Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Ectomesenchymal Hamartoma (Benign ectomesenchymoma ) of the VIIIth Nerve: Case Report

WE REPORT A previously undescribed hamartoma of the VIIIth nerve, consisting of adipose tissue, Schwann cells associated with myelinated nerve fibers, well-differentiated smooth and striated muscle fibers, and rare ganglion cells. The tumor was found in a 35-year-old Caucasian female who presented with right-sided hearing loss. The mass, which we designate an “ectomesenchymal†hamartoma, most likely developed from pluripotent neural crest cells (“ectomesenchymeâ€), which are capable of differentiating into a variety of neuroectodermal and mesenchymal cell types. The development of the neural crest, the concept of “ectomesenchyme,†and the histogenesis of this tumor are reviewed. Copyright © by the Congress of Neurological Surgeons

Surgical of Superficial Siderosis Associated With a Treatment Spinal Arteriovenous Malformation

In many patients with superficial siderosis of the central nervous system (CNS) no source of bleeding can be established, despite extensive examinations. The authors report a patient with superficial siderosis and a spinal arteriovenous malformation (AVM) that was not visible on magnetic resonance (MR) imaging or myelography but was identified on angiographic studies. This 71-year-old man presented with a 2-year history of progressive gait difficulties and heating loss. Examination showed ataxia, hearing loss, and quadriparesis. On MR imaging superficial siderosis of the brain and spinal cord as seen; however, MR imaging of the CNS, as well as cerebral angiography and myelography studies, did not reveal the source of hemorrhage. Spinal angiography revealed a small slow-flow pial AVM at the C-5 level originating from the anterior spinal artery. A C-5 corpectomy was performed and the AVM was obliterated. The patient did well and reported no further progression of his symptoms during 3 months of follow up. Spinal angiography is indicated to complete the evaluation of patients with superficial siderosis, even if results of spinal MR imaging and myelography studies are normal. Obliteration of spinal AVMs may successfully prevent the progression of superficial siderosis

Dynamics of synapsin I gene expression during the establishment and restoration of functional synapses in the rat hippocampus

Synapse development and injury-induced reorganization have been extensively characterized morphologically, yet relatively little is known about the underlying molecular and biochemical events. To examine molecular mechanisms of synaptic development and rearrangement, we looked at the developmental pattern of expression of the neuron-specific gene synapsin I in granule cell neurons of the dentate gyrus and their accompanying mossy fibers during the main period of synaptogenic differentiation in the rat hippocampus. We found a significant difference between the temporal expression of synapsin I messenger RNA in dentate granule somata and the appearance of protein in their mossy fiber terminals during the postnatal development of these neurons. Next, to investigate the regulation of neuron-specific gene expression during the restoration of synaptic contacts in the central nervous system, we examined the expression of the synapsin I gene following lesions of hippocampal circuitry. These studies show marked changes in the pattern and intensity of synapsin I immunoreactivity in the dendritic fields of dentate granule cell neurons following perforant pathway transection. In contrast, changes in synapsin I messenger RNA expression in target neurons, and in those neurons responsible for the reinnervation of this region of the hippocampus, were not found to accompany new synapse formation. On a molecular level, both developmental and lesion data suggest that the expression of the synapsin I gene is tightly regulated in the central nervous system, and that considerable changes in synapsin I protein may occur in neurons without concomitant changes in the levels of its messenger RNA. Finally, our results suggest that the appearance of detectable levels of synapsin I protein in in developing and sprouting synapses coincides with the acquisition of function by those central synapses

Intra-Aortic Balloon Pump Counterpulsation in the Management of Concomitant Cerebral Vasospasm and Cardiac Failure After Subarachnoid Hemorrhage: Technical Case Report

