Optimization of an adeno-associated viral vector for epidermal keratinocytes in vitro and in vivo.

BACKGROUND: Local gene therapies, including in vivo genome editing, are highly anticipated for the treatment of genetic diseases in skin, especially the epidermis. While the adeno-associated virus (AAV) is a potent vector for in vivo gene delivery, the lack of efficient gene delivery methods has limited its clinical applications. OBJECTIVE: To optimize the AAV gene delivery system with higher gene delivery efficiency and specificity for epidermis and keratinocytes (KCs), using AAV capsid and promoter engineering technologies. METHODS: AAV variants with mutations in residues reported to be critical to determine the tropism of AAV2 for KCs were generated by site-directed mutagenesis of AAVDJ. The infection efficiency and specificity for KCs of these variants were compared with those of previously reported AAVs considered to be suitable for gene delivery to KCs in vitro and in vivo. Additionally, we generated an epidermis-specific promoter using the most recent short-core promoter and compared its specificity with existing promoters. RESULTS: A novel AAVDJ variant capsid termed AAVDJK2 was superior to the existing AAVs in terms of gene transduction efficiency and specificity for epidermis and KCs in vitro and in vivo. A novel tissue-specific promoter, termed the K14 SCP3 promoter, was superior to the existing promoters in terms of gene transduction efficiency and specificity for KCs. CONCLUSION: The combination of the AAVDJK2 capsid and K14 SCP3 promoter improves gene delivery to epidermis in vivo and KCs in vitro. The novel AAV system may benefit experimental research and development of new epidermis-targeted gene therapies.

Treatment Effectiveness and Recurrence of Extracranial Arteriovenous Malformations Following Surgical Operations: A 15-Year Retrospective Cohort Study.

BACKGROUND: At present, there is no golden standard for treatment of extracranial arteriovenous malformations (AVMs) and recurrence remains a major challenge with limited available evidence on the associated factors. This study aimed to evaluate the effectiveness of surgical treatment options, in terms of size reduction, symptoms, and early recurrence in patients treated surgically for AVMs. METHODS: A retrospective cohort study was conducted to evaluate patients with AVMs following surgical treatment in 2 centers from 2005 to 2020. Posttreatment lesion size and symptoms, as well as recurrence, were assessed. Multiple regression analysis was performed to identify factors associated with recurrence. RESULTS: Forty-four surgical treatment cases in 31 patients were assessed with a mean follow-up duration period of 67.9 ± 39.5 months. Treatment included total resection in 26 cases (59.1%) and partial resection 18 (40.9%), with free flap coverage used in 19 cases (43.2%). No acute exacerbation following treatment was observed in our cohort. Total resection significantly reduced posttreatment lesion size ( P < 0.001), symptoms ( P < 0.001), and recurrence (20.0%, P = 0.03). The recurrence rate was significantly higher after partial resection (73.7%, P = 0.03). Total resection was identified as an associated factor for significantly reduced AVM recurrence (odds ratio: 0.12; 95% confidence interval: 0.03, 0.52). However, the use of free flaps did not significantly reduce recurrence, post treatment size or improve AVM symptoms. CONCLUSIONS: Total resection is the optimal treatment for AVMs. Free flaps are useful in covering large defects but the regulative effect of free flap remains controversial.

Performance of artificial intelligence chatbots in interpreting clinical images of pressure injuries.

To evaluate the accuracy of AI chatbots in staging pressure injuries according to the National Pressure Injury Advisory Panel (NPIAP) Staging through clinical image interpretation, a cross-sectional design was conducted to assess five leading publicly available AI chatbots. As a result, three chatbots were unable to interpret the clinical images, whereas GPT-4 Turbo achieved a high accuracy rate (83.0%) in staging pressure injuries, notably outperforming BingAI Creative mode (24.0%) with statistical significance (p < 0.001). GPT-4 Turbo accurately identified Stages 1 (p < 0.001), 3 (p = 0.001), and 4 (p < 0.001) pressure injuries, and suspected deep tissue injuries (p < 0.001), while BingAI demonstrated significantly lower accuracy across all stages. The findings highlight the potential of AI chatbots, especially GPT-4 Turbo, in accurately diagnosing images and aiding the subsequent management of pressure injuries.

Blepharoptosis Consultation with Artificial Intelligence: Aesthetic Surgery Advice and Counseling from Chat Generative Pre-Trained Transformer (ChatGPT).

