Degree of basal cisterns compression predicting mortality and functional outcome after craniotomy and primary decompressive craniectomy in acute subdural hematoma population.

OBJECTIVES: The compression of basal cisterns on CT is one of the signs of intracranial hypertension in TBI population. This study evaluates the relationship between the degree of basal cisterns effacement and outcomes in aSDH population. METHODS: The study includes prospectively collected data from 290 patients who underwent osteoplastic craniotomy (OC) or primary decompressive craniectomy (pDC) for aSDH from 2016 to 2021. Univariate and multivariate regression analyses were performed to evaluate the association of baseline characteristics and extent of basal cisterns compression on pre-operative and post-operative CT scans with the outcomes at the time of discharge. Outcomes were dichotomized into mortality (and unfavourable (GOS 1-3 vs GOS 4-5). The degree of cisternal compression was evaluated using the cisternal effacement score of perimesencephalic and quadrigeminal cisternal components. Critical thresholds associated with the outcomes were calculated. RESULTS: Age and pre-/post-operative degree of cisternal compression were the strongest independent predictors of intrahospital mortality in a whole sample and separately in OC and pDC subgroups. The unfavourable outcome was independently predicted by age, pre-/post-operative status of cisternal compression and initial GCS. Critical thresholds associated with the mortality and poor functional outcome were, respectively, age ≥ 70 (OR 3.14 [CI 95% 1.82-5.46], p < 0.001) and ≥ 67 (OR 3.87 [CI 95% 2.33-6.54], p < 0.001), pre-operative cisternal effacement score ≥ 9 (OR 6.39 [CI 95% 3.62-11.53], p < 0.001) and ≥ 7 (OR 4.93 [CI 95% 2.96-8.38], p < 0.001), post-operative cisternal effacement score ≥ 6 (OR 20.6 [CI 95% 10.08-45.10], p < 0.001) and ≥ 3 (OR 7.47 [CI 95% 3.87-15.73], p < 0.001) and initial GCS ≤ 8 (OR 0.24 [CI 95% 0.13-0.43], p < 0.001 and OR 0.12 [CI 95% 0.07-0.21], p < 0.001). CONCLUSIONS: After adjusting for baseline characteristics, age and degree of cisternal compression remained the independent predictors of mortality, whereas unfavourable outcomes were associated with age, cisternal obliteration and GCS on presentation.

Importance of the putative furin recognition site 742RNRR745 for antiangiogenic Sema3C activity in vitro.

Angiogenesis is one of the key processes in the growth and development of tumors. Class-3 semaphorins (Sema3) are characterized as axon guidance factors involved in tumor angiogenesis by interacting with the vascular endothelial growth factor signaling pathway. Sema3 proteins convey their regulatory signals by binding to neuropilins and plexins receptors, which are located on the effector cell. These processes are regulated by furin endoproteinases that cleave RXRR motifs within the Sema, plexin-semaphorins-integrin, and C-terminal basic domains of Sema3 protein. Several studies have shown that the furin-mediated processing of the basic domain of Sema3F and Sema3A is critical for association with receptors. It is unclear, however, if this mechanism can also be applied to other Sema3 proteins, including the main subject of this study, Sema3C. To address this question, we generated a variant of the full-length human Sema3C carrying point mutation R745A at the basic domain at the hypothetical furin recognition site 742RNRR745, which would disable the processing of Sema3C at this specific location. The effects produced by this mutation were tested in an in vitro angiogenesis assay together with the wild-type Sema3C, Sema3A, and Sema3F proteins. Our results showed that the inhibitory effect of Sema3C on microcapillary formation by human umbilical vein endothelial cells could be abrogated upon mutation at the Sema3C basic domain within putative furin cleavage site 742RNRR745, indicating that this site was essential for the Sema3 biological activity.