WE REPORT TWO patients who had symptomatic cerebral vasospasm and cardiac failure after aneurysmal subarachnoid hemorrhage and who were treated successfully with intra-aortic balloon pump counterpulsation therapy. Both patients developed congestive heart failure and pulmonary edema while receiving postoperative hypertensive, hypervolemic, hemodilutional (Triple- H) therapy for symptomatic cerebral vasospasm. Both cases of cardiac failure were refractory to maximum pressor and inotropic infusions. Intra-aortic balloon pump counterpulsation was used to optimize cardiac performance to allow continuation of Triple-H therapy and to maintain adequate cerebral perfusion in an attempt to decrease the risk of cerebral ischemic complications. Both patients have had good long-term outcomes. These two cases illustrate the potential usefulness of the intra-aortic balloon pump as an adjunct to Triple-H therapy in patients with symptomatic cerebral vasospasm and cardiac failure. To our knowledge, this report documents the first clinical application of this adjunctive therapy for vasospasm after aneurysmal subarachnoid hemorrhage

Threaded Steinmann Pin Fusion of the Craniovertebral Junction

Study Design. In a clinical retrospective study, the authors review Long-term results of occipitocervical fusion using a wide diameter, contoured, threaded Steinmann pin. Objectives. To evaluate the clinical and radiographic results of occipitocervical fusion using this technique in a variety of abnormalities including rheumatoid arthritis. Summary of Background Data. The various surgical techniques and hardware developed for occipitocervical fusion have been associated with mixed results, particularly in patients with rheumatoid arthritis or basilar invagination. Methods. Thirty-nine patients with occipitocervical instability were internally fixed with a wide diameter, contoured, threaded Steinmann pin wired to the occiput and cervical laminae or facets. Fusion was facilitated using autologous iliac crest bone graft and a cervical orthosis. Instability resulted from rheumatoid arthritis (n = 12), congenital anomalies (n = 12), trauma (n = 10), tumor (n = 4), or osteogenesis imperfects (n = 1). Fifteen patients had radiographic evidence of basilar invagination. Long-term outcome (mean follow-up period, 38.9 months; range, 12-78 months) was based on clinical and radiographic review. Results. Thirty-seven patients (97%) had a stable postoperative occipitocervical construct: there were 35 osseous unions, two fibrous unions, and one nonunion. There was one postoperative death from pulmonary complications. No patient developed evidence of new, recurrent, or progressive basilar invagination. Conclusion. The authors concluded that rigid segmental fixation of the craniovertebral junction using a wide diameter, contoured, threaded Steinmann pin end supplemental autograft creates excellent fusion with minimal complications. This technique is appropriate for a variety of abnormalities including rheumatoid arthritis

Biomechanical analysis of multilevel cervical corpectomy and plate constructs

Object. The authors compared the biomechanical stability of two multilevel cervical constructs involving the placement of equal size anterior cervical plates (ACPs) after decompressive surgery: the first is placed after three-level corpectomy with strut graft and the second after two-level corpectomy and aggressive discectomy with strut graft. In addition, both constructs were evaluated with and without the application of a screw attaching the ACP to the strut graft to determine whether the additional screw enhanced stability in any mode of loading. Methods. Nondestructive repeated- measures in vitro flexibility tests were performed in human cadaveric cervical spines. Nonconstraining pure moments of up to 1.5 Nm were applied while recording three-dimensional angular motion stereophotogrammetrically at each level from C4-5 to C7-T1. Nine specimens underwent the three-level corpectomy/strut graft procedure and eight specimens the two-level corpectomy/discectomy strut graft procedure. Failures during testing eliminated two of the former specimens and three of the latter specimens from analysis. The construct applied after the two-level procedure allowed a significantly smaller normalized neutral zone during flexion-extension than the three-level construct (p = 0.04). Normalized elastic zone and range of motion were consistently smaller in the two- than in the three-level construct, but the differences were not significant. Addition of a screw to the strut graft significantly reduced motion in the three-level procedure-treated specimens during flexion and lateral bending but had no effect on two-level corpectomy-treated specimens. Conclusions. The construct associated with the two-level corpectomy/discectomy provided better immediate postoperative stability than that associated with the three-level corpectomy. The addition of a screw to the strut graft conferred stability on the three-level construct but not the two-level construct