Machine learning-based prediction of mild cognitive impairment among individuals with normal cognitive function.

Background: Previous studies mainly focused on risk factors in patients with mild cognitive impairment (MCI) or dementia. The aim of the study was to provide basis for preventing MCI in cognitive normal populations. Methods: The data came from a longitudinal retrospective study involving individuals with brain magnetic resonance imaging scans, clinical visits, and cognitive assessment with interval of more than 3 years. Multiple machine-learning technologies, including random forest, support vector machine, logistic regression, eXtreme Gradient Boosting, and naïve Bayes, were used to establish a prediction model of a future risk of MCI through a combination of clinical and image variables. Results: Among these machine learning models; eXtreme Gradient Boosting (XGB) was the best classification model. The classification accuracy of clinical variables was 65.90%, of image variables was 79.54%, of a combination of clinical and image variables was 94.32%. The best result of the combination was an accuracy of 94.32%, a precision of 96.21%, and a recall of 93.08%. XGB with a combination of clinical and image variables had a potential prospect for the risk prediction of MCI. From clinical perspective, the degree of white matter hyperintensity (WMH), especially in the frontal lobe, and the control of systolic blood pressure (SBP) were the most important risk factor for the development of MCI. Conclusion: The best MCI classification results came from the XGB model with a combination of both clinical and imaging variables. The degree of WMH in the frontal lobe and SBP control were the most important variables in predicting MCI.

Olanzapine for the treatment of ICU delirium: a systematic review and meta-analysis.

Background: As an atypical antipsychotic drug, olanzapine is one of the most commonly used drugs for delirium control. There are no systematic evaluations or meta-analyses of the efficacy and safety of olanzapine for delirium control in critically ill adults. Objectives: In this meta-analysis, we evaluated the efficacy and safety of olanzapine for delirium control in critically ill adults in the intensive care unit (ICU). Data Sources and Methods: From inception to October 2022, 12 electronic databases were searched. We retrieved randomized controlled trials (RCTs) and retrospective cohort studies of critically ill adults with delirium that compared the effects of olanzapine and other interventions, including routine care (no intervention), nonpharmaceutical interventions and pharmaceutical interventions. The main outcome measures were the (a) relief of delirium symptoms and (b) a decrease in delirium duration. Secondary outcomes were ICU and in-hospital mortality, ICU and hospital length of stay, incidence of adverse events, cognitive function, sleep quality, quality of life, mechanical ventilation time, endotracheal intubation rate and delirium recurrence rate. We applied a random effects model. Results: Data from 10 studies (four RCTs and six retrospective cohort studies) involving 7076 patients (2459 in the olanzapine group and 4617 in the control group) were included. Olanzapine did not effectively relieve delirium symptoms (OR = 1.36, 95% CI [0.83, 2.28], p = 0.21), nor did it shorten the duration of delirium [standardized mean difference (SMD) = 0.02, 95% CI [-1.04, 1.09], p = 0.97] when compared with other interventions. Pooled data from three studies showed that the use of olanzapine reduced the incidence of hypotension (OR = 0.44, 95% CI [0.20, 0.95], p = 0.04) compared with other pharmaceuticals. There was no significant difference in other secondary outcomes, including ICU or hospital length of stay, in-hospital mortality, extrapyramidal reactions, QTc interval prolongation, or overall incidence of other adverse reactions. The number of included studies was not sufficient for performing a comparison between olanzapine and no intervention. Conclusion: Compared with other interventions, olanzapine has no advantage in alleviating delirium symptoms and shortening delirium duration in critically ill adults. However, there is some evidence that the rate of hypotension was lower in patients who received olanzapine than in those who received other pharmaceutical interventions. There was a nonsignificant difference in the length of ICU or hospital stay, in-hospital mortality, and other adverse reactions. This study provides reference data for delirium research and clinical drug intervention strategies in critically ill adults. Registration: Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42021277232).

Efficacy and safety of ciprofol for agitation and delirium in the ICU: A multicenter, single-blind, 3-arm parallel randomized controlled trial study protocol.

