therapeutic effects and mechanisms of T-MSCs were investigated in a 2,4-dinitrochlorobenzene (DNCB)-induced skin inflammation model, with a focus on NET formation and T cell migration. T-MSCs were intravenously administered to mice with DNCB-induced skin inflammation; inflammation severity and immune cell dynamics were evaluated using histological analysis, flow cytometry, immunostaining, microarray profiling, NET assays, and T cell migration assays. T-MSC treatment reduced DNCB-induced skin inflammation, as demonstrated by decreased epidermal thickness and neutrophil infiltration. Although T-MSCs enhanced NET formation in vitro, they suppressed neutrophil accumulation in vivo. T-MSCs also modulated the distribution and activation of T cell subsets in the skin and secondary lymphoid organs. Gene expression profiling revealed that T-MSCs regulated pathways associated with inflammation and neutrophil activity, including those involved in immune cell trafficking and NET formation. Moreover, T-MSCs promoted T cell migration, although this effect was influenced by neutrophil presence, indicating complex interplay among immune cells. These findings demonstrate that T-MSCs exert anti-inflammatory effects in DNCB-induced skin inflammation by modulating NET formation and T cell migration, revealing a novel immunoregulatory mechanism and supporting their therapeutic potential for inflammatory skin diseases.

Justifying model complexity: Evaluating transfer learning against classical models for intraoperative nociception monitoring under anesthesia

by Chanseo Lee, Jaihyoung Lee, Kimon-Aristotelis Vogt, Muhammad Munshi

Background

Accurate intraoperative detection of nociceptive events is essential for optimizing analgesic administration and improving postoperative outcomes. Although deep learning approaches promise improved modeling of complex physiologic dynamics, their added computational and operational complexity may not translate into clinically meaningful benefit, particularly in small, high-resolution perioperative datasets.

Methods

We performed a head-to-head evaluation of classical supervised models (L1-regularized logistic regression and 50-, 200-tree Random Forests, with and without drug dosing features) against a Temporal Convolutional Network (TCN) transfer-learning framework for intraoperative nociception detection. Using 101 adult surgical cases with 30 physiologic and 18 drug dosing features sampled in 5-second windows, models were assessed under leave-one-surgery-out cross-validation using AUROC and AUPRC. We further examined probability calibration, multiple ensemble strategies, permutation importance features, and computational cost in terms of inference operations and memory footprint.

Results

Drug-aware Random Forests of various trees (50 trees vs. 200 trees) achieved the highest discrimination (AUROC 0.716; AUPRC 0.399), outperforming the TCN transfer-learning model (AUROC 0.649; AUPRC 0.311). However, increasing personalization windows in the TCN yielded inconsistent and modest gains (p > 0.05). Isotonic calibration substantially improved probability calibration but did not affect discrimination. No ensemble method surpassed the standalone Random Forest; the gated network consistently assigned >84% weight to the classical model. Computational analysis revealed that while the TCN was more compact in total memory footprint, the smaller, 50-tree Random Forest inference required two orders of magnitude fewer operations, with faster training and lower operational complexity.

Conclusions

In this clinically realistic benchmark, interpretable classical models operating on well-engineered features without personalization matched or exceeded the performance of a personalized deep learning approach while remaining computationally cheaper and simpler to deploy. These findings underscore the importance of rigorously justifying model complexity in perioperative machine learning and suggest that, for intraoperative nociception monitoring, classical approaches may offer a more favorable balance of accuracy, interpretability, and operational efficiency.

Transscleral photodynamic therapy with a chlorin e6: An experimental study of exposure parameters and therapeutic window

by Ernest V. Boiko, Elena V. Samkovich, Irina E. Panova, Alexander A. Ivanov, Sergey B. Shevchenko, Sergey L. Vorobyev, Elizaveta S. Kalashnikova, Victoria G. Gvazava, Elizaveta A. Masian, Alexandra E. Kim

Purpose

To define optimal exposure parameters and the therapeutic window for transscleral photodynamic therapy (TSPDT) with chlorin e6 by evaluating clinical, histological, and thermal effects of subthreshold, therapeutic, and suprathreshold settings in rabbit eyes.

