Incidence trends for common subtypes of T-cell lymphoma in Taiwan and the United States from 2008-2020.

The incidence of T-cell lymphoma (TCL) has been continually increasing in Taiwan and the United States (US) in recent years. This epidemiological study using population-based registry data aimed to determine the incidence patterns of common subtypes of TCL in Taiwan from 2008-2020 and compare them with those in the US and the Asian/Pacific Islander (API) population. Subtypes included angioimmunoblastic T-cell lymphoma (AITL); extranodal NK/T-cell lymphoma, nasal or other type (ENKTL); peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); and anaplastic large cell lymphoma (ALCL). The total number of patients newly diagnosed with TCL during 2008-2020 was 4477, 3171, and 48,889 in Taiwan, API, and the US, respectively. Except the incidence rate of AITL in Taiwan, the incidence rates of these common TCL subtypes showed downward trends in all studied populations. There was also a significant increase in the relative frequency of AITL among TCL in Taiwan, with an annual percent change of 4.44 (p < 0.001), from 8.44% in 2002 to 20.63% in 2020. The rapid development of diagnostics may be the main factor contributing to this rise in incidence.

Monitoring the transition from corneal ulceration to healed scar using a Scheimpflug tomography-based densitometry.

PURPOSE: To compare corneal haze between active ulcer and healed scarring using a Scheimpflug densitometry. MATERIALS AND METHODS: A prospective longitudinal study enrolled 30 patients (30 eyes) with ulcerative keratitis (UK). Each subject's corneal optical density (COD) was measured with a Scheimpflug corneal densitometry, Pentacam® AXL (Oculus GmbH, Wetzlar, Germany), at the active ulcerative and complete scarring stage. The COD data were analyzed through distinct methods (inbuilt, sorted annular partitions, and ulcer-matching densitometric maps). We compared different CODs to select the better index for clinically monitoring the transition from corneal ulceration to healed scar. RESULTS: The CODs of the periphery (P = 0.0024) and outside of the active ulcer (P = 0.0002) significantly decreased after scarring. Partitioning the cornea into different depths and annular zones, the anterior layer, center layer, and the 2-6 mm annular zone had a more remarkable COD decrease after scar formation. The 3rd-sorted COD in the anterior layer revealed the highest area under the receiver-operating characteristic curves (0.709), in which 90% of subjects had COD reduction during the ulcer-to-scar transition. CONCLUSIONS: Aside from subjective judgment based on clinical signs, the Scheimpflug tomography-based densitometry could provide objective and efficient monitoring of the corneal opacity evolution in UK patients. Because the 3rd-sorted annular COD is a better index than the inbuilt or mapping CODs in differentiating active ulcers from healed scars, this COD could be a clinically promising parameter to monitor the progression of UK patients.

Monitoring the Progression of Clinically Suspected Microbial Keratitis Using Convolutional Neural Networks.

Purpose: For this study, we aimed to determine whether a convolutional neural network (CNN)-based method (based on a feature extractor and an identifier) can be applied to monitor the progression of keratitis while managing suspected microbial keratitis (MK). Methods: This multicenter longitudinal cohort study included patients with suspected MK undergoing serial external eye photography at the 5 branches of Chang Gung Memorial Hospital from August 20, 2000, to August 19, 2020. Data were primarily analyzed from January 1 to March 25, 2022. The CNN-based model was evaluated via F1 score and accuracy. The area under the receiver operating characteristic curve (AUROC) was used to measure the precision-recall trade-off. Results: The model was trained using 1456 image pairs from 468 patients. In comparing models via only training the identifier, statistically significant higher accuracy (P < 0.05) in models via training both the identifier and feature extractor (full training) was verified, with 408 image pairs from 117 patients. The full training EfficientNet b3-based model showed 90.2% (getting better) and 82.1% (becoming worse) F1 scores, 87.3% accuracy, and 94.2% AUROC for 505 getting better and 272 becoming worse test image pairs from 452 patients. Conclusions: A CNN-based approach via deep learning applied in suspected MK can monitor the progress/regress during treatment by comparing external eye image pairs. Translational Relevance: The study bridges the gap between the investigation of the state-of-the-art CNN-based deep learning algorithm applied in ocular image analysis and the clinical care of suspected patients with MK.

