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Angiogenic and Immunomodulatory effects of embryonic stem cell derived mesenchymal stem cells in a murine model of ischemic hindlimb
No full textIn critical limb-threatening ischemia (CLTI), failed revascularization and pharmacotherapy substantially increase amputation and mortality risks. Mesenchymal stem cells (MSCs) are a promising therapeutic option for CLTI. This study evaluated the therapeutic effects of embryonic stem cell-derived MSCs (E-MSCs) on inflammation and angiogenesis under ischemic conditions across different E-MSC doses. Hindlimb ischemia was induced in 85 BALB/c nude mice by cauterizing the femoral and branched arteries. The mice were divided into five groups: non-ischemia (G1); saline-treated ischemia (G2); and ischemia treated with E-MSCs at low, medium, and high doses (G3-G5). Therapeutic effects were assessed using the rotarod test, blood perfusion ratio, and histological and cytokine analyses. G1 exhibited normal blood perfusion and motor function, whereas E-MSC-treated groups (G3-G5) demonstrated improved perfusion compared to G2. Although the medium-dose group (G4) showed numerically greater recovery, differences between G3, G4, and G5 were not statistically significant, suggesting no dose-response. All E-MSC-treated groups exhibited reduced inflammation and increases in motor function and angiogenic factors. Histological analysis revealed enhanced myofiber regeneration, reduced inflammatory infiltration, and diminished collagen deposition in the ischemic muscle of G3-G5. These changes were observed across all dose groups without significant dose-dependent differences. These results suggest E-MSCs enhance blood perfusion and modulate inflammation and angiogenesis in ischemic limbs, regardless of dose. These findings support the therapeutic potential of E-MSCs in CLTI, although further investigation is needed to optimize dosing and elucidate the mechanisms involved
Comparative analysis of the tumor microenvironment in primary CNS and testicular large B-cell lymphomas using digital image analysis and its implications for immunotherapy
No full textPrimary large B-cell lymphomas of immune-privileged sites, including primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL), exhibit distinct clinicopathologic features contributing to aggressive behavior and immune evasion. While the molecular characteristics of PCNSL and PTL have been extensively studied, the tumor microenvironment (TME) remains insufficiently understood. In particular, no study has directly compared the TME of PCNSL and PTL, highlighting a critical gap in understanding their immunobiology. We analyzed 55 cases of diffuse large B-cell lymphoma involving the central nervous system (CNS) and testis using deep learning-based digital image analysis. Immunohistochemical staining was performed for key immune markers, including CD3, CD4, CD8, FOXP3, PD-1, TIM-3, CD68, and CD163, to characterize TME composition. PTL exhibited significantly higher levels of tumor-infiltrating lymphocytes, including CD3(+) and CD8(+) T-cells, compared to PCNSL (P < 0.001). The T-cell exhaustion index was significantly lower in PTL (P < 0.001), while CD163(+) macrophages were more predominant in PCNSL, suggesting a more immunosuppressive TME in the CNS. Correlation analyses of TME factors revealed differences between the CNS and testis, with stronger interrelationships among immune markers in PCNSL. Our findings highlight distinct TME characteristics between PCNSL and PTL. The predominance of CD163(+) macrophages and higher T-cell exhaustion in PCNSL suggests potential benefits of macrophage-targeted therapies. In contrast, PTL, with a more active TME, may be more responsive to immune checkpoint blockade. This study provides novel insights into the immune landscape of primary large B-cell lymphomas of immune-privileged sites, emphasizing the need for site-specific treatment approaches
Feasibility and clinical utility of stone extraction balloon catheter-assisted endoscopic stenting for malignant distal duodenal and proximal jejunal obstruction (with video)
No full textBACKGROUND: Endoscopic stenting for malignant distal duodenal and jejunal obstructions is challenging because the length of conventional gastroscopes is insufficient to reach the obstruction point. A fully inflated balloon catheter freely navigates the duodenum and jejunum without causing bowel injury by burying the catheter tip. It easily changes its direction for guidewire relocation, conforming to the angulation of the small bowel flexures. This study evaluated the feasibility and efficacy of stone extraction balloon catheter-assisted endoscopic stenting for malignant distal duodenal and proximal jejunal obstructions. METHODS: Patients with malignant distal duodenal or jejunal obstructions who underwent stone extraction balloon catheter-assisted duodenal stenting between January 2015 and December 2022 were retrospectively