Engineering a "muco-trapping" ACE2-immunoglobulin hybrid with picomolar affinity as an inhaled, pan-variant immunotherapy for COVID-19.

Soluble angiotensin-converting enzyme 2 (ACE2) can act as a decoy molecule that neutralizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by blocking spike (S) proteins on virions from binding ACE2 on host cells. Based on structural insights of ACE2 and S proteins, we designed a "muco-trapping" ACE2-Fc conjugate, termed ACE2-(G4S)6-Fc, comprised of the extracellular segment of ACE2 (lacking the C-terminal collectrin domain) that is linked to mucin-binding IgG1-Fc via an extended glycine-serine flexible linker. ACE2-(G4S)6-Fc exhibits substantially greater binding affinity and neutralization potency than conventional full length ACE2-Fc decoys or similar truncated ACE2-Fc decoys without flexible linkers, possessing picomolar binding affinity and strong neutralization potency against pseudovirus and live virus. ACE2-(G4S)6-Fc effectively trapped fluorescent SARS-CoV-2 virus like particles in fresh human airway mucus and was stably nebulized using a commercial vibrating mesh nebulizer. Intranasal dosing of ACE2-(G4S)6-Fc in hamsters as late as 2 days postinfection provided a 10-fold reduction in viral load in the nasal turbinate tissues by Day 4. These results strongly support further development of ACE2-(G4S)6-Fc as an inhaled immunotherapy for COVID-19, as well as other emerging viruses that bind ACE2 for cellular entry.

Optimising operating theatre (OT) efficiency while maintaining the standardised patient care in adolescent idiopathic scoliosis (AIS) surgery with the dedicated spine team approach: a specialised spine unit experience.

PURPOSE: To report the efficiency of OT utilisation and perioperative outcomes with a dedicated spine team approach in AIS patients who underwent posterior spinal fusion (PSF) surgeries in a consecutive case operation list. METHODS: Three AIS patients operated in a day (8:00 AM-8:00 PM) by a dedicated spine team were recruited between 2021 and 2022. The dedicated team comprised of three senior spine consultants who operated using a dual attending surgeon strategy, an anaesthetic consultant, dedicated surgical scrub nurses, anaesthesiology nurses, radiographers, and neuromonitoring technicians. Patients were categorised according to the sequence of operation list of the day (Case 1, Case 2, and Case 3). OT efficiency was represented by OT time in five stages (preoperative time, operative time, postoperative time, total OT time, and turnover time). OT time and perioperative outcomes were compared. RESULTS: 102 cases were analysed. On average, Case 1 began at 8:38 AM whereas Case 3 ended by 5:54 PM. OT efficiency was consistent throughout the day of operation with comparable OT time in all five stages between groups (p > 0.05). The mean turnover time was 15.1 ± 13.5 min and the mean operative time was 123.0 ± 28.1 min. Intraoperative arterial blood gas (ABG) parameters were maintained in an optimal range. The complication rate was 2.0% (N = 2/102). CONCLUSION: Consistent OT efficiency was demonstrated with a dedicated spine team approach. Despite performing three AIS cases in a consecutive case operation list, patients' safety was not compromised as perioperative outcomes between groups were comparable.

The Impact of Acute Exercise on Hemostasis and Angiogenesis Mediators in Patients With Continuous-Flow Left Ventricular Assist Devices: A Prospective Observational Pilot Study.

Impaired primary hemostasis and dysregulated angiogenesis, known as a two-hit hypothesis, are associated with gastrointestinal (GI) bleeding in patients with continuous-flow left ventricular assist devices (CF-LVADs). Exercise is known to influence hemostasis and angiogenesis in healthy individuals; however, little is known about the effect in patients with CF-LVADs. The objective of this prospective observational study was to determine whether acute exercise modulates two-hit hypothesis mediators associated with GI bleeding in patients with a CF-LVAD. Twenty-two patients with CF-LVADs performed acute exercise either on a cycle ergometer for approximately 10 minutes or on a treadmill for 30 minutes. Blood samples were taken pre- and post-exercise to analyze hemostatic and angiogenic biomarkers. Acute exercise resulted in an increased platelet count (p < 0.00001) and platelet function (induced by adenosine diphosphate, p = 0.0087; TRAP-6, p = 0.0005; ristocetin, p = 0.0009). Additionally, high-molecular-weight vWF multimers (p < 0.00001), vWF collagen-binding activity (p = 0.0012), factor VIII (p = 0.034), angiopoietin-1 (p = 0.0026), and vascular endothelial growth factor (p = 0.0041) all increased after acute exercise. This pilot work demonstrates that acute exercise modulated two-hit hypothesis mediators associated with GI bleeding in patients with CF-LVADs.

