CHAMP1-Related Disorder: Sharing 20 Years of thorough Clinical Follow-Up and Review of the Literature.

Intellectual disability (ID) is a prevalent neurodevelopmental disorder characterized by limitations in intellectual functioning and adaptive behavior. While the causes of ID are still largely unknown, it is believed to result from a combination of environmental exposures and genetic abnormalities. Recent advancements in genomic studies and clinical genetic testing have identified numerous genes associated with neurodevelopmental disorders (NDDs), including ID. One such gene is CHAMP1, which plays a role in chromosome alignment and has been linked to a specific type of NDD called CHAMP1 disease. This report presents the case of a 21-year-old Lebanese female patient with a de novo mutation in CHAMP1. In addition to ID and NDD, the patient exhibited various clinical features such as impaired language, dysmorphic features, macrocephaly, thoracic hyperkyphosis, decreased pain sensation, and metabolic syndrome. These findings expand the understanding of the clinical spectrum associated with CHAMP1 mutations and highlight the importance of comprehensive follow-up for improved prognosis. Overall, this case contributes to the knowledge of CHAMP1-related NDDs by describing additional clinical features associated with a CHAMP1 mutation. The findings underscore the need for accurate diagnosis, thorough follow-up, and personalized care for individuals with CHAMP1 mutations to optimize their prognosis.

Respiratory Adverse Events After LMA® Mask Removal in Children: A Randomized Trial Comparing Propofol to Sevoflurane.

BACKGROUND: The removal of the laryngeal mask airway (LMA®) in children may be associated with respiratory adverse events. The rate of occurrence of these adverse events may be influenced by the type of anesthesia. Studies comparing total intravenous anesthesia (TIVA) with propofol and sevoflurane are limited with conflicting data whether propofol is associated with a lower incidence of respiratory events upon removal of LMA as compared to induction and maintenance with sevoflurane. We hypothesized that TIVA with propofol is superior to sevoflurane in providing optimal conditions and improved patient's safety during emergence. METHODS: In this prospective, randomized, double-blind clinical trial, children aged 6 months to 7 years old were enrolled in 1 of 2 groups: the TIVA group and the sevoflurane group. In both groups, patients were mechanically ventilated. At the end of the procedure, LMAs were removed when patients were physiologically and neurologically recovered to a degree to permit a safe, natural airway. The primary aim of this study was to compare the occurrence of at least 1 respiratory adverse event, the prevalence of individual respiratory adverse events, and the airway hyperreactivity score following emergence from anesthesia between the 2 groups. Secondary outcomes included ease of LMA insertion, quality of anesthesia during the maintenance phase, hemodynamic stability, time to LMA removal, and incidence of emergence agitation. RESULTS: Children receiving TIVA with propofol had a significantly lower incidence (10.8.% vs 36.2%; relative risk, 0.29; 95% CI [0.14-0.64]; P = .001) and lower severity ( P = .01) of respiratory adverse outcomes compared to the patients receiving inhalational anesthesia with sevoflurane. There were no statistically significant differences in secondary outcomes between the 2 groups, except for emergence agitation that occurred more frequently in patients receiving sevoflurane ( P < .001). CONCLUSIONS: Propofol induction and maintenance exerted a protective effect on healthy children with minimal risk factors for developing perioperative respiratory complications, as compared to sevoflurane.

Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway.

BACKGROUND: Topotecan (TP) is an anticancer drug acting as topoisomerase I inhibitor that is used in the treatment of many types of cancers including leukemia, but it has significant side effects. Andrographolide, a compound extracted from Andrographis paniculata, was recently proven to inhibit the growth of cancer cells and can induce apoptosis. The aim of this study is to investigate the possible synergism between TP and andrographolide in acute myeloid cells in vitro. MATERIALS AND METHODS: U937 acute myeloid leukemic cells were cultured using Roswell Park Memorial Institute (RPMI) medium and then treated for 24 h with TP and andrographolide prepared through the dilution of dimethyl sulfoxide (DMSO) stocks with RPMI on the day of treatment. Cell proliferation was assessed using cell proliferation assay upon treatment with both compounds separately and in combination. Cell-cycle study and apoptosis detection were performed by staining the cells with propidium iodide (PI) stain and Annexin V/PI stain, respectively, followed by flow cytometry analysis. Western blotting was used to assess the expression of various proteins involved in apoptotic pathways. RESULTS: Both TP and andrographolide showed an antiproliferative effect in a dose-dependent manner when applied on U937 cells separately; however, pretreating the cells with andrographolide before applying TP exhibited a synergistic effect with lower inhibitory concentrations (half-maximal inhibitory concentration). Treating the cells with TP alone led to specific cell-cycle arrest at S phase that was more prominent upon pretreatment combination with andrographolide. Using Annexin V/PI staining to assess the proapoptotic effect following the pretreatment combination showed an increase in the number of apoptotic cells, which was supported by the Western blot results that manifested an upregulation of several proapoptotic proteins expression. CONCLUSION: The pretreatment of U937 with andrographolide followed by low doses of TP showed an enhancement in inducing apoptosis when compared to the application of each compound separately.