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Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, presenting a persisting global health burden. Neutrophils have a double-edged role in tumor progression exhibiting both pro-tumor and anti-tumor functions. CD71, also known as transferrin receptor 1, performs a critical role in cellular iron uptake and is highly expressed on proliferating cells, and especially on activated immune cells. CD71 is known to be elevated in various types of solid cancers and is associated with poor prognosis, however, the expression of CD71 on neutrophils in PDAC and its potential clinical impact is still unknown. Therefore, we analyzed CD71 on circulating neutrophils in PDAC and clinical control patients and found a significant increased expression in PDAC patients. High expression of CD71 on neutrophils in PDAC patients was associated with reduced outcome compared to low expression. CD71 on neutrophils correlated positively with the levels of proinflammatory cytokines IL-6, IFN-γ, and growth factor ligands CD40-L, and BAFF in plasma of PDAC patients. Finally, we have demonstrated that high expression of CD71 on neutrophils was also associated with an increased expression of CD39 and CD25 on circulating T-cells. Based on our findings, we hypothesize that CD71 on neutrophils is associated with tumor progression in PDAC. Further studies are required to investigate the distinct functionality of CD71 expressing neutrophils and their potential clinical application.

Abstract Background With advancements in burn treatment and intensive care leading to decreased mortality rates, a growing cohort of burn survivors is emerging. These individuals may be susceptible to frailty, characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging, which significantly complicates their recovery process. To date, no study has investigated burns as a potential risk factor for frailty. This study aimed to determine the short-term prevalence of frailty among burn survivors’ months after injury and compare it with that of the general population. Methods A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury (RE-ENERGIZE) trial, an international randomized-controlled trial involving 1200 burn injury patients with partial- or full-thickness burns. Participants who did not complete the 36-Item Short Form Health Survey (SF-36) questionnaire were excluded. Data for the general population were obtained from the 2022 National Health Interview Survey (NHIS). Frailty was assessed using the FRAIL (Fatigue, Resistance, Ambulation, Illness, Loss of weight) scale. Due to lack of data on loss of weight, for the purposes of this study, malnutrition was used as the fifth variable. Illness and malnutrition were based on admission data, while fatigue, resistance, and ambulation were determined from post-discharge responses to the SF-36. The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status. Within the burn group, patients were divided into different subgroups based on their frailty status, and the differences in their (instrumental) activities of daily living (iADL and ADL) were compared. A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL. Results Out of the 1200 burn patients involved in the study, 600 completed the required questionnaires [follow-up time: (5.5 ± 2.3) months] and were matched to 1200 adults from the general population in the U.S. In comparison to the general population, burn patients exhibited a significantly higher likelihood of being pre-frail (42.3% vs. 19.8%, P

Abstract 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

Abstract Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues, including the skeletal and immune systems. Recent studies have elucidated the intricate bidirectional interactions between these two systems. In this review, we provide a comprehensive synthesis of molecular mechanisms of cell ageing. We further discuss how age-related skeletal changes influence the immune system and the consequent impact of immune system alterations on the skeletal system. Finally, we highlight the clinical implications of these findings and propose potential strategies to promote healthy ageing and reduce pathologic deterioration of both the skeletal and immune systems.

Abstract Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.

(1) Background: As the field of artificial intelligence (AI) evolves, tools like ChatGPT are increasingly integrated into various domains of medicine, including medical education and research. Given the critical nature of medicine, it is of paramount importance that AI tools offer a high degree of reliability in the information they provide. (2) Methods: A total of n = 450 medical examination questions were manually entered into ChatGPT thrice, each for ChatGPT 3.5 and ChatGPT 4. The responses were collected, and their accuracy and consistency were statistically analyzed throughout the series of entries. (3) Results: ChatGPT 4 displayed a statistically significantly improved accuracy with 85.7% compared to that of 57.7% of ChatGPT 3.5 (p < 0.001). Furthermore, ChatGPT 4 was more consistent, correctly answering 77.8% across all rounds, a significant increase from the 44.9% observed from ChatGPT 3.5 (p < 0.001). (4) Conclusions: The findings underscore the increased accuracy and dependability of ChatGPT 4 in the context of medical education and potential clinical decision making. Nonetheless, the research emphasizes the indispensable nature of human-delivered healthcare and the vital role of continuous assessment in leveraging AI in medicine.

