Late Onset of Primary Hemophagocytic Lymphohistiocytosis (HLH) with a Novel Constellation of Compound Heterozygosity Involving Two Missense Variants in the PRF1 Gene.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but in most cases life-threatening immune-mediated disease of the hematopoietic system frequently associated with hematologic neoplasms. Here, we report on a case in which we detected a novel constellation of two missense variants affecting the PRF1 gene, leading to de novo primary HLH. Diagnostics included a comprehensive clinical work-up and standard methods of hematopathology as well as extended molecular genomics based on polymerase chain reaction (PCR) reactions and the calculation of three-dimensional molecule reconstructions of PRF1. Subsequently, a comprehensive review of the literature was performed, which showed that this compound heterozygosity has not been previously described. The patient was a 20-year-old female. Molecular diagnostics revealed two heterozygous missense variants in the PRF1 gene (A91V and R104C) on exon 2. Apart from the finding of two inconclusive genetic variants, all clinical criteria defined by the HLH study group of Histiocyte Society were met at initial presentation. The final diagnosis was made in cooperation with the Consortium of German HLH-reference centers. Here, chemotherapy did not lead to sufficient sustained disease control. Therefore, the decision for allogenic hematopoietic stem cell transplantation (alloHSCT) was made. Hitherto, the duration of response was 6 months. Due to severe and unmanageable hepatic graft-versus-host disease (GvHD), the patient died. We report on a novel constellation of a compound heterozygosity containing two missense variants on exon 2 of the PRF1 gene. To the authors' best knowledge, this is the first presentation of a primary HLH case harboring this genomic constellation with late-onset clinical manifestation.

[Significance of natural language processing and chat-based generative language models]. / Stellenwert von Natural Language Processing und chatbasierten Generative Language Models.

BACKGROUND: Natural language processing (NLP) has experienced significant growth in recent years and shows potential for broad impacts in scientific research and clinical practice. OBJECTIVE: This study comprises an exploration of the role of NLP in scientific research and its subsequent effects on traditional publication practices, as well as an evaluation of the opportunities and challenges offered by large language models (LLM) and a reflection on necessary paradigm shifts in research culture. MATERIALS AND METHODS: Current LLMs, such as ChatGPT, and their potential applications were compared and assessed. An analysis of the literature and case studies on the integration of LLMs into scientific and clinical practice was conducted. RESULTS AND CONCLUSION: LLMs provide enhanced access to and processing capabilities of text-based information and represent a vast potential for (medical) research as well as daily clinical practice. Chat-based LLMs enable efficient completion of often time-consuming tasks, but due to their tendency for hallucinations, have a significant limitation. Current developments require critical examination and a paradigm shift to fully exploit the benefits of LLMs and minimize potential risks.

[Artificial intelligence: How will ChatGPT and other AI applications change our everyday medical practice?] / Künstliche Intelligenz: Wie werden ChatGPT und andere KI-Anwendungen unseren ärztlichen Alltag verändern?

BACKGROUND: With the free provision of the chat robot "ChatGPT" by the company OpenAI in November 2022, an application of artificial intelligence (AI) became tangible for everyone. OBJECTIVES: An explanation of the basic functionality of large language models (LLM) is given, followed by a presentation of application options of ChatGPT in medicine, and an outlook and discussion of possible dangers of AI applications. METHODS: Problem solving with ChatGPT using concrete examples. Analysis and discussion of the available scientific literature. RESULTS: There has been a significant increase in the use of AI applications in scientific work, especially in scientific writing. Wide application of LLM in writing medical documentation is conceivable. Technical functionality allows the use of AI applications as a diagnostic support system. There is a risk of spreading and entrenching inaccuracies and bias through application of LLM. Regulation of this new technology is pending. CONCLUSION: AI applications such as ChatGPT have the potential to permanently change everyday medical practice. An examination of this technology and evaluation of opportunities and risks is warranted.

Assessing the weak links - Necessity and impact of regional cardiac arrest awareness campaigns for laypersons.

Introduction: Public knowledge of out-of-hospital cardiac arrest (OHCA), and initiation of basic life support (BLS) is crucial to increase survival in OHCA. Methods: The study analysed the knowledge and willingness to perform BLS of laypersons passing an AED at a public train station. Interviewees were recruited at two time points before and after a four year-long structured regional awareness campaign, which focused on call, compress, shock in a mid-size European city (270,000 inhabitants). Complete BLS was defined as multiple responses for call for help; initiation of chest compressions; and usage of an AED, without mentioning recovery position. Minimal BLS was defined as call for help and initiation of chest compressions. Results: A total of 784 persons were interviewed, 257 at baseline and 527 post-campaign. Confronted with a fictional OHCA, at baseline 8.5% of the interviewees spontaneously mentioned actions for complete BLS and 17.9% post-campaign (p = 0.009). An even larger increase in knowledge was seen in minimal BLS (34.6% vs 60.6%, p < 0.001). Conclusion: After a regional cardiac arrest awareness campaign, we found an increase in knowledge of BLS actions in the lay public. However, our investigation revealed severe gaps in BLS knowledge, possibly resulting in weak first links of the chain of survival.

Infective endocarditis - A review of current therapy and future challenges.

Etiological, microbiological and epidemiological factors changed over time, but mortality rates remain high in infective endocarditis (IE). Healthcare-associated IE is nowadays responsible for a significant proportion of cases due to increasing numbers of cardiac devices. Cardiac implantable electronic devices, transcatheter aortic valve replacement, and percutaneous valve repair are meanwhile used, especially in old and sick patients. In suspected IE modified Duke criteria, integrating clinical results, imaging, and biomarkers are traditionally applied. Newer imaging technologies such as multi-slice computed tomography, photon-emission computed tomography, and magnetic resonance imaging might add value to conventional echocardiography in diagnosis and management of IE. Treatment consists of long-term antibiotic therapy, infectiological source control and/or cardiac surgery. Recently, antibiotic parenteral outpatient regimens and partial oral treatment strategies were shown to shorten hospital stays in patients suffering from IE. However, it remains unclear how to best select patients for partial oral therapy. This review describes new trends in diagnosing, imaging, and treating IE in a changing patient collective with particular focus on patients with implantable cardiac devices.