Immediate vs Gradual Brace Weaning Protocols in Adolescent Idiopathic Scoliosis: A Randomized Clinical Trial.

Importance: Lack of evidence and consensus for brace weaning protocol in adolescent idiopathic scoliosis (AIS) results in clinicians prescribing gradual weaning in the hope of avoiding curve deterioration after weaning. However, gradual weaning contributes to prolonged brace wear, which can affect spinal stiffness and health-related quality of life (HRQoL). Objective: To determine whether gradual weaning results in better curve magnitude and truncal balance maintenance after brace weaning vs immediate brace removal for patients with AIS. Design, Setting, and Participants: This was an open-labeled randomized clinical trial commenced in April 2017 with 24-month follow-up completed in January 2023. Outcome assessors were masked to weaning protocol assigned. The study took place at a territory-wide tertiary scoliosis clinic serving the largest number of referrals in the local population. Patients with AIS ready to wean off of brace wear were eligible (402 were screened; 33 were excluded [15 for <18 hours/day of brace-wear compliance before weaning, 11 were treated with Milwaukee brace, and 7 declined to participate]; and 369 were included), and those who were treated with a custom molded thoracolumbosacral orthosis and had reached skeletal maturity were consecutively recruited. Interventions: Patients were randomized to gradual weaning protocol (n = 176) with an additional 6 months of nighttime wear before completely stopping or immediate weaning protocol (n = 193) with immediate brace removal at recruitment. Main Outcomes and Measures: Changes in major curve Cobb angle and truncal balance from the time of weaning to 6-month, 12-month, and 24-month follow-up. HRQoL was also assessed using the refined Scoliosis Research Society 22-item and EuroQol 5-dimension questionnaires. Results: A total of 369 patients (mean [SD] age, 14.9 [1.1] years; 304 [83.4%] girls) were randomized with 284 (77.0%) completing 24-month longitudinal follow-up. Immediate and gradual weaning groups had no significant differences in change of major Cobb angle at postweaning 6-month (difference, -0.6°; 95% CI, -1.4 to 0.2; P = .17), 12-month (difference, -0.3°; 95% CI, -1.2 to 0.6; P = .47), and 24-month (difference, -0.3°; 95% CI, -1.2 to 0.7; P = .60) follow-up. The number of curve progression, nonprogression, and rebound cases were comparable (χ22 = 2.123; P = .35). Postweaning changes in truncal balance and HRQoL demonstrated no significant differences between groups. Conclusions: Gradual weaning did not demonstrate superiority to immediate weaning with predefined criteria of Cobb angle and truncal balance maintenance and HRQoL after brace weaning. Gradual and immediate weaning achieved very similar maintenance of brace outcomes in AIS. We therefore recommend the consideration of immediate brace weaning, which aims to benefit patients with earlier time for increased exercises and activity level. Trial Registration: ClinicalTrials.gov Identifier: NCT03329716.

Supine correction index as a predictor for brace outcome in adolescent idiopathic scoliosis.