Validation of ICD-10-CM Diagnostic Codes for Identifying Patients with ST-Elevation and Non-ST-Elevation Myocardial Infarction in a National Health Insurance Claims Database.

Purpose: Distinguishing ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) is crucial in acute myocardial infarction (AMI) research due to their distinct characteristics. However, the accuracy of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for STEMI and NSTEMI in Taiwan's National Health Insurance (NHI) database remains unvalidated. Therefore, we developed and validated case definition algorithms for STEMI and NSTEMI using ICD-10-CM and NHI billing codes. Patients and Methods: We obtained claims data and medical records of inpatient visits from 2016 to 2021 from the hospital's research-based database. Potential STEMI and NSTEMI cases were identified using diagnostic codes, keywords, and procedure codes associated with AMI. Chart reviews were then conducted to confirm the cases. The performance of the developed algorithms for STEMI and NSTEMI was assessed and subsequently externally validated. Results: The algorithm that defined STEMI as any STEMI ICD code in the first three diagnosis fields had the highest performance, with a sensitivity of 93.6% (95% confidence interval [CI], 91.7-95.2%), a positive predictive value (PPV) of 89.4% (95% CI, 87.1-91.4%), and a kappa of 0.914 (95% CI, 0.900-0.928). The algorithm that used the NSTEMI ICD code listed in any diagnosis field performed best in identifying NSTEMI, with a sensitivity of 82.6% (95% CI, 80.7-84.4%), a PPV of 96.5% (95% CI, 95.4-97.4), and a kappa of 0.889 (95% CI, 0.878-0.901). The algorithm that included either STEMI or NSTEMI ICD codes listed in any diagnosis field showed excellent performance in defining AMI, with a sensitivity of 89.4% (95% CI, 88.2-90.6%), a PPV of 95.6% (95% CI, 94.7-96.4%), and a kappa of 0.923 (95% CI, 0.915-0.931). External validation confirmed these algorithms' efficacy. Conclusion: Our results provide valuable reference algorithms for identifying STEMI and NSTEMI cases in Taiwan's NHI database.

The Impact of Emergency Department Arrival Time on Door-to-Balloon Time in Patients with ST-Segment Elevation Myocardial Infarction Receiving Primary Percutaneous Coronary Intervention.

Door-to-balloon (DTB) time significantly affects the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). The effects of temporal differences in emergency department (ED) arrival time on DTB time and on different segments of DTB time remain inconclusive. Therefore, we performed a retrospective study in a tertiary hospital between January 2013 and December 2021 and investigated the relationship between a patient's arrival time and both their DTB time and different segments of their DTB time. Of 732 STEMI patients, 327 arrived during the daytime (08:01-16:00), 268 during the evening (16:01-24:00), and 137 at night (00:01-08:00). Significantly higher odds of delay in DTB time were observed during the nighttime (adjusted odds ratio (aOR): 2.87; 95% confidence interval (CI): 1.50-5.51, p = 0.002) than during the daytime. This delay was mainly attributed to a delay in cardiac catheterization laboratory (cath lab) activation-to-arrival time (aOR: 6.25; 95% CI: 3.75-10.40, p < 0.001), particularly during the 00:00-04:00 time range. Age, sex, triage level, and whether patients arrived during the COVID-19 pandemic also had independent effects on different segments of DTB time. Further studies are required to investigate the root causes of delay in DTB time and to develop specific strategies for improvement.

Ultraviolet A at levels experienced outdoors suppresses transforming growth factor-beta signaling and collagen production in human scleral fibroblasts.

Previous studies have highlighted the importance of outdoor time in reducing the risk of myopia progression. Although ultraviolet A (UVA) radiation dominates in terms of energy with respect to the UV radiation reaching the Earth's surface, its effects on the exposed anterior sclera have not been well studied. This study was designed to investigate the UVA-induced biological effects at peak sunlight levels in human scleral fibroblasts (HSFs). Using next-generation sequencing (NGS), we analyzed the differentially expressed genes (DEGs) in UVA-treated and normal HSFs. Further, we then identified the functions and key regulators of the DEGs using bioinformatics analysis, and verified the effects of UVA on gene and protein expression in HSFs using real-time PCR, western blotting, and immunofluorescence imaging. The highest level of solar UVA (365 nm) was 3.4 ± 0.18 (mW/cm2). The results from the functional analysis of the DEGs were related to structural changes in the extracellular matrix (ECM) and protein metabolism. Transforming growth factor-ß1 (TGF-ß1) and Smad3 were predicted to be potential upstream regulators, associated with ECM organization. Exposure to a single wavelength of UVA (365 nm, 3 mW/cm2) for 1 h for 5 consecutive days induced the downregulation of the mRNA of ECM genes including COL1A1, COL3A1, COL5A1, VCAN and collagen I protein in HSF. UVA downregulated Smad3 protein and reduced TGF-ß-induced collagen I protein production following UVA exposure in HSF. In conclusion, high UVA exposure reduces TGF-ß signaling and collagen I production by modulating Smad levels in HSF. The effects of overexposure to high-intensity UVA on myopia control require further investigations.