Background:. This study aims to fill the gap in large-scale, registry-based assessments by examining postoperative outcomes across diverse races/ethnicities. The focus is on identifying disparities and comparing them with socioeconomic demographics. Methods:. In a registry-based cohort study using the 2008 to 2020 American College of Surgeons National Surgical Quality Improvement Program, we evaluated 24 postoperative outcomes through multivariable analysis, incorporating 28 preoperative risk factors. In a separate, independent analysis of the 2019 to 2020 National Health Interview Survey (NHIS) database, we examined sociodemographic racial/ethnic normative data. Results:. Among 7,504,734 American College of Surgeons National Surgical Improvement Database patients specifying race, 83.8% were White (WT), 11.8% Black or African American (B/AA), 3.3% Asian (AS), 0.7% American Indian or Alaska Native (AI/AN), 0.4% Native Hawaiian or Pacific Islander (NH/PI), 7.3% Hispanic. Reoperation trends reveal favorable outcomes for WT, AS, and NH/PI patients compared with B/AA and AI/AN patients. AI/AN patients exhibit higher rates of wound healing issues, while AS patients experience lower rates. AS and B/AA patients are more prone to transfusions, with B/AA patients showing elevated rates of pulmonary embolism, deep vein thrombosis, renal failure, and insufficiency. Disparities in discharge destinations exist. Hispanic patients fare better than non-WT Hispanic patients, contingent on race. Racial groups (excluding Hispanic patients) with superior surgical outcomes from the NSQIP analysis were found in the NHIS analysis to report higher wealth, better healthcare access, improved food security, greater functional and societal independence, and lower frailty. Conclusions:. Our study underscores racial disparities in surgical outcomes. Focused investigations into these complications could reveal underlying causes, informing healthcare policies to enhance surgical care universally.

Background:. The Plastic Surgery In-Service Training Examination (PSITE) remains a critical milestone in residency training. Successful preparation requires extensive studying during an individual’s residency. This study focuses on the capacity of Generative Pre-trained Transformer 4 (GPT-4) to generate PSITE practice questions. Methods:. GPT-4 was prompted to generate multiple choice questions for each PSITE section and provide answer choices with detailed rationale. Question composition via readability metrics were analyzed, along with quality. Descriptive statistics compared GPT-4 and the 2022 PSITE. Results:. The overall median Flesch–Kincaid reading ease for GPT-4-generated questions was 43.90 (versus 50.35 PSITE, P = 0.036). GPT-4 provided questions that contained significantly fewer mean sentences (1 versus 4), words (16 versus 56), and percentage of complex words (3 versus 13) than 2022 PSITE questions (P < 0.001). When evaluating GPT-4 generated questions for each examination section, the highest median Flesch–Kincaid reading ease was on the core surgical principles section (median: 63.30, interquartile range [54.45–68.28]) and the lowest was on the craniomaxillofacial section (median: 36.25, interquartile range [12.57–58.40]). Most readability metrics were higher for the 2022 PSITE compared with GPT-4 generated questions. Overall question quality was poor for the chatbot. Conclusions:. Our study found that GPT-4 can be adapted to generate practice questions for the 2022 PSITE, but its questions are of poor quality. The program can offer general explanations for both the correct and incorrect answer options but was observed to generate false information and poor-quality explanations. Although trainees should navigate with caution as the technology develops, GPT-4 has the potential to serve as an effective educational adjunct under the supervision of trained plastic surgeons.

Background:. Maintenance of functional independence is an important patient-centered outcome. As the evidence on loss of independence (LOI) in older patients undergoing plastic surgery is lacking, this study investigates the extent of LOI, identifying factors associated with LOI. Methods:. The 2021–2022 American College of Surgeons National Surgical Quality Improvement Program database was searched to identify patients (>65 years old) who underwent plastic surgery and provided data on their functional independence. The primary outcome was LOI on discharge. Data on perioperative factors, including patient characteristics and comorbidities, surgical details, and outcome measures such as operation time, length of hospital stay, surgical and medical complications, mortality, and discharge destination were extracted. Results:. Of 2112 patients who underwent plastic surgery, most were independent on discharge (n = 1838, 87%). A total of 163 patients lost their independence (LOI rate: 7.7%). Patients discharged as dependent were more likely to have experienced surgical and medical complications, and less likely to be discharged home (all

