Distribution of delirium motor subtypes in the intensive care unit:a systematic scoping review

BACKGROUND: Delirium is the most common cerebral dysfunction in the intensive care unit (ICU) and can be subdivided into a hypoactive, hyperactive, or mixed motor subtype based on the clinical manifestation. The aim of this review was to describe the distribution, pharmacological interventions, and outcomes of delirium motor subtypes in ICU patients. METHODS: This systematic scoping review was performed according to the PRISMA-ScR and Cochrane guidelines. We performed a systematic search in six major databases to identify relevant studies. A meta-regression analysis was performed where pooled estimates with 95% confidence intervals were computed by a random effect model. RESULTS: We included 131 studies comprising 13,902 delirious patients. There was a large between-study heterogeneity among studies, including differences in study design, setting, population, and outcome reporting. Hypoactive delirium was the most prevalent delirium motor subtype (50.3% [95% CI 46.0–54.7]), followed by mixed delirium (27.7% [95% CI 24.1–31.3]) and hyperactive delirium (22.7% [95% CI 19.0–26.5]). When comparing the delirium motor subtypes, patients with mixed delirium experienced the longest delirium duration, ICU and hospital length of stay, the highest ICU and hospital mortality, and more frequently received administration of specific agents (antipsychotics, α2-agonists, benzodiazepines, and propofol) during ICU stay. In studies with high average age for delirious patients (> 65 years), patients were more likely to experience hypoactive delirium. CONCLUSIONS: Hypoactive delirium was the most prevalent motor subtype in critically ill patients. Mixed delirium had the worst outcomes in terms of delirium duration, length of stay, and mortality, and received more pharmacological interventions compared to other delirium motor subtypes. Few studies contributed to secondary outcomes; hence, these results should be interpreted with care. The large between-study heterogeneity suggests that a more standardized methodology in delirium research is warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-022-03931-3

Midkine characterization in human ovaries:potential new variants in follicles

Objective: To characterize the growth factor midkine (MDK) in the human ovary to determine whether MDK is produced locally within the ovary, examine whether different ovarian cell types are more likely to produce MDK, and determine whether there are any stage-specific variations during follicle growth. Previous studies have revealed that MDK potentially affects human follicle growth and oocyte maturation. Proteomic analyses in follicular fluid (FF) have identified MDK to functionally cluster together and follow a similar expression profile to that of well-known proteins involved in ovarian follicle development. Midkine has not yet been characterized in the human ovary. Design: Descriptive study. Setting: University Hospital. Patients: The study included samples from 121 patients: 71 patients (aged 17–37 years) who underwent ovarian tissue cryopreservation provided granulosa cells (GC), cumulus cells, ovarian cortex, medulla tissue, and FF from small antral follicles (SAF); and 50 patients (aged 20–35 years) receiving in vitro fertilization treatment provided FF from preovulatory follicles before and after induction of final follicle maturation. Interventions: None. Main Outcome Measures: MDK relative gene expression was quantified using a real-time quantitative polymerase chain reaction in cumulus cells, GC, and medulla tissue. Additionally, immunostaining and western blotting assays were used to detect MDK protein in the ovarian cortex, which contains preantral follicles, SAF, and medulla tissue. Furthermore, enzyme-linked immunosorbent assay analyses were performed to measure the concentration of MDK in FF aspirated from SAF and preovulatory follicles both before and 36 hours after inducing the final maturation of follicles. Results: Immunostaining and reverse transcription-quantitative polymerase chain reaction revealed a more prominent expression of MDK in GC compared with other ovarian cell types. Intrafollicular MDK concentration was significantly higher in SAF compared with preovulatory follicles. In addition, different molecular weight species of MDK were detected using western blotting in various ovarian sample types: GC and FF samples presented primarily one band of approximately 15 kDa and an additional band of approximately 13 kDa, although other bands with higher molecular weight (between 30 and 38 kDa) were detected in medulla tissue. Conclusions: This is the first time that MDK has been immunolocalized in human ovarian cells at the protein level and that potentially different MDK variants have been detected in human FF, GC, and ovarian medulla tissue. Future studies are needed to sequence and identify the different potential MDK variants found to determine their functional importance for ovary and oocyte competence.</p