AIMS: The aim of this study was to assess the ability of morphological spinal parameters to predict the outcome of bracing in patients with adolescent idiopathic scoliosis (AIS) and to establish a novel supine correction index (SCI) for guiding bracing treatment. METHODS: Patients with AIS to be treated by bracing were prospectively recruited between December 2016 and 2018, and were followed until brace removal. In all, 207 patients with a mean age at recruitment of 12.8 years (SD 1.2) were enrolled. Cobb angles, supine flexibility, and the rate of in-brace correction were measured and used to predict curve progression at the end of follow-up. The SCI was defined as the ratio between correction rate and flexibility. Receiver operating characteristic (ROC) curve analysis was carried out to assess the optimal thresholds for flexibility, correction rate, and SCI in predicting a higher risk of progression, defined by a change in Cobb angle of ≥ 5° or the need for surgery. RESULTS: The baseline Cobb angles were similar (p = 0.374) in patients whose curves progressed (32.7° (SD 10.7)) and in those whose curves remained stable (31.4° (SD 6.1)). High supine flexibility (odds ratio (OR) 0.947 (95% CI 0.910 to 0.984); p = 0.006) and correction rate (OR 0.926 (95% CI 0.890 to 0.964); p < 0.001) predicted a lower incidence of progression after adjusting for Cobb angle, Risser sign, curve type, menarche status, distal radius and ulna grading, and brace compliance. ROC curve analysis identified a cut-off of 18.1% for flexibility (sensitivity 0.682, specificity 0.704) and a cut-off of 28.8% for correction rate (sensitivity 0.773, specificity 0.691) in predicting a lower risk of curve progression. A SCI of greater than 1.21 predicted a lower risk of progression (OR 0.4 (95% CI 0.251 to 0.955); sensitivity 0.583, specificity 0.591; p = 0.036). CONCLUSION: A higher supine flexibility (18.1%) and correction rate (28.8%), and a SCI of greater than 1.21 predicted a lower risk of progression. These novel parameters can be used as a guide to optimize the outcome of bracing. Cite this article: Bone Joint J 2022;104-B(4):495-503.

Curve type, flexibility, correction, and rotation are predictors of curve progression in patients with adolescent idiopathic scoliosis undergoing conservative treatment : a systematic review.

AIMS: The aim of this study was to review the current evidence surrounding curve type and morphology on curve progression risk in adolescent idiopathic scoliosis (AIS). METHODS: A comprehensive search was conducted by two independent reviewers on PubMed, Embase, Medline, and Web of Science to obtain all published information on morphological predictors of AIS progression. Search items included 'adolescent idiopathic scoliosis', 'progression', and 'imaging'. The inclusion and exclusion criteria were carefully defined. Risk of bias of studies was assessed with the Quality in Prognostic Studies tool, and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. In all, 6,286 publications were identified with 3,598 being subjected to secondary scrutiny. Ultimately, 26 publications (25 datasets) were included in this review. RESULTS: For unbraced patients, high and moderate evidence was found for Cobb angle and curve type as predictors, respectively. Initial Cobb angle > 25° and thoracic curves were predictive of curve progression. For braced patients, flexibility < 28% and limited in-brace correction were factors predictive of progression with high and moderate evidence, respectively. Thoracic curves, high apical vertebral rotation, large rib vertebra angle difference, small rib vertebra angle on the convex side, and low pelvic tilt had weak evidence as predictors of curve progression. CONCLUSION: For curve progression, strong and consistent evidence is found for Cobb angle, curve type, flexibility, and correction rate. Cobb angle > 25° and flexibility < 28% are found to be important thresholds to guide clinical prognostication. Despite the low evidence, apical vertebral rotation, rib morphology, and pelvic tilt may be promising factors. Cite this article: Bone Joint J 2022;104-B(4):424-432.

Compound Heterozygous Factor VII Deficiency c.1025G>A p.(Arg342Gln) With Novel Missense Variant c.194C>G p.(Ala65Gly).

Factor VII (FVII) deficiency manifests as prolonged prothrombin time (PT) and reduced FVII activity. We report a case of an asymptomatic 60-year-old gentleman with discrepancies in PT and FVII coagulant activity levels (FVII:C) on three different thromboplastin reagents used. Further sequence analysis on genomic DNA showed double heterozygosity for c.1025G>A p.Arg342Gln and c.194C>G p.Ala65Gly in the F7 gene. To date, p.Ala65Gly in exon 2 of the F7 gene represents a novel variant in patients with FVII deficiency and is classified as likely pathogenic. Computational prediction tools support a deleterious effect on the gene. The genotype-phenotype association and the clinical significance of this exon 2 missense variant is proposed in this case report.

Low incidence of venous thrombosis but high incidence of arterial thrombotic complications among critically ill COVID-19 patients in Singapore.

BACKGROUND: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. METHOD AND RESULTS: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). CONCLUSIONS: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis.

Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blood was collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19 who were on either mechanical ventilation or on high flow oxygen with a PaO2/FiO2 ratio of <300 mmHg. Laboratory tests were performed for parameters of haemostasis, clot waveform analysis and anti-phospholipid antibodies. CWA parameters were raised with elevated aPTT median Min1 (clot velocity) 9.3%/s (IQR 7.1-9.9%/s), elevated PT median Min1 10.3%/s (IQR 7.1-11.1%/s), elevated aPTT median Min2 (clot acceleration) 1.5%/s2 (IQR 1.0-1.6%/s2), elevated PT median Min2 5.2%/s2 (3.6-5.7%/s2), elevated aPTT median Max2 (clot deceleration) 1.3%/s2 (IQR 0.8-1.4%/s2) elevated PT median Max2 3.8%/s2 (IQR 2.6-4.2%/s2), increased aPTT median Delta change (decreased light transmission due to increased clot formation) 87.8% (IQR 70.2-91.8%) and PT median Delta change 33.0%. This together with raised median Factor VIII levels of 262.5%, hyperfibrinogenemia (median fibrinogen levels 7.5 g/L), increased median von Willebrand factor antigen levels 320% and elevated median D-dimer levels 1.7 µg/dl support the diagnosis of COVID-19 associated coagulopathy. A lupus anticoagulant was present in 50% of patients. Our laboratory findings further support the view that severe SARS-CoV-2 infection is associated with a state of hypercoagulability.

Evaluation of the matrix effect of thermophilic anaerobic digestion on inactivation of infectious laryngotracheitis virus using real-time PCR and viral cell culture.

The matrix effect of the thermophilic anaerobic digestion (TAD) process on inactivation of infectious laryngotracheitis virus (ILTV) was evaluated. Viral cell culture and real-time PCR were used for assessing removal of the viral infectivity and degradation of viral DNA, respectively. Results showed that the TAD-derived matrix alone can inactivate the virus and destroy the nucleic acid helix core of ILTV in a time-and- dose-dependent manner. No cytopathogenic effect (CPE) was observed in the cells exposed to ILTV pre-treated with TAD matrix for 1.5h in experiment 1 and for 16h in experiment 2. There was a significant statistical difference between TAD matrix treated and non-treated cultures (p<0.001, Chi-test). Amplifiable ILT viral DNA was reduced 2.27 log by 1.5h-treatment and was not present by 16h-treatment with TAD matrix, indicating complete viral DNA fragmentation. The TAD process is an environmentally friendly way for disposing of poultry biowaste and carcasses.

Epicardially Based Pulmonary Vein Isolation for the Treatment of Atrial Fibrillation Utilizing Laser Energy in the Pig Model.

Purpose: Atrial fibrillation is a common disease that increases the incidence of cerebrovascular embolic events and cardiac dysfunction. Foci for atrial fibrillation have been mapped and found to be for the most part located within the ostia of the pulmonary veins. Since 2002 microwave and radiofrequency energy sources have been used to create pulmonary vein isolation lesions. This abstract summarizes the safety and efficacy of performing vein isolation lesions with laser as the energy source. Description: The large pig model was utilized for creation of isolation lesions around the pulmonary veins. The Optimaze E360 Surgical Ablation Handpiece from Edwards Lifesciences was utilized, it contains a 4 centimeter diffusing diode laser (980nm). All six of the pig models tolerated the procedure with a 40-day normal post procedure growth pattern. Evaluation: Upon reoperation one pig developed ventricular fibrillation with resection of adhesions. All five remaining pigs were fully tested and demonstrated complete electrical isolation. Gross pathology revealed intact well defined ablation lesions with an otherwise completely normal cardiac structure. All lesions were fully transmural at each histological sectioned point. Conclusions: Laser technology in the form of the Optimaze E360 Surgical Ablation Handpiece from Edwards Lifesciences, is able to reliably and consistently produce well defined electrical isolation scars around the pulmonary veins. This device is also amenable to performing the isolation procedure using a minimally invasive approach.