Methods

The study was conducted on 21 healthy rabbits. TSPDT was performed using a 660 nm laser and chlorin e6 (2.5 mg/kg). Transscleral probes (5 mm: 0.1 W, 0.17 W, 0.3 W; 10 mm: 0.3 W, 0.6 W) with integrated thermosensors were used. Enucleation and histological analysis were performed 14 days post-irradiation.

Results

Fundus examination on day 14 revealed distinct treatment zones correlating with laser settings. The therapeutic window was defined as 0.14–0.17 W (5 mm probe; power density: 0.693–0.866 W/cm²; energy density: 415.8–519.6 J/cm²) and 0.48–0.6 W (10 mm probe; 0.611–0.764 W/cm²; 366.6–458.4 J/cm²) with 600 s exposure time, achieving selective choroidal damage without scleral or retinal injury (ΔT ≤ 4.5°C). Suprathreshold settings (≥0.3 W for 5 mm; ≥ 0.6 W for 10 mm) induced retinal necrosis (up to 50%) and scleral coagulation (ΔT ≥ 8°C) with power densities exceeding 0.866 W/cm² (5 mm) and 0.764 W/cm² (10 mm).

Conclusion

TSPDT with chlorin e6 enables selective targeting of intraocular pathological tissues while preserving scleral and retinal integrity. Defining the therapeutic window and using real-time thermal monitoring enhances treatment safety. These findings lay a foundation for clinical protocols for uveal melanoma and other intraocular tumors.

Association between event-related disclosure and posttraumatic growth: Targeting Japanese people, measuring attitudes toward disclosure, and examining event-related rumination as a mediating variable

by Yuto Kimura, Takahiro Kozuka

This study examined the association between event-related disclosure and posttraumatic growth (PTG). Specifically, it targeted the Japanese adult, assessed attitudes toward event-related disclosure, and examined event-related rumination as a mediating variable. A cross-sectional online survey was conducted among Japanese adults aged 20–59. Participants completed measures of demographic characteristics, stressful life events attributes, attitudes toward disclosure, event-related rumination, and PTG. Analysis of data from 480 individuals revealed that neither willingness to disclose nor resistance to disclose was directly associated with PTG. However, both willingness to disclose and resistance to disclose were positively associated with PTG through deliberate rumination and negatively associated with PTG through intrusive rumination. The effect sizes for willingness to disclose were approximately three times greater than those for resistance to disclose. These findings suggest that event-related disclosure may enhance PTG by promoting deliberate meaning-making processes, while also potentially hindering it by reinforcing involuntary negative thinking. Furthermore, these effects may be stronger when individuals are more proactive and disclose more frequently. These results have important implications for interventions aimed at enhancing PTG through event-related disclosure.

Pharmacokinetic profiles of Moutan Cortex after single and repeated administration in a dinitrobenzene sulfonic acid-induced colitis model

by Jin-Hwa Kim, Ji-Soo Jeong, Jeong-Won Kim, Eun-Hye Chung, Su-Ha Lee, Je-Won Ko, Youn-Hwan Hwang, Tae-Won Kim

Moutan Cortex (MC), the dried root bark of Paeonia suffruticosa, is used in traditional Chinese and Korean medicine to treat enteritis for its anti-inflammatory properties. This study compared the pharmacokinetic (PK) profiles of paeonol and paeoniflorin in normal and dinitrobenzene sulfonic acid (DNBS)-induced colitis rats, and to determine how repeated low-dose MC [MC(L), 0.5 g/kg] or high-dose MC [MC(H), 2.5 g/kg] alters PK and disease severity. Using ultra-performance liquid chromatography–tandem mass spectrometry, we found that DNBS modestly increased paeonol AUC_last (NC: 247.8 ± 63.7 vs DNBS: 337.0 ± 120.8 hr*ng/mL) and decreased paeoniflorin (NC: 474.1 ± 11.7 vs DNBS: 463.7 ± 106.8 hr*ng/mL) compared to controls (ns). After repeated dosing, the maximum plasma concentration (C_max) of paeonol was higher in the MC(H) than that in the MC(L) group (MC(L): 63.81 ± 29.74 vs MC(H): 4221.5 ± 1579.2 ng/mL, p max in the MC(H) group was also higher than MC(L) group (MC(L): 60.5 ± 15.3 vs MC(H): 164.7 ± 74.7 ng/mL, p 

