Carbenoxolone mitigates extensive fibrosis formation in PLP-induced EAE model and multiple sclerosis serum-exposed pericyte culture.

Introduction: Multiple sclerosis (MS) is one of the most common causes of disability in young adults. Nearly, 85% of MS cases start with attacks and remissions, classified as relapsing-remitting multiple sclerosis (RRMS). With repeating attacks, MS causes brain-spinal cord atrophy and enhanced disability as disease progresses. PLP-induced EAE is one of the most established models for pathophysiology and treatment of RRMS. Recent studies demonstrated the possible role of pericytes in perivascular and intra-lesional fibrosis in PLP-induced EAE, whose importance remains elusive. Hence, we have investigated the possible role of pericytes in fibrosis formation and amelioration with a hemichannel blocker, Carbenoxolone (CBX). Methods: PLP-induced experimental autoimmune encephalitis (EAE) model is used and the effect of CBX is investigated. Clinical scores were recorded and followed. Perivascular Collagen 1 and 3 accumulations were demonstrated as markers of fibrosis in the spinal cord. To delineate the role of pericytes, human brain vascular pericytes (HBVP) were incubated with the sera of MS patients to induce in-vitro MS model and the fibrosis formation was investigated. Results: In the PLP induced in-vivo model, both intracerebroventricular and intraperitoneal CBX have significantly mitigated the disease progression followed by clinical scores, demyelination, and fibrosis. Moreover, CBX significantly mitigated MS-serum-induced fibrosis in the HBVP cell culture. Discussion: The study demonstrated two important findings. First, CBX decreases fibrosis formation in both in-vivo and in-vitro MS models. Secondly, it improves neurological scores and decreases demyelination in the EAE model. Therefore, CBX can be potential novel therapeutic option in treating Multiple Sclerosis.

Can Dynamic Spinal Stabilization Be an Alternative to Fusion Surgery in Adult Spinal Deformity Cases?

BACKGROUND: Rigid stabilization and fusion surgery are widely used for the correction of spinal sagittal and coronal imbalance (SCI). However, instrument failure, pseudoarthrosis, and adjacent segment disease are frequent complications of rigid stabilization and fusion surgery in elderly patients. In this study, we present the results of dynamic stabilization and 2-stage dynamic stabilization surgery for the treatment of spinal SCI. The advantages and disadvantages are discussed, especially as an alternative to fusion surgery. METHODS: In our study, spinal, sagittal, and coronal deformities were corrected with dynamic stabilization performed in a single session in patients with good bone quality (without osteopenia and osteoporosis), while 2-stage surgery was performed in patients with poor bone quality (first stage: percutaneous placement of screws; second stage: placement of dynamic rods and correction of spinal SCI 4-6 months after the first stage). One-stage dynamic spinal instrumentation was applied to 20 of 25 patients with spinal SCI, and 2-stage dynamic spinal instrumentation was applied to the remaining 5 patients. RESULTS: Spinal SCI was corrected with these stabilization systems. At 2-year follow-up, no significant loss was observed in the instrumentation system, while no significant loss of correction was observed in sagittal and coronal deformities. CONCLUSION: In adult patients with spinal SCI, single or 2-stage dynamic stabilization is a viable alternative to fusion surgery due to the very low rate of instrument failure. CLINICAL RELEVANCE: This study questions the use of dynamic stabilization systems for the treatment of adult degenerative deformities.

Use of Dynamic Spinal Instruments (Dynesys) in Adult Spinal Deformities According to Silva-Lenke and Berjano-Lamartina Classifications.

BACKGROUND: Adult spinal deformities (ASD) present complex challenges in spine surgery. The diverse nature of these deformities requires a comprehensive understanding of their classification and treatment options. Traditional approaches, such as fusion and rigid stabilization are associated with complications, including screw loosening, breakage, proximal junctional kyphosis (PJK), and pseudoarthrosis. Dynamic stabilization techniques have emerged as promising alternatives, to reduce these complications and preserve spinal motion. OBJECTIVE: This study investigated the effectiveness of dynamic stabilization using the Dynesys system in the surgical treatment of adult degenerative spinal deformities, with a particular emphasis on their classification. METHODS: ASDs were classified according to the Berjano-Lamartina (BL) and Silva-Lenke (SL) classifications. We analyzed the efficacy of the Dynesys system in enhancing sagittal balance, radiological parameters, and clinical outcomes in this context. RESULTS: Dynamic stabilization of patients with ASDs using the Dynesys system significantly improved the visual analog scale and Oswestry Disability Index scores and decreased the complication rates. Patients with BL types 2, 3, and 4 experienced a significant improvement in sagittal balance followed by sagittal vertical axis measurements (p = 0.045, p = 0.015, and p < 0.0001, respectively). CONCLUSION: The SL and BL classifications, which were originally developed for rigid spinal stabilization, can be applied in dynamic stabilization. Furthermore, dynamic stabilization using the Dynesys system can be used as an alternative to rigid stabilization in SL levels 2 and 3, and BL types 1, 2, and 3, and in some patients with type 4 ASDs.

