The law code of ChatGPT and artificial intelligence-how to shield plastic surgeons and reconstructive surgeons against Justitia's sword.

Large Language Models (LLMs) like ChatGPT 4 (OpenAI), Claude 2 (Anthropic), and Llama 2 (Meta AI) have emerged as novel technologies to integrate artificial intelligence (AI) into everyday work. LLMs in particular, and AI in general, carry infinite potential to streamline clinical workflows, outsource resource-intensive tasks, and disburden the healthcare system. While a plethora of trials is elucidating the untapped capabilities of this technology, the sheer pace of scientific progress also takes its toll. Legal guidelines hold a key role in regulating upcoming technologies, safeguarding patients, and determining individual and institutional liabilities. To date, there is a paucity of research work delineating the legal regulations of Language Models and AI for clinical scenarios in plastic and reconstructive surgery. This knowledge gap poses the risk of lawsuits and penalties against plastic surgeons. Thus, we aim to provide the first overview of legal guidelines and pitfalls of LLMs and AI for plastic surgeons. Our analysis encompasses models like ChatGPT, Claude 2, and Llama 2, among others, regardless of their closed or open-source nature. Ultimately, this line of research may help clarify the legal responsibilities of plastic surgeons and seamlessly integrate such cutting-edge technologies into the field of PRS.

Single-cell chromatin accessibility and transposable element landscapes reveal shared features of tissue-residing immune cells.

Tissue adaptation is required for regulatory T (Treg) cell function within organs. Whether this program shares aspects with other tissue-localized immune populations is unclear. Here, we analyzed single-cell chromatin accessibility data, including the transposable element (TE) landscape of CD45+ immune cells from colon, skin, adipose tissue, and spleen. We identified features of organ-specific tissue adaptation across different immune cells. Focusing on tissue Treg cells, we found conservation of the Treg tissue adaptation program in other tissue-localized immune cells, such as amphiregulin-producing T helper (Th)17 cells. Accessible TEs can act as regulatory elements, but their contribution to tissue adaptation is not understood. TE landscape analysis revealed an enrichment of specific transcription factor binding motifs in TE regions within accessible chromatin peaks. TEs, specifically from the LTR family, were located in enhancer regions and associated with tissue adaptation. These findings broaden our understanding of immune tissue residency and provide an important step toward organ-specific immune interventions.

Biomarker-guided acute kidney injury risk assessment under liberal versus restrictive fluid therapy - the prospective-randomized MAYDAY-trial.

Acute kidney injury (AKI) prevalence in surgical patients is high, emphasizing the need for preventative measures. This study addresses the insufficient evidence on nephroprotective intraoperative fluid resuscitation and highlights the drawbacks of relying solely on serum creatinine/urine output to monitor kidney function. This study assessed the impact of intraoperative fluid management on AKI in female breast cancer patients undergoing autologous breast reconstruction, utilizing novel urinary biomarkers (TIMP-2 and IGFBP-7). In a monocentric prospective randomized controlled trial involving 40 patients, liberal (LFA) and restrictive (FRV) fluid management strategies were compared. TIMP-2 and IGFBP-7 biomarker levels were assessed using the NephroCheck (bioMerieux, France) test kit at preoperative, immediate postoperative, and 24-h postoperative stages. FRV showed significantly higher immediate postoperative biomarker levels, indicating renal tubular stress. FRV patients had 21% (4/19) experiencing AKI compared to 13% (2/15) in the LFA group according to KDIGO criteria (p = 0.385). Restrictive fluid resuscitation increases the risk of AKI in surgical patients significantly, emphasizing the necessity for individualized hemodynamic management. The findings underscore the importance of urinary biomarkers in early AKI detection.

Preliminary Single-Cell RNA-Sequencing Analysis Uncovers Adipocyte Heterogeneity in Lipedema.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

Continuous protein-density gradients: A new approach to correlate physical cues with cell response.

