Downregulation of the LncRNA MEG3 Promotes Osteogenic Differentiation of BMSCs and Bone Repairing by Activating Wnt/β-Catenin Signaling Pathway

Background: Previous studies have demonstrated that long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explores the use of MEG3 in skull defects bone repairing. Methods: Endogenous expression of MEG3 during BMSCs osteogenic differentiation was detected by quantitative real-time polymerase chain reaction (qPCR). MEG3 was knockdown in BMSCs by lentiviral transduction. The proliferation, osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs were assessed by Cell Counting Kit-8 (CCK-8) assay, qPCR, alizarin red and alkaline phosphatase staining. Western blot was used to detect β-catenin expression in MEG3 knockdown BMSCs. Dickkopf 1 (DKK1) was used to block wnt/β-catenin pathway. The osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs after wnt/β-catenin inhibition were assessed by qPCR, alizarin red and alkaline phosphatase staining. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model. Micro-computed tomography(micro-CT), hematoxylin and eosin staining and immunohistochemistry were performed to evaluate the bone repairing. Results: Endogenous expression of MEG3 was increased during osteogenic differentiation of BMSCs. Downregulation of MEG3 could promote osteogenic differentiation of BMSCs in vitro. Notably, a further mechanism study revealed that MEG3 knockdown could activate Wnt/β-catenin signaling pathway in BMSCs. Wnt/β-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using poly (3-hydroxybutyrate-co-3-hydroxyhexanoate, PHBHHx)-mesoporous bioactive glass (PHMG) scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerate bone repairing in a critical-sized skull defects rat model. Conclusions: Our study reveals the important role of MEG3 during osteogenic differentiation and bone regeneration. Thus, MEG3 engineered BMSCs may be effective potential therapeutic targets for skull defects.

Three dimensional custom-made PEEK cranioplasty

Background: An optimal reconstruction of calvarial skull defects is a challenge for neurosurgeons, and the strategy used to achieve the best result remains debatable. Therefore, we conducted this study to compare the esthetic and functional outcome of custom-made three-dimensional (3D) cranioprostheses to handmade bone cement in reconstructing calvarial skull defects. Methods: We included 66 patients above 10 years of age with calvarial skull defects and undergoing reconstruction: 33 were enrolled in the custom-made 3D implants group and 33 in the handmade implants group in the period from August 2017 to December 2020 in the neurosurgery department of Fayoum University Hospital. Results: Complete success of the esthetic end-point was insignificantly higher in the custom-made 3D prostheses group based on the doctor’s and patients’ assessment (60.6% vs. 42.4%; 33.3% vs. 9.1%, P > 0.05), respectively. Complete success of the functional end-point was significantly higher in the custom-made 3D group compared to the handmade cement bone group according to the doctor’s and patients’ assessment (60.6% vs. 0%; 21.2% vs. 0%, P < 0.05). There were no late complications noted in the custom-made 3D prosthesis group, whereas 50% of the handmade bone group had late complications (P < 0.05). Full improvement of the symptoms of the “syndrome of trephined” was achieved in the 3D custom-made group compared to the handmade bone cement group (20% vs. 0%). Conclusion: Cranioplasty using three dimensional customs made PEEK prosthesis is a reliable method which saves operative time, lowers cost and provides less complications if compared with other cranioplasty techniques. Custom-made 3D cranioprostheses are better than handmade bone cement in reconstructing calvarial defects in terms of esthetic and functional outcome as well as complications.

Disseminated Mycobacterium avium Complex Infection Causing Multiple Skull Defects in an Immunocompetent Patient: A Case Report

Mycobacterium avium complex (MAC) infection mainly causes pulmonary disease. However, in 20% to 30% of cases, it also induces various extrapulmonary diseases. Disseminated MAC infection occasionally occurs in immunocompromised patients but very rarely in immunocompetent patients. An 80-year-old immunocompetent woman presented with multiple chronic wounds on the scalp that had not improved despite prolonged treatment. A scalp abscess caused by disseminated MAC infection 4 years ago had gone through repeated cycles of improvement and aggravation despite continued use of anti-mycobacterial agents and active wound care. Enhanced brain computed tomography and magnetic resonance imaging revealed multiple skull defects and abscesses invading the dura mater. Under general anesthesia, the infected scalp skin and bone were sufficiently removed, and the bone and soft tissue defects were repaired with cranioplasty using a titanium mesh plate and local flap. As exemplified in this case, multiple chronic wounds unresponsive to treatment need to be screened for MAC infection. As chronic MAC infection in the scalp can cause skull destruction and brain infection, it needs to be treated aggressively at an early stage to prevent serious morbidity and mortality. Effective MAC infection management involves adequate medication, regular follow-up imaging, and active surgical procedure.