Perivascular PDGFRB+ cells accompany lesion formation and clinical evolution differentially in two different EAE models.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that may lead to progressive disability. Here, we explored the behavioral pattern and the role of vasculature especially PDGFRB+ pericytes/ perivascular cells, in MS pathogenesis. METHODS: We have evaluated vascular changes in two different experimental allergic encephalomyelitis (EAE) mice models (MOG and PLP-induced). PDGFRB+ cells demonstrated distinct and different behavioral patterns. In both models, fibrosis formation was detected via collagen, fibronectin, and extracellular matrix accumulation. RESULTS: The PLP-induced animal model revealed that fibrosis predominantly occurs in perivascular locations and that PDGFRB+ cells are accumulated around vessels. Also, the expression of fibrotic genes and genes coding extracellular matrix (ECM) proteins are upregulated. Moreover, the perivascular thick wall structures in affected vessels of this model presented primarily increased PDGFRB+ cells but not NG2+ cells in the transgenic NG2-DsRed transgenic animal model. On the other hand, in MOG induced model, PDGFRB+ perivascular cells were accumulated at the lesion sites. PDGFRB+ cells colocalized with ECM proteins (collagen, fibronectin, and lysyl oxidase L3). Nevertheless, both MOG and PLP-immunized mice showed increasing EAE severity, and disability parallel with enhanced perivascular cell accumulation as the disease progressed from earlier (day 15) to later (day 40). CONCLUSION: As a result, we have concluded that PDGFRB+ perivascular cells may be participating in lesion progression and as well as demonstrating different responses in different EAE models.

ANTIBACDUS-PAN: Antibacterial Utilization among Adult Patients Before and During COVID-19 Pandemic within 12-Months Period: A Tertiary Hospital Pharmacoepidemiology Study.

Objective: Irrational use of antibacterials is a concern during the COVID-19 pandemic. Hospital pharmacoepidemiology studies are important for evaluating the rational use of medicines, especially antibacterials, during pandemics. Defined daily doses (DDD) and drug utilization 90% (DU90%) are established methods for the evaluation of drug utilization. We aimed to evaluate antibacterial utilization in a tertiary hospital setting at Koç University Hospital (KUH). Materials and Methods: This cross-sectional, descriptive study was retrospectively conducted with data extracted from KUH Inpatient Electronic Order System (CP) and was carried out for a period of one year. Antibacterial utilization of adult (aged ≥ 18 years) inpatients, who were prescribed at least one type of systemic antibacterial (ATC code J01), was evaluated using the recommended parameter DDD/100 admission and compared between 6 months before COVID-19 and during COVID-19 periods. March 11, 2020, the very first COVID-19 diagnosed case in Turkey, was set as the cutoff date of the 6-month period for the selection of the compared antibacterials using the DU90% method. Results: Finally, 3280 of 5942 and 2605 of 4942 prescriptions for pre-COVID-19 and COVID-19 periods were included, respectively. Antibacterial utilization according to DDD/100 admissions increased from 193.96 to 201.26 DDD/100 admissions after the initiation of COVID-19 pandemic. The most utilized antibacterials were piperacillin and enzyme inhibitors in pre-COVID-19 period, whereas meropenem was utilized the most during COVID-19 period. Azithromycin utilization increased by 656.24%, whereas clarithromycin utilization decreased by 52.12%. Antibacterials were utilized most in general surgery department, with an increase of 17.57%. Conclusion: There is an increase in antibacterial utilization in KUH during COVID-19 pandemic, especially reserved antibacterials, which is a concern for antibacterial resistance.