To assess cellular behavior within heterogeneous tissues, such as bone, skin, and nerves, scaffolds with biophysical gradients are required to adequately replicate the in vivo interaction between cells and their native microenvironment. In this study, we introduce a strategy for depositing ultrathin films comprised of laminin-111 with precisely controlled biophysical gradients onto planar substrates using the Langmuir-Blodgett (LB) technique. The gradient is created by controlled desynchronization of the barrier compression and substrate withdrawal speed during the LB deposition process. Characterization of the films was performed using techniques such as atomic force microscopy and confocal fluorescence microscopy, enabling the comprehensive analysis of biophysical parameters along the gradient direction. Furthermore, human adipose-derived stem cells were seeded onto the gradient films to investigate the influence of protein density on cell attachment, showing that the distribution of the cells can be modulated by the arrangement of the laminin at the air-water interface. The presented approach not only allowed us to gain insights into the intricate interplay between biophysical cues and cell behavior within complex tissue environments, but it is also suited as a screening approach to determine optimal protein concentrations to achieve a target cellular output.

In-depth analysis of ChatGPT's performance based on specific signaling words and phrases in the question stem of 2377 USMLE step 1 style questions.

ChatGPT has garnered attention as a multifaceted AI chatbot with potential applications in medicine. Despite intriguing preliminary findings in areas such as clinical management and patient education, there remains a substantial knowledge gap in comprehensively understanding the chances and limitations of ChatGPT's capabilities, especially in medical test-taking and education. A total of n = 2,729 USMLE Step 1 practice questions were extracted from the Amboss question bank. After excluding 352 image-based questions, a total of 2,377 text-based questions were further categorized and entered manually into ChatGPT, and its responses were recorded. ChatGPT's overall performance was analyzed based on question difficulty, category, and content with regards to specific signal words and phrases. ChatGPT achieved an overall accuracy rate of 55.8% in a total number of n = 2,377 USMLE Step 1 preparation questions obtained from the Amboss online question bank. It demonstrated a significant inverse correlation between question difficulty and performance with rs = -0.306; p < 0.001, maintaining comparable accuracy to the human user peer group across different levels of question difficulty. Notably, ChatGPT outperformed in serology-related questions (61.1% vs. 53.8%; p = 0.005) but struggled with ECG-related content (42.9% vs. 55.6%; p = 0.021). ChatGPT achieved statistically significant worse performances in pathophysiology-related question stems. (Signal phrase = "what is the most likely/probable cause"). ChatGPT performed consistent across various question categories and difficulty levels. These findings emphasize the need for further investigations to explore the potential and limitations of ChatGPT in medical examination and education.

Breast Lipofilling: Is the Bra Really Full? Clinical Bra Pressure Measurement and In Vitro Testing of Processed and Unprocessed Fat Cells.

BACKGROUND: Breast lipofilling, a popular cosmetic and reconstructive procedure, involves the transplantation of autologous fat to enhance breast volume and contour. Despite its widespread use, cell processing and the aftertreatment remain controversial. This study investigates the pressure applied by a compression bra and reports in vitro stress tests of processed and unprocessed fat cells. METHODS: Clinical bra pressure measurements were conducted on a cohort of 45 patients following lipofilling, reduction mammoplasties and DIEP flaps. Laboratory analysis included cell vitality testing using Resazurin assays of processed and unprocessed fat cells after exposure to mechanical or hyperbaric pressure. RESULTS: Our findings show a mean overall pressure value of the compression bra for all patients of 6.7 ± 5.7 mmHg (range 0-35). Cell processing is superior to sedimentation only regarding fat cell vitality. However, neither mechanical pressure within the specified range nor hyperbaric oxygen exposure significantly affected fat graft survival as measured by Resazurin assays. CONCLUSION: The in vitro measurements showed that it was impossible to harm fat cells with external pressure during lipofilling procedures, regardless of their processing. In the clinical context, the compression bra applied pressure values deceeding the perfusion pressure and may therefore not diminish oxygen supply nor harm the transplanted cells. Therefore, we recommend the use of a compression bra for all lipofilling procedures around the breast. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Intra-Articular Application of Autologous, Fat-Derived Orthobiologics in the Treatment of Knee Osteoarthritis: A Systematic Review.

