Impairing proliferation of glioblastoma multiforme with CD44+ selective conjugated polymer nanoparticles.

Glioblastoma is one of the most aggressive types of cancer with success of therapy being hampered by the existence of treatment resistant populations of stem-like Tumour Initiating Cells (TICs) and poor blood-brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs were designed to include fluorescein-conjugated Hyaluronic Acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood-brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake of HA-CPNs in CD44 positive GBM-patient derived cultures. Interestingly, we found that uptake alone regulated the levels and signaling activity of the CD44 receptor, decreasing stemness, invasive properties and proliferation of the CD44-TIC populations in vitro and in a patient-derived xenograft zebrafish model. This work proposes a novel, CPN- based, and surface moiety-driven selective way of targeting of TIC populations in brain cancer.

Instrumented Four-Level Anterior Cervical Discectomy and Fusion: Long-Term Clinical and Radiographic Outcomes.

BACKGROUND: There is a paucity of data on outcomes following four-level anterior cervical discectomy and fusions (ACDFs), especially the sagittal balance (SB) parameters. OBJECTIVE: We aimed to review the long-term clinical and radiographic outcomes for 41 consecutive patients that underwent instrumented four-level ACDF. MATERIALS AND METHODS: Records of 27 men and 14 women, aged 40-68 years, who underwent instrumented four-level ACDF and plating at C3-C7 (n = 37) or C4-T1 (n = 4) were retrospectively analyzed. Clinical outcomes that were assessed were the visual analog scale (VAS) for pain, neck disability index (NDI), Odom's criteria, improvement of symptoms, intraoperative and postoperative complications, SB, and need for revision surgery. RESULTS: The mean follow-up was 65 ± 36.3 months. The mean VAS for arm and neck pain significantly improved from 7.7 ± 1.4 to 3.5 ± 1.7 (P < 0.001). The NDI score significantly improved from 31 ± 8.2 to 19.3 ± 8.1 (P < 0.001). Concerning Odom's criteria, the grades were excellent (14), good (17), fair (9), and poor (1). Concerning intraoperative and postoperative complications, 10 cases developed dysphagia, 3 cases developed temporary dysphonia, 2 cases developed a postoperative hematoma, 1 patient developed C5 palsy, 1 vertebral artery (VA) injury, and 1 case had superficial infection. The average length of stay (LOS) was 2.9 ± 3.7 days. Three patients needed another surgery (one adjacent segment and two posterior foraminotomies). Regarding the mean change in SB parameters, Cobb's angle (CA) (C2-C7) was 14° ± 8.3°, fusion angle (FA) was 10.9 ± 10.9°, cervical straight vertical alignment (cSVA) was 0.6 ± 0.5 cm, T1 slope was 2.3° ± 3.4°, and disc height (DH) was 1.3 ± 0.9 mm. CONCLUSION: Instrumented four-level ACDF is safe with a satisfactory outcome and supplementary posterior fusion was not required in any case.

Primary Spinal Melanoma: Case Report and Systematic Review.

INTRODUCTION: Primary malignant melanoma of the spinal cord (PSM) is a rare condition with limited evidence regarding its diagnosis (clinical and radiographic), management, and prognosis. Our aim was to report an extremely rare two cases of primary malignant melanoma of the spine one of them is sacral melanoma which represents the second reported case in the literature and to conduct a systematic review of the relevant literature. METHODS: The diagnosis and management of these cases were retrospectively reviewed. Using the PRISMA guideline, we conducted a systematic review of the literature to analyze different management strategies and the prognosis of such pathology. RESULTS: All two patients were operated on, and received gross total removal of their tumors, with extended follow up for tumor recurrences. One of the cases involved a sacral tumor, which was resected without adjuvant therapy. The other one was seen by oncology and received post-operative chemo- and radio- therapy. In addition to the aforementioned cases, we present a comprehensive review of the literature on PSM from 1950 to the present, demonstrating that PSM is a very rare tumor, with a limited counted number of cases reported worldwide. CONCLUSION: In conclusion, we report an exceedingly rare two cases of primary malignant melanoma of the spine. Early surgical intervention is key to the management of these rare and aggressive tumors. GTR should be attempted if possible.

Surgical intervention for spontaneous intracranial hypotension Type 4 CSF leak: A case report.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a rare condition that can be very debilitating. SIH is well understood to be due to a CSF leak, however, identifying the source of the leak is still a challenge. We are presenting a case of Type 4 CSF leak and reviewing the related literature. CASE DESCRIPTION: A 46-year-old female presenting with intractable orthostatic headaches was diagnosed with SIH. She was unable to mobilize due to the severity of her symptoms. MRI scans of the brain and spine did not identify a source of the leak. After failing conservative therapy and multiple epidural blood patches, the patient underwent surgery which resulted in significant improvement in symptoms. CONCLUSION: This study has shown that surgical intervention improves symptoms in patients who do not have an identifiable source of CSF leak. Further studies need to be done to fully understand the role of surgery in Type 4 CSF leaks.

Challenges, Learning Curve, and Safety of Endoscopic Endonasal Surgery of Sellar-Suprasellar Lesions in a Community Hospital.

BACKGROUND AND OBJECTIVE: Endoscopic endonasal surgery (EES) for the management of sellar, suprasellar, and anterior skull base lesions is gaining popularity. Our aim was to analyze and present the clinical outcomes of EES for the management of these lesions in a community hospital setting. METHODS: We retrospectively reviewed the charts of 56 patients with sellar, suprasellar, and anterior skull base lesions who underwent EES between 2010 and 2018. RESULTS: There was male predominance (53.6%) with a mean age of 54.9 ± 13.7 years. Lesions were 45 pituitary adenomas, 5 meningiomas, 3 metastatic, 1 craniopharyngioma, 1 Rathke cyst, and 1 mucocele. Gross total excision was achieved in 57.1%, subtotal excision occurred in 37.5%, and decompression and biopsy were achieved in 5.4% patients. Postoperative vision normalized or improved in 27 patients (86.1%) and was stable in 4 patients (13.9%). Recovery of a preexisting hormonal deficit occurred in 13 (23.2%) patients, and a new hormonal deficit occurred in 9 patients (16.1%). The mean hospital stay was 6.1 ± 4.9 days. Postoperative complications included cerebrospinal fluid leak in 8 patients (14.3%). Four patients (7.1%) had meningitis. Diabetes insipidus was present in 19 patients (33.9%), and postoperative intracranial hematoma requiring evacuation was necessary in 2 patients (3.6%). The mean follow-up duration was 47.5 ± 25.8 months. Lesion progression or recurrence requiring redo surgery occurred in 5 patients (8.9%). Regarding the learning curve, the postoperative cerebrospinal fluid leak, meningitis, new hormonal deficits, and diabetes insipidus decreased in the second half of the patients. CONCLUSIONS: EES provides an effective and safe surgical option with low morbidity and mortality for the treatment of sellar, suprasellar, and anterior skull base lesions in a community hospital setting.