Prediction of postoperative curve correction based on the supine radiographs for adult idiopathic scoliosis patients.

BACKGROUND CONTEXT: Preoperative supine radiographs are mandatory in the new adult idiopathic scoliosis (AdIS) classification. Supine radiographs are easily reproducible and highly predictive of side bending radiographs. However, few studies evaluated the use of supine radiographs in predicting postoperative curve correction after posterior spinal fusion (PSF) in AdIS. PURPOSE: To investigate the use of supine and side bending (SB) radiographs in predicting postoperative curve correction in AdIS patients who underwent PSF. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 93 AdIS patients who underwent PSF between 2022 and 2023 were included. OUTCOME MEASURES: Demographic data were age, gender, height, weight, body mass index (BMI), Risser grade, Lenke curve types and Cobb angles. Main outcome measures were preoperative and immediate postoperative Cobb angle (proximal thoracic [PT], main thoracic [MT] and thoracolumbar/lumbar [TL/L] curves), Supine Cobb angle and Flexibility rate (PT, MT and TL/L), and Correction rate (PT, MT and TL/L). METHODS: Correlation study was performed between Supine Cobb angle vs postoperative Cobb angle for PT, MT and TL/L curves. A predictive formula was derived from the correlation plots. RESULTS: A total of 93 subjects were included in our study with a median age of 24.7 years and comprised of 80 females (86.0%). Preoperative Supine Cobb angle (r=0.835, r=0.881, r=0.767, p<.001) and preoperative SB Cobb angle (r=0.815, r=0.872, r=0.801, p<.001) showed similar strong positive correlation with postoperative PT, MT and TL/L Cobb angle, but preoperative Supine Cobb angle had slightly stronger correlation in PT and MT, whereas preoperative SB Cobb angle had stronger correlation in TL/L curve. Using the derived predictive formulae, there was a significant, strong, positive correlation between the predicted value and actual value of postoperative standing Cobb angle, (r=0.852, p<.001), with 71.0% of the patients had predicted postoperative Cobb angle from the supine radiographs within 5° of the actual value. CONCLUSION: Both supine radiographs and side bending radiographs had strong predictability of the postoperative Cobb angle for PT, MT and TL/L curves. In 71.0% of patients, the actual postoperative Cobb angle was within 5° of the predicted postoperative Cobb angle using the predictive formulae.

The widths of the medial and lateral pedicle walls in adolescent idiopathic scoliosis with major thoracic curves.