The aim of this study was to review the current literature regarding the effects of intra-articularly applied, fat-derived orthobiologics (FDO) in the treatment of primary knee osteoarthritis over a mid-term follow-up period. A systematic literature search was conducted on the online databases of Scopus, PubMed, Ovid MEDLINE, and Cochrane Library. Studies investigating intra-articularly applied FDO with a minimum number of 10 knee osteoarthritis patients, a follow-up period of at least 2 years, and at least 1 reported functional parameter (pain level or Patient-Reported Outcome Measures) were included. Exclusion criteria encompassed focal chondral defects and techniques including additional arthroscopic bone marrow stimulation. In 28 of 29 studies, FDO showed a subjective improvement in symptoms (pain and Patient-Reported Outcome Measures) up to a maximum follow-up of 7.2 years. Radiographic cartilage regeneration up to 3 years postoperatively, as well as macroscopic cartilage regeneration investigated via second-look arthroscopy, may corroborate the favorable clinical findings in patients with knee osteoarthritis. The methodological heterogeneity in FDO treatments leads to variations in cell composition and represents a limitation in the current state of knowledge. However, this systematic review suggests that FDO injection leads to beneficial mid-term results including symptom reduction and preservation of the affected joint in knee osteoarthritis patients.

Hard shell, soft core? Multi-disciplinary and multi-national insights into mental toughness among surgeons.

Background: With the prevalence of burnout among surgeons posing a significant threat to healthcare outcomes, the mental toughness of medical professionals has come to the fore. Mental toughness is pivotal for surgical performance and patient safety, yet research into its dynamics within a global and multi-specialty context remains scarce. This study aims to elucidate the factors contributing to mental toughness among surgeons and to understand how it correlates with surgical outcomes and personal well-being. Methods: Utilizing a cross-sectional design, this study surveyed 104 surgeons from English and German-speaking countries using the Mental Toughness Questionnaire (MTQ-18) along with additional queries about their surgical practice and general life satisfaction. Descriptive and inferential statistical analyses were applied to investigate the variations in mental toughness across different surgical domains and its correlation with professional and personal factors. Results: The study found a statistically significant higher level of mental toughness in micro-surgeons compared to macro-surgeons and a positive correlation between mental toughness and surgeons' intent to continue their careers. A strong association was also observed between general life satisfaction and mental toughness. No significant correlations were found between the application of psychological skills and mental toughness. Conclusion: Mental toughness varies significantly among surgeons from different specialties and is influenced by professional dedication and personal life satisfaction. These findings suggest the need for targeted interventions to foster mental toughness in the surgical community, potentially enhancing surgical performance and reducing burnout. Future research should continue to explore these correlations, with an emphasis on longitudinal data and the development of resilience-building programs.

Therapist versus Machine-Immediate Effects of Manual versus Mechanical Lymphatic Drainage in Patients with Secondary Lymphedema.

Background: Complex decongestive therapy (CDT) is the standard and basic therapy for lymphedema. The central component of CDT is manual lymphatic drainage (MLD). In addition to CDT, other measures such as intermittent pneumatic compression therapy (IPCT) (active compression machine therapy) are available. In this prospective research study, the objective and subjective effects of MLD and IPCT on lymphedema of the lower extremity were investigated and both therapies were directly compared. Furthermore, the patients' body mass index (BMI) and stage of lymphedema were tested for their effect on the respective therapy. Methods: Patients participating in the study received both therapies (MLD and IPCT) on the same lymphedema-affected limb at an interval of two days. The objective volumetric therapy effect was measured by the digital volume measurement of the affected limb. The subjective effects of the therapies were measured using two specially designed questionnaires. Results: A total of 40 patients were included in the study. There was no significant difference in the volume differences between the interventions, BMI categories, lymphedema, or treatment order regarding the immediate and two-day effect. Conclusions: No significant difference was found in the subjective or objective therapy efficacy of the two methods. Intermittent pneumatic compression therapy is considered a comparable therapeutic procedure when properly indicated.

Negative Pressure Wound Therapy-A Vacuum-Mediated Positive Pressure Wound Therapy and a Closer Look at the Role of the Laser Doppler.