BACKGROUND: Chat generative pre-trained transformer (ChatGPT) is a publicly available extensive artificial intelligence (AI) language model that leverages deep learning to generate text that mimics human conversations. In this study, the performance of ChatGPT was assessed by offering insightful and precise answers to a series of fictional questions and emulating a preliminary consultation on blepharoplasty. METHODS: ChatGPT was posed with questions derived from a blepharoplasty checklist provided by the American Society of Plastic Surgeons. Board-certified plastic surgeons and non-medical staff members evaluated the responses for accuracy, informativeness, and accessibility. RESULTS: Nine questions were used in this study. Regarding informativeness, the average score given by board-certified plastic surgeons was significantly lower than that given by non-medical staff members (2.89 ± 0.72 vs 4.41 ± 0.71; p = 0.042). No statistically significant differences were observed in accuracy (p = 0.56) or accessibility (p = 0.11). CONCLUSIONS: Our results emphasize the effectiveness of ChatGPT in simulating doctor-patient conversations during blepharoplasty. Non-medical individuals found its responses more informative compared with the surgeons. Although limited in terms of specialized guidance, ChatGPT offers foundational surgical information. Further exploration is warranted to elucidate the broader role of AI in esthetic surgical consultations. LEVEL OF EVIDENCE V: Observational study under respected authorities. 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 the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Appropriateness of Artificial Intelligence Chatbots in Diabetic Foot Ulcer Management.

Type 2 diabetes is a significant global health concern. It often causes diabetic foot ulcers (DFUs), which affect millions of people and increase amputation and mortality rates. Despite existing guidelines, the complexity of DFU treatment makes clinical decisions challenging. Large language models such as chat generative pretrained transformer (ChatGPT), which are adept at natural language processing, have emerged as valuable resources in the medical field. However, concerns about the accuracy and reliability of the information they provide remain. We aimed to assess the accuracy of various artificial intelligence (AI) chatbots, including ChatGPT, in providing information on DFUs based on established guidelines. Seven AI chatbots were asked clinical questions (CQs) based on the DFU guidelines. Their responses were analyzed for accuracy in terms of answers to CQs, grade of recommendation, level of evidence, and agreement with the reference, including verification of the authenticity of the references provided by the chatbots. The AI chatbots showed a mean accuracy of 91.2% in answers to CQs, with discrepancies noted in grade of recommendation and level of evidence. Claude-2 outperformed other chatbots in the number of verified references (99.6%), whereas ChatGPT had the lowest rate of reference authenticity (66.3%). This study highlights the potential of AI chatbots as tools for disseminating medical information and demonstrates their high degree of accuracy in answering CQs related to DFUs. However, the variability in the accuracy of these chatbots and problems like AI hallucinations necessitate cautious use and further optimization for medical applications. This study underscores the evolving role of AI in healthcare and the importance of refining these technologies for effective use in clinical decision-making and patient education.

Generating Informed Consent Documents Related to Blepharoplasty Using ChatGPT.

PURPOSE: This study aimed to demonstrate the performance of the popular artificial intelligence (AI) language model, Chat Generative Pre-trained Transformer (ChatGPT) (OpenAI, San Francisco, CA, U.S.A.), in generating the informed consent (IC) document of blepharoplasty. METHODS: A total of 2 prompts were provided to ChatGPT to generate IC documents. Four board-certified plastic surgeons and 4 nonmedical staff members evaluated the AI-generated IC documents and the original IC document currently used in the clinical setting. They assessed these documents in terms of accuracy, informativeness, and accessibility. RESULTS: Among board-certified plastic surgeons, the initial AI-generated IC document scored significantly lower than the original IC document in accuracy ( p < 0.001), informativeness ( p = 0.005), and accessibility ( p = 0.021), while the revised AI-generated IC document scored lower compared with the original document in accuracy ( p = 0.03) and accessibility ( p = 0.021). Among nonmedical staff members, no statistical significance of 2 AI-generated IC documents was observed compared with the original document in terms of accuracy, informativeness, and accessibility. CONCLUSIONS: The results showed that current ChatGPT cannot be used as a distinct patient education resource. However, it has the potential to make better IC documents when improving the professional terminology. This AI technology will eventually transform ophthalmic plastic surgery healthcare systematics by enhancing patient education and decision-making via IC documents.

Analysis of Pharmaceutical Demand in the Region for Chronic Medicine Users Using National Health Insurance Data: Examination for Disaster Preparedness in Hakui City, Ishikawa Prefecture.