Deep Learning Approach in Image Diagnosis of Pseudomonas Keratitis.

This investigation aimed to explore deep learning (DL) models' potential for diagnosing Pseudomonas keratitis using external eye images. In the retrospective research, the images of bacterial keratitis (BK, n = 929), classified as Pseudomonas (n = 618) and non-Pseudomonas (n = 311) keratitis, were collected. Eight DL algorithms, including ResNet50, DenseNet121, ResNeXt50, SE-ResNet50, and EfficientNets B0 to B3, were adopted as backbone models to train and obtain the best ensemble 2-, 3-, 4-, and 5-DL models. Five-fold cross-validation was used to determine the ability of single and ensemble models to diagnose Pseudomonas keratitis. The EfficientNet B2 model had the highest accuracy (71.2%) of the eight single-DL models, while the best ensemble 4-DL model showed the highest accuracy (72.1%) among the ensemble models. However, no statistical difference was shown in the area under the receiver operating characteristic curve and diagnostic accuracy among these single-DL models and among the four best ensemble models. As a proof of concept, the DL approach, via external eye photos, could assist in identifying Pseudomonas keratitis from BK patients. All the best ensemble models can enhance the performance of constituent DL models in diagnosing Pseudomonas keratitis, but the enhancement effect appears to be limited.

Tear Proteomics Approach to Distinguishing Primary from Secondary Sjögren's Syndrome for Dry Eye Patients with Long-Term Instillation of Eyedrops.

The diagnosis and monitoring of Sjögren syndrome (SS) is often difficult, requiring a multidisciplinary approach with invasive procedures. Our aim is to elucidate the tear protein alterations of dry eye disease (DED) with primary SS (pSS) and secondary SS (sSS) with the long-term instillation of eyedrops. We collected clinical demographics and tear fluid (TF) samples from DED patients with no autoimmune diseases (non-SS-DED), pSS-DED, and sSS-DED patients, followed by TF screening with tandem mass tagging-labeling gel-free proteomics assay. Bioinformatic analysis via Ingenuity Pathway Analysis was used to identify functional pathways and interacting networks. Validation of candidate proteins with enzyme-linked immunosorbent assay on the tear samples was done. The top functional pathways of the two comparisons (sSS-DED vs. pSS-DED and sSS-DED vs. non-SS-DED) were both associated with inflammation and stress-related signaling. After constructing an interaction network model with the selected candidate proteins, five proteins were identified. A Disintegrin and Metalloproteinase domain-containing protein 10 (ADAM10) was found to be an important candidate biomarker in all groups, followed by epidermal growth factor (EGF) in TF. This study revealed novel DED markers, ADAM10 and EGF, in differentiating between primary and secondary SS patients from tears by in-depth proteomic analysis.

5-Lipoxygenase Inhibition Protects Retinal Pigment Epithelium from Sodium Iodate-Induced Ferroptosis and Prevents Retinal Degeneration.