analyzed. RESULTS: We evaluated 30 patients in this study. Pancreatic cancer is the primary cause of duodenal obstruction, with the third portion of the duodenum being the most common obstruction site. Technical success was achieved in 100% of cases, and the clinical success rate was 100%. The median procedure time was 35 min, and the mean gastric outlet obstruction score (GOOSS) improved from 1.20 (pre-procedure) to 2.87 (post-procedure). Early stent migration was encountered in one patient. During follow-up, stent dysfunction was noted in nine (30%) patients, and the overall stent patency time was 145 days. CONCLUSION: Stone extraction balloon catheter-assisted endoscopic stenting is an effective and reproducible technique for treating malignant distal duodenal and jejunal obstructions
Detection of neonatal pneumoperitoneum on radiographs using deep multi-task learning
No full textNeonatal pneumoperitoneum is a life-threatening condition requiring prompt diagnosis, yet its subtle radiographic signs pose diagnostic challenges, especially in emergency settings. To develop and validate a deep multi-task learning model for diagnosing neonatal pneumoperitoneum on radiographs and to assess its clinical utility across clinicians of varying experience levels. Retrospective diagnostic study using internal and external datasets. Internal data were collected between January 1995 and August 2018, while external data were sourced from 11 neonatal intensive care units. Tertiary hospital and multicenter validation settings. Internal dataset: 204 neonates (546 radiographs), external dataset: 378 radiographs (125 pneumoperitoneum cases, 214 non-pneumoperitoneum cases). Radiographs were reviewed by two pediatric radiologists. A reader study involved 4 physicians with varying experience levels. A deep multi-task learning model combining classification and segmentation tasks for pneumoperitoneum detection. The primary outcomes included diagnostic accuracy, area under the receiver operating characteristic curve (AUC), and inter-reader agreement. AI-assisted and unassisted reader performance metrics were compared. The AI model achieved an AUC of 0.98 (95 % CI, 0.94-1.00) and accuracy of 94 % (95 % CI, 85.1-99.6) in internal validation, and AUC of 0.89 (95 % CI, 0.85-0.92) with accuracy of 84.1 % (95 % CI, 80.4-87.8) in external validation. AI assistance improved reader accuracy from 82.5 % to 86.6 % (p < .001) and inter-reader agreement (kappa increased from 0.33 to 0.71 to 0.54-0.86). The multi-task learning model demonstrated excellent diagnostic performance and improved clinicians' diagnostic accuracy and agreement, suggesting its potential to enhance care in neonatal intensive care settings. All code is available at https://github.com/brody9512/NEC_MTL
Clinical Performance and Communication Skills of ChatGPT Versus Physicians in Emergency Medicine: Simulated Patient Study
No full textBACKGROUND: Emergency medicine can benefit from artificial intelligence (AI) due to its unique challenges, such as high patient volume and the need for urgent interventions. However, it remains difficult to assess the applicability of AI systems to real-world emergency medicine practice, which requires not only medical knowledge but also adaptable problem-solving and effective communication skills. OBJECTIVE: We aimed to evaluate ChatGPT's (OpenAI) performance in comparison to human doctors in simulated emergency medicine settings, using the framework of clinical performance examination and written examinations. METHODS: In total, 12 human doctors were recruited to represent the medical professionals. Both ChatGPT and the human doctors were instructed to manage each case like real clinical settings with 12 simulated patients. After the clinical performance examination sessions, the conversation records were evaluated by an emergency medicine professor on history taking, clinical accuracy, and empathy on a 5-point Likert scale. Simulated patients completed a 5-point scale survey including overall comprehensibility, credibility, and concern reduction for each case. In addition, they evaluated whether the doctor they interacted with was similar to a human doctor. An additional evaluation was performed using vignette-based written examinations to assess diagnosis, investigation, and treatment planning. The mean scores from ChatGPT were then compared with those of the human doctors. RESULTS: ChatGPT scored significantly higher than the physicians in both history-taking (mean score 3.91, SD 0.67 vs mean score 2.67, SD 0.78, P<.001) and empathy (mean score 4.50, SD 0.67 vs mean score 1.75, SD 0.62, P<.001). However, there was no significant difference in clinical accuracy. In the survey conducted with simulated patients, ChatGPT scored higher for concern reduction (mean score 4.33, SD 0.78 vs mean score 3.58, SD 0.90, P=.04). For comprehensibility and credibility, ChatGPT showed better performance, but the difference was not significant. In the similarity assessment score, no significant difference was observed (mean score 3.50, SD 1.78 vs mean score 3.25, SD 1.86, P=.71). CONCLUSIONS: ChatGPT's performance highlights its potential as a valuable adjunct in emergency medicine, demonstrating comparable proficiency in knowledge application, efficiency, and empathetic patient interaction. These results suggest that a collaborative health care model, integrating AI with human expertise, could enhance patient care and outcomes
