To investigate whether the use of mycophenolate mofetil (MMF) could reduce the relapse risk in patients with myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-associated disorders (MOGADs).This prospective observational cohort study included patients with MOGAD at Peking Union Medical College Hospital between January 1, 2017, and April 30, 2019. The patients were divided into 2 groups: those with (MMF+) or without (MMF-) MMF therapy. The primary outcome was relapse at follow-up. We used Cox proportional hazards models to calculate hazard ratios (HRs) for relapse.Seventy-nine patients were included in our MOG cohort. Fifty (63.3%) were adults at index date, and 47 (59.5%) were women. Fifty-four (68.4%) were in the MMF+ group, and 25 (31.6%) were in the MMF- group. Clinical and demographic factors, MOG-IgG titer, and follow-up time (median, 472.5 days for MMF+, 261.0 days for MMF-) were comparable between the groups. Relapse rates were 7.4% (4/54) in the MMF+ group and 44.0% (11/25) in the MMF- group. Of all potential confounders, only the use of MMF was associated with reduced risk of relapse. The HR for relapse among patients in the MMF+ group was 0.14 (95% CI, 0.05-0.45) and was 0.08 (95% CI, 0.02-0.28) in a model adjusted for age, sex, disease course, and MOG-IgG titer. MMF therapy also remained associated with a reduced relapse risk in sensitivity analyses. Only one patient (1.9%) discontinued MMF therapy because of adverse effect.These findings provide a clinical evidence that MMF immunosuppression therapy may prevent relapse in patients with MOGAD.This study provides class IV evidence that for patients with MOGAD, MMF reduces relapse risk.
Abstract Background: Unawareness of stroke symptoms and low income are two barriers that affect the seeking of emergency medical service (EMS). This study aimed to assess the effect of unawareness and low income on seeking EMS and to investigate the regional distribution of the unawareness and low-income status and their associations with failing to call EMS in China. Methods: A total of 187,723 samples from the China National Stroke Screening Survey was interviewed cross-sectionally. Four status of awareness and annual income were identified: unaware and low-income, unaware-only, low-income-only, and aware and regular income. The outcomes were whether they intended to call EMS or not. The regional distribution of each status and their associations with not calling EMS were presented. Results: The status of unaware and low-income, unaware-only, and low-income-only accounted for 6.3% (11,806/187,673), 11.9% (22,241/187,673), and 21.5% (40,289/187,673) of the total sample, respectively. Not calling EMS was significantly associated with the status of unaware and low-income (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 3.07–3.35), unaware-only (OR: 2.38, 95% CI: 2.31–2.46), and low-income-only (OR: 1.67, 95% CI: 1.63–1.71), compared with the aware and regular income status. The Midwest regions had higher percentages of people in the unaware and low-income status; the East, South, and Central had higher percentages of unaware-only status; the North and Northeast regions had a higher percentage of low-income-only status, compared with other regions. Conclusion: The existence of the regional difference in unawareness and low income justifies the specific stroke education strategies for the targeted regions and population.
Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke.
Abstract Background Sugammadex reverses neuromuscular blockade induced by steroidal relaxants. We compared the recovery for neuromuscular blockade reversal with sugammadex in children aged 1–12 years. Methods From August 2019 to August 2020, patients who received 2.0 mg·kg − 1 sugammadex for neuromuscular blockade reversal after surgery were recruited. The primary outcome was the time for the train-of-four ratio (TOFR) to recover to 0.9; secondary outcomes included the incidence of the TOFR < 0.9, extubation time, length of stay at the post-anesthesia care unit, and adverse events. Hemodynamic parameters before and 5 min after sugammadex administration and vital signs in the recovery room were also recorded. Results Eighty-six children were recruited (1 to < 3 years, n = 23; 3 to < 5 years, n = 33; 5 to ≤12 years, n = 30). Intergroup differences in the recovery of the TOFR to 0.9 were not statistically significant (F = 0.691, p = 0.504). Recurrence of the TOFR < 0.9 was not observed in any group. Five minutes after sugammadex administration, the heart rates of patients aged 3 to < 5 and 5 to ≤12 years were significantly lower than those at baseline ( p < 0.05). Extubation time was similar in patients aged 1 to ≤12 years. Length of stay and end-tidal capnography at the post-anesthesia care unit as well as adverse events did not differ significantly. Conclusion A moderate (TOF count two) rocuronium-induced neuromuscular blockade can be effectively and similarly reversed with sugammadex 2 mg·kg − 1 in Chinese children aged 1–12 years. Trial registration Chinese Clinical Trial Registry: ChiCTR1900023715 (June 8, 2019).
