Background and Aims:
When the world was frantically searching for a drug effective against the coronavirus disease (COVID)-19, remdesivir, a broad-spectrum anti-viral medication, became a part of the COVID treatment. We planned a study to evaluate improvement in clinical outcomes with remdesivir treatment for five days.
Methods:
Participants more than 40-years old and with moderate to severe COVID-19 but not on mechanical ventilation were randomly assigned into two groups-remdesivir group (34 cases) to receive the study drug intravenous (IV) remdesivir for five days plus the standard care (SC) and non-remdesivir group (36 cases) to receive the SC but not to receive the study drug. Follow-up was continued for 12 days after the beginning of treatment or until discharge/death. Patient's clinical status was assessed by laboratory investigations and physical examination (from day 1 to day 12 on a 4-point ordinal scale and from day 12 to 24 on a 6-point ordinal scale). Oxygen support requirements and adverse events were recorded. The data were entered and analysed using Statistical Package for the Social Sciences (SPSS) version 22.0.
Results:
High-flow oxygen support and non-invasive ventilation was required at baseline by lesser patients in the remdesivir group. In the end, both groups had similar outcomes after adjustment for baseline clinical status. There was no statistical difference in mortality between the two groups (p = 0.749). Patients in both groups had an equal time to recovery. There was no difference in the occurrence of adverse effects of remdesivir between the two groups.
Conclusion:
Remdesivir therapy for five days did not produce improvement in clinical outcomes in moderate to severe COVID-19 cases.
Transplantation of neural progenitors remains a promising therapeutic approach to spinal cord injury (SCI), but the anatomical and functional evaluation of their effects is complex, particularly when using human cells. We investigated the outcome of transplanting human glial-restricted progenitors (hGRP) and astrocytes derived from hGRP (hGDA) in spinal cord contusion with respect to cell fate and host response using athymic rats to circumvent xenograft immune issues. Nine days after injury hGRP, hGDA, or medium were injected into the lesion center and rostral and caudal to the lesion, followed by behavioral testing for 8 weeks. Both hGRP and hGDA showed robust graft survival and extensive migration. The total number of cells increased 3.5-fold for hGRP, and twofold for hGDA, indicating graft expansion, but few proliferating cells remained by 8 weeks. Grafted cells differentiated into glia, predominantly astrocytes, and few remained at progenitor state. About 80% of grafted cells around the injury were glial fibrillary acidic protein (GFAP)-positive, gradually decreasing to 40-50% at a distance of 6 mm. Conversely, there were few graft-derived oligodendrocytes at the lesion, but their numbers increased away from the injury to 30-40%. Both cell grafts reduced cyst and scar formation at the injury site compared to controls. Microglia/macrophages were present at and around the lesion area, and axons grew along the spared tissue with no differences among groups. There were no significant improvements in motor function recovery as measured by the Basso, Beattie, and Bresnahan (BBB) scale and grid tests in all experimental groups. Cystometry revealed that hGRP grafts attenuated hyperactive bladder reflexes. Importantly, there was no increased sensory or tactile sensitivity associated with pain, and the hGDA group showed sensory function returning to normal. Although the improved lesion environment was not sufficient for robust functional recovery, the permissive properties and lack of sensory hypersensitivity indicate that human GRP and astrocytes remain promising candidates for therapy after SCI.
An abundance of protein gene product 9.5 reactive nerve fibers indicates an extensive innervation of the cervical facet joint capsules. The presence of substance P and calcitonin gene-related peptide reactive nerve fibers in a population of these lends credence to cervical facet joint capsules as a key source of neck pain.
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