Importance of the putative furin recognition site 742RNRR745 for antiangiogenic Sema3C activity in vitro

Angiogenesis is one of the key processes in the growth and development of tumors. Class-3 semaphorins (Sema3) are characterized as axon guidance factors involved in tumor angiogenesis by interacting with the vascular endothelial growth factor signaling pathway. Sema3 proteins convey their regulatory signals by binding to neuropilins and plexins receptors, which are located on the effector cell. These processes are regulated by furin endoproteinases that cleave RXRR motifs within the Sema, plexin-semaphorins-integrin, and C-terminal basic domains of Sema3 protein. Several studies have shown that the furin-mediated processing of the basic domain of Sema3F and Sema3A is critical for association with receptors. It is unclear, however, if this mechanism can also be applied to other Sema3 proteins, including the main subject of this study, Sema3C. To address this question, we generated a variant of the full-length human Sema3C carrying point mutation R745A at the basic domain at the hypothetical furin recognition site 742RNRR745, which would disable the processing of Sema3C at this specific location. The effects produced by this mutation were tested in an in vitro angiogenesis assay together with the wild-type Sema3C, Sema3A, and Sema3F proteins. Our results showed that the inhibitory effect of Sema3C on microcapillary formation by human umbilical vein endothelial cells could be abrogated upon mutation at the Sema3C basic domain within putative furin cleavage site 742RNRR745, indicating that this site was essential for the Sema3 biological activity.

Evaluation of morphological issues of central nervous system glioblastoma on chicken embryo chorioallantoic membrane.

Glioblastoma is the most common brain malignancy and is marked by an extremely poor prognosis, despite advances in surgical and clinical neuro-oncology. That is why central nervous system glioblastoma is quite a challenging neoplasm, requiring much further research to understand the molecular and cellular clinical basis. Existing in vivo glioblastoma models are based on the inoculation of glioma cells into rodent brains or the use of transgenic mice. For decades the avian model was the model of choice in developmental biology. However, the reports on chorioallantoic membrane glioblastoma model are quite rare. The objective of these experiments was to evaluate morphological issues of glioblastoma on CAM and the interaction between transplant and CAM. Chicken embryos obtained from a local poultry farm were put in an incubator. Fresh samples of glioblastoma obtained during the operation were grafted on CAM, which is formed on the 7-9 th day of embryo development. The growth and morphological issues of cells were observed with a stereo microscope and the histological preparations were done in particular intervals of time, starting from 24 hours after the transplantation. We observed peritumoral edema, necrotic zones and angiogenesis on the chorioallantoic membrane. This evidence, together with the immunohistological proof, shows that glioblastoma survives on CAM and has its typical morphological features.

Management of patients with ruptured cerebral aneurysms in hospital population of Lithuania.

A retrospective analysis of ruptured cerebral aneurysms among the hospital population of Lithuania was performed. A total of 507 patients were enrolled in the study during a 5 year period. The unadjusted annual incidence of ruptured cerebral aneurysms was found to be 2.7/100,000 in the hospital population of Lithuania and 3.9/100,000 in the hospital population of the defined area of the city of Kaunas. Overall management results showed a 45. 6% good recovery and 31.6% death rate in this group of patients. Surgical results showed a 52.1% good outcome and 20.9% death rate. Despite the fact that the death rate according to the timing of surgery after the initial subarachnoid haemorrhage did not differ significantly (p >0.05) among early (0-3 days post SAH), moderate (4-7 days post SAH) and late (more than 7 days post SAH) surgery groups, it was found that 75 (14.8%) patients deteriorated while awaiting surgery. Initial bleeding together with rebleeding, medical complications and vasospasm were the main causes of death, constituting 61.3%, 18.1% and 9.4% of all deaths, respectively. The results of this study showed that the annual incidence of ruptured cerebral aneurysms in Lithuania is similar to that in other European countries except for Finland. Overall management results in the Lithuanian hospital population indicated only a slight improvement compared to management results of previous population-based studies in other countries.