BACKGROUND CONTEXT: The widths of medial and lateral pedicle walls in the normal spine of middle-aged and elderly adults have been investigated and these studies found that the medial pedicle wall was thicker than the lateral pedicle wall. However, none had evaluated the widths of medial and lateral pedicle walls on adolescent or young adult scoliotic spines. PURPOSE: This study aims to identify the distribution and variation of medial and lateral pedicle wall widths throughout the different vertebral levels of the scoliotic spine and its differences according to age, gender, body mass index (BMI), maturity, curve types and curve severity in adolescent idiopathic scoliotic (AIS) patients with major thoracic curves. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 6,230 pedicles (right: 3,064, left: 3,166) from 191 patients were included in this study, with 264 (right: 183, left: 81) fully corticalized pedicles excluded from analysis. OUTCOME MEASURES: Demographic data were age, gender, height, weight, BMI, Risser grade, Lenke curve types and Cobb angles. The main outcome measures were medial and lateral pedicle wall widths. Associations between pedicle wall widths and demographic data were calculated. METHODS: This was a subanalytical retrospective study done on the same patient population as the previously published study on pedicle grading. The data was obtained from the main computed tomography (CT) scan pedicle study dataset. Medial and lateral pedicle wall widths were measured in the axial slices of CT scans from T1 to L5 vertebrae. RESULTS: A total of 6,230 pedicles (right: 3,064, left: 3,166) from 191 patients were included in this study with 264 (right: 183, left: 81) fully corticalized pedicles excluded from analysis. Right-sided medial pedicle wall widths were narrower from T4-T10 (0.75±0.23 mm) compared to T1-T3 (0.89±0.28 mm) and T11-L5 (0.92±0.30 mm). Left-sided medial pedicle wall widths were narrower from T4 to T7 (0.76±0.24 mm) compared to T1-T3 (0.88±0.26 mm) and T8-L5 (0.90±0.27 mm). Medial cortical wall widths were significantly thicker compared to lateral cortical wall widths for all vertebras from T1 to L5 (right medial 0.85±0.28 mm vs lateral 0.64±0.26 mm (p<.001), left medial 0.86±0.26 mm vs lateral 0.64±0.26 mm (p<.001)). The left medial pedicle wall widths were marginally significantly (p<.001) thicker than the right side (right medial 0.85±0.28 mm vs left 0.86±0.26 mm). The main notable significant differences were located at the periapical region of the thoracic curve between T7 to T10 with the left concave medial pedicle width being thicker than the right convex medial pedicle width. The thinnest medial pedicle walls were located at right concave T7 (0.73±0.24 mm) and T8 (0.73±0.23 mm). We generally found no significant associations between the medial and lateral pedicle wall widths with age, gender, BMI, Risser grade, Cobb angle and curve types. CONCLUSIONS: Knowledge on the widths of medial and lateral pedicle walls, their distribution and differences in a scoliotic spine is important for pedicle screw fixation, especially during pedicle probing to find the pedicle channel. The medial pedicle wall widths were significantly thicker than the lateral pedicle wall widths in AIS patients with major thoracic curves. The right concave periapical region had the thinnest medial pedicle walls.

Analysis of duration of different stages of surgery in posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) patients: comparison between severe versus non-severe AIS.

PURPOSE: Prolonged surgical duration in severe adolescent idiopathic scoliosis (AIS) patients is associated with increased blood loss and perioperative complications. The aim of this study was to compare the duration of each stage of posterior spinal fusion (PSF) in severe AIS (Cobb angle ≥ 90°) with non-severe AIS patients. This analysis will identify the most time-consuming stage of PSF and help surgeons formulate strategies to shorten operative time. METHODS: Retrospective study whereby 90 AIS patients (Lenke type 2, 3, 4, and 6) who underwent PSF from 2019 to 2023 were recruited. Twenty-five severe AIS patients were categorized in Gp1 and 65 non-severe AIS patients in Gp2. Propensity score matching (PSM) with one-to-one with nearest neighbor matching (match tolerance 0.05) was performed. Outcomes measured via operation duration of each stage of surgery, blood loss, number of screws, fusion levels and screw density. RESULTS: Twenty-five patients from each group were matched. Total operative time was significantly higher in Gp1 (168.2 ± 30.8 vs. 133.3 ± 24.0 min, p < 0.001). The lengthiest stage was screw insertion which took 58.5 ± 13.4 min in Gp1 and 44.7 ± 13.7 min in Gp2 (p = 0.001). Screw insertion contributed 39.5% of the overall increased surgical duration in Gp1. Intraoperative blood loss (1022.2 ± 412.5 vs. 714.2 ± 206.7 mL, p = 0.002), number of screws (17.1 ± 1.5 vs. 15.5 ± 1.1, p < 0.001) and fusion level (13.1 ± 0.9 vs. 12.5 ± 1.0, p = 0.026) were significantly higher in Gp1. CONCLUSION: Screw insertion was the most time-consuming stage of PSF and was significantly longer in severe AIS. Adjunct technologies such as CT-guided navigation and robotic-assisted navigation should be considered to reduce screw insertion time in severe AIS.

A comparison between Boston brace and European braces in the treatment of adolescent idiopathic scoliosis (AIS) patients: a systematic review based on the standardised Scoliosis Research Society (SRS) inclusion criteria for brace treatment.