Background: Negative pressure wound therapy (NPWT) is an intensely investigated topic, but its mechanism of action accounts for one of the least understood ones in the area of wound healing. Apart from a misleading nomenclature, by far the most used diagnostic tool to investigate NPWT, the laser Doppler, also has its weaknesses regarding the detection of changes in blood flow and velocity. The aim of the present study is to explain laser Doppler readings within the context of NPWT influence. Methods: The cutaneous microcirculation beneath an NPWT system of 10 healthy volunteers was assessed using two different laser Dopplers (O2C/Rad-97®). This was combined with an in vitro experiment simulating the compressing and displacing forces of NPWT on the arterial and venous system. Results: Using the O2C, a baseline value of 194 and 70 arbitrary units was measured for the flow and relative hemoglobin, respectively. There was an increase in flow to 230 arbitrary units (p = 0.09) when the NPWT device was switched on. No change was seen in the relative hemoglobin (p = 0.77). With the Rad-97®, a baseline of 92.91% and 0.17% was measured for the saturation and perfusion index, respectively. No significant change in saturation was noted during the NPWT treatment phase, but the perfusion index increased to 0.32% (p = 0.04). Applying NPWT compared to the arteriovenous-vessel model resulted in a 28 mm and 10 mm increase in the venous and arterial water column, respectively. Conclusions: We suspect the vacuum-mediated positive pressure of the NPWT results in a differential displacement of the venous and arterial blood column, with stronger displacement of the venous side. This ratio may explain the increased perfusion index of the laser Doppler. Our in vitro setup supports this finding as compressive forces on the bottom of two water columns within a manometer with different resistances results in unequal displacement.

The Triple Adipose-Derived Stem Cell Exosome Technology as a Potential Tool for Treating Triple-Negative Breast Cancer.

BACKGROUND: Extracellular vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties and clinical and therapeutical applications. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates cancer's growth and spread. METHODS: The most significant PubMed literature about extracellular vesicles and Adipose-Derived Stem Cell Exosomes and breast cancer was selected in order to report their biological properties and potential applications, in particular in treating triple-negative breast cancer. RESULTS: Adipose-Derived Stem Cell Exosomes represent a potential tool in targeting triple-negative breast cancer cells at three main levels: the tumor core, the tumor microenvironment and surrounding tissues, including metastases. CONCLUSIONS: The possibility of impacting triple-negative breast cancer cells with engineered Adipose-Derived Stem Cell Exosomes is real. The opportunity to translate our current in vitro analyses into a future in vivo scenario is even more challenging.

Digital Volumetric Measurements Based on 3D Scans of the Lower Limb: A Valid and Reproducible Method for Evaluation in Lymphedema Therapy.

BACKGROUND: Exact quantification of volumetric changes of the extremities is difficult and often error-prone. The aim of this study was to establish a standardized method based on 3-dimensional (3D) scans. Furthermore, this study tests the method in terms of reproducibility and evaluates volume changes after surgical therapy in patients suffering from lymphedema on the lower extremity. METHODS: 3D scans of the lower limb were performed with a mobile 3D scanner; "repeatability" and "interobserver reliability" of digital volumetry were tested. Furthermore, the method was applied on 31 patients suffering from chronic lymphedema. RESULTS: Calculations of repeatability of the volume based on 20 3D scans of the same lower leg showed a mean volume of 2.488 ± 0.011 liters (range: 2.470-2.510). The mean volume of the different examiners did not differ significantly (F(2,18) = 1.579, P = 0.233). The paired t-test showed a significant mean volume decrease of 375 mL (95% confidence interval = 245/505 mL) between pretreatment and post-treatment (t (30) = 5.892, P < 0.001). CONCLUSIONS: 3D volumetry is a noninvasive, easy, and quick method to assess volume changes of the lower leg. Other than the low costs, it is reproducible and precise and therefore ideal for evolution of therapy in lymphedema.

Recent advances in mesenchymal stem cell therapy for myocardial infarction.