Excessive reactive oxygen species (ROS) contribute to damage of retinal cells and the development of retinal diseases including age-related macular degeneration (AMD). ROS result in increased metabolites of lipoxygenases (LOXs), which react with ROS to induce lipid peroxidation and may lead to ferroptosis. In this study, the effect of 5-LOX inhibition on alleviating ROS-induced cell death was evaluated using sodium iodate (NaIO3) in the retinal pigment epithelium (RPE) cell line ARPE-19 and a mouse model investigating oxidative stress in AMD. We demonstrated that NaIO3 induced cell death in the RPE cells through mechanisms including ferroptosis. Inhibition of 5-LOX with specific inhibitor, Zileuton, or siRNA knockdown of ALXO5 mitigated NaIO3-induced lipid peroxidation, mitochondrial damage, DNA impairment, and cell death in ARPE-19 cells. Additionally, in the mouse model, pretreatment with Zileuton reduced the NaIO3-induced lipid peroxidation of RPE cells, cell death in the photoreceptor layer of the retina, inflammatory responses, and degeneration of both the neuroretina and RPE monolayer cells. Our results suggest that 5-LOX plays a crucial role in ROS-induced cell death in the RPE and that regulating 5-LOX activity could be a useful approach to control ROS and ferroptosis-induced damage, which promote degeneration in retinal diseases.

Steroid-Induced Ocular Hypertension in a Pediatric Patient with Acute Lymphoblastic Leukemia: A Case Report.

Glucocorticoids play a pivotal role in therapeutic protocols in acute lymphoblastic leukemia (ALL) treatment. Systemic steroids are known to be less likely to elevate the intraocular pressure when compared to topical administration, and reports addressing hypertensive ocular response in the Asian pediatric ALL population are currently limited. We report a case of a nine-year-old girl with acute lymphoblastic leukemia (ALL) who was found to have highly elevated intraocular pressure (IOP) during maintenance treatment when taking oral dexamethasone (6 mg/m2/day). Her IOP increased on day 5 after taking dexamethasone, reached a peak on day 7 or 8, and returned back to baseline on day 13 before anti-glaucoma medications were used. Thus, we prescribed IOP-lowering agents for 10 consecutive days starting on the day oral dexamethasone was administered, and observed that not only did the peak levels lower remarkably, but the IOP levels returned to baseline more rapidly as well.

Acute Transverse Myelitis after COVID-19 Vaccination.

The adverse effects of the COVID-19 vaccine have been discovered as the rapid application of the vaccines continues. Neurological complications such as transverse myelitis raise concerns as cases were observed in clinical trials. Transverse myelitis is a rare immune-mediated disease with spinal cord neural injury, resulting in neurological deficits in the motor, sensory, and autonomic system. Vaccine-related transverse myelitis is even rarer. We present a case of acute transverse myelitis after vaccination against COVID-19 with the ChAdOx1 nCOV-19 vaccine (AZD1222), which was the first case reported in Taiwan. Although it rarely occurs, post-vaccination neurological complications should not be ignored. As the pandemic of SARS-CoV-2 continues to spread and concern about vaccination efficacy and safety rises, heterologous vaccination were implemented in health public policy in several countries. A literature review of several clinical trials shows promising effects of mix-and-match vaccination. Further study on different combinations of vaccines can be expected.

Decarboxylative Radical Addition to Methylideneoxazolidinones for Stereocontrolled Synthesis of Selectively Protected Diamino Diacids.

Syntheses of stereochemically pure and selectively protected diamino diacids can be achieved by redox decarboxylation of distal N-hydroxyphthalimide esters of protected aspartic, glutamic or α-aminoadipic acids via radical addition to methylideneoxazolidinones. The products are useful for solid-supported syntheses of robust bioactive carbocyclic peptide analogs. Yields of reactive primary radical addition are superior to those of more stabilized radicals, and the reaction fails if the alkylideneoxazolidinone has a methyl substituent on its terminus (i.e., 13a/13b).

Triamcinolone acetonide modulates TGF­ß2­induced angiogenic and tissue­remodeling effects in cultured human retinal pigment epithelial cells.

