Since the emergence of coronavirus disease 2019 (Covid-19), many studies have been performed to characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and find the optimum way to combat this virus. After suggestions and assessments of several therapeutic options, remdesivir (GS-5734), a direct-acting antiviral drug previously tested against Ebola virus disease, was found to be moderately effective and probably safe for inhibiting SARS-CoV-2 replication. Finally, on 1 May 2020, remdesivir (GS-5734) was granted emergency use authorization as an investigational drug for the treatment of Covid-19 by the Food and Drug Administration. However, without a doubt, there are challenging days ahead. Here, we provide a review of the latest findings (based on preprints, post-prints, and news releases in scientific websites) related to remdesivir efficacy and safety for the treatment of Covid-19, along with covering remdesivir history from bench-to-bedside, as well as an overview of its mechanism of action. In addition, active clinical trials, as well as challenging issues related to the future of remdesivir in Covid-19, are covered. Up to the date of writing this review (19 May 2020), there is one finished randomized clinical trial and two completed non-randomized studies, in addition to some ongoing studies, including three observational studies, two expanded access studies, and seven active clinical trials registered on the clinicaltrials.gov and isrctn.com websites. Based on these studies, it seems that remdesivir could be an effective and probably safe treatment option for Covid-19. However, more randomized controlled studies are required.
Background Several inflammatory and vascular molecules, and neurotrophins have been suggested to have a possible role in the development of migraine. However, pathophysiological events leading to migraine onset and transformation of episodic migraine (EM) to chronic migraine (CM) are not fully understood. Thus, we aimed to assess peripheral levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in EM and CM patients, and controls. Methods From September 2017 to June 2020, 89 subjects were enrolled in a case-control study; 23 and 36 EM and CM patients, respectively, and 30 age and sex-matched controls. Demographic data and medical history were obtained from all patients. Headache characteristics were recorded at baseline visit and ensuing 30 days for persons with migraine disease. Serum levels of NGF, BDNF, VEGF, and PGE2 were measured once for controls and EM and CM patients, and adjusted for age, sex, and body mass index. Results Serum levels of NGF were significantly lower in EM patients compared to controls and CM patients (P-value=0.003 and 0.042, respectively). Serum levels of BDNF were significantly lower in EM and CM patients as opposed to controls (P-value<0.001), but comparable between EM and CM patients (P-value=0.715). Peripheral blood levels of VEGF were significantly higher in EM and CM patients as opposed to controls (P-value<0.001), but not different between EM and CM patients (P-value=0.859). Serum levels of PGE2 were significantly lower in EM patients compared to controls (P-value=0.011), however similar between EM and CM patients (P-value=0.086). In migraine patients, serum levels of NGF and PGE2 positively correlated with headache frequency (NGF: ρ = 0.476 and P-value<0.001; PGE2: ρ = 0.286 and P-value=0.028), while corresponding levels of BDNF and VEGF did not correlate with headache frequency (BDNF: ρ = 0.037 and P-value=0.778; VEGF: ρ= -0.025 and P-value=0.850). Conclusions Our findings suggest that NGF, BDNF, PGE2, and VEGF may play a significant role in migraine pathogenesis and/or chronification, and therefore might bear potential value for novel targeted abortive and prophylactic migraine therapy. Further prospective cohort studies with larger sample sizes can more robustly evaluate the implications of these findings.
Background Cranial autonomic symptoms are common in migraine, with eye redness and tearing being the most common ones. Their identification can help to avoid misdiagnosis, predict the disease course, and select the appropriate treatment. Methods This was a cross-sectional study of 904 patients who presented with migraine to a headache referral clinic. The participants filled out a questionnaire about their headache characteristics, as well as the presence of cranial autonomic symptoms. A total of 904 patients, 698 women (77.2%) and 206 men (22.8%), were included in the study, with a mean (SD) age of 38.05 (11.76) years. Results About 70% of subjects with chronic migraine and 56.2% of those with episodic migraine reported one or more cranial autonomic symptoms. The two most commonly reported autonomic symptoms were eye redness (36.06%) and tearing (21.02%). Chronic migraine (43.4% vs. 29.5%), unilateral headache (56.8% vs. 48.7%), and blurred vision (20% vs. 14.7%) were significantly more frequent in migraineurs with cranial autonomic symptoms. Headache intensity and frequency in subjects with cranial autonomic symptoms were significantly higher than in those without cranial autonomic symptoms. Conclusion We found higher percentages of cranial autonomic symptoms in patients with unilateral headaches, frequent and severe attacks and blurred vision. A diagnosis of cranial autonomic symptoms accompanying migraine may predict more severe disease and the possibility of evolution into chronic migraine.
Background Undifferentiated arthritis is a condition in which the problem cannot be classified into any definite diagnosis category. Various methods have been suggested to clarify the definite diagnosis in this class. The synovial biopsy is suggested as the last diagnostic approach to determine the precise histopathological diagnosis. In this study, we aimed to evaluate the efficacy of synovial biopsy for establishing a definite diagnosis in patients with undifferentiated chronic knee monoarthritis. Methods The present retrospective case series was conducted in 2005 in the rheumatology research center of Shariati hospital and the 501 hospital in Tehran, Iran. The study included the synovial biopsy of patients with chronic knee monoarthritis who did not have a definite diagnosis after all the diagnostic steps before the synovial biopsy. Pathology slides of the patients’ synovial biopsy were reevaluated with a senior expert pathologist. Results Eighty patients with a mean age of 37.6 ± 17.32 years (range: 6–68) were included, of whom 50% were female. The gap time between the onset of knee monoarthritis and the decision-making for synovial biopsy was 14.34 ± 19.61 months. Histopathologic evaluations revealed non-specific synovitis in 65% of the patients and a definite diagnosis in 35%. The most common definite diagnosis was rheumatoid arthritis (9%), followed by septic arthritis (5%). The most common pathologic findings were endothelial proliferation (89%) and synovial proliferation (88%), and the most common infiltrating cell was lymphocyte (54%). Patients with non-specific synovitis were more likely to have neovascularization, cellular infiltration (p-value < 0.001), synovial proliferation, endothelial proliferation (p-value = 0.001), pannus formation (p-value = 0.009), and fibrosis (p-value = 0.022) compared to the patients with a definite pathologic diagnosis. However, age, gender, and the gap time between disease symptoms to synovial biopsy were not significantly different between the different groups of diagnosis (p-value > 0.05). Conclusion Non-specific synovitis remains the most common histopathologic finding, highlighting the importance of physician expert opinion for most of the patients with undifferentiated chronic knee monoarthritis. Studies with larger samples and immunohistochemistry analyses are needed to clarify this uncategorized entity further.
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