To date, little is known about the mechanisms of rejection in vascularized composite allotransplantation, particularly for antibody mediated rejection. Additionally, no clear guidelines exist for the diagnosis and management of antibody-mediated rejection in vascularized composite allotransplantation. A systematic review of electronic databases (Embase and PubMed) was conducted to evaluate the relationship of donor specific antibodies and C4d deposition in correlation with cellular rejection following hand and face transplantation reported by centers between 1998 and July 2023. We extracted data on serum donor specific antibodies at the time of biopsy proven rejection according to Banff classification and C4d staining of target tissues. Mann-Whitney U tests were performed to compare rejection grade between groups divided by status of C4d deposition and serum donor specific antibodies, and Fisher's Exact test was used to assess association between the two markers. This review adhered to PRISMA guidelines. A total of 26 patients (5 face, 21 hand) were identified and data on 90 acute rejection episodes with information on Banff grade, donor specific antibody status, and C4d deposition were available. Donor specific antibodies were found to be associated with higher rejection grade (p = 0.005). C4d was not found to be associated with higher rejection grade (p = 0.33). Finally, no significant association was found between concurrent status of the two markers (p = 0.23). These findings suggest that the presence of donor specifc antibodies may be associated with higher grades of acute cellular rejection following hand and face transplantation. More consistent reporting on rejection episodes is needed in order to better understand antibody-mediated rejection in vascularized composite allotransplantation.

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.

BackgroundThe search for an ideal bone substitute in reconstructive surgery has led to the exploration of various materials, with hydroxyapatite (HaP) emerging as a promising candidate due to its biocompatibility, osteoconductive properties, and structural similarity to human bone. Despite its potential, there is a paucity of data on the long-term safety and efficacy of HaP in facial skeletal reconstruction and augmentation.MethodsWe conducted a systematic review following PRISMA 2020 guidelines, searching PubMed/MEDLINE, Google Scholar, CENTRAL, and Web of Science databases for studies on hydroxyapatite facial implants in reconstruction and augmentation.ResultsOur search yielded 12 studies that met our inclusion criteria, encompassing 74 patients treated with HaP implants for various indications including facial fractures/defects, aesthetic facial balancing, and after tumor resection. The studies reported on outcomes such as implant integration, complications, aesthetic results, and patient satisfaction, with a general trend indicating positive outcomes for the use of HaP in facial reconstruction.ConclusionHydroxyapatite appears to be a viable and effective material for facial skeletal reconstruction and augmentation, offering benefits in terms of biocompatibility, osteoconductivity, and patient outcomes. However, limitations such as low mechanical strength and the need for further research on long-term safety and efficacy were identified. This review underscores the potential of HaP in craniofacial surgery while highlighting areas for future investigation.

Prairie voles are among a small group of mammals that display long-term social attachment between mating partners. Many pharmacological studies show that signaling via the oxytocin receptor (Oxtr) is critical for the display of social monogamy in these animals. We used CRISPR mutagenesis to generate three different Oxtr-null mutant prairie vole lines. Oxtr mutants displayed social attachment such that males and females showed a behavioral preference for their mating partners over a stranger of the opposite sex, even when assayed using different experimental setups. Mothers lacking Oxtr delivered viable pups, and parents displayed care for their young and raised them to the weanling stage. Together, our studies unexpectedly reveal that social attachment, parturition, and parental behavior can occur in the absence of Oxtr signaling in prairie voles.

Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, the discovery of neddylation, a new type of post-translational modification, has been found to regulate various crucial biological processes including cell metabolism and the cell cycle. Nevertheless, its capacity to control the healing of wounds in diabetic patients remains unknown. This study shows that MLN49224, a compound that inhibits neddylation at low concentrations, enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors. Moreover, it concurrently stimulates the growth, movement, and formation of blood vessel endothelial cells, leading to expedited healing of wounds in individuals with diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area. The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes, along with the polarization of macrophages towards the anti-inflammatory M2 phenotype. By loading M-NPs/MLN4924 into a hydrogel, the final formulation is able to meaningfully repair a diabetic wound, suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.

Abstract Lagophthalmos is the incomplete closure of the eyelids posing the risk of corneal ulceration and blindness. Lagophthalmos is a common symptom of various pathologies. We aimed to program a convolutional neural network to automatize lagophthalmos diagnosis. From June 2019 to May 2021, prospective data acquisition was performed on 30 patients seen at the Department of Plastic, Hand, and Reconstructive Surgery at the University Hospital Regensburg, Germany (IRB reference number: 20-2081-101). In addition, comparative data were gathered from 10 healthy patients as the control group. The training set comprised 826 images, while the validation and testing sets consisted of 91 patient images each. Validation accuracy was 97.8% over the span of 64 epochs. The model was trained for 17.3 min. For training and validation, an average loss of 0.304 and 0.358 and a final loss of 0.276 and 0.157 were noted. The testing accuracy was observed to be 93.41% with a loss of 0.221. This study proposes a novel application for rapid and reliable lagophthalmos diagnosis. Our CNN-based approach combines effective anti-overfitting strategies, short training times, and high accuracy levels. Ultimately, this tool carries high translational potential to facilitate the physician’s workflow and improve overall lagophthalmos patient care.