Vitamin K: a potential missing link in critical illness-a scoping review.

BACKGROUND: Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency, prevalent in critically ill ICU patients, impacts coagulation and increases the risk of bleeding and other complications. This review aims to elucidate the metabolism of vitamin K in the context of critical illness and identify a potential therapeutic approach. METHODS: In December 2023, a scoping review was conducted using the PRISMA Extension for Scoping Reviews. Literature was searched in PubMed, Embase, and Cochrane databases without restrictions. Inclusion criteria were studies on adult ICU patients discussing vitamin K deficiency and/or supplementation. RESULTS: A total of 1712 articles were screened, and 13 met the inclusion criteria. Vitamin K deficiency in ICU patients is linked to malnutrition, impaired absorption, antibiotic use, increased turnover, and genetic factors. Observational studies show higher PIVKA-II levels in ICU patients, indicating reduced vitamin K status. Risk factors include inadequate intake, disrupted absorption, and increased physiological demands. Supplementation studies suggest vitamin K can improve status but not normalize it completely. Vitamin K deficiency may correlate with prolonged ICU stays, mechanical ventilation, and increased mortality. Factors such as genetic polymorphisms and disrupted microbiomes also contribute to deficiency, underscoring the need for individualized nutritional strategies and further research on optimal supplementation dosages and administration routes. CONCLUSIONS: Addressing vitamin K deficiency in ICU patients is crucial for mitigating risks associated with critical illness, yet optimal management strategies require further investigation. IMPACT RESEARCH: To the best of our knowledge, this review is the first to address the prevalence and progression of vitamin K deficiency in critically ill patients. It guides clinicians in diagnosing and managing vitamin K deficiency in intensive care and suggests practical strategies for supplementing vitamin K in critically ill patients. This review provides a comprehensive overview of the existing literature, and serves as a valuable resource for clinicians, researchers, and policymakers in critical care medicine.

Does vitamin B12 deficiency explain psychiatric symptoms in recreational nitrous oxide users? A narrative review.

Background Recreational use of nitrous oxide (N2O) is associated with many side effects, of which neurological complications are most common. Nitrous oxide abuse is also associated with psychiatric symptoms, but these have received less attention so far. Vitamin B12 deficiency may play a role in the development of these psychiatric symptoms.Aims To explore the relationship among the occurrence of recreational nitrous oxide-induced psychiatric symptoms, accompanying neurological symptoms, vitamin B12 status and choice of treatment.Methods A retrospective search for case reports was conducted across multiple databases (Pubmed, Embase, Web of Science, PsycINFO and CINAHL). Keywords included variants of "nitrous oxide", "case report" and "abuse". No restrictions to language or publication date were applied.Results The search retrieved 372 articles. A total of 25 case reports were included, representing 31 patients with psychiatric complications following nitrous oxide abuse. The most often reported symptoms were: hallucinations (n = 16), delusions (n = 11), and paranoia (n = 11). When neurological symptoms were present, patients were treated more frequently with vitamin B12 supplementation.Conclusions This review highlights the need to recognize that psychiatric symptoms may appear in association with nitrous oxide use. Approximately half of the cases that presented with nitrous oxide-induced psychiatric complaints did not show neurological symptoms, and their vitamin B12 concentration was often within the hospital's reference range. Psychiatrists and emergency physicians should be aware of isolated psychiatric symptoms caused by recreational nitrous oxide abuse. We suggest asking all patients with new psychiatric symptoms about nitrous oxide use and protocolizing the management of nitrous oxide-induced psychiatric symptoms.

Nicotine intoxication by e-cigarette liquids: a study of case reports and pathophysiology.

Background: Electronic cigarettes (e-cigarettes), the smokeless alternative to conventional tobacco cigarettes, have become increasingly popular. E-cigarettes vaporise e-liquid, a solution of highly concentrated nicotine, propylene glycol (PG) and vegetable glycerine (VG). With the popularity of e-cigarettes, e-liquid refills have become easily accessible and several cases of intoxication due to the ingestion of e-liquid have been reported. We provide an overview of these cases, their pathophysiology and patients' characteristics.Methods: We carried out a retrospective evaluation of the scientific literature reporting on cases of liquid nicotine intoxication, using the following inclusion criteria: (1) the article is or contains a case report, (2) describes an intoxication with e-liquid, (3) the substance contains nicotine, and (4) intake is oral, intravenous or subcutaneous.Results: We found 26 case reports describing a total of 31 patients who suffered from e-liquid intoxication. All intoxications up to the age of six were reported as unintentional, whereas nearly all cases from ages 13 to 53 were due to suicide attempts. The three most prevalent symptoms of e-liquid intoxication were tachycardia, altered mental status and vomiting. Eleven cases resulted in the death of the patient. In the survivors, the highest plasma concentration of nicotine was 800 µg L-1, while the lowest concentration in the non-survivors was 1600 µg L-1.Conclusions: There is a mismatch between the generally accepted lethal oral nicotine dose of 60 mg, resulting in approximately 180 µg L-1 plasma concentration, and the 4.4- to 8.9-fold higher lethal plasma concentrations we found in cases of e-liquid intoxication. In these severe intoxications, plasma cotinine concentration does not act as a more reliable indicator of nicotine intoxication than nicotine itself. The ages of the patients display a bimodal distribution. In patients above the age of 10, intoxication results mainly from suicide attempts rather than accidental ingestion. The role of PG and VG in e-liquid intoxications is remarkably unclear. However, the similarity across nicotine and PG toxicity symptoms leads us to believe a cumulative effect cannot be excluded.

Pituitary tumorigenesis targeted by the ovine follicle-stimulating hormone beta-subunit gene regulatory region in transgenic mice.

Targeted tumorigenesis in transgenic mice has been a powerful tool for the study of gene expression and oncogenesis, as well as for the production of differentiated immortal cell lines from rare cell types. Follicle-stimulating hormone (FSH) is secreted by the gonadotrope cells of the anterior pituitary gland and plays a pivotal role in mammalian reproduction. Here we have used the regulatory region of the ovine FSH beta gene to direct expression of the SV40 T antigen oncogene to gonadotrope cells in the pituitary of transgenic mice. Two of five transgenic mouse lines bearing this fusion gene rapidly developed pituitary tumors, with appearance of adenomatous foci as early as 6 weeks of age, resulting in death by 12 weeks of age in both genders. Histologic examination of tumor development over time revealed that increases in cell proliferation and dysplasia were accompanied by decreases in synthesis of pituitary hormones, indicating dedifferentiation of the pituitary cells. Histological features observed in these tumors were in agreement with this rapid transformation of cell phenotype. Tumors were multifocal in origin, and the most highly transformed cell types observed consisted of giant pale basophilic cells with enormous hyperploid nuclei associated with infiltrating neuronal-like cells, which were very abundant at later stages of tumor development. Mitotic indices were much higher in transgenic than wild-type pituitaries, as expected. Morphologic analysis of the gonads of these transgenic mice showed no major developmental differences, as compared to wild-type littermates, however the length of the seminiferous tubules in transgenic males was greater than age-matched wild-type animals. Despite this phenotype difference, both genders were fertile, with normal sperm development observed in males and normal estrous cycle stages in females. Moreover, while 8 -- 10-week-old transgenic males had much lower blood levels of FSH than littermates, transgenic female FSH levels were the same as those of wild-type females. These animals offer a unique and potentially useful model of organ-specific tumorigenesis, where a multistage pathway of tumor development is evident, both histologically and temporally. Study of such models will advance our knowledge on the physiological and molecular mechanisms involved in gene expression as well as tumor formation.