Myocardial infarction refers to the ischemic necrosis of myocardium, characterized by a sharp reduction or interruption of blood flow in the coronary arteries due to the coronary artery occlusion, resulting in severe and prolonged ischemia in the corresponding myocardium and ultimately leading to ischemic necrosis of the myocardium. Given its high risk, it is considered as one of the most serious health threats today. In current clinical practice, multiple approaches have been explored to diminish myocardial oxygen consumption and alleviate symptoms, but notable success remains elusive. Accumulated clinical evidence has showed that the implantation of mesenchymal stem cell for treating myocardial infarction is both effective and safe. Nevertheless, there persists controversy and variability regarding the standardizing MSC transplantation protocols, optimizing dosage, and determining the most effective routes of administration. Addressing these remaining issues will pave the way of integration of MSCs as a feasible mainstream cardiac treatment.

Health Implications of Lipedema: Analysis of Patient Questionnaires and Population-Based Matched Controls.

We conducted a comparative study involving 39 female patients with lipedema and group-matched controls at a ratio of 1:5. The primary survey tool was the German Health Update (GEDA 2019/2020-EHIS) questionnaire, which was developed by the Robert Koch Institute (RKI), Germany. The secondary survey tool was the German Pain Questionnaire. The prevalence of hypertension (p = 0.041) and high blood lipids (p = 0.024) was lower in the lipedema group compared to the control group. General health and well-being indicators demonstrated lower overall health ratings (p < 0.001) and higher physiotherapy use in patients with lipedema (p = 0.016). Mental health assessment revealed higher depression prevalence and severity (p = 0.001), together with a lower number of close contacts (p = 0.032). Furthermore, patients with lipedema experienced higher levels of pain (p < 0.001) and more significant pain-related disability in daily activities (p < 0.001) than controls. Correlation analysis among patients with lipedema showed a positive correlation between pain severity and depressive symptoms (ρ = 0.612, p < 0.001) and a moderate positive correlation with impaired health-related quality of life (ρ = 0.418, p = 0.010). In summary, our findings highlight significant differences in health and well-being between patients with lipedema and matched controls, especially in overall, metabolic, and mental health, as well as pain perception. The findings emphasize the need for a validated lipedema-specific questionnaire and a multidisciplinary treatment approach with a combination of physical therapies, lifestyle adjustments, and psychological strategies.

Exosomes from Adipose-Tissue-Derived Stem Cells Induce Proapoptotic Gene Expression in Breast Tumor Cell Line.

Lipofilling is an option for breast reconstruction after tumor resection to avoid the complications of an implant-based reconstruction. Although some concerns exist regarding the oncological safety of tissue rich in mesenchymal stem cells with their proangiogenic and proliferation-supportive properties, there are also reports that adipose-tissue-derived stem cells can exhibit antitumoral properties. We isolated primary adipose-tissue-derived stem cells. Both conditioned medium and exosomes were harvested from the cell culture and used to treat the breast cancer cell line MCF-7. Cell viability, cytotoxicity, and gene expression of MCF-7 cells in response to the indirect co-culture were evaluated. MCF-7 cells incubated with exosomes from adipose-tissue-derived stem cells show reduced cell viability in comparison to MCF-7 cells incubated with adipose-tissue-derived stem-cell-conditioned medium. Expression of proapoptotic genes was upregulated, and expression of antiapoptotic genes was downregulated. The debate about the oncological safety of autologous fat grafting after tumor resection continues. Here, we show that exosomes from adipose-tissue-derived stem cells exhibit some antitumoral properties on breast cancer cell line MCF-7.

"Utility of Smartphone-based Three-dimensional Surface Imaging for Digital Facial Anthropometry".

