Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols. Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation. The systematic review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events). This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design. This study was funded in part by Italian Ministry of Health-Current researchIRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.

Sepsis is a complex syndrome characterized by physiological, pathological, and biochemical abnormalities induced by infection, with up to 70% of patients experiencing coagulation alterations, ranging from subclinical coagulopathy to disseminated intravascular coagulation (DIC). The multifactorial nature of sepsis-related coagulopathy and the limitations of standard diagnostic parameters, such as platelet count and traditional coagulation tests, complicate its definition and management. Assessing coagulopathy related to sepsis presents significant challenges due to current definitions primarily focusing on diagnosing advanced stages of coagulation dysfunction, thereby overlooking the dynamic and evolving nature of the condition. Viscoelastic hemostatic assays (VHAs) have emerged as valuable tools in this context, offering real-time insights into clot formation, stabilization, and lysis by integrating both plasma and cellular contributions to coagulation. Data from clinical studies suggest that early stages of sepsis coagulopathy are characterized by hypercoagulability, while advanced stages may lead to hypocoagulability and DIC. Moreover, specific point-of-care assays can evaluate platelet performance in the clotting mechanism and potentially help the diagnosis of platelet dysfunction in sepsis. Additionally, the phenomenon of fibrinolysis inhibition contributes to the persistence of fibrin clots, promoting tissue ischemia and multiorgan dysfunction. Modified VHAs appear promising for detecting fibrinolysis impairment, which is associated with poorer outcomes, but the standardization of results is still a work in progress. Incorporating VHAs data into treatment strategies could lead to more targeted therapies, potentially improving outcomes in septic patients by addressing both hypercoagulable and hypocoagulable states, as well as fibrinolysis abnormalities. ^* These authors contributed equally to this article. Article published online: 24 May 2025 © 2025. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

Cardiac arrest, one of the leading causes of death, accounts for numerous clinical studies published each year. This review summarizes the findings of all the randomized controlled clinical trials (RCT) on cardiac arrest published in the year 2022. The RCTs are presented according to the following categories: out-of- and in-hospital cardiac arrest (OHCA, IHCA) and post-cardiac arrest care. Interestingly, more than 80% of the RCTs encompassed advanced life support and post-cardiac arrest care, while no studies focused on the treatment of IHCA, except for one that, however, explored the temperature control after resuscitation in this population. Surprisingly, 9 out of 11 RCTs led to neutral results demonstrating equivalency between the newly tested interventions compared to current practice. One trial was negative, showing that oxygen titration in the immediate pre-hospital post-resuscitation period decreased survival compared to a more liberal approach. One RCT was positive and introduced new defibrillation strategies for refractory cardiac arrest. Overall, data from the 2022 RCTs discussed here provide a solid basis to generate new hypotheses to be tested in future clinical studies.

The causes of cardiac arrest are extremely heterogeneous. Among these, both hypokalemia and hypocalcemia are known reversible factors that can lead to cardiac arrest. In this report, we present a unique case report of a patient with previously undiagnosed coeliac disease who experienced cardiac arrest due a combination of hypokalemia and hypocalcemia resulting from malabsorption. A 66-year-old male presented to the emergency department with symptoms of malaise, weakness, weight loss, and persistent diarrhea. The patient exhibited characteristic signs of hypokalemia and hypocalcemia, including fasciculations, weakness, and swelling. An electrocardiogram showed a normal rhythm, and blood tests confirmed the electrolyte imbalances. Despite initial treatment, the patient experienced sudden cardiac arrest. Prompt resuscitation efforts were successful in restoring spontaneous circulation. However, recurrent episodes of ventricular arrhythmias and cardiac arrest occurred. Large doses of intravenous potassium chloride, in conjunction with magnesium, were needed prior to restore electrolyte balance. The concomitant severe hypocalcemia required caution calcium supplementation, to avoid further decreases in serum potassium levels. Appropriate ion replacements ultimately led to successful resuscitation with good functional recovery. During the hospital stay, the patient was diagnosed with coeliac disease. This case is noteworthy for its uniqueness, as there are no documented instances in the scientific literature linking cardiac arrest directly to coeliac disease. It is important to emphasize the need for investigating potential reversible causes of cardiac arrest, such as hypokalemia and hypocalcemia, and implementing appropriate interventions to address these factors.