Comparative outcomes of swing segment revisions of radiocephalic arteriovenous fistula between endovascular and surgical approaches

by Suehyun Park, Sangho Lee, Hyeon Ju Kim, Hyung-Kee Kim, Seung Huh, Deokbi Hwang

Objective

Regarding revision of vascular access (VA), endovascular methods are commonly employed owing to their procedural simplicity, yet their durability remains uncertain. This study aimed to compare clinical outcomes of swing segment (SwS) revision of radiocephalic arteriovenous fistula (RC-AVF) between endovascular and surgical approaches.

Materials and methods

A retrospective cohort study comparing two groups was conducted at one tertiary hospital in South Korea. A total of 131 patients underwent endovascular or surgical revision of SwS in RC-AVF for the first time after AVF creation between 2016 and 2023. Endovascular and surgical revisions were performed in 114 and 17 patients, respectively (interposition, n = 10; patch angioplasty, n = 5; transposition, n = 1; proximalization, n = 1). Kaplan-Meier survival analysis was used to assess post-intervention primary patency (PP) and post-intervention secondary patency (SP). Multivariable Cox regression analysis was performed to adjust for potential confounders, and a subgroup analysis was conducted based on whether the SwS was in stenosis or occlusion.

Results

The median minimal diameter of SwS was 1.3 mm in the endovascular group and 1.4 mm in the surgical group, and the median lesion length was 2.5 cm and 4.0 cm, respectively. Twelve-month PP was 63.5% vs 73.7% (endo vs surgical, P = 0.79). While PP did not differ in the stenosis subgroup, the occlusion subgroup showed significantly higher PP after surgical revision (P = 0.002), with surgery associated with a markedly lower risk of loss of PP events (HR 0.073).

Conclusion

Surgical revision may be preferentially considered for long-segment occlusive lesions, given its superior early PP and the longer lesions typically associated with occlusions, whereas percutaneous transluminal angioplasty (PTA) remains appropriate for focal or stenotic lesions within the SwS. Consistent follow-up is essential to enable timely interventions, thereby maximizing the functionality of RC-AVF.

Safety profile of metformin in adolescents with type 2 diabetes: A pharmacovigilance analysis of the FDA Adverse Event Reporting System

by Mengsi Peng, Peng Shen, Kyung-In Joung, Kwang Joon Kim

Background

Although metformin is the first-line medicine for type 2 diabetes (T2D), its safety profile in adolescents remains poorly understood. This study seeks to investigate the adverse events linked to metformin use in adolescents diagnosed with T2D.

Methods

Data from the Food and Drug Administration Adverse Event Reporting System (FAERS), spanning Q1 2004 to Q2 2024, were retrospectively analyzed in this study. Adverse reactions were standardized using the Medical Dictionary for Regulatory Activities, then significant adverse drug reaction signals were identified through disproportionality analysis employing reporting odds ratio (ROR) and information component (IC) methods.

Results

Of 17,956,653 FAERS reports, 80,187 involved metformin, including 973 in adolescents (10–19 years), with 174 cases were identified with a T2D indication. Analysis at the system organ class level revealed that congenital, familial, and genetic disorders [ROR: 8.8 (4.0, 19.3); IC: 2.2 (1.1, 2.9)] and pregnancy conditions [ROR: 4.9 (2.5, 9.5); IC: 1.8 (0.8, 2.5)] showed the most significant signals. At the preferred term (PT) level, three signals were identified across all sexes and subgroups: treatment noncompliance [ROR: overall 4.14 (2.44, 7.02), male 4.27 (2.00, 9.12), and female 4.65 (2.22, 9.74); IC: overall 1.67 (0.88, 2.22), male 1.60 (0.46, 2.36), and female 1.74 (0.60, 2.50)], lactic acidosis [IC: overall 2.99 (1.91, 3.72), male 2.53 (0.76, 3.61), and female 2.76 (1.34, 3.67)], and gastrointestinal disorder [ROR: overall 13.09 (4.73, 36.23), male 54.33 (6.05, 487.96), female 5.34 (1.10, 25.84)]. Neurological disorders were observed only in males, while pregnancy-related adverse effects and renal disorders occurred exclusively in females. Additionally, the study identified potential new signals not documented in metformin labeling, including areflexia, muscle weakness, ataxia, decreased vibratory sense, rhabdomyolysis, substance use, and axillary pain.

