The effectiveness of pre-contoured titanium alloy rods in inducing thoracic kyphosis after sequential spinal releases in an in vitro biomechanical model

PurposeEvaluate the ability of pre-contoured rods to induce thoracic kyphosis (TK) in human cadaveric spines and determine the effectiveness of sequential surgical adolescent idiopathic scoliosis (AIS) release procedures.MethodsSix thoracolumbar (T3-L2) spine specimens were instrumented with pedicle screws bilaterally (T4–T12). Over correction using pre-contoured rods was performed for intact condition and Cobb angle was measured. Rod radius of curvature (RoC) was measured pre- and post-reduction. The process was repeated following sequential release procedures of (1) interspinous and supraspinous ligaments (ISL); (2) ligamentum flavum; (3) Ponte osteotomy; (4) posterior longitudinal ligament (PLL); and (5) transforaminal discectomy. Cobb measurements determined the effective contribution of release on TK and RoC data displayed effects of reduction to the rods.ResultsThe intact TK (T4–12) was 38.0° and increased to 51.7° with rod reduction and over correction. Each release resulted in 5°–7°of additional kyphosis; the largest releases were ISL and PLL. All releases resulted in significant increases in kyphosis compared to intact with rod reduction and over correction. Regionally, kyphosis increased ∼2° for each region following successive releases. Comparing RoC before and after reduction showed significant 6° loss in rod curvature independent of release type.ConclusionKyphosis increased in the thoracic spine using pre-contoured and over corrected rods. Subsequent posterior releases provided a substantial, meaningful clinical change in the ability to induce additional kyphosis. Regardless of the number of releases, the ability of the rods to induce and over correct kyphosis was reduced following reduction

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Ten-year Outcomes of Cervical Disc Replacement With the BRYAN Cervical Disc: Results From a Prospective, Randomized, Controlled Clinical Trial.

STUDY DESIGN: A prospective, randomized multicenter IDE trial between May 2002 and October 2004. OBJECTIVE: The aim of this study was to report on the 10-year safety and efficacy of BRYAN cervical disc arthroplasty (CDA). SUMMARY OF BACKGROUND DATA: Cervical disc arthroplasty (CDA) is a potential alternative for anterior cervical decompression and fusion (ACDF) with the hope that maintenance of motion may decrease the likelihood of adjacent segment disease. METHODS: This is an analysis of a US Food and Drug Administration (FDA) investigation comparing CDA with ACDF for single-level patients. Eligible patients were ≥ 21 years of age with symptomatic cervical disc disease who had failed conservative care. Patients were followed at regular intervals with the current data set at \u3e 10 years. Protocol for overall success: ≥ 15-point improvement in NDI scores, maintenance or improvement in neurologic status, no serious adverse events related to implant or implant/surgical procedure, and no subsequent surgery or intervention classified as failure. RESULTS: At 10-year follow-up, 128 (CDA) and 104 (ACDF) patients were available for evaluation. Overall success rate was significantly higher for CDA group (81.3% vs. 66.3%; P = 0.005). The rate of second surgeries at adjacent levels was lower for CDA group (9.7% vs. 15.8%; P = 0.146). NDI scores improved significantly in CDA group (Δ38.3 vs. Δ31.1; P = 0.010). Visual Analog Scale (VAS) neck and arm improved in the CDA group (Δ54.3 vs. Δ49.2; P = 0.119), (Δ58.1 vs. Δ51.6; P = 0.0.60) respectively. About 4.1% of CDA patients and 4.9% of ACDF patients had serious adverse events related to study device. Mean angular motions at index level for BRYAN disc and ACDF were 8.69° and 0.60°, respectively. CONCLUSION: CDA can preserve and maintain motion in the long term compared with ACDF. There was a trend toward fewer adjacent segment surgeries for BRYAN disc that did not reach significance. Significant improvement in CDA NDI scores may suggest better long-term success for CDA as compared to fusion. LEVEL OF EVIDENCE: 2