Isolation and comparative analysis of antibodies that broadly neutralize sarbecoviruses

The devastation caused by SARS-CoV-2 has made clear the importance of pandemic preparedness. To address future zoonotic outbreaks due to related viruses in the sarbecovirus subgenus, we identified a human monoclonal antibody, 10-40, that neutralized or bound all sarbecoviruses tested in vitro and protected against SARS-CoV-2 and SARS-CoV in vivo. Comparative studies with other receptor-binding domain (RBD)-directed antibodies showed 10-40 to have the greatest breadth against sarbecoviruses and thus its promise as an agent for pandemic preparedness. Moreover, structural analyses on 10-40 and similar antibodies not only defined an epitope cluster in the inner face of the RBD that is well conserved among sarbecoviruses, but also uncovered a new antibody class with a common CDRH3 motif. Our analyses also suggested that elicitation of this class of antibodies may not be overly difficult, an observation that bodes well for the development of a pan-sarbecovirus vaccine. One sentence summaryA monoclonal antibody that neutralizes or binds all sarbecoviruses tested and represents a reproducible antibody class.

Neuropathic Pain after Adolescent Idiopathic Scoliosis Correction Surgery.

STUDY DESIGN: Prospective study. PURPOSE: To investigate the prevalence and the associated risk factors of chronic neuropathic pain symptoms using painDETECT questionnaire in adolescent idiopathic scoliosis (AIS) patients who underwent posterior spinal fusion (PSF) surgery. OVERVIEW OF LITERATURE: Post-lumbar surgery syndrome is a disease entity that describes neuropathic pain following spinal surgery. However, few studies have investigated the prevalence and risk factors for neuropathic pain in pediatric population undergoing corrective spinal surgery. METHODS: Forty AIS patients were recruited. Demographic, preoperative, and postoperative data were recorded. The magnitude and characteristics of postoperative pain were assessed using the painDETECT questionnaire through telephone enquiries at intervals of 2, 6, 12, and 24 weeks. Statistical analyses were followed by Pearson correlation test to determine the relationship between pain scores at 6, 12, and 24 weeks with the risk factors. RESULTS: Based on the painDETECT questionnaire, 90% of the patients had nociceptive pain, and 10% had a possible neuropathic pain component at 2 weeks postoperatively as per a mean painDETECT score of 7.1±4.5. Assessments at 6, 12, and 24 weeks showed that no patients had neuropathic pain with painDETECT scores of 4.4±3.2, 2.9±2.9, and 1.5±2.0, respectively. There was a significant correlation between total postoperative morphine use during 48 hours after the surgery and a tendency to develop neuropathic pain (p=0.022). CONCLUSIONS: Chronic neuropathic pain was uncommon in AIS patients who had undergone PSF surgery. Higher opioid consumption will increase the possibility of developing chronic neuropathic pain.

Neuropathic Pain after Adolescent Idiopathic Scoliosis Correction Surgery

Methods@#Forty AIS patients were recruited. Demographic, preoperative, and postoperative data were recorded. The magnitude and characteristics of postoperative pain were assessed using the painDETECT questionnaire through telephone enquiries at intervals of 2, 6, 12, and 24 weeks. Statistical analyses were followed by Pearson correlation test to determine the relationship between pain scores at 6, 12, and 24 weeks with the risk factors. @*Results@#Based on the painDETECT questionnaire, 90% of the patients had nociceptive pain, and 10% had a possible neuropathic pain component at 2 weeks postoperatively as per a mean painDETECT score of 7.1±4.5. Assessments at 6, 12, and 24 weeks showed that no patients had neuropathic pain with painDETECT scores of 4.4±3.2, 2.9±2.9, and 1.5±2.0, respectively. There was a significant correlation between total postoperative morphine use during 48 hours after the surgery and a tendency to develop neuropathic pain (p=0.022). @*Conclusions@#Chronic neuropathic pain was uncommon in AIS patients who had undergone PSF surgery. Higher opioid consumption will increase the possibility of developing chronic neuropathic pain.

Surgical reduction technique (transpedicle) for unstable thoracolumbar burst fractures with retropulsion resulting in severe spinal canal stenosis: a preliminary case report.

Thoracolumbar burst fractures are common entity in polytraumatized patients. The retropulsed burst vertebral fracture may result in spinal canal invasion with or without neurological deficit. In this situation, early surgical stabilization with decompression is vital to restore neurological function. We employed a posterior approach with a unique transpedicular reduction technique at the level of fracture for decompression and stabilisation.

Prediction of height increment using preoperative radiological parameters following selective thoracic fusion with alternate-level pedicle screw construct in Lenke 1 and 2 adolescent idiopathic scoliosis patients.