Transforming growth factor­ß2 (TGF­ß2) has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), due to its ability to stimulate the overproduction of pro­angiogenic factors, such as vascular endothelial growth factor (VEGF), and remodeling of the extracellular matrix (ECM). Although intravitreal triamcinolone acetonide (TA) is clinically useful in the treatment of PVR and PDR, its molecular mechanism has yet to be fully elucidated. The present study investigated whether TA treatment altered TGF­ß2­driven biological effects on the behavior of cultured human retinal pigment epithelial (RPE) cells, in order to determine which signaling pathway may be essential for the pharmacological action of TA. The R­50 human RPE cell line was treated with TA in the presence of TGF­ß2, followed by analyses of cell viability and contraction using cell viability and collagen gel contraction assays. VEGF mRNA expression and protein production were measured using reverse transcription­quantitative PCR and ELISA, respectively. The phosphorylation status of signaling mediators and the protein expression of type I collagen (COL1A1), α­smooth muscle actin (α­SMA), and ECM­remodeling enzymes, including MMP­2 and MMP­9, were analyzed using western blotting. The gelatinolytic activity of MMPs was detected using gelatin zymography. TA treatment exhibited no prominent cytotoxicity but markedly antagonized TGF­ß2­induced cytostatic effects on RPE cell viability and TGF­ß2­enhanced contractility in collagen gels. In the context of TGF­ß2­related signaling, TA significantly attenuated TGF­ß2­elicited Smad2, extracellular­regulated kinase (ERK)1/2 and p38 mitogen­activated protein kinase (MAPK) phosphorylation. Moreover, TA markedly mitigated TGF­ß2­induced VEGF upregulation through ablation of p38 signaling activity. TA also partially attenuated TGF­ß2­elicted expression of COL1A1, α­SMA, MMP­2, and MMP­9, but only suppressed TGF­ß2­induced MMP­9 gelatinolytic activity. Mechanistically, the MEK/ERK signaling pathway may have a critical role in the TGF­ß2­induced upregulation of COL1A1, α­SMA and MMP­9. In conclusion, TA may be considered a useful therapeutic agent for treating TGF­ß2­associated intraocular angiogenesis and tissue remodeling, the underlying mechanism of which may involve the ERK and p38 MAPK signaling pathways.

Simultaneously Monitoring Whole Corneal Injury with Corneal Optical Density and Thickness in Patients Undergoing Cataract Surgery.

To pursue the least corneal implication during cataract surgery, this study aimed to monitor corneal wound injury after cataract surgery with a novel method. The prospective cohort study involved thirty-two patients, who were assessed by a Scheimpflug tomography AxL® (Oculus GmbH, Wetzlar, Germany) via the following two kinds of indices: whole corneal optical density (COD) and corneal thickness (CT), two weeks before and one month after cataract surgery. The results of the COD revealed that corneal annuli 0.0-2.0 mm and 2.0-6.0 mm, and the average and maximal values at the incisional site significantly increased postoperatively. Also, the anterior and central stroma of 0.0-2.0 mm, and all three depths of 2.0-6.0 mm, increased remarkably after the operation. For the CT, all ranges of diameters plus incisional sites showed significant increases postoperatively. Furthermore, we analyzed the differences (delta) of COD and CT between pre- and post-operation, and found significant correlations between the delta of COD and the delta of CT, regarding annuli 0.0-2.0 mm, 2.0-6.0 mm, and 6.0-10.0 mm, but no correlation at the incisional site, with either average density or maximal density, was detected. We concluded that whole COD and CT, especially at the central zones of the cornea (annulus < 6 mm), are both valuable parameters in the assessment of corneal damage post-cataract surgery, and are independent indices at the incisional site.

Multiple Single Nucleotide Polymorphism Testing Improves the Prediction of Diabetic Retinopathy Risk with Type 2 Diabetes Mellitus.

Diabetic retinopathy (DR) is one of the most frequent causes of irreversible blindness, thus prevention and early detection of DR is crucial. The purpose of this study is to identify genetic determinants of DR in individuals with type 2 diabetic mellitus (T2DM). A total of 551 T2DM patients (254 with DR, 297 without DR) were included in this cross-sectional research. Thirteen T2DM-related single nucleotide polymorphisms (SNPs) were utilized for constructing genetic risk prediction model. With logistic regression analysis, genetic variations of the FTO (rs8050136) and PSMD6 (rs831571) polymorphisms were independently associated with a higher risk of DR. The area under the curve (AUC) calculated on known nongenetic risk variables was 0.704. Based on the five SNPs with the highest odds ratio (OR), the combined nongenetic and genetic prediction model improved the AUC to 0.722. The discriminative accuracy of our 5-SNP combined risk prediction model increased in patients who had more severe microalbuminuria (AUC = 0.731) or poor glycemic control (AUC = 0.746). In conclusion, we found a novel association for increased risk of DR at two T2DM-associated genetic loci, FTO (rs8050136) and PSMD6 (rs831571). Our predictive risk model presents new insights in DR development, which may assist in enabling timely intervention in reducing blindness in diabetic patients.

