Durability of response to immune checkpoint blockade following treatment discontinuation and efficacy of rechallenge in advanced Merkel cell carcinoma.

BACKGROUND: Advanced Merkel cell carcinoma (MCC) has a high response rate to immune checkpoint blockade (ICB) therapy, but the durability of responses once treatment is discontinued remains unclear. We therefore reviewed the long-term outcomes of advanced patients with MCC who discontinued ICB treatment after achieving favorable initial response. METHODS: We performed a retrospective review of advanced patients with MCC treated at a single high-volume referral center, including all patients who received at least one dose of anti-programmed death receptor 1 (ligand) monotherapy for unresectable or metastatic disease, achieved stable disease (SD) or better, and discontinued treatment for a reason other than disease progression. RESULTS: Of 195 advanced patients with MCC treated with ICB, we identified 45 who met the study criteria. Of these, 21 (46.6%) had a complete response (CR) to initial ICB treatment, 23 (51.1%) a partial response and 1 (2.2%) SD. 25 (55.6%) patients discontinued ICB electively and 20 (44.4%) discontinued due to toxicity. In total, 21 of the 45 patients (46.6%) experienced disease progression at a median of 11.3 months (range 2.1-22.7 months) from ICB cessation. There was a lower rate of progression in patients who achieved CR versus non-CR (23.8% vs 66.7%, p=0.006) and a trend towards a lower rate in those who discontinued electively versus due to toxicity (36.0% vs 60.0%, p=0.14). There was a higher risk for progression in patients with viral positive MCC compared with viral negative MCC (75.0 vs 30.8%, p=0.02). 16 of the 21 patients who experienced progression were retreated subsequently with ICB therapy, including both single-agent rechallenge (12) and escalation to combination ICB (4). 11 of 15 evaluable ICB-retreated patients (73.3%) achieved an objective response. CONCLUSIONS: Patients with advanced MCC have a substantial risk of disease progression following treatment discontinuation despite initial favorable ICB response, particularly in those that achieve less than a CR. Most of these patients maintain sensitivity to retreatment with the same drug class. Virus-positive MCC may be a risk factor for post-discontinuation relapse, which should be validated in future studies.

Decoding medical educators' perceptions on generative artificial intelligence in medical education.

Generative AI (GenAI) is a disruptive technology likely to generate a major impact on faculty and learners in medical education. This work aims to measure the perception of GenAI among medical educators and to gain insights into its major advantages and concerns in medical education. A survey invitation was distributed to medical education faculty of colleges of allopathic and osteopathic medicine within a single university during the fall of 2023. The survey comprised 12 items, among those assessing the role of GenAI for students and educators, the need to modify teaching approaches, GenAI's perceived advantages, applications of GenAI in the educational context, and the concerns, challenges, and trustworthiness associated with GenAI. Responses were obtained from 48 faculty. They showed a positive attitude toward GenAI and disagreed on GenAI having a very negative effect on either the students' or faculty's educational experience. Eighty-five percent of our medical schools' faculty responded to had heard about GenAI, while 42% had not used it at all. Generating text (33%), automating repetitive tasks (19%), and creating multimedia content (17%) were some of the common utilizations of GenAI by school faculty. The majority agreed that GenAI is likely to change its role as an educator. A perceived advantage of GenAI in conducting more effective background research was reported by 54% of faculty. The greatest perceived strengths of GenAI were the ability to conduct more efficient research, task automation, and increased content accessibility. The faculty's major concerns were cheating in home assignments in assessment (97%), tendency for blunder and false information (95%), lack of context (86%), and removal of human interaction in important feedback processes (83%). The majority of the faculty agrees on the lack of guidelines for safe use of GenAI from both a governmental and an institutional policy. The main perceived challenges were cheating, the tendency of GenAI to make errors, and privacy concerns.The faculty recognized the potential impact of GenAI in medical education. Careful deliberation of the pros and cons of GenAI is needed for its effective integration into medical education. There is general agreement that plagiarism and lack of regulations are two major areas of concern. Consensus-based guidelines at the institutional and/or national level need to start to be implemented to govern the appropriate use of GenAI while maintaining ethics and transparency. Faculty responses reflect an optimistic and favorable outlook on GenAI's impact on student learning.

Topical Iron Chelator Therapy: Current Status and Future Prospects.

Systemic iron chelation therapy has long been used for iron overload, providing a role in returning iron levels to proper homeostatic concentrations. Recently, topical iron chelation therapy has emerged as a potential strategy for treating skin damage. This narrative review explores the current status and future prospects of topical iron chelation therapy for treating ultraviolet (UV) and non-UV skin damage, as well as its potential application in wound healing. The review was conducted through a literature search across PubMed, Web of Science, and EMBASE databases, spanning publications from 1990 to 2023. The selection of articles was focused on primary research studies, either experimental or clinical, that explored the implications and formulations of topical iron chelators used alone or in conjunction with another therapeutic agent. The search strategy employed a combination of terms, including "topical iron chelation", "topical deferoxamine", "UV", "wound healing", "skin inflammation", "radiation-induced fibrosis", and "skin cancer". Relevant studies, including methods, intervention strategies, measured outcomes, and findings, are summarized. The review also considered the potential challenges in translating research findings into clinical practice. Results indicate that topical iron chelators, such as deferoxamine, are effective in mitigating UV-induced skin damage, reducing tumorigenesis, and decreasing oxidative damage. In addition, the use of these agents in radiation-induced fibrosis has been shown to significantly increase skin elasticity and reduce dermal fibrosis. Several studies also highlight the use of topical iron chelators in difficult-to-treat chronic wounds, such as diabetic neuropathic ulcers and sickle cell ulcers. In conclusion, topical iron chelation therapy represents a novel and promising approach for skin protection and wound healing. Its potential makes it a promising area of future research.

Compartment Syndrome Secondary to Calcium Gluconate Extravasation.

This case report highlights a rare yet severe complication of calcium gluconate extravasation, namely, compartment syndrome. We present the case of an 86-year-old female who developed compartment syndrome following an extravasation of intravenously administered calcium gluconate for the management of hyperkalemia. Initially, mild erythema and edema were observed at the site of extravasation, which eventually progressed to severe pain, a reduction in the joint range of motion due to increased compartment pressure. Despite undergoing a series of fasciotomies, the patient's condition did not improve, and extensive tissue necrosis and gangrene necessitated amputation. This case emphasizes that calcium gluconate extravasation can lead to life-threatening complications, such as compartment syndrome, underscoring the critical importance of employing proper infusion techniques.