It has been shown that propofol can induce widespread apoptosis in neonatal mouse brains followed by long-term cognitive dysfunction. However, selective brain area and cell vulnerability to propofol remains unknown. This study was aimed to dissect toxic effect of propofol on multiple brain cells, including neurons, astrocytes, oligodendrocytes, and neural stem cells (NSCs). Seven-day-old mice were intraperitoneally administrated propofol or intralipid as a vehicle control for 6 hours. To identify vulnerable cells undergoing apoptosis following propofol exposure, brain sagittal sections were co-stained with antibodies against an apoptosis marker along with neuron, astrocyte, oligodendrocyte, or NSC markers using immunofluorescence staining. The results showed widespread apoptosis in propofol-treated brains (apoptotic cells: 1.55 ± 0.04% and 0.06 ± 0.01% in propofol group and intralipid-treated control group, respectively). Apoptotic cell distribution exhibits region- and cell-specific patterns. Several brain regions (e.g., cerebral cortex and hippocampus) were more vulnerable to propofol than other brain regions. Most apoptotic cells in the hippocampus were located in the cornus ammonis 1 (CA1) subfield. These apoptotic cells were only detected in neurons and not astrocytes, oligodendrocytes, or NSCs. These data demonstrate that different brain regions, subfields, and different types of neuronal cells in mice exhibit various vulnerabilities to propofol. Understanding region- and cell-specific susceptibility to propofol will help to better understand cellular contribution to developmental neurotoxicity and further develop novel therapeutic targets.
Bioelectrical impedance analysis (BIA) is a body composition assessment method. We aimed to determine its accuracy in the detection of sarcopenia in patients with liver cirrhosis (LC), using skeletal muscle index (SMI) at the level of third lumbar vertebra (L3-SMI) obtained using multislice computed tomography as the reference method. Patients with LC were enrolled in the period October 2019–March 2022 and follow-ups were conducted until January 2023. Their BIA parameters were compared against L3-SMI, and BIA cut-off values were proposed using AUROC analysis. Patients underwent outcome analysis based on obtained clinical characteristics. A total of 106 patients were included. We found a fair correlation between BIA parameters with the L3-SMI. We determined cut-off values of ≤11.1 kg/m2 for BIA-SMI (Se 73%, Sp 66%, AUROC 0.737, p < 0.001) and ≤5.05° for phase angle (PA) (Se 79%, Sp 60%, AUROC 0.762, p < 0.001) in the detection of sarcopenia. The relative risk of death was 2.2 times higher in patients with skeletal muscle mass (SMM) ≤ 36.5 kg. SMM was significantly associated with outcome in Kaplan–Meier analysis. This non-invasive and simple method that showed fair performances and a very good outcome prediction could provide for the unmet need for fast and affordable detection of sarcopenia in patients with LC and should be further evaluated.
Gallbladder drainage is a treatment option in high-risk surgical patients with moderate or severe acute cholecystitis. It may be applied as a bridge to cholecystectomy or a definitive treatment option. Apart from the simple and widely accessible percutaneous cholecystostomy, new attractive techniques have emerged in the previous decade, including endoscopic transpapillary gallbladder drainage and endoscopic ultrasound-guided gallbladder drainage. The aim of this paper is to present currently available drainage techniques in the treatment of AC; evaluate their technical and clinical effectiveness, advantages, possible adverse events, and patient outcomes; and illuminate the decision-making path when choosing among various treatment modalities for each patient, depending on their clinical characteristics and the accessibility of methods.
Sarcopenia refers to a disorder involving the gradual and overall reduction in skeletal muscle mass and physical capability. It occurs in over one-third of individuals with liver cirrhosis and serves as an independent predictor of increased mortality risk. Assessment of sarcopenia is necessary in all patients with liver cirrhosis, as recommended by the European Association for the Study of the Liver (EASL) and the European Society for Clinical Nutrition and Metabolism (ESPEN). The evaluation of muscle mass can be performed using several validated methods such as the multislice computed tomography (MSCT), abdominal magnetic resonance imaging (MRI), dual X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), or muscle ultrasound. Assessment of muscle function encompasses measurements of both muscle strength and physical performance. Sarcopenia has a significant negative impact on the course of the disease, quality of life and outcomes of patients with liver cirrhosis. Considering the global healthcare impact and the significant influence on the course of disease, characteristics of simplicity, swiftness, safety, availability, reproducibility, and diagnostic accuracy are certainly the key factors to consider when choosing the proper diagnostic method for nutritional assessment. The aim of this review is to analyze the pathophysiological mechanisms underlying muscle mass loss in patients with liver cirrhosis, as well as to assess strengths and limitations of the methods currently in use to diagnose sarcopenia.
Background and Objectives: Anticoagulants are a well-known risk factor for gastrointestinal bleeding (GIB). In recent years, direct oral anticoagulants (DOACs) have taken a leading role in the treatment and prevention of thromboembolic incidents. The aim of this study was to investigate the prevalence of DOAC-treated patients with GIB whose plasma drug concentrations exceeded the cut-off values reported in the literature and to evaluate their clinical characteristics. Materials and Methods: Patients who were admitted to the Intensive Care Unit in the period 2/2020–3/2022 due to GIB were prospectively included in the study and classified into three groups according to the prescribed type of DOAC (apixaban, rivaroxaban, and dabigatran). For all participants, it was determined if the measured plasma drug levels exceeded the maximum serum concentration (Cmax) or trough serum concentration (Ctrough) obtained from the available data. A comparison of clinical parameters between the patients with and without excess drug values was performed. Results: There were 90 patients (54.4% men) included in the study, of whom 27 were treated with dabigatran, 24 with apixaban, and 39 with rivaroxaban. According to Cmax, there were 34 (37.8%), and according to Ctrough, there were 28 (31.1%) patients with excess plasma drug values. A statistically significant difference regarding excess plasma drug values was demonstrated between DOACs according to both Cmax (p = 0.048) and Ctrough (p < 0.001), with the highest rate in the group treated with dabigatran (55.6% for Cmax and 59.3% for Ctrough). Multivariate logistic regression showed that age (OR 1.177, p = 0.049) is a significant positive and glomerular filtration rate (OR 0.909, p = 0.016) is a negative predictive factor for excess plasma drug values. A total of six (6.7%) patients had fatal outcomes. Conclusions: Plasma drug concentrations exceed cut-off values reported in the literature in more than one-third of patients with GIB taking DOAC, with the highest rate in the dabigatran group. Clinicians should be more judicious when prescribing dabigatran to the elderly and patients with renal failure. In these patients, dose adjustment, plasma drug monitoring, or substitution with other, more appropriate DOACs should be considered.
Subjects with inflammatory bowel diseases (IBDs) have a higher opportunity for fractures due to the inflammatory potential of the disorder and because of the glucocorticoid therapy that is often inevitable. The fracture risk can be assessed by dual-energy X-ray absorptiometry and can also be combined with assessing the trabecular bone score (TBS). The evaluation of the TBS offers additional advantages in particular conditions, such as glucocorticoid-induced osteoporosis, and thus optimizes the fracture risk evaluation in the IBD subject group. A limited number of studies involving TBS in other digestive diseases is unlikely to provide sufficient evidence regarding the usefulness of TBS in gastroenterology. Our aim is to review the clinical utility of TBS in digestive diseases.