PURPOSE: To compare the Boston brace and European braces using a standardised Scoliosis Research Society (SRS) inclusion criteria for brace treatment as well as consensus recommendations for treatment outcome. METHODS: This was a systematic review that was carried out using MeSH terminology in our search protocol in PubMed, Cochrane Library, Scopus, Clinicaltrials.gov and Web of Science database between 1976 and 29th of Jan 2023. All studies that were included in this review had applied fully/partially the SRS inclusion criteria for brace wear. Outcome measures were divided into primary and secondary outcome measures. RESULTS: 3830 literatures were found in which 176 literatures were deemed relevant to the study once duplicates were removed and titles and abstracts were screened. Of these literatures, only 15 had fulfilled the eligibility criteria and were included in the study. 8 of the studies were Level IV studies, 5 were Level III studies and 2 studies were Level I studies (1 prospective randomised controlled trial (RCT) and 1 Quasi-RCT). The percentage of patients who avoided surgery for European braces ranged from 88 to 100%, whereas for Boston brace ranged from 70 to 94%. When treatment success was assessed based on the final Cobb angle > 45°, approximately 15% of patients treated with European braces had treatment failure. In contrast, 20-63% of patients treated with Boston brace had curves > 45° at skeletal maturity. The BrAIST study used a cut-off point of 50° to define failure of treatment and the rate of treatment failure was 28%. Curve correction was not achieved in most patients (24-51% of patients) who were treated with the Chêneau brace and its derivatives. However, none of the patients treated with Boston brace achieved curve correction. CONCLUSION: Boston brace and European braces were effective in the prevention of surgery. In addition, curve stabilisation was achieved in most studies. Limitation in current literature included lack of studies providing high level of evidence and lack of standardisation in terms of compliance to brace as well as multidisciplinary management of brace wear.

Variations in the Number of Vertebrae, Prevalence of Lumbosacral Transitional Vertebra and Prevalence of Cervical Rib Among Surgical Patients With Adolescent Idiopathic Scoliosis: An Analysis of 998 Radiographs.

STUDY DESIGN: Retrospective Study. OBJECTIVE: This study aims to investigate variation in the number of thoracic and lumbar vertebrae, the prevalence of lumbosacral transitional vertebra (LSTV) and the prevalence of cervical ribs among surgical patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Due to variation in the number of thoracic or lumbar vertebrae, inaccurate identification of vertebral levels has been found to be a contributory factor to wrong-level surgery. METHODS: This was a retrospective study on AIS patients who underwent posterior spinal fusion. Demographic and anthropometric data (age, gender, height, weight, and body mass index), radiographic data (Lenke curve type, pre-operative Cobb angle, vertebra numbering of cervical, thoracic, and lumbar spine, presence of LSTV based on the Castellvi classification and the presence of cervical ribs) and clinical data were collected. Data were analysed and reported with mean and standard deviation for quantitative parameters and number and percentage for qualitative parameters. Multinomial logistic regression analyses were performed to identify factors associated with the outcomes of interest. RESULTS: A total of 998 patients met inclusion criteria, of which 135 (13.5%) were males and 863 (86.5%) were females. The vertebrae number varied between 23 to 25 total vertebrae with 24 vertebrae considered as the typical number of vertebrae. The prevalence of atypical number of vertebrae (23 or 25) was 9.8% (98 patients). We found a total of 7 different variations in number of cervical, thoracic, and lumbar vertebrae (7C11T5L, 7C12T4L, 7C11T6L, 7C12T5L, 7C13T4L, 7C12T6L, and 7C13T5L) with 7C12T5L considered as the typical vertebrae variation. The total prevalence of patients with atypical vertebrae variation was 15.5% (155 patients). Cervical ribs were found in 2 (0.2%) patients while LSTV were found in 250 (25.1%) of patients. The odds of 13 thoracic vertebrae were higher in males (OR 5.17; 95% CI: 1.25, 21.39) and the odds of 6 lumbar vertebrae were higher in LSTV (OR 3.93; 95% CI: 2.58, 6.00). CONCLUSION: In this series, we identified a total of 7 different variations in the number of cervical, thoracic, and lumbar vertebrae. The total prevalence of patients with atypical vertebrae variation was 15.5%. LSTV was found in 25.1% of the cohort. It is important to ascertain atypical vertebrae variations rather than the absolute number of vertebrae because variants such as 7C11T6L and 7C13T4L may still have typical numbers of vertebrae in total. However, due to the differences in the number of morphologically thoracic and lumbar vetrebrae, there may still be a risk of inaccurate identification.

