Background: Photoimmunotherapy involves targeted delivery of photosensitizers via an antibody conjugate (i.e., photoimmunoconjugate, PIC) followed by light activation for selective tumor killing. The trade-off between PIC selectivity and PIC uptake is a major drawback limiting the efficacy of photoimmunotherapy. Despite ample evidence showing that photoimmunotherapy is most effective when combined with chemotherapy, the design of nanocarriers to co-deliver PICs and chemotherapy drugs remains an unmet need. To overcome these challenges, we developed a novel photoimmunoconjugate-nanoliposome (PIC-Nal) comprising of three clinically used agents: anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab (Cet), benzoporphyrin derivative (BPD) photosensitizer, and irinotecan (IRI) chemotherapy.Results: The BPD photosensitizers were first tethered to Cet at a molar ratio of 6:1 using carbodiimide chemistry to form PICs. Conjugation of PICs onto nanoliposome irinotecan (Nal–IRI) was facilitated by copper-free click chemistry, which resulted in monodispersed PIC–Nal–IRI with an average size of 158.8 ± 15.6 nm. PIC–Nal–IRI is highly selective against EGFR-overexpressing epithelial ovarian cancer cells with 2- to 6-fold less accumulation in low EGFR expressing cells. Successful coupling of PIC onto Nal–IRI enhanced PIC uptake and photoimmunotherapy efficacy by up to 30% in OVCAR-5 cells. Furthermore, PIC–Nal–IRI synergistically reduced cancer viability via a unique three-way mechanism (i.e., EGFR downregulation, mitochondrial depolarization, and DNA damage).Conclusion: It is increasingly evident that the most effective therapies for cancer will involve combination treatments that target multiple non-overlapping pathways while minimizing side effects. Nanotechnology combined with photochemistry provides a unique opportunity to simultaneously deliver and activate multiple drugs that target all major regions of a cancer cell—plasma membrane, cytoplasm, and nucleus. PIC–Nal–IRI offers a promising strategy to overcome the selectivity-uptake trade-off, improve photoimmunotherapy efficacy, and enable multi-tier cancer targeting. Controllable drug compartmentalization, easy surface modification, and high clinical relevance collectively make PIC–Nal–IRI extremely valuable and merits further investigations in living animals.

We read Gupta et al's manuscript on ChatGPT (OpenAI; San Francisco, CA) with anticipation and excitement.¹ They built upon their previous article about utilizing ChatGPT to develop ideas for systematic reviews.^2,3 This iteration had the chatbot generate 10 specific and 10 general systematic reviews for 12 different cosmetic surgery ideas. This resulted in a total of 240 systematic reviews designed for investigation purposes, and Gupta et al set out to determine their true novelty using popular search engines. The novelty was higher for the specific prompting scheme than for the general (75% specific vs 35% general).

The rise of artificial intelligence (AI) has revolutionized multiple disciplines within the healthcare sector, having large-scale impact within diagnostics, medical education, and clinical research. The latest breakthrough within AI that has caught the attention of many is ChatGPT or GPT-3.5 (OpenAI, San Francisco, CA), a large language model (LLM) that was released.¹ ChatGPT is unique because it responds to inputs in a humanistic fashion, continuously learning from inputs and prior mistakes. These additional features, which enhance the abilities of ChatGPT, allow it to potentially be applied to other avenues including grant writing. We aimed to apply ChatGPT to grant writing, with the future implications of chatbots helping secure R01 and other application-based grants.

We read with interest the recently published Aesthetic Surgery Journal article on OpenAI's ChatGPT chatbot (OpenAI; San Francisco, CA).¹ Gupta and colleagues introduce a unique case of leveraging ChatGPT to write cosmetic surgery systematic reviews, and in this way generate novel ideas for research in areas that have not been investigated. We commend the authors for their innovative use of ChatGPT to address potential knowledge gaps in aesthetic surgery and the Aesthetic Surgery Journal for its receptiveness to such an important article. However, we want to highlight some of the implications and limitations of ChatGPT.

Introduction: Patients with spontaneous intracranial hemorrhage (sICH) have high mortality and morbidity, which are associated with blood pressure variability. Additionally, blood pressure variability is associated with acute kidney injury (AKI) in critically ill patients, but its association with sICH patients in emergency departments (ED) is unclear. Our study investigated the association between blood pressure variability in the ED and the risk of developing AKI during sICH patients’ hospital stay.Methods: We retrospectively analyzed patients with sICH, including those with subarachnoid and intraparenchymal hemorrhage, who were admitted from any ED and who received an external ventricular drain at our academic center. Patients were identified by the International Classification of Diseases, Ninth Revision (ICD-9). Outcomes were the development of AKI, mortality, and being discharged home. We performed multivariable logistic regressions to measure the association of clinical factors and interventions with outcomes.Results: We analyzed the records of 259 patients: 71 (27%) patients developed AKI, and 59 (23%) patients died. Mean age (± standard deviation [SD]) was 58 (14) years, and 150 (58%) were female. Patients with AKI had significantly higher blood pressure variability than patients without AKI. Each millimeter of mercury increment in one component of blood pressure variability, SD in systolic blood pressure (SBPSD), was significantly associated with 2% increased likelihood of developing AKI (odds ratio [OR] 1.02, 95% confidence interval [CI], 1.005-1.03, p = 0.007). Initiating nicardipine infusion in the ED (OR 0.35, 95% CI, 0.15-0.77, p = 0.01) was associated with lower odds of in-hospital mortality. No ED interventions or blood pressure variability components were associated with patients’ likelihood to be discharged home.Conclusion: Our study suggests that greater SBPSD during patients’ ED stay is associated with higher likelihood of AKI, while starting nicardipine infusion is associated with lower odds of in-hospital mortality. Further studies about interventions and outcomes of patients with sICH in the ED are needed to confirm our observations.