[Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy].

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

A quick data mining and analysis of lopinavir/ritonavir (LPV/r) adverse events based on Eudravigilance Medicines Safety Database

Objective: This study used data mining to conduct real-world research on adverse drug events (ADEs) after LPV/r was launched on the market, providing a reference for clinical identification and treatment of early ADEs. Methods: MedDRA terminology in different levels of the reproductive system were selected, and all LPV/r-related ADE reports were extracted from the European Drug Adverse Event Reporting Database (Eudravigilance). Results: Until February 1, 2020, 3 753 reports of LPV/r-related ADEs were collected in Eudravigilance, with 5 833 drug-related adverse events. In terms of gender composition, males (54.5%) are higher than females (37.5%), and the age is concentrated between 18~64 years (69.0%). The reporting population is mainly "medical staff reporting" (82.8%). The ADE reports are focused on the system classification, much involving the following systems: gastrointestinal system, hepatobiliary system, nervous system, nutritional metabolism system, and cardiovascular system, etc. This research uses PT terminology to query each system report, showing that LPV/r-related ADEs invaded the gastrointestinal system and often manifested as diarrhea 205 (22.4%), vomiting 135 (14.7%), nausea124 (13.5%), and severe of pancreatitis 89 (9.7%) and gastrointestinal bleeding 57 (6.2%), etc. Liver and gallbladder system mainly showed abnormal liver function 93 (14.7%), changes in liver function indicators and jaundice 67 (10.6%). Nervous system mainly involved symptoms of mild headache 199 (31.6%), dizziness 70 (11.1%). It is worth noting that LPV/r induced seizures 54 (8.6%) and peripheral neuropathy 33 (5.2%). Other severe system effects: 21 (3.3%) decrease in blood glucose, 163 (28.5%) hypotension, 50 (8.7%) increase in blood pressure, 10 (1.6%) hyperkalemia, 36 (6.3%) AV block, deep vein thrombosis 17 (3.0%), electrocardiogram QT interval prolongation 16 (2.8%), anemia 168 (37.3%), acute kidney injury 129 (32.3%), etc. Conclusion: In the clinical use of LPV/r, we should be alert to gastrointestinal bleeding, seizures, hypotension, thrombosis, prolonged QT interval, acute serious adverse events such as kidney injury and severe liver injury, in addition to some mild adverse events such as diarrhea, rash, and headache, etc. © 2020, Chinese Journal of New Drugs Co. Ltd. All right reserved.