P21-activated kinase 1 (PAK1)-mediated cytoskeleton rearrangement promotes SARS-CoV-2 entry and ACE2 autophagic degradation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has had a significant impact on healthcare systems and economies worldwide. The continuous emergence of new viral strains presents a major challenge in the development of effective antiviral agents. Strategies that possess broad-spectrum antiviral activities are desirable to control SARS-CoV-2 infection. ACE2, an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system, is the receptor for SARS-CoV-2. ACE2 interacts with the spike protein and facilitates viral attachment and entry into host cells. Yet, SARS-CoV-2 infection also promotes ACE2 degradation. Whether restoring ACE2 surface expression has an impact on SARS-CoV-2 infection is yet to be determined. Here, we show that the ACE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton rearrangement. In contrast, free cellular spike protein is selectively cleaved into S1 and S2 subunits in a lysosomal-dependent manner. Importantly, we show that the pan-PAK inhibitor FRAX-486 restores ACE2 surface expression and suppresses infection by different SARS-CoV-2 strains. FRAX-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated hamsters. In summary, our findings have identified novel pathways regulating viral entry, as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-CoV-2 infection.

Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking.

SARS-CoV-2 continues to evolve, with many variants evading clinically authorized antibodies. To isolate monoclonal antibodies (mAbs) with broadly neutralizing capacities against the virus, we screened serum samples from convalescing COVID-19 patients. We isolated two mAbs, 12-16 and 12-19, which neutralized all SARS-CoV-2 variants tested, including the XBB subvariants, and prevented infection in hamsters challenged with Omicron BA.1 intranasally. Structurally, both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, uncovering a site of vulnerability on SARS-CoV-2 spike. These antibodies prevented viral receptor engagement by locking the receptor-binding domain (RBD) of spike in the down conformation, revealing a mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but such mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.

SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters1.

Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury.

What is the prevalence and distribution of narrow dysplastic and fully corticalized pedicles in Asian adolescent idiopathic scoliosis patients with major main thoracic curves? A computed tomography scan analysis of 6,494 pedicles.

BACKGROUND CONTEXT: Patients with adolescent idiopathic scoliosis (AIS) have higher prevalence of abnormal or dysplastic pedicles. PURPOSE: To investigate the prevalence and distribution of narrow dysplastic and fully corticalized pedicles in Asian AIS patients with major main thoracic curves. DESIGN: Retrospective study. PATIENT SAMPLE: A total of 6,494 pedicles in 191 patients were measured and evaluated. OUTCOME MEASURES: The primary outcomes measures were the pedicle width measurements (total transverse pedicle width, transverse cancellous width, total transverse cortical width) and classification of pedicles. Demographic data (age, gender, height, weight, body mass index), proximal thoracic Cobb angle, main thoracic Cobb angle and lumbar Cobb angle were also obtained. METHODS: AIS patients with major (largest Cobb angle) main thoracic curves and had computed tomography (CT) scans prior to corrective spine surgery were reviewed. The pedicles were classified as Grade A: cancellous channel >4 mm; Grade B: cancellous channel 2 to 4 mm; Grade C: cancellous channel <2 mm or corticalized pedicle >4 mm; Grade D: corticalized pedicle ≤4 mm. Grades B, C, and D were dysplastic pedicles while grades C and D were narrow dysplastic pedicles. RESULTS: The prevalence of dysplastic pedicles (grades B, C, and D) was 61.7%. There were 22.6% narrow dysplastic pedicles (grades C and D) and 4.1% fully corticalized pedicles (grade D). In the thoracolumbar region, there was a sharp transition from larger and less dysplastic pedicles at T11 and T12 to narrower and more dysplastic pedicles at L1 and L2 (narrow dysplastic pedicles at T11: 3.1%, T12: 3.1%, L1: 39.8% and L2: 23.6%). Higher prevalences of narrow dysplastic pedicles were located at right T3 to T5 (71.2%-83.7%) and left T7-T9 (51.3%-61.2%). Higher prevalences of fully corticalized pedicles were located at right T3 to T5 (20.9%-34.0%) and left T7 to T8 (11.0%-12.0%). These were the concave pedicles of proximal thoracic and main thoracic curves, respectively. CONCLUSION: There were 95.9% pedicles with cancellous channels (grades A, B, and C) can allow pedicle screw fixation and only 4.1% fully corticalized pedicles (grade D) that require an alternative method of fixation. For grade C pedicles (18.5%), pedicle screws can still be attempted with caution. Precautions should also be observed at the L1 and L2 levels as there was a transition to narrower pedicles.