When large earthquakes occur over wide areas, in addition to damage to medical facilities, the disaster response capabilities of local governments are severely compromised. There is a very high possibility that the supply-demand balance of medicines will collapse within the disaster area, and that appropriate supplies of medicines will not be provided to disaster victims. Therefore, it is important to estimate in advance the quantity of pharmaceuticals that may be needed during disasters. In this study, the purpose is to clarify the quantity and quality of pharmaceuticals used by chronically ill patients by using Japanese National Health Insurance data regarding the issues mentioned above. The methodology used was to extract the status of pharmaceutical prescriptions based on receipt information from National Health Insurance data for Hakui, Ishikawa Prefecture, a small regional city in Japan, as the analysis target area. Through the analysis in this study, the quantity and quality of medicines supplied to chronically ill patients in Hakui, Ishikawa Prefecture, were clarified on a town-by-town basis.

Fungal-Type Terpene Synthases in Marchantia polymorpha Are Involved in Sesquiterpene Biosynthesis in Oil Body Cells.

The liverwort Marchantia polymorpha possesses oil bodies in idioblastic oil body cells scattered in its thallus. Oil bodies are subcellular organelles in which specific sesquiterpenes and bisbibenzyls are accumulated. Therefore, a specialized system for the biosynthesis and accumulation of these defense compounds specifically in oil bodies has been implied. A recent study on M. polymorpha genome sequencing revealed 10 genes that shared high similarities with fungal-type terpene synthases (TPSs). Eight of these fungal-type TPS-like genes in M. polymorpha (MpFTPSL1-6, -9 and -10) are located within a 376-kb stretch on chromosome 6 and share similarities of over 94% at the nucleotide level. Therefore, these genes have likely originated from recent gene duplication events. The expression of a subset of MpFTPSLs was induced under non-axenic growth on vermiculite, which increased the amounts of sesquiterpenes and number of oil bodies. The tdTomato fluorescent protein-based in-fusion reporter assay with MpFTPSL2 promoter revealed fluorescent signals specifically in oil body cells of the thallus, indicating that MpFTPSL2 functions in oil body cells. Recombinant MpFTPSL2 expression in Escherichia coli led to sesquiterpene synthesis from farnesyl pyrophosphate. Moreover, suppression of a subset of MpFTPSLs through RNA interference reduced sesquiterpene accumulation in thalli grown on vermiculite. Taken together, these results suggest that at least a subset of MpFTPSLs is involved in sesquiterpene synthesis in oil body cells.

Endoscopic open rhinoplasty enables a cosmetic approach for a rare case of intraosseous cavernous hemangioma in the nasal bone.

A rare case of intraosseous cavernous hemangioma was identified in the nasal root. Using a combination of endoscopic surgery and open rhinoplasty, an osteotomy was performed and resection of the hemangioma was successfully achieved with transcolumellar and infracartilaginous incisions and 2 stab incisions. No adverse side effects were observed after the procedure, no tumor recurrence was observed at the 16-month-postoperative follow-up. The preserved periosteum contributed to the osteogenesis and thus, a need for a reconstructive surgery was indicated. The favorable outcomes associated with this approach justify and authenticate the use of endoscopy-assisted open rhinoplasty in the treatment of intraosseous cavernous hemangiomas without leaving ventral surgical scarring.

Treating Pulsatile Exophthalmos in Child with Minimally Invasive Approach and Custom-made Titanium Mesh Plate.

Orbital roof fracture is a relatively rare trauma. In most cases, surgical intervention is not needed since the fracture is slight. However, invasive surgical procedures are inevitable once pulsatile exophthalmos occurs if vision impairment is to be avoided. We report our rare experience of orbital roof fracture in a child with pulsatile exophthalmos. Good reconstruction of the anterior cranial base was achieved using a custom-made titanium mesh and a minimally invasive approach. A 3-year-old girl who had been diagnosed with subdural hematoma, brain contusion, and fracture of the right orbital roof caused by facial bruising underwent emergent external decompression by coronal skin incision and a transcranial approach on the same day as the trauma. Cranioplasty using autologous frozen bone in the same approach was performed 103 days posttrauma, but this was followed by pulsatile exophthalmos. After recovering from critical stage, the girl was brought to our department for reconstruction of the anterior base. Risk of vision impairment was also one reason for reconstruction, but the neurosurgeon hesitated to approach the region using a coronal approach considering the possibility of infection in the frozen autologous bone. Through cross-team discussion, reconstruction using a subeyebrow incision was performed with a custom-made titanium mesh plate. Pulsatile exophthalmos completely disappeared. Pulsatile exophthalmos is a very rare but serious complication that carries a risk of vision impairment. By applying a custom-made titanium mesh plate, precise reconstruction was enabled with minimal invasiveness and low risk.