Background: Agitation is very common in the intensive care unit (ICU). The causes include pain, delirium, underlying disease, withdrawal syndrome, and some drug treatments. The practical goal of ICU treatment is to find an appropriate sedation regimen to reduce pain, restlessness, and delirium. Previous trials have examined the use of dexmedetomidine, but no trials have evaluated the efficacy and safety of ciprofol, a new sedative drug. Methods: This study was a multicenter, single-blind, 3-arm parallel randomized controlled trial. ICU patients aged ≥ 18 years with agitation and delirium who met the eligibility criteria were included. The main outcome was the proportion of patients who needed additional study medication or midazolam due to agitation within 4 h after the first intravenous injection of the study medication. The secondary outcomes included the pass rate as indicated by a Richmond Agitation-Sedation Scale (RASS) score < +1, the effectiveness rate of improving delirium symptoms, the number of recurrences of agitation within 24 h, the incidence of rescue treatment, the dose and cost of analgesic and sedative drugs, the length and cost of ICU stay, and the 30-day survival period. The safety evaluation included the incidence of adverse events (hypotension, bradycardia, hypoxia, etc.) and the rate of endotracheal intubation. The subjects were randomly assigned to receive ciprofol, dexmedetomidine, or normal saline at a ratio of 1:1:1. The rates of additional drug administration within 4 h after the first injection of the study drug in the three groups were 40, 50, and 90%, respectively. A total sample size of 81 subjects was required to reach 90% power and an α of 0.05. Considering a 20% loss rate, 102 patients were enrolled and randomly assigned to the three groups in equal proportions. Ethics and communication: This trial was approved by the Ethics Committee of Dalian Municipal Central Hospital. The communication plan includes presentations at scientific conferences, scientific publications, and presentations to the public through non-professional media. Clinical trial registration: www.ClinicalTrials.gov, identifier ChiCTR220006 2799.

Inhibition of Poly-(ADP-Ribose) Polymerase Protects the Kidney in a Canine Model of Endotoxic Shock.

Poly-(ADP-ribose) polymerases (PARPs), a super family of enzymes, play important roles in preserving genomic integrity, regulating transcriptions, protecting telomeres and determining cell fate. PARP overactivation leads to metabolic disorder and cell injury via depletion of energy substance. However, it is still unclear whether PARP overactivation happens during acute kidney injury (AKI) caused by endotoxic shock (ES). Here, we built a canine model of lipopolysaccharide-induced ES to explore the role of PARP during the development AKI. We also used an intravenous injection of 3-aminobenzamide (3-AB) to further explore whether PARP inhibition rescues the kidney from injury. Cell fate and energy metabolism were detected to explore the underlying mechanisms. As a result, Western blot and immunohistochemistry assays showed PARP overactivation in the very early phase of ES. Through PARP inhibition by 3-AB, we observed significant improvement of systemic hemodynamics, renal hemodynamics, renal oxygen metabolism and renal tubular cell apoptosis. These findings indicated that overactivation of PARP plays an important role in septic AKI. Inhibition of PARP overactivation may protect renal function against hemodynamic disorder, renal metabolism disturbance and renal cell apoptosis during endotoxic AKI.

Energy and oxygen metabolism disorder during septic acute kidney injury.

BACKGROUND/AIMS: Acute kidney injury (AKI) during septic shock, which is one of the most common clinical syndromes in the intensive care unit (ICU), has a high mortality rate and poor prognosis, partly because of a poor understanding of the pathogenesis of renal dysfunction during septic shock. Although ischemic injury of the kidney has been reported to result from adenosine triphosphate (ATP) depletion, increasing evidence has demonstrated that AKI occurs in the absence of renal hypoperfusion and even occurs during normal or increased renal blood flow (RBF); nevertheless, whether energy metabolism disorder is involved in septic AKI and whether it changes according to renal hemodynamics have not been established. Moreover, tubular cell apoptosis, which is closely related to ATP depletion, rather than necrosis, has been shown to be the major form of cell injury during AKI. METHODS: We used canine endotoxin shock models to investigate the hemodynamics, renal energy metabolism, renal oxygen metabolism, and pathological changes during septic AKI and to explore the underlying mechanisms of septic AKI. RESULTS: The present results revealed that the nicotinamide adenine dinucleotide (NAD+) pool and the ATP/adenosine diphosphate (ADP) ratio were significantly decreased during the early phase of septic AKI, which is accompanied by a decreased renal oxygen extraction ratio (O2ER%) and decreased renal oxygen consumption (VO2). Furthermore, significant apoptosis was observed following renal dysfunction. RBF and renal oxygen delivery were not significantly altered. CONCLUSION: These results suggest that imbalanced energy metabolism, rather than tubular cell apoptosis, may be the initiator of renal dysfunction during septic shock.