Association between intraoperative remifentanil use and postoperative hyperalgesia in adolescent idiopathic scoliosis surgery: a retrospective study.

BACKGROUND: The liberal use of remifentanil in spine surgery has been associated with an increased incidence of postoperative hyperalgesia. Nevertheless, controversies remain as the existing evidence is inconclusive to determine the relationship between remifentanil use and the development of opioid-induced hyperalgesia. We hypothesized that intraoperative infusion of higher dose remifentanil during scoliosis surgery is associated with postoperative hyperalgesia, manifesting clinically as greater postoperative morphine consumption and pain scores. METHODS: Ninety-seven patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion surgery at a single tertiary institution from March 2019 until June 2020 were enrolled in this retrospective study. Anesthesia was maintained using a target-controlled infusion of remifentanil combined with volatile anesthetic desflurane in 92 patients, while five patients received it as part of total intravenous anesthesia. Intravenous ketamine, paracetamol, and fentanyl were administered as multimodal analgesia. All patients received patient-controlled analgesia (PCA) morphine postoperatively. Pain scores at rest and on movement, assessed using the numerical rating scale, and the cumulative PCA morphine consumption were collected at a six-hourly interval for up to 48 h. According to the median intraoperative remifentanil dose usage of 0.215 µg/kg/min, patients were divided into two groups: low dose and high dose group. RESULTS: There were no significant differences in the pain score and cumulative PCA morphine consumption between the low and high dose remifentanil group. The mean duration of remifentanil infusion was 134.9 ± 22.0 and 123.4 ± 23.7 min, respectively. CONCLUSION: Intraoperative use of remifentanil as an adjuvant in AIS patients undergoing posterior spinal fusion surgery was not associated with postoperative hyperalgesia.

Antibodies that neutralize all current SARS-CoV-2 variants of concern by conformational locking.

SARS-CoV-2 continues to evolve and evade most existing neutralizing antibodies, including all clinically authorized antibodies. We have isolated and characterized two human monoclonal antibodies, 12-16 and 12-19, which exhibited neutralizing activities against all SARS-CoV-2 variants tested, including BQ.1.1 and XBB.1.5. They also blocked infection in hamsters challenged with Omicron BA.1 intranasally. Structural analyses revealed both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, revealing a previously unrecognized site of vulnerability on SARS-CoV-2 spike. These antibodies prevent viral receptor engagement by locking the receptor-binding domain of spike in the down conformation, revealing a novel mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but the responsible mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.

Diamond-like carbon films prepared by a low temperature periodic process for application in ventricular assist devices.

Due to the poor tribological properties of titanium (Ti) and its alloy Ti6Al4V (commonly used for ventricular assist devices manufacturing), diamond-like carbon (DLC) films with excellent anti-wear properties are pursued to improve the wear resistance of Ti and its alloys. Considering the effect of temperature on magnets inside pump impellers and workpiece deformation, DLC films are preferred to be prepared under low temperature. In this study, DLC films were prepared on Ti6Al4V alloys by periodic and continuous processes, and the corresponding maximum deposition temperature was 85 and 154°C, respectively. The periodic DLC films exhibited the feature of columnar structure, and the surface hillocks were less uniform than that of continuous DLC films. The periodic DLC films possessed more sp3 -bonded structures, and the accessorial sp3 -bonding mainly existed in the form of CH. Compared to continuous DLC films, the periodic DLC films had lower residual stress and better adhesion with Ti6Al4V substrates. Both DLC films could effectively reduce the friction coefficient and wear rate of Ti6Al4V alloys both in air and fetal bovine serum (FBS), and the periodic DLC films exhibited superior anti-wear properties to that of continuous DLC films in FBS. Haemocompatibility evaluation revealed that both DLC films presented similar levels of more human platelet adhesion and activation as compared with that of bare Ti6Al4V. However, both DLC films significantly prolonged plasma clotting time in comparison to bare Ti6Al4V. This study demonstrates the potential of low-temperature DLC films as wear-resistant surface modification for VADs.