Statins are 3-hydroxy-3-methyl glutaryl (HMG)-coenzyme A (CoA) reductase inhibitors, acting on the rate-limiting enzyme for the conversion of HMG-CoA to L-mevalonate to reduce cholesterol biosynthesis. Apart from reducing cardiovascular events by lowering low-density lipoprotein cholesterol concentrations, pleiotropic cholesterol-independent functions of statins, including immunomodulatory and anti-inflammatory effects, are increasingly recognized. The current coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),[1] has caused >500,000 deaths worldwide as of July 2, and it continues to spread without specific antiviral therapies. Statins, with potential antiviral functions as a host-directed therapy (HDT), could be a safe means of improving outcomes for patients with COVID-19.[2,3] Clinical Evidence Statin use reduces viral infection and improves clinical outcomes in patients with influenza,[4] human immunodeficiency virus (HIV), and other viruses.[3] It markedly and dose-dependently reduces mortality from influenza.[4] Studies on patients with HIV found that statins reduce viral copies and lower markers of inflammation, including high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α).[5] Among all COVID-19 patients, 60.7% show CRP ≥10 mg/L, rising to 81.5% in those with severe disease.[6] RNAemia, immune dysregulation, and elevated serum cytokines, such as interleukin (IL)-6, IL-10, and TNF-α, have been observed and might indicate disease severity.[7] Another finding was that coexisting cardiovascular diseases are more frequent in patients with severe disease and are associated with poor prognosis for COVID-19.[6] Since statins show antiviral, anti-inflammatory, and immunomodulatory effects, they might be effective for COVID-19 treatment and reducing cardiovascular events in those with underlying cardiovascular diseases.[3] However, more clinical studies are needed to decide whether statin treatment should be started for patients without underlying cardiovascular diseases. Although statins have a well-established, safe therapeutic profile, their use is not risk-free. Side effects include rhabdomyolysis, statin-induced necrotizing autoimmune myopathy, new onset diabetes mellitus, and potential hemorrhagic stroke, which appear to be dose-dependent for common types of statins.[8] Meanwhile, patients with COVID-19 might show serum creatine kinase ≥ 200 U/L (13.7% of patients) and rhabdomyolysis (0.2%),[6] suggesting that statin use could increase myopathy frequency. In addition, studies on influenza have found that statin use reduces the effectiveness of vaccines against medically attended acute respiratory illness.[9] As such, the potential side effects of statins during future COVID-19 vaccination should be considered. Another concern is that statin-induced IL-18 production might increase COVID-19 severity via cytokine storms,[10,11] but this is unconfirmed. Pre-clinical evidence Antiviral function SARS-CoV-2 is a member of the betacoronavirus (β-CoVs), similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).[1] Ongoing virological studies on SARS-CoV-2 have shown that angiotensin converting enzyme 2 (ACE2) is a receptor bound by SARS-CoV-2 for cell entry,[12] similar to that with SARS-CoV, which uses spike glycoproteins (S protein) on the viral envelope for binding. Depleting cholesterol in ACE2-expressing cells decreases ACE-S protein binding by 50%,[13] indicating that decreased cholesterol levels in host cells might inhibit SARS-CoV-2 replication, as lipid rafts and cholesterol are required for SARS-CoV entry into host cells. Such inhibitory effects on CoV entry could be restored by the addition of exogenous cholesterol. In addition, statins inhibit HMG-CoA reductase, resulting in reduced mevalonate synthesis and suppressed cholesterol production,[3] and cholesterol is required by viruses for replication.[2] For example, influenza virus causes infected cells to produce lipid droplets, potentially as materials for their lipid components, but this can be effectively inhibited by atorvastatin, resulting in reduced viral replication.[14] Third, statins also inhibit the downstream production of lipid isoprenoid intermediates such as farnesyl pyrophosphate and geranyl-geranyl pyrophosphate, which are crucial for host-cell protein prenylation functions.[3,15] During prenylation, isoprenoids are required for G protein subunits such as Ras, Rab, Rho, Rac, and Rap, as their activation induces host cell proliferation or inflammatory factor production.[3] For example, statins directly inhibit HIV via Rho pathway downregulation.[16] Defined as detectable serum SARS-CoV-2 viral loads, RNAemia was observed in patients with COVID-19 and can trigger cytokine storms, which was associated with increased IL-6 levels and poor prognosis.[7] Statins might decrease the risk of RNAemia and reduce respiratory viral loads, which might help suppress transmission.[17] Anti-inflammatory function In clinical practice, the uncontrolled hyperproduction of cytokines and chemokines such as IL-6, IL-8, TNF-α, interferon (IFN), C-C motif chemokine 8, and C-X-C motif chemokine ligand 10 (CXCL10) can have disastrous consequences. In an in vitro study, imbalanced host responses to SARS-CoV-2 have been reported, as inhibited innate antiviral defense coexists with the excess release of inflammatory cytokines, especially IL-6, which is in line with highly elevated IL-6 in COVID-19 patients.[7,18] Statins can markedly reduce pro-inflammatory cytokines and chemokines by targeting multiple functions of virus-infected host cells.[19] For example, Rho proteins can increase levels of pro-inflammatory cytokines such as TNF-α and IL-6 via nuclear factor-κB (NF-κB) signaling.