Background: The utilization of three-dimensional (3D) surface imaging for facial anthropometry is a significant asset for patients undergoing maxillofacial surgery. Notably, there have been recent advancements in smartphone technology that enable 3D surface imaging.In this study, anthropometric assessments of the face were performed using a smartphone and a sophisticated 3D surface imaging system. Methods: 30 healthy volunteers (15 females and 15 males) were included in the study. An iPhone 14 Pro (Apple Inc., USA) using the application 3D Scanner App (Laan Consulting Corp., USA) and the Vectra M5 (Canfield Scientific, USA) were employed to create 3D surface models. For each participant, 19 anthropometric measurements were conducted on the 3D surface models. Subsequently, the anthropometric measurements generated by the two approaches were compared. The statistical techniques employed included the paired t-test, paired Wilcoxon signed-rank test, Bland-Altman analysis, and calculation of the intraclass correlation coefficient (ICC). Results: All measurements showed excellent agreement between smartphone-based and Vectra M5-based measurements (ICC between 0.85 and 0.97). Statistical analysis revealed no statistically significant differences in the central tendencies for 17 of the 19 linear measurements. Despite the excellent agreement found, Bland-Altman analysis revealed that the 95% limits of agreement between the two methods exceeded ±3 mm for the majority of measurements. Conclusion: Digital facial anthropometry using smartphones can serve as a valuable supplementary tool for surgeons, enhancing their communication with patients. However, the proposed data suggest that digital facial anthropometry using smartphones may not yet be suitable for certain diagnostic purposes that require high accuracy.

The effector program of human CD8 T cells supports tissue remodeling.

CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity but also promoted tissue remodeling. Activated CD8 T cells could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial cells for enhanced regeneration potential. Blocking the EGFR or the effector cytokines IFN-γ and TNF could inhibit tissue remodeling. This regenerative program enhanced tumor spheroid and stem cell-mediated organoid growth. Using single-cell gene expression analysis, we identified an AREG+, tissue-resident CD8 T cell population in skin and adipose tissue from patients undergoing abdominal wall or abdominoplasty surgery. These tissue-resident CD8 T cells showed a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. These findings may help to understand the complex CD8 biology in tumors and could become relevant for the design of therapeutic T cell products.

Pure Wisdom or Potemkin Villages? A Comparison of ChatGPT 3.5 and ChatGPT 4 on USMLE Step 3 Style Questions: Quantitative Analysis.

BACKGROUND: The United States Medical Licensing Examination (USMLE) has been critical in medical education since 1992, testing various aspects of a medical student's knowledge and skills through different steps, based on their training level. Artificial intelligence (AI) tools, including chatbots like ChatGPT, are emerging technologies with potential applications in medicine. However, comprehensive studies analyzing ChatGPT's performance on USMLE Step 3 in large-scale scenarios and comparing different versions of ChatGPT are limited. OBJECTIVE: This paper aimed to analyze ChatGPT's performance on USMLE Step 3 practice test questions to better elucidate the strengths and weaknesses of AI use in medical education and deduce evidence-based strategies to counteract AI cheating. METHODS: A total of 2069 USMLE Step 3 practice questions were extracted from the AMBOSS study platform. After including 229 image-based questions, a total of 1840 text-based questions were further categorized and entered into ChatGPT 3.5, while a subset of 229 questions were entered into ChatGPT 4. Responses were recorded, and the accuracy of ChatGPT answers as well as its performance in different test question categories and for different difficulty levels were compared between both versions. RESULTS: Overall, ChatGPT 4 demonstrated a statistically significant superior performance compared to ChatGPT 3.5, achieving an accuracy of 84.7% (194/229) and 56.9% (1047/1840), respectively. A noteworthy correlation was observed between the length of test questions and the performance of ChatGPT 3.5 (ρ=-0.069; P=.003), which was absent in ChatGPT 4 (P=.87). Additionally, the difficulty of test questions, as categorized by AMBOSS hammer ratings, showed a statistically significant correlation with performance for both ChatGPT versions, with ρ=-0.289 for ChatGPT 3.5 and ρ=-0.344 for ChatGPT 4. ChatGPT 4 surpassed ChatGPT 3.5 in all levels of test question difficulty, except for the 2 highest difficulty tiers (4 and 5 hammers), where statistical significance was not reached. CONCLUSIONS: In this study, ChatGPT 4 demonstrated remarkable proficiency in taking the USMLE Step 3, with an accuracy rate of 84.7% (194/229), outshining ChatGPT 3.5 with an accuracy rate of 56.9% (1047/1840). Although ChatGPT 4 performed exceptionally, it encountered difficulties in questions requiring the application of theoretical concepts, particularly in cardiology and neurology. These insights are pivotal for the development of examination strategies that are resilient to AI and underline the promising role of AI in the realm of medical education and diagnostics.