The use of LLIF technology in adult patients with degenerative scoliosis: retrospective cohort analysis and literature review

Introduction Incidence of adult degenerative scoliosis (ADS) among individuals over 50 years old reaches 68%. Surgical interventions aimed at correcting the spinal deformity in patients of the older age group are accompanied by a high risk of complications. The use of LLIF is associated with lower complications as compared with open anterior or posterior fusion. Materials and methods Seventy-one patients with ADS (13 men, 58 women) were operated at the Federal Neurosurgical Center. Their average age was 60.4/60 (average/median) [55;64.5] (1: 3 quartile) years. The follow-up was from 12 to 18 months. X-ray study, SCT, MRI of the lumbar spine were used. Questionnaire surveys were conducted using the visual analog pain scale (VAS), Oswestry Disability Index (ODI) and the Short Form-36 (SF-36). Deformity correction was estimated in the frontal plane with Cobb’s method. Scoliosis was classified according to SRS-Schwab classification. Parameters of sagittal balance were estimated: PI (Pelvic incidence), SS (Sacral slope), PT (Pelvic tilt), LL (Lumbar lordosis). SVA, PT and PILL (PI minus LL) were defined adjusted for the age. Results Back pain according to VAS relieved from 6.1/6 [4;8] to 2.2/2 [2;3] points (p < 0.001) and was statistically significant at 12 months after the surgery. Leg pain according to VAS decreased from 5.4/5 [4;8] to 2.1/2 [1;3] points (p < 0.001) and was statistically significant at 12 months after the surgery. Functional adaptation according to ODI improved from 51.2/52.2 [38.6;64.1] to 31.8/33.3 [26.1;35.9] (p < 0.001). According to SF36, PH before the surgery was 25.7/24.3 [21.8;28.9] on average and at 12 months after the surgery - 38.7/38.7 [35.4;41.2] (p < 0.001). SF-36 MH before surgery was 27.1/26.3 [21.8;31.4] on average and 12 months later – 41.3/40.6 [36.5;43.7] (p < 0.001). PT before the surgery was 23.3/22° [17.5;28], 12 months later it was 17.9/17° [15;20] (p < 0.001). PI-LL was 11.5/10 ° [4;17.5], 12 months later – 8.4/8 ° [5.5;11.5] (p = 0.11). Transient paresis of femur flexors on the ipsilateral side was observed in five (7 %) cases; transient hyposthesia on the anterior thigh surface occurred in eight (11.2 %) cases. There were two cases of medial malposition (0.4 %) of pedicle screws (474 screws), pseudoarthrosis at two levels (1.2 %) (Grade 4 Bridwell) out of 166 levels performed, and seven (4.2 %) cases of damage to cortical endplates. Conclusion Restoration of local sagittal balance in ADS patients by short-segment fixation using LLIF technology leads to a statistically significant improvement in the quality of life and increases functional adaptation. Few early and late postoperative complications, less intraoperative blood loss and shorter hospital stay make LLIF in combination with MIS transpedicular fixation a method of choice in determining the surgical tactics for ADS in elderly and old age patients

Global neurosurgery amongst the EANS community: where are we at?

Antibody-drug conjugates (ADC) are antineoplastic agents recently introduced into the antitumor arsenal. T-DM1, a trastuzumab-based ADC that relies on lysosomal processing to release the payload, is approved for HER2-positive breast cancer. Next-generation ADCs targeting HER2, such as [vic-]trastuzumab duocarmazine (SYD985), bear linkers cleavable by lysosomal proteases and membrane-permeable drugs, mediating a bystander effect by which neighboring antigen-negative cells are eliminated. Many antitumor therapies, like DNA-damaging agents or CDK4/6 inhibitors, can induce senescence, a cellular state characterized by stable cell-cycle arrest. Another hallmark of cellular senescence is the enlargement of the lysosomal compartment. Given the relevance of the lysosome to the mechanism of action of ADCs, we hypothesized that therapies that induce senescence would potentiate the efficacy of HER2-targeting ADCs. Treatment with the DNA-damaging agent doxorubicin and CDK4/6 inhibitor induced lysosomal enlargement and senescence in several breast cancer cell lines. While senescence-inducing drugs did not increase the cytotoxic effect of ADCs on target cells, the bystander effect was enhanced when HER2-negative cells were cocultured with HER2-low cells. Knockdown experiments demonstrated the importance of cathepsin B in the enhanced bystander effect, suggesting that cathepsin B mediates linker cleavage. In breast cancer patient-derived xenografts, a combination treatment of CDK4/6 inhibitor and SYD985 showed improved antitumor effects over either treatment alone. These data support the strategy of combining next-generation ADCs targeting HER2 with senescence-inducing therapies for tumors with heterogenous and low HER2 expression. Significance: combining ADCs against HER2-positive breast cancers with therapies that induce cellular senescence may improve their therapeutic efficacy by facilitating a bystander effect against antigen-negative tumor cells