Conclusion

The study reveals a complex safety profile of metformin in adolescents with T2D, warranting further research to confirm risks.

Clinical impact of prophylactic antibiotics in kidney transplantation: A retrospective observational cohort study with historical comparison

by Sang Ah Lee, Jin-Myung Kim, Hye Eun Kwon, Youngmin Ko, Joo Hee Jung, Sung Shin, Young Hoon Kim, Sung-Han Kim, Hyunwook Kwon

Purpose

Optimal perioperative antibiotic prophylaxis in kidney transplantation remains undefined despite routine antibiotic administration to prevent infections. In this retrospective observational cohort study with historical comparison, we compared the clinical efficacy of 6 days of ampicillin/sulbactam vs. a single dose of cefazolin.

Materials and methods

We retrospectively analyzed 2322 kidney transplantation recipients at a single center, with the evaluation period spanning from 2015 through 2021. Patients were divided into 2 groups based on the perioperative antibiotic regimen received: 971 patients received ampicillin/sulbactam, and 1351 received cefazolin. This study focused on evaluating the impact of these regimens on postoperative infection incidence and the 6-month acute rejection (AR) rates.

Results

The cefazolin group exhibited a tendency toward higher urinary tract infection rates within 1 month after transplantation (3.4% vs. 2.2%, p= = 0.078). There were no significant differences in surgical site infections between the groups. The 6-month AR rates were significantly lower in the cefazolin group than in the ampicillin/sulbactam group (5.1% vs. 7.9%, p= = 0.009). Cefazolin was also confirmed to be significantly associated with reduced 6-month AR rates in the multivariable logistic regression analysis (odds ratio 0.63, 95% confidence interval [0.45-0.89], p= = 0.009).

Conclusion

In this study, we observed that a single dose of cefazolin as perioperative antibiotic prophylaxis may lead to higher rates of postoperative urinary tract infections, but it could potentially lower the incidence of acute rejection within six months.

Effect of fascial closure using barbed sutures on incisional hernias in midline laparotomy for gynecological diseases: A multicenter randomized controlled trial (KGOG 4001)

by Yong Jae Lee, Nam Kyeong Kim, Kidong Kim, Chel Hun Choi, Keun Ho Lee, Jong-Min Lee, Kwang Beom Lee, Dong Hoon Suh, Sunghoon Kim, Min Kyu Kim, Seok Ju Seong, Myong Cheol Lim

Objective

To identify the effect of fascial closure using barbed sutures on the incidence of incisional hernia in patients undergoing elective midline laparotomy for gynecological diseases.

Methods

In this multicenter, non-blind randomized controlled trial conducted from February to December 2021, patients with a BMI 2 and aged >18 years, scheduled for midline laparotomy, were randomly assigned to receive either barbed (experimental) or non-barbed sutures (control) for fascial closure. The primary outcome was the cumulative incidence rate of incisional hernia up to 1-year post-surgery. Secondary outcomes included incisional hernia up to 2-years post-surgery, wound complications, and postoperative pain assessed by Brief Pain Inventory-Korean scores, and Numeric Rating Scale.

Results

Out of 174 patients (experimental, 86; control, 88), 36 were excluded due to dropout or loss to follow-up, leaving 138 patients (experimental, 67; control, 71) included in the analysis. The groups were balanced in terms of cancer surgeries, mean wound length, and mean surgery time. The cumulative incidence rates of incisional hernia up to 1-year (0.0% vs. 1.4%; p > 0.999) and 2-years (0.0% vs. 3.4%, p = 0.496) post-surgery did not differ significantly between the experimental and control groups. Additionally, no significant differences were observed in the incidence of wound dehiscence 4 weeks post-surgery, cumulative incidences of wound dehiscence and wound infection up to 4 weeks post-surgery, or postoperative pain scores between the groups.