Bsi(OTf)3-mediated tandem annulation of 1-aryl isochroman-3-ones with oxygenated arenes: one-pot synthesis of polyoxygenated homotriptycenes.

Bi(OTf)3 (bismuth triflate)-mediated one-pot tandem annulation of oxygenated 1-aryl isochroman-3-ones with oxygenated arenes provides polyoxygenated homotriptycenes in moderate to good yields in MeNO2 at reflux (101 °C) for 10 h under an air atmosphere and easy-operational conditions via intermolecular and intramolecular Friedel-Crafts type procedures. A plausible mechanism is proposed and discussed. This protocol provides a highly effective ring-closure via three carbon-carbon (C-C) bond formations.

Pneumomediastinum, Pneumoretroperitoneum, Pneumoperitoneum and Subcutaneous Emphysema Secondary to a Penetrating Anal Injury.

Simultaneous occurrence of pneumoperitoneum, pneumoretroperitoneum, pneumomediastinum and subcutaneous emphysema is rare. The most reported mechanisms are barotrauma, thermal injury and instrument puncture caused by colonoscopy. Ectopic air may travel into different body compartments through distinct anatomical fascial planes. Definite curative treatment involves surgical repair of the bowel wall defect. Conservative treatment is available in selected patients. Here, we present a case of traumatic penetrating rectal injury leading to developing air in the peritoneum, retroperitoneum, mediastinum, and subcutaneous space with good recovery under conservative treatment.

Axial length of cataract eyes: a comparison of two cohorts over a span of 10 years apart.

BACKGROUND: To assess the associations of axial length with age-related cataract within a span of 10 years in an Asian population in southern Taiwan. METHODS: A retrospective cohort study examined 960 adults who underwent cataract surgery at the Kaohsiung Chang Gung Memorial Hospital in year 2008 and year 2018. Axial length was assessed with the ultrasound biometry and/or the Zeiss IOLMaster. Eyes with prior blunt eye trauma or had underwent vitrectomy operations were excluded. The significance of the changes in axial length between the two cohorts was determined after performing age-matched analyses. Due to utilization of ultrasound biometry and/or Zeiss IOLMaster, axial length corrections with our mean difference in measurement results, which were similar to previous studies on comparison between the two measurement tools, were carried out. RESULTS: Axial length showed an age-related elongation in 10-year cross-sectional data, from a mean of 23.65 ± 1.80 mm in year 2008 to a mean of 24.30 ± 1.90 in year 2018 (p = 0.003). Patients with high myopia (axial length > 26 mm) increased significantly over the 10-year period from 8.1 to 16 % (p < 0.001). A birth cohort effect on axial length was evident as the axial lengths of year 2008 cohort were shorter than the 2018 cohort when they were in the same operation age group. In particular, persons born after the 1960s demonstrated a predominant increase in axial length in both cohorts. CONCLUSIONS: Our study confirms a trend in increase of axial myopia, especially high myopias, over the 10-year period. A novel finding of this study was discovering a birth cohort effect on axial length, especially in persons born after the 1960s in southern Taiwan.

Development of a Novel Interactive Multimedia E-Learning Model to Enhance Clinical Competency Training and Quality of Care among Medical Students.

Clinical competencies consisting of skills, knowledge, and communication techniques should be acquired by all medical graduates to optimize healthcare quality. However, transitioning from observation to hands-on learning in clinical competencies poses a challenge to medical students. The aim of this study is to evaluate the impact of a novel interactive multimedia eBook curriculum in clinical competency training. Ninety-six medical students were recruited. Students in the control group (n = 46) were taught clinical competencies via conventional teaching, while students in the experimental group (n = 50) were taught with conventional teaching plus interactive multimedia eBooks. The outcomes of clinical competencies were evaluated using Objective Structured Clinical Examination (OSCE) scores, and feedback on their interactive eBook experiences was obtained. In the experimental group, the average National OSCE scores were not only higher than the control group (214.8 vs. 206.5, p < 0.001), but also showed a quicker improvement when comparing between three consecutive mock OSCEs (p < 0.001). In response to open-ended questions, participants emphasized the importance of eBooks in improving their abilities and self-confidence when dealing with 'difficult' patients. Implementing interactive multimedia eBooks could prompt a more rapid improvement in clinical skill performance to provide safer healthcare, indicating the potential of our innovative module in enhancing clinical competencies.