[3,19] Statins can reduce IL-6 synthesis by inhibiting NF-κB and Rho pathways.[20] To inhibit virus-induced cytokine storms, immunosuppressive therapy has been proposed, with tocilizumab (blocking IL-6 receptors) suggested to treat severe cases. Despite their anti-inflammatory effects, statins have not been investigated for applications to COVID-19. Immunomodulatory function Statins could inhibit major histocompatibility complex (MHC)-II-mediated T-cell activation, affect the ability of phagocytes and lymphocytes, and influence lymphocyte proliferation. Since an increase in this ratio indicates poor prognosis for patients with COVID-19, statins might be helpful as simvastatin decreased CD4+/CD8+ ratio.[21] In addition, lovastatin can attenuate ambient particulate matter-induced recruitment and activation of alveolar polymorphonuclear leukocytes and macrophages, reduce local inflammatory responses, and facilitate foreign particle clearance from lung tissues.[22] However, decreased T-cell numbers might reduce earlier viral clearance and could be associated with severe cases, thus possibly worsening COVID-19 disease.[23] Third, elevated levels of ACE2 are associated with reduced disease severity in patients and animal models with ARDS,[24,25] whereas atorvastatin could upregulate ACE2 activity in rat models. Although the effects of statins, as an HDT, are antiviral, anti-inflammatory, and immunomodulatory, which will help clinicians design serum or viral biomarkers for statin therapy in COVID-19 patients, these effects are always seen together. We noticed that although high-dose statins might be more effective against viral infections,[4,26] the effects might vary depending on the type of statin, dose, treatment duration, and disease severity; this will need to be carefully assessed to avoid exacerbating COVID-19 or producing deleterious side effects. Unfortunately, no large-scale clinical trial has provided direct evidence regarding the use of statins for COVID-19 patients, indicating the necessities of further in-depth analysis on COVID-19, including pre-clinical and clinical studies. In summary, statins might be useful in inhibiting SARS-CoV-2 replication, suppressing the release of inflammatory factors, and reducing local pulmonary immune responses, thus attenuating cytokine storms and reducing damage to lung tissue, but this warrants further clinical studies. Conflicts of interest None.
Objective
To explore the clinical, hereditary, imaging features and genetic testing results of adult-onset autosomal dominant leukodystrophy (ADLD), hoping to help physicians recognize this rare disease early.
Methods
The first Chinese case of ADLD in a 52-year-old male was reported. Important laboratory data including brain MRI and genetic findings were summarized. The related literatures were also reviewed.
Results
The patient presented with insidious onset of constipation and erectile dysfunction, and then got worse progressively. Brain MRI showed extensive and symmetrical white matter hyperintensities, predominantly involving cerebral white matter and the middle cerebellar peduncles. A duplication of 1-11 coding exons in the LMNB1 gene was identified in this case. Several affected members with a homogeneous phenotype were found in the family.
Conclusion
LMNB1-related ADLD should be considered as a diagnostic possibility for patients with autonomic dysfunction and symmetrical white-matter abnormalities.
Key words:
Leukodystrophy; Chromosome disorders; Genes, dominant; LMNB1 gene
Objective:To investigate the neuromuscular effect of cisatracurium underpropofol Target controlled infusion (TCI) anesthesia or sevoflurane anesthesia.Methods:Forty-eight ASA classⅠorⅡgroup P,paLienls undergoing selective operations(n=24) and Sevooflurane inhalation group (group S n=24) were randomly divided into propofol TCI and sevoflurane groups(group S n=24).Methods:Forty eight patients undergoing selective surgeries were randomized into two groups.After intravenous midazoline 0.15 mg.kg-land fentanyl 4 ug.kg-1,anesthesia maintenance was achieved by sevoflurane inhalation end-tidal concentionl.7 Vol% in group S and remifentainyl(n=24),patients in group P were main- tained by propofol Target controlled and remifentainyl(n=24sinfusion).In all groups neuromusclecular was induced by rocuronium and monitored by using train-of-four(TOF) stimulation ulnar nerve.The onset time,no response time,the time recovering to 25% of control,recover index and TOF ratio(TOFr to 0.25) were recorded.Results:The no response time, the time recovering to 25% of control,recover index and TOF ratio(TOFr to 0.25) were great longer than those in propo- fol-remifentainyl group.(P0.05).But there was no difference in the onset time between the two groups.Conclusion: Propofol TCI-remifentainyl has no effect on neuromuscular of cisatracurium 1 MAC sevoflurane can potentiate the neuromus- cular of cisatracurium.
Anemia and hyperhemoglobin are not common stroke risk factors, and the association between hemoglobin concentration and stroke remains inconclusive. Through searching the literature, the impact of hypo- and hyper-hemoglobin on the risks of incident stroke, mortality, and poor functional prognosis was analyzed. The review revealed a U-shaped relationship between hemoglobin and the risks of incidental ischemic stroke, and mortality of ischemic stroke and intracranial hemorrhage, separately. However, the optimal hemoglobin concentration was undetermined.
Key words:
Stroke; Brain ischemia; Intracranial hemorrhage; Hemoglobins; Anemia; Prognosis
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