1.Concurrent Presence of Thoracolumbar Scoliosis and Chiari Malformation: Is Operative Risk Magnified?
Sara NAESSIG ; Peter TRETIAKOV ; Karan PATEL ; Waleed AHMAD ; Katherine PIERCE ; Nicholas KUMMER ; Rachel JOUJON-ROCHE ; Bailey IMBO ; Tyler WILLIAMSON ; Oscar KROL ; Muhammad Burhan JANJUA ; Shaleen VIRA ; Bassel DIEBO ; Daniel SCIUBBA ; Peter PASSIAS
Asian Spine Journal 2023;17(4):703-711
Methods:
The KID was used to identify all pediatric inpatients with CM and scoliosis. The patients were stratified into three groups: those with concomitant CM and scoliosis (CMS group), those with only CM (CM group), and those with only scoliosis (Sc group). Multivariate logistic regressions were used to assess association between surgical characteristics and diagnosis with complication rate.
Results:
A total of 90,707 spine patients were identified (61.8% Sc, 37% CM, 1.2% CMS). Sc patients were older, had a higher invasiveness score, and higher Charlson comorbidity index (all p<0.001). CMS patients had significantly higher rates of surgical decompression (36.7%). Sc patients had significantly higher rates of fusions (35.3%) and osteotomies (1.2%, all p<0.001). Controlling for age and invasiveness, postoperative complications were significantly associated with spine fusion surgery for Sc patients (odds ratio [OR], 1.8; p<0.05). Specifically, posterior spinal fusion in the thoracolumbar region had a greater risk of complications (OR, 4.9) than an anterior approach (OR, 3.6; all p<0.001). CM patients had a significant risk of complications when an osteotomy was performed as part of their surgery (OR, 2.9) and if a spinal fusion was concurrently performed (OR, 1.8; all p<0.05). Patients in the CMS cohort were significantly likely to develop postoperative complications if they underwent a spinal fusion from both anterior (OR, 2.5) and posterior approach (OR, 2.7; all p<0.001).
Conclusions
Having concurrent scoliosis and CM increases operative risk for fusion surgeries despite approach. Being independently inflicted with scoliosis or Chiari leads to increased complication rate when paired with thoracolumbar fusion and osteotomies; respectively.
2.The Discovery of Putative Small Molecules via Ligand-based Pharmacophore Modelling Targeting Human Tau Protein for an Effective Treatment of Parkinson’s Disease
Yahaya Sani Najib ; Yusuf Oloruntoyin Ayipo ; Waleed Abdullah Ahmad Alananzeh ; Mustapha Muhammed ; Mohd Nizam Mordi
Malaysian Journal of Medicine and Health Sciences 2023;19(No.6):83-94
Introduction: The human tau protein is a key protein involved in various neurodegenerative disease (NDs) including
Parkinson’s disease (PD). The protein has high tendency to aggregate into oligomers, subsequently generating insoluble mass in the brain. Symptoms of PD include tremor, bradykinesia, rigidity, and postural instability. Currently drugs
for PD treatment are only symptom-targeted while effective therapeutic treatment remains a challenge. The objective
of this study is to identify novel promising anti-PD drugs using computational techniques. Method: ligand-based
(LB) receptor modelling was conducted using LigandScout, validated and subjected to Glide XP docking, virtual
screening, ADMET, and molecular dynamics predictions. Results: The adopted LB modelling generated pharmacophoric features of 5 hydrogen bond donors, 1 aromatic rings, and 7 hydrogen bond acceptors. The validation result
indicated GH score of 0.73 and EF of 36.30 as validation protocols, probing it to be an ideal model. Using 3D query
of the modelling a total of 192 compounds were retrieved from interbioscreen database containing 70,436 natural
compounds. Interestingly, ligands 1, 2, 3, 4 and 5 orderly indicated higher binding affinities to the receptor with
Glide XP docking of -7.451, -7.368, -7.101, -6.878, and -6.789 compared to a clinical drug Anle138b with -4.552
kcal/mol respectively. Furthermore, molecular dynamics and pkCSM pharmacokinetics demonstrated ligands 1, 2, &
4 having better stability and low toxicity profiles compared to the reference. Conclusion: In summary, the study pave
way for discovery of small molecules that could be recommended as adjuvant /single candidate as ant-PD candidates
upon further translational study.