Mitigation effect of cell exclusion on blood damage in spiral groove bearings.

Cell exclusion in spiral groove bearing (SGB) excludes red blood cells from high shear regions in the bearing gaps and potentially reduce haemolysis in rotary blood pumps. However, this mechanobiological phenomenon has been observed in ultra-low blood haematocrit only, whether it can mitigate blood damage in a clinically-relevant blood haematocrit remains unknown. This study examined whether cell exclusion in a SGB alters haemolysis and/or high-molecular-weight von Willebrand factor (HMW vWF) multimer degradation. Citrated human blood was adjusted to 35 % haematocrit and exposed to a SGB (n = 6) and grooveless disc (n = 3, as a non-cell exclusion control) incorporated into a custom-built Couette test rig operating at 2000RPM for an hour; shearing gaps were 20, 30, and 40 µm. Haemolysis was assessed via spectrophotometry and HMW vWF multimer degradation was detected with gel electrophoresis and immunoblotting. Haemolysis caused by the SGB at gaps of 20, 30 and 40 µm were 10.6 ± 3.3, 9.6 ± 2.7 and 10.5 ± 3.9 mg/dL.hr compared to 23.3 ± 2.6, 12.8 ± 3.2, 9.8 ± 1.8 mg/dL.hr by grooveless disc. At the same shearing gap of 20 µm, there was a significant reduced in haemolysis (P = 0.0001) and better preserved in HMW vWF multimers (p < 0.05) when compared SGB to grooveless disc. The reduction in blood damage in the SGB compared to grooveless disc is indicative of cell exclusion occurred at the gap of 20 µm. This is the first experimental study to demonstrate that cell exclusion in a SGB mitigates the shear-induced blood damage in a clinically-relevant blood haematocrit of 35 %, which can be potentially utilised in future blood pump design.

A Comparison Between the Perioperative Outcomes of Female Adolescent Idiopathic Scoliosis (AIS) Versus Adult Idiopathic Scoliosis (AdIS) Following Posterior Spinal Fusion: A Propensity Score Matching Analysis Involving 425 Patients.

STUDY DESIGN: Retrospective propensity score matching (PSM) study. OBJECTIVE: To investigate the perioperative outcomes comparing adolescent idiopathic scoliosis (AIS) and adult idiopathic scoliosis (AdIS) patients following posterior spinal fusion (PSF). METHODS: 425 female AIS and AdIS patients who were operated (between January 2015 to March 2020) using a dual attending surgeon strategy were stratified into G1 (AIS aged 10-16 years old) and G2 (AdIS > 20 years old). PSM analysis with one-to-one, nearest neighbor matching technique with match tolerance of 0.001 was used to matched 357 AIS patients to 68 AdIS patients. Operation duration, intraoperative blood loss (IBL), blood loss percentage, hemoglobin drift, blood salvaged, postoperative wound length, allogenic blood transfusion requirement, postoperative hospital stay, postoperative Cobb, correction rate and postoperative complications were documented and reported. RESULTS: Following PSM, G1 and G2 each had 50 patients with comparable and balanced covariates. As anticipated, G2 patients were heavier, taller and had higher body mass index compared to G1 patients (P < 0.05). We could not find any significant differences in the perioperative outcome comparing this 2 groups. AIS and AdIS patients had similar operation duration (125.9 ± 27.2 min vs 127.3 ± 37.8 min), IBL (749.8 ± 315.7 ml vs 723.8 ± 342.1 ml) and length of hospital stay (3.3 ± 0.4 days vs 3.5 ± 0.8 days) (P > 0.05). Hemoglobin drift and amount of blood salvaged were comparable (P > 0.05). G2 had stiffer curves. There was a trend toward a lower correction rate in G2 in the immediate postoperative period, however it did not reach statistical significance (61.8 ± 11.2% vs. 66.3 ± 11.6%, P = 0.051). No patients required blood transfusion and none had any postoperative complications. CONCLUSION: Adolescent and adult female scoliosis patients had comparable perioperative outcome following PSF surgery that was carried out using a dual attending surgeon strategy.

Preoperative "Cervical Axis" Deviation Increases the Risk of Distal Adding-On Following Surgery in Lenke 1 and 2 Adolescent Idiopathic Scoliosis Patients.