Unsustainable and overworked: unpacking the challenges faced by pediatric cardiologists and cardiac surgeons in Korea
No full textBACKGROUND: Pediatric cardiologists (PCs) and pediatric cardiac surgeons (PedCSs) in Korea face growing workforce shortages due to declining birth rates, decreasing interest among trainees, and increasing burnout. PURPOSE: This study investigated the working conditions, job satisfaction, and burnout levels among Korean PCs and PedCSs. METHODS: In June 2023, the Korean Pediatric Heart Society distributed a structured questionnaire via email to 149 members actively practicing pediatric cardiac care (115 PCs, 34 PedCSs). Responses from 122 members were analyzed. Descriptive statistics and regression analyses were performed to identify the factors associated with burnout (P<0.05). RESULTS: A total of 122 physicians (96 PCs, 26 PedCSs) completed the survey (response rates: overall, 81.9%; PCs, 83.5%; PedCSs, 76.5%). Among the PCs, 79.2% worked more than 51 hr/wk, 57.3% worked night shifts, and 70.8% experienced emergency callbacks at least once per month. PedCSs reported comparably heavy burdens, with 80.8% working >51 hr/wk and 88.5% experiencing monthly emergency callbacks. Regional disparities were notable: 48.2% of PCs in the Seoul metropolitan area (SMA) performed >51 catheterizations annually versus 7.1% in other regions, while 62.5% of PedCSs in the SMA performed >30 surgeries annually versus 20% elsewhere. Litigation, reported by 66.7% of PCs versus 84.6% of PedCSs, contributed to dissatisfaction and burnout. The key drivers included limited research time, legal risks, and nonspecialized duties. Overall, 64.0% of the PCs and 61.6% of the PedCSs reported experiencing burnout. In the multivariable analysis, answering >/=6 emergency callbacks/mo (adjusted odds ratio [aOR], 7.91; 95% confidence interval [CI], 1.28-48.79), occupational dissatisfaction (aOR, 2.57; 95% CI, 1.09-6.04), and work environment dissatisfaction (aOR, 2.74; 95% CI, 1.16-7.14) independently predicted burnout, whereas the working >51 hr/wk variable did not remain significant postadjustment. CONCLUSION: Excessive workload, frequent emergency callbacks, regional maldistribution of case volumes, litigation pressure, and occupational dissatisfaction drive high burnout among Korean pediatric cardiac specialists. These findings highlight persistent workforce challenges in Korea's pediatric cardiac system. Regular surveys and ongoing research are essential to ensuring sustainable pediatric cardiac care
Comprehensive analysis of patients with rheumatoid arthritis associated interstitial lung disease
No full textBACKGROUND/AIMS: To investigate the demographics, disease characteristics, and treatment modalities of patients with rheumatoid arthritis (RA) associated interstitial lung disease (ILD), focusing on ILD exacerbation and mortality. METHODS: This retrospective study included individuals aged >/= 18 years diagnosed with RA-ILD at Ajou University Hospital from January 1999 to March 2022. Diagnosis was based on chest computed tomography (CT) scans; progression was monitored based on available follow-up pulmonary function tests (PFTs) and chest CTs. Logistic regression analysis identified factors associated with ILD progression and mortality. RESULTS: The study included participants with a mean age of 64.3 years, 48.3% of whom were male. Smoking status: 13.2% ex-smokers, 25.2% current smokers, 61.6% non-smokers. Mean RA and ILD duration were 134.0 and 87.5 months, respectively. Mean Disease Activity Score in 28 joints was 4.9. The usual interstitial pneumonia (UIP) pattern was seen in 60.3%. Baseline PFT showed a mean FVC of 81.9 L, diffusing capacity for carbon monoxide (DLco) of 58.7 mL/min/mm, and DLco corrected for alveolar volume of 83.4 mL/min. With a mean follow-up of 4 years, ILD progressed in 58.3% of patients, with a mortality rate of 21.2%. ILD progression and UIP pattern significantly influenced mortality. Methotrexate use did not impact progression or mortality. CONCLUSION: RA-ILD patients showed diverse clinical profiles, with ILD duration and UIP pattern significantly affecting prognosis. Personalized management and vigilant monitoring are essential to improve outcomes for RA-ILD patients
Intrarenal reflux is linked to subsequent kidney scarring: a retrospective study