Conclusions

Fascial closure using barbed sutures resulted in no cases of incisional hernia up to 2-years post-surgery, but did not demonstrate a significant reduction in incisional hernia rates compared with the non-barbed suture.

Trial registration

ClinicalTrials.gov NCT04643197

Prognostic role of effective radiation dose to immune cells in esophageal cancer treated with definitive chemoradiation

by Yoo Kyung Choi, Seok Hyun Son, Hong Seok Jang, In-Ho Kim, Sea-Won Lee, Soo-Yoon Sung

Background

Radiotherapy for locally advanced esophageal cancer can induce lymphopenia, potentially worsening outcomes. This study examines the association between clinical outcomes and the effective dose to the immune cells (EDIC), a measure of lymphocyte radiation exposure.

Methods

We retrospectively analyzed 107 patients with locally advanced esophageal squamous cell carcinoma treated with definitive concurrent chemoradiotherapy (CCRT). The EDIC was calculated based on the mean lung dose, mean heart dose, and integral total body dose using established models. Patients were stratified into high (n = 42) and low (n = 65) effective dose to the immune cells (EDIC) groups using a cut-off value of 4.28 Gy. Survival outcomes, including overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS), were assessed.

Results

The 5-year OS and PFS rates were significantly lower in the high EDIC group than in the low EDIC group (51.9% vs. 66.6%, p = 0.043; 20.8% vs. 31.8%, p = 0.002, respectively). Multivariate analysis identified high EDIC as an independent predictor of poorer OS (hazard ratio (HR): 2.06, 95% confidence interval (CI): 1.1–3.86, p = 0.024) and PFS (HR: 1.7, 95% CI: 1.04–2.78, p = 0.034). Similarly, the 5-year LRFS and DMFS rates were significantly lower in the high EDIC group than in the low EDIC group (24.1% vs. 34.9%, p = 0.003; 29.0% vs. 44.0%, p = 0.018, respectively).

Conclusion

A higher EDIC is an independent predictor of poor survival in patients with esophageal squamous cell carcinoma undergoing CCRT. Reducing radiation exposure to the immune system through optimized radiation planning and lymphocyte-sparing techniques may improve patient outcomes.

Safety and efficacy of quick-soluble gelatin microparticles for transarterial embolization of the lower urinary tract: Preclinical study in a rabbit urinary bladder embolization model

by Sunghoon Jeon, Keunho Kim, Cheolwon Choe, Juil Choi, Gun Lee, Chung-Do Lee, Hyeon-Jeong Moon, Jun-Gyu Park, Jin-kyung Kim, Namsoon Lee, Dongwoo Chang

Quick-soluble gelatin microparticles (QS-GMP) are emerging embolic agents under investigation for temporary vascular occlusion, offering reduced ischemic risk compared to permanent materials. The aim of this preclinical study was to evaluate the safety and efficacy of QS-GMP for transarterial embolization in a rabbit model of urinary bladder embolization. Twelve male New Zealand White rabbits underwent bilateral umbilical artery embolization using QS-GMP. Animals were assigned to four time-points (immediately, 3, 7, and 14 days post-embolization), with comprehensive assessments including clinical observations, hematologic and serum biochemical analysis, angiography, and histopathology. The procedure was technically feasible in all animals without intraoperative complications. Temporary hematuria and a transient decrease in body weight were observed post-procedure, both of which resolved spontaneously. Complete occlusion of the cranial vesical artery and absence of bladder wall perfusion were achieved immediately after embolization, followed by full recanalization at 3 days. Angiographic imaging at 7 and 14 days revealed transient hypervascularization of the bladder wall. Histopathological analysis showed marked edema, epithelial necrosis, and inflammatory infiltration at 3 and 7 days, with full urothelial regeneration observed at 14 days. No signs of ureteral or renal injury, or adverse systemic responses were detected. These findings suggest that QS-GMP may serve as a feasible option for temporary arterial occlusion in future veterinary lower urinary tract applications, although further long-term evaluation is warranted.