Aldehyde Dehydrogenase Isoform 1 Predicts a Poor Prognosis of Acute Cerebral Infarction.

To investigate the prognostic potential of serum aldehyde dehydrogenase isoform 1 (ALDH1) level in acute cerebral infarction, and the molecular mechanism in mediating neurological deficits, a total of 120 acute cerebral infarction cases within 72 h of onset were retrospectively analyzed. Serum ALDH1 level in them was detected by qRT-PCR. Receiver operating characteristic (ROC) and Kaplan-Meier curves were depicted for assessing the diagnostic and prognostic potentials of ALDH1 in acute cerebral infarction, respectively. An in vivo acute cerebral infarction model in rats was established by performing MCAO, followed by evaluation of neurological deficits using mNSS and detection of relative levels of ALDH1, Smad2, Smad4, and p21 in rat brain tissues. Pearson's correlation test was carried out to verify the correlation between ALDH1 and mNSS and relative levels of Smad2, Smad4, and p21. Serum ALDH1 level increased in acute cerebral infarction patients. A high level of ALDH1 predicted a poor prognosis of acute cerebral infarction patients. In addition, ALDH1 was sensitive and specific in distinguishing acute cerebral infarction cases, presenting a certain diagnostic potential. mNSS was remarkably higher in acute cerebral infarction rats than that of controls. Compared with sham operation group, relative levels of ALDH1, Smad2, and Smad4 were higher in brain tissues of modeling rats, whilst p21 level was lower. ALDH1 level in brain tissues of modeling rats was positively correlated to mNSS, and mRNA levels of Smad2 and Smad4, but negatively correlated to p21 level. Serum ALDH1 level is a promising prognostic and diagnostic factor of acute cerebral infarction, which is correlated to 90-day mortality. Increased level of ALDH1 in the brain of cerebral infarction rats is closely linked to neurological function, which is associated with the small mothers against decapentaplegic (Smad) signaling and p21.

General recommendation for assessment and management on the risk of glucocorticoid-induced osteonecrosis in patients with COVID-19.

BACKGROUND/OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a disaster in human medical history and glucocorticoids remain the most promising therapy. Osteonecrosis is a disease caused by reduced intraosseous blood flow to bones in the joints, which will rapidly induce joint destruction. Approximately one-third patients with severe acute respiratory syndrome (SARS) who received high cumulative doses and long treatment durations of glucocorticoids occurred osteonecrosis. Considering the similarity of SARS and COVID-19 on their pathogen, clinical characteristics, and therapeutic strategies, it is particularly desirable to investigate whether osteonecrosis will become a common sequela among convalescent COVID-19 patients. METHODS: This multi-strategy study was designed by integrating different research methods, such as meta-analysis, systematic review, and cross-sectional investigations to address above study objectives. At first, two meta-analyses were performed on the osteonecrosis incidence among SARS patients and the clinical data of glucocorticoid exposure among COVID-19 patients. Then, a systematic review of low-dosage glucocorticoid associated osteonecrosis and a cross-sectional investigation of glucocorticoid exposure of COVID-19 patients in Wuhan city of China were also conducted. Moreover, the pathogenesis, diagnosis, prevention, and treatment options for osteonecrosis patients with COVID-19 infection were further presented and discussed. RESULTS: Our meta-analysis showed that 32% of SARS patients had developed osteonecrosis after receiving glucocorticoid treatment with high dose, and our system review supported that low level glucocorticoid exposure might also lead to the occurrence of osteonecrosis. Similarly, 40% of COVID-19 patients had undergone glucocorticoid treatment according to our meta-analysis. The cross-sectional investigation in Wuhan city of China found that the average of cumulative glucocorticoid exposure level was 504 â€‹mg calculated by the dosage of methylprednisolone. Notably, a confirmed osteonecrosis case was identified from 1406 patients with COVID-19 during our cross-sectional investigation, implying that preventive management of osteonecrosis should be better started with regular clinical follow-up observation. CONCLUSION: Growing evidence of the glucocorticoid therapy for COVID-19 patients prompts us to establish risk-classification-based early screening and to introduce early prevention protocol of its associated osteonecrosis that will be of clinical significance in favor of improved prognosis of this disease. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To establish risk-classification-based early screening and to introduce early prevention protocol of glucocorticoid-induced osteonecrosis will be of clinical significance in favor of improved prognosis of COVID-19.