On the issue of closure of defects of the skull and cerebral frills with free plastics

The practical surgeon often has to decide on the method of closing the skull defects, as is known, which do not have the ability to close on their own due to the insignificant plastic abilities of pericranium.

Replacement of extensive skull defects

In recent years, at the Hospital Surgical Clinic of Kazan University, there have been several rather interesting cases of replacement of extensive defects of the skull after traumatic injuries, accompanied by epileptic seizures.

Computed tomography angiography scoring systems and the role of skull defects in the confirmation of brain death

To assess and compare all current computed tomography angiography (CTA) scoring systems for the diagnostic workup of brain death (BD) to digital subtraction angiography (DSA) and clinical tests. Fifty-two patients with a clinical suspicion of BD underwent CTA and subsequently DSA. The diagnostic performance of all current CTA scoring systems was compared to that of DSA, in all patients with a suspicion of BD. A comparison to clinical tests was made only in DSA-positive for BD patients (n = 49), since in DSA-negative BD patients (n = 3) clinical tests were not performed. Further subgroup analysis was performed in relation to skull defects (SDs) stratification. Statistical analysis was conducted by applying statistics-contingency tables, Cochran’s-Q test and McNemar’s test. The CTA -10, and -7- and all 4-point scoring systems, showed overall sensitivities of 81,6%, 87.8% and 95.9% respectively and 100% specificity, when compared to DSA. In patients with a clinical verification of BD, the CTA -10 and -7-point scoring systems were significantly inferior to clinical tests (p = 0.004 and p = 0.031), while the 4-point scoring systems showed no such difference (p = 0.5). All 4-point scoring systems showed 100% sensitivity in patients with a minor SD or no SD. In patients with a major SD, all CTA scoring systems (− 10, − 7- and all 4-point) were less sensitive (62.5%, 62.5% and 75% respectively). The presence of a major SD was associated with an 8 × relative risk for false negative results in all 4-point scoring systems. CTA showed excellent diagnostic performance in patients with a suspicion of BD. The 4-point CTA scoring systems are the most sensitive for the diagnosis of BD, although in patients with a major SD patient, the role of CTA is ambiguous.

Intracranial Compliance Assessed by Intracranial Pressure Pulse Waveform

Background: Morphological alterations in intracranial pressure (ICP) pulse waveform (ICPW) secondary to intracranial hypertension (ICP >20 mmHg) and a reduction in intracranial compliance (ICC) are well known indicators of neurological severity. The exclusive exploration of modifications in ICPW after either the loss of skull integrity or surgical procedures for intracranial hypertension resolution is not a common approach studied. The present study aimed to assess the morphological alterations in ICPW among neurocritical care patients with skull defects and decompressive craniectomy (DC) by comparing the variations in ICPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of acute brain injury were included. A continuous record of 10 min-length for the beat-by-beat analysis of ICPW was performed, with ICP elevation produced by means of ultrasound-guided manual internal jugular vein compression at the end of the record. ICPW features (peak amplitude ratio (P2/P1), time interval to pulse peak (TTP) and pulse amplitude) were counterweighed between baseline and compression periods. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. A total of 21 (36%) presented no skull defects, 21 (36%) belonged to group 2, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±15.11 for intact, 15.33 for group 2 and ±20.81 mmHg for group 3, with ICP-induced elevation also similar between groups (p = 0.56). Significant elevation was observed for the P2/P1 ratio for groups 1 and 2, whereas a reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, but a reduction of 0.03 for group 3, p = 0.01), and no significant results were obtained for TTP and pulse amplitudes. Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPW indicated DC to be protective for further influences of ICP elevations over the brain. The analysis of ICPW seems to be an alternative to real-time ICC assessment.