Efficacy and safety of donepezil for mild cognitive impairment: A systematic review and meta-analysis.

OBJECTIVE: This study intends to systematically evaluate the efficacy and safety of donepezil for improving cognitive function in patients with mild cognitive impairment (MCI), and to provide evidence-based foundation for donepezil in MCI treatment. METHODS: We searched in PubMed, Embase, Cochrane Library, Clinical trials.gov, Web of Science, CQVIP, and CNKI databases, and then we summarized the interventional and observational studies on the use of donepezil for improving the cognitive function of MCI patients. The literature was collected according to the inclusion criteria for data extraction. We evaluated the quality of the selected literature and used Stata 15.0 for meta-analysis. RESULTS: A total of 12 randomized controlled trials (RCTs) and 5 non-randomized concurrent controlled trials (CCTs) were included, and a total of 2847 patients were included. In terms of efficacy, meta-analysis showed that donepezil could significantly improve the MMSE (SMD: 0.85, 95%CI: 0.40-1.31) and MoCA (SMD: 1.88, 95%CI: 0.32-3.45) scores of MCI patients. Donepezil could not significantly reduce ADAS-cog score, nor could it significantly delay disease progression. The quality of the evidence was low overall. In terms of safety, donepezil could significantly increase the risk of adverse reactions such as nausea, vomiting, diarrhea in patients with MCI. CONCLUSION: Donepezil can improve the cognitive function of MCI patients to a certain extent. However, there is no trend of significantly delaying the progression of the disease, and it is easy to lead to the occurrence of adverse reactions.

Toxic epidermal necrolysis in a patient on atorvastatin therapy expressing human leukocyte antigen alleles: A case report.

RATIONALE: Toxic epidermal necrolysis (TEN) is a rare, severe mucosal response of the skin associated with a high mortality rate. TEN is most commonly caused by drugs, and is characterized by extensive skin epidermal exfoliation. PATIENT CONCERNS: A 68-year-old woman presented with a rash that had persisted for four days. The patient who had undergone a mitral valve replacement 1 month prior and was taking atorvastatin at the time of admission. DIAGNOSES: The patient exhibited more than 30% exfoliation surfaces and the severe drug eruption was considered to be TEN. According to human leukocyte antigen (HLA) allele detection and ALDEN score, HLA alleles which found in this case report may be an cause of TEN induced by atorvastatin. INTERVENTIONS: All drugs used prior to admission were discontinued and the patient was given antiallergic drugs. OUTCOMES: After 3 weeks following Antiallergic treatment, the rash on patient's calf had subsided, the edema was relieved, and the patient was no longer experiencing pain. After 60 days following discharge, the patient's skin has regrown. LESSONS: This is the first report describing the induction of TEN by atorvastatin in a HLA alleles carrier. For HLA alleles carrier, atorvastatin may need to be used with caution to avoid TEN. Future systematic research is also required to confirm this finding and avoid similar serious skin adverse reactions.

Which Is the Most Appropriate PI3K Inhibitor for Breast Cancer Patients with or without PIK3CA Status Mutant? A Systematic Review and Network Meta-Analysis.

OBJECTIVE: The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a promising treatment target for patients with breast cancer (BC). Our study aimed to evaluate the most effective and safe PI3K inhibitor for patients with BC, especially in PIK3CA mutation. METHODS: Electronics databases were systematically searched from their inception to June 2020 for published randomized controlled trials (RCTs) comparing PI3K inhibitor therapy versus non-PI3K inhibitor therapy in patients with BC that mentioned or reported data of PIK3CA-mutated patient subgroups. Eligible RCTs had to report at least one of the following clinical outcomes: objective response rate (ORR), progression-free survival (PFS), or adverse events (AE). RESULTS: Nine eligible RCTs involving 3872 BC patients and four PI3K inhibitor therapy arms (i.e., alpelisib, buparlisib, pictilisib, and taselisib) were included. In evaluating ORR, beneficial significant results of PI3K inhibitors could be found in the PIK3CA mutated group (1.952, 1.012 to 3.766); analogous results could also be found in 6m-PFS (1.519, 1.144 to 2.018) and PFS from HR data (-0.346, -0.525 to -0.168). From pairwise and network meta-analyses, buparlisib showed the most favorable ORR, as it was significantly different from fulvestrant in the PIK3CA-mutated patient group (2.80, 1.56 to 5.03). Alpelisib ranked first in the assessment of 6m-PFS and was significantly different from fulvestrant in the PIK3CA-mutated group (2.33, 1.45 to 3.44). The above PI3K inhibitors had good safety with few serious AEs. PROSPERO registration CRD42020193932. CONCLUSION: The PI3K inhibitors alpelisib and buparlisib appear to have superior efficacy and safety therapeutic choices for patients with BC, especially in PIK3CA-mutated patients.

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats.

BACKGROUND/AIMS: Mitochondrial perturbation is a well-established cause of cognitive decline, but as yet it is unclear how mitochondria-associated neuronal abnormalities in type 1 diabetic (T1DM) brain contribute to cognitive decline. METHODS: The streptozotocin (STZ)-induced mouse model of T1DM was used. The Morris water maze test was applied to assess the effect of T1DM on learning and memory. We detected changes in mitochondrial morphology, function and dynamics. Furthermore, we employed metabolomic analysis to reveal the underlying mechanisms of mitochondrial perturbation which contribute to cognitive decline. RESULTS: Our results show that T1DM impairs mitochondrial dynamics, morphology and function in neurons, associated with a decline in cognitive ability. Metabolomic analyses revealed that T1DM mainly affects metabolic pathways involved in mitochondrial energy failure and impairs the antioxidative system. CONCLUSION: These results lay the basis for understanding the underlying mitochondria-associated causes of T1DM-associated cognitive decline and may provide a potential treatment strategy for this condition in future.