STUDY DESIGN: Retrospective. PURPOSE: To evaluate the relationship between shoulder/ neck imbalance with distal adding-on phenomenon and to identify other risk factors in Lenke 1 and 2 (non-AR curves) adolescent idiopathic scoliosis (AIS) patients. METHODS: 100 Lenke 1 and 2 AIS patients with lowest instrumented vertebra (LIV) cephalad to or at L1 were recruited. Medial shoulder/ neck balance was represented by T1-tilt and cervical axis (CA). Lateral shoulder balance was represented by clavicle angle (Cla-A) and radiographic shoulder height (RSH). Distal adding-on phenomenon was diagnosed when there was disc wedging below LIV of >5o at final follow-up. Predictive factors and odds ratio were derived using univariate and multivariate logistic regression analysis. RESULTS: Mean age of this cohort was 15.9 ± 4.4 years. Mean follow-up duration was 30.9 ± 9.6 months. Distal adding-on phenomenon occurred in 19 patients (19.0%). Only Risser grade, preoperative CA and final follow-up lumbar Cobb angle were the independent factors. A positive preoperative CA deviation increased the odds of distal adding-on by 5.4 times (95% CI 1.34-21.51, P = 0.018). The mean immediate postoperative T1-tilt, CA, RSH and Cla-A were comparable between the group with distal adding-on and the group without. CONCLUSION: Distal adding-on phenomenon occurred in 19.0% of patients. Preoperative "Cervical Axis" was an important factor and it increased the risk of distal adding-on by 5.4 times. Other significant predictive factors were Risser grade and lumbar Cobb angle at final follow-up. Immediate postoperative shoulder or neck imbalance was not a significant factor for postoperative distal adding-on phenomenon.

Patients' Perception and Satisfaction on Neck and Shoulder Imbalance in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To evaluate the perception and satisfaction among adolescent idiopathic scoliosis (AIS) patients on Neck Tilt with Medial Shoulder Imbalance and Lateral Shoulder Imbalance. METHODS: Lenke 1 and 2 AIS patients were stratified into 6 groups of preoperative/ postoperative Balanced (B), Lateral Shoulder Imbalance (LSI) (>2 cm), and Neck Tilt with Medial Shoulder Imbalance (NT) (Grade 3). Patients were interviewed using Modified Neck and Shoulder Appearance and SRS-22r questionnaires. T1 tilt, Cervical Axis (CA), Clavicle Angle (Cla-A) and Radiographic Shoulder Height (RSH) were measured. RESULTS: A total of 120 Lenke 1 and 2 AIS patients were recruited. NT patients were aware and unhappy with their abnormal neck with medial shoulder appearances (P < .001). Similarly, LSI patients were aware and unhappy with their abnormal lateral shoulder appearances (P < .001). NT group had larger preoperative/ postoperative T1 tilt (9.2 ± 5.0°; 9.5 ± 5.3°) and CA (4.6 ± 3.1°; 7.0 ± 2.0°) (P < .01). LSI group had larger preoperative/ postoperative Cla-A (4.8 ± 2.8°; 4.0 ± 1.3°) and RSH (20.1 ± 9.4 mm; 17.0 ± 6.6 mm) (P < .001). Postoperative B group scored higher in overall SRS-22r scores, self-image and satisfaction domains (4.2 ± 0.3; 4.0 ± 0.5; 4.4 ± 0.5) while preoperative LSI scored the lowest comparatively (3.5 ± 0.4; 2.4 ± 0.5; 3.3 ± 0.5) (P < .001). CONCLUSION: NT and LSI were major concerns among AIS patients. Both NT and LSI groups were unhappy with their appearances. NT group had larger T1 tilt/ CA whereas LSI group had larger Cla-A/ RSH. Postoperative B group scored higher in overall SRS-22r scores, self-image and satisfaction domains.

A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo.

"Pan-coronavirus" antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations. H84T-BanLec protects against MERS-CoV and SARS-CoV-2 infection in vivo. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Mechanistic assays show that H84T-BanLec targets virus entry. High-speed atomic force microscopy depicts real-time multimolecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modeling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the drug compound's broad-spectrum antiviral activity and the lack of resistant mutants.