Working in low- and middle-income countries. Learning from each other

Barriers may limit LMICs-HICs collaborations: infrastructure, equipment's lack/inadequacy, political issues, brain drain.•Local training is crucial for universal health coverage; several activities are headed by Global Neurosurgery organisations.•The ​EANS Global and Humanitarian Neurosurgery Committee aims to become a gateway for partnerships between HICs and LMICs

Table_2_Brain but not serum BDNF levels are associated with structural alterations in the hippocampal regions in patients with drug-resistant mesial temporal lobe epilepsy.docx

Mesial temporal lobe epilepsy is the most common type of focal epilepsy, imposing a significant burden on the health care system worldwide. Approximately one-third of patients with this disease who do not adequately respond to pharmacotherapy are considered drug-resistant subjects. Despite having some clues of how such epileptic activity and resistance to therapy emerge, coming mainly from preclinical models, we still witness a scarcity of human data. To narrow this gap, in this study, we aimed to estimate the relationship between hippocampal and serum levels of brain-derived neurotrophic factor (BDNF), one of the main and most widely studied neurotrophins, and hippocampal subfield volumes in patients with drug-resistant mesial temporal epilepsy undergoing neurosurgical treatment. We found that hippocampal (but not serum) BDNF levels were negatively correlated with the contralateral volumes of the CA1 and CA4 subfields, presubiculum, subiculum, dentate gyrus, and molecular layer of the hippocampus. Taken together, these findings are generally in accordance with existing data, arguing for a proepileptic nature of BDNF effects in the hippocampus and related brain structures.</p

Image_1_Brain but not serum BDNF levels are associated with structural alterations in the hippocampal regions in patients with drug-resistant mesial temporal lobe epilepsy.png

Mesial temporal lobe epilepsy is the most common type of focal epilepsy, imposing a significant burden on the health care system worldwide. Approximately one-third of patients with this disease who do not adequately respond to pharmacotherapy are considered drug-resistant subjects. Despite having some clues of how such epileptic activity and resistance to therapy emerge, coming mainly from preclinical models, we still witness a scarcity of human data. To narrow this gap, in this study, we aimed to estimate the relationship between hippocampal and serum levels of brain-derived neurotrophic factor (BDNF), one of the main and most widely studied neurotrophins, and hippocampal subfield volumes in patients with drug-resistant mesial temporal epilepsy undergoing neurosurgical treatment. We found that hippocampal (but not serum) BDNF levels were negatively correlated with the contralateral volumes of the CA1 and CA4 subfields, presubiculum, subiculum, dentate gyrus, and molecular layer of the hippocampus. Taken together, these findings are generally in accordance with existing data, arguing for a proepileptic nature of BDNF effects in the hippocampus and related brain structures.</p

Table_1_Brain but not serum BDNF levels are associated with structural alterations in the hippocampal regions in patients with drug-resistant mesial temporal lobe epilepsy.docx

Mesial temporal lobe epilepsy is the most common type of focal epilepsy, imposing a significant burden on the health care system worldwide. Approximately one-third of patients with this disease who do not adequately respond to pharmacotherapy are considered drug-resistant subjects. Despite having some clues of how such epileptic activity and resistance to therapy emerge, coming mainly from preclinical models, we still witness a scarcity of human data. To narrow this gap, in this study, we aimed to estimate the relationship between hippocampal and serum levels of brain-derived neurotrophic factor (BDNF), one of the main and most widely studied neurotrophins, and hippocampal subfield volumes in patients with drug-resistant mesial temporal epilepsy undergoing neurosurgical treatment. We found that hippocampal (but not serum) BDNF levels were negatively correlated with the contralateral volumes of the CA1 and CA4 subfields, presubiculum, subiculum, dentate gyrus, and molecular layer of the hippocampus. Taken together, these findings are generally in accordance with existing data, arguing for a proepileptic nature of BDNF effects in the hippocampus and related brain structures.</p