No full textBACKGROUND: This study investigates whether intrarenal reflux (pyelotubular backflow) is associated with kidney scarring in children with urinary tract infection (UTI). METHODS: We retrospectively reviewed 441 children diagnosed with UTI who underwent voiding cystourethrography (VCUG) and a technetium-99 m dimercaptosuccinic acid (DMSA) scan more than 3 months after the UTI. Intrarenal reflux was identified on VCUG. Using multivariable logistic regression, we analyzed the association between intrarenal reflux and kidney scarring on DMSA scans, adjusting for vesicoureteral reflux (VUR) grade and other clinical variables. RESULTS: Out of 874 kidney units, VUR was detected in 255 units (29.1%), with intrarenal reflux present in 35 units (13.7%). Kidney scarring was observed in 12.7% of all kidney units. Intrarenal reflux was significantly associated with an increased risk of kidney scarring (odds ratio 3.35, 95% confidence interval 1.31-8.58) after adjusting for VUR grade. Notably, 92% of photon defects on DMSA scans in units with intrarenal reflux were located at the reflux site. CONCLUSIONS: Intrarenal reflux is an independent predictor of kidney scarring beyond conventional VUR grading. Recognizing and reporting intrarenal reflux during VUR assessment may aid in developing tailored management strategies for children with UTI and VUR
Investigation of the prevalence and treatment of atopic dermatitis in South Korea using a large national dataset
No full textBACKGROUND: Updated reports on the population-based analysis of atopic dermatitis (AD) in Korea are rare. This study aimed to investigate the nationwide prevalence and systemic medication prescription trends of AD in Korea. METHODS: Based on the Korean National Health Insurance database, the prevalence of AD and systemic medication prescription trends in patients with AD were analyzed according to age groups and regional districts from 2010 to 2015. RESULTS: The prevalence of AD was the highest among patients aged 0-1 year (18.6%-24.5%), decreasing rapidly with increasing age (<2% in patients aged >/=20 years). From 2010 to 2015, the prevalence of AD decreased in children but increased slightly in adolescents and adults. In 2015, the proportion of systemic steroid prescriptions increased from 11.2% in the 0-9 years age group to 41.1% in the 50-59 years age group, while that of systemic antibiotic prescriptions gradually decreased from 6.2% in the 0-9 years age group to 1.8% in the 80-89 years age group. The proportion of systemic steroid prescriptions by region remained consistently high in Gyeongbuk (34.2%- 34.9%) and low in Daejeon (20.2%-22.5%). The annual proportion of systemic cyclosporine prescriptions increased significantly from 0.6% in 2010 to 1.2% in 2015, with the highest rates observed in patients in their 30s (1.5%-2.4%), followed by those in their 20s (1.3%-2.3%) and 40s (1.1%-2.0%). CONCLUSION: From 2010 to 2015, the prevalence of AD decreased in children but increased slightly in adolescents and adults. Approximately one-fourth of the patients with AD were prescribed systemic steroids, and the percentage of cyclosporine prescriptions doubled during the study period
Protective Effects of Lindera obtusiloba Leaf Extract on Osteoarthritis in Mouse Primary Chondrocytes and a Medial Meniscus Destabilization Model
No full textOsteoarthritis (OA) is a degenerative joint disorder characterized by progressive articular cartilage degradation, leading to pain, stiffness, and impaired mobility. This study investigated the anti-osteoarthritic effects of Lindera obtusiloba (LO) leaf extract in primary cultured chondrocytes and a mouse model of destabilization of the medial meniscus (DMM)-induced OA. Mouse primary chondrocytes were treated with IL-1beta and various concentrations of LO leaf extract (50-150 mug/mL), and analyzed by RT-PCR, Western blotting, and ELISA. For the in vivo experiments, male C57BL/6 mice underwent DMM surgery and were administered LO leaf extract (50-200 mg/kg/day) for eight weeks, followed by micro-CT, histological, and immunohistochemical analyses. LO leaf extract exhibited no cytotoxicity in chondrocytes. In interleukin-1beta-induced inflammatory chondrocytes, LO leaf extract significantly suppressed the expression of OA-associated catabolic factors, including cyclooxygenase-2 (Cox-2), matrix metalloproteinases (MMP3 and MMP13), and phosphorylated nuclear factor-kappa B (NF-kappaB). It also reduced the production of destructive mediators, such as prostaglandin E(2) (PGE(2)) and collagenase, in a dose-dependent manner. In vivo, LO leaf extract-treated mice demonstrated significant reductions in articular cartilage degradation, subchondral bone sclerosis, and the expression of catabolic and inflammatory mediators. Additionally, LO leaf extract administration significantly decreased systemic pro-inflammatory cytokine levels in DMM-induced mice. Collectively, these findings indicate that LO leaf extract attenuates OA progression by suppressing both local and systemic inflammatory responses, supporting its potential as a natural therapeutic agent for the prevention and treatment of OA