PURPOSE: This study aims to derive a formula to predict post-operative height increment in Lenke 1 and Lenke 2 adolescent idiopathic scoliosis (AIS) patients using preoperative radiological parameters. METHODS: This study involved 70 consecutive Lenke 1 and 2 AIS patients who underwent scoliosis correction with alternate-level pedicle screw instrumentation. Preoperative parameters that were measured included main thoracic (MT) Cobb angle, proximal thoracic (PT) Cobb angle, lumbar Cobb angle as well as thoracic kyphosis. Side-bending flexibility (SBF) and fulcrum-bending flexibility (FBF) were derived from the measurements. Preoperative height and post-operative height increment was measured by an independent observer using a standardized method. RESULTS: MT Cobb angle and FB Cobb angle were significant predictors ( p < 0.001) of height increment from multiple linear regression analysis ( R = 0.784, R2 = 0.615). PT Cobb angle, lumbar, SB Cobb angle, preoperative height and number of fused segment were not significant predictors for the height increment based on the multivariable analysis. Increase in post-operative height could be calculated by the formula: Increase in height (cm) = (0.09 × preoperative MT Cobb angle) - (0.04 x FB Cobb angle) - 0.5. CONCLUSION: The proposed formula of increase in height (cm) = (0.09 × preoperative MT Cobb angle) - (0.04 × FB Cobb angle) - 0.5 could predict post-operative height gain to within 5 mm accuracy in 51% of patients, within 10 mm in 70% and within 15 mm in 86% of patients.

Biomechanical comparison between cortical screw-rod construct versus pedicle screw-rod construct in transforaminal lumbar interbody fusion.

OBJECTIVE: To compare construct stiffness of cortical screw (CS)-rod transforaminal lumbar interbody fusion (TLIF) construct (G2) versus pedicle screw (PS)-rod TLIF construct (G1) in the standardized porcine lumbar spine. METHODS: Six porcine lumbar spines (L2-L5) were separated into 12 functional spine units. Bilateral total facetectomies and interlaminar decompression were performed for all specimens. Non-destructive loading to assess stiffness in lateral bending, flexion and extension as well as axial rotation was performed using a universal material testing machine. RESULTS: PS and CS constructs were significantly stiffer than the intact spine except in axial rotation. Using the normalized ratio to the intact spine, there is no significant difference between the stiffness of PS and CS: flexion (1.41 ± 0.27, 1.55 ± 0.32), extension (1.98 ± 0.49, 2.25 ± 0.44), right lateral flexion (1.93 ± 0.57, 1.55 ± 0.30), left lateral flexion (2.00 ± 0.73, 2.16 ± 0.20), right axial rotation (0.99 ± 0.21, 0.83 ± 0.26) and left axial rotation (0.96 ± 0.22, 0.92 ± 0.25). CONCLUSION: The CS-rod TLIF construct provided comparable construct stiffness to a traditional PS-rod TLIF construct in a 'standardized' porcine lumbar spine model.

Accuracy and Safety of Pedicle Screw Placement in Adolescent Idiopathic Scoliosis Patients: A Review of 2020 Screws Using Computed Tomography Assessment.

STUDY DESIGN: Retrospective review of CT scan. OBJECTIVE: To investigate the accuracy and safety of pedicle screws placed in adolescent idiopathic scoliosis (AIS) patients. SUMMARY OF BACKGROUND DATA: The reported pedicle screws perforation rates for corrective AIS surgery vary widely from 1.2% to 65.0%. Knowledge regarding the safety of pedicle screws in scoliosis surgery is very important in preventing complications. METHODS: This study investigates the accuracy and safety of pedicle screws placed in 140 AIS patients. CT scans were used to assess the perforations that were classified according to Rao et al (2002): grade 0, grade 1 (<2 mm), grade 2 (2-4 mm), and grade 3 (>4 mm). Anterior perforations were classified into grade 0, grade 1 (<4 mm), grade 2 (4-6 mm), and grade 3 (>6 mm). Grade 2 and 3 (excluding lateral grade 2 and 3 perforation over thoracic vertebrae) were considered as critical perforations. RESULTS: A total of 2020 pedicle screws from 140 patients were analyzed. The overall total perforation rate was 20.3% (410 screws) with 8.2% (166 screws) grade 1, 2.9% (58 screws) grade 2 and 9.2% (186 screws) grade 3 perforations. Majority of the perforations was because of lateral perforation occurring over the thoracic region, as a result of application of extrapedicular screws at this region. When the lateral perforations of the thoracic region were excluded, the perforation rate was 6.4% (129 screws), grade 2, 1.4% (28 screws) and grade 3, 0.8% (16 screws). There were only two symptomatic left medial grade 2 perforations: one screw at T12 presented with postoperative iliac crest numbness and another screw at L2 presented with radicular pain that subsided with conservative treatment. There were six anterior perforations abutting the right lung, four anterior perforations abutting the aorta, two anterior perforations abutting the esophagus, and one abutting the trachea was noted. CONCLUSION: Pedicle screws insertion in AIS has a total perforation rate of 20.3%. After exclusion of lateral thoracic perforations, the overall perforation rate was 8.6% with a critical perforation rate of 2.2% (44/2020). The rate of symptomatic screw perforation leading to radicular symptoms was 0.1%. There was no spinal cord, aortic, esophageal, or lung injuries caused by malpositioned screws in this study. LEVEL OF EVIDENCE: 4.

COMPLEXO: identifying the missing heritability of breast cancer via next generation collaboration.

Linkage analysis, positional cloning, candidate gene mutation scanning and genome-wide association study approaches have all contributed significantly to our understanding of the underlying genetic architecture of breast cancer. Taken together, these approaches have identified genetic variation that explains approximately 30% of the overall familial risk of breast cancer, implying that more, and likely rarer, genetic susceptibility alleles remain to be discovered.