Bone flap infections after craniotomy: a review of 63 cases and the implications for definitions, classification and surveillance methodologies.

BACKGROUND: Bone flap infections (BFIs) occur following neurosurgical procedures such as craniotomies. However, they are poorly defined and often not clearly differentiated from other surgical site infection in neurosurgery. AIM: To review data from a national adult neurosurgical centre to explore some clinical aspects to better inform definitions, classification and surveillance methodologies. METHODS: We retrospectively reviewed data on clinical samples sent for culture from patients with suspected BFI. We also accessed information recorded prospectively from national and local databases for evidence of BFI or related conditions based on terms used in surgical operative notes or discharge summaries and documented monomicrobial and polymicrobial infections related to craniotomy sites. FINDINGS: Between January 2016 and December 2020, we documented 63 patients with a mean age of 45 years (16-80). Craniectomy for infection of the skull was the most common terminology used to describe BFI in the coding used in a national database, 40/63 (63%), but other terms were used. A malignant neoplasm was the most common underlying condition necessitating craniectomy in 28/63 (44%) cases. Specimens submitted for microbiological investigation included 48/63 (76%) bone flaps, 38/63 (60%) fluid/pus, and 29/63 (46%) tissue. Fifty-eight (92%) patients had at least one culture-positive specimen; 32 (55%) were monomicrobial and 26 (45%) were polymicrobial. Gram-positive bacteria predominated and Staphylococcus aureus was the most common. CONCLUSION: Greater clarity on how to define BFI is required to enable better classification and the carrying out of appropriate surveillance. This will inform preventative strategies and more effective patient management.

Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma) in the setting of cowden syndrome: a case report and literature review on COLD syndrome.

Lhermitte-Duclos Disease is a rare clinical entity involving a dysplastic lesion of the cerebellum. The dysplastic cerebellar ganglioblastoma is often seen in association with Cowden Syndrome, an autosomal dominant disorder consisting of a mutation in the phosphatase and homologous tensin (PTEN) gene. Characteristic findings on neuroimaging allow for a pre-operative diagnosis to be made, which guides further management of the condition. This report describes the diagnosis and management of Lhermitte-Duclos Disease in a 51-year-old lady, spanning a period of almost seven years. The characteristic radiological and histological findings are presented, along with the clinical features associated with Cowden Syndrome. This patient ultimately underwent surgical intervention for symptomatic relief, which is described here.

Ellipsometric modeling of serially bi-deposited glancing-angle-deposition coatings.

Ellipsometric modeling of serially bi-deposited glancing-angle-deposition (GLAD) coatings with a high degree of accuracy is imperative for multilayer coatings. High-precision dispersion curves are demonstrated for a wide variety of applications.

Glancing-angle-deposited silica films for ultraviolet wave plates.

Birefringent silica films are formed by glancing-angle deposition to fabricate quarter- and half-wave plates at a wavelength of 351 nm. A multilayer design is implemented to achieve low-loss transmittance with a high 351-nm laser-induced damage threshold.

Growth of a progesterone receptor-positive meningioma in a female patient with congenital adrenal hyperplasia.

Meningioma growth has been previously described in patients receiving oestrogen/progestogen therapy. We describe the clinical, radiological, biochemical and pathologic findings in a 45-year-old woman with congenital adrenal hyperplasia secondary to a defect in the 21-hydroxylase enzyme who had chronic poor adherence to glucocorticoid therapy with consequent virilisation. The patient presented with a frontal headache and marked right-sided proptosis. Laboratory findings demonstrated androgen excess with a testosterone of 18.1 nmol/L (0-1.5 nmol) and 17-Hydroxyprogesterone >180 nmol/L (<6.5 nmol/L). CT abdomen was performed as the patient complained of rapid-onset increasing abdominal girth and revealed bilateral large adrenal myelolipomata. MRI brain revealed a large meningioma involving the right sphenoid wing with anterior displacement of the right eye and associated bony destruction. Surgical debulking of the meningioma was performed and histology demonstrated a meningioma, which stained positive for the progesterone receptor. Growth of meningioma has been described in postmenopausal women receiving hormone replacement therapy, in women receiving contraceptive therapy and in transsexual patients undergoing therapy with high-dose oestrogen and progestogens. Progesterone receptor positivity has been described previously in meningiomas. 17-Hydroxyprogesterone is elevated in CAH and has affinity and biological activity at the progesterone receptor. Therefore, we hypothesise that patients who have long-standing increased adrenal androgen precursor concentrations may be at risk of meningioma growth. LEARNING POINTS: Patients with long-standing CAH (particularly if not optimally controlled) may present with other complications, which may be related to long-standing elevated androgen or decreased glucocorticoid levels.Chronic poor control of CAH is associated with adrenal myelolipoma and adrenal rest tissue tumours.Meningiomas are sensitive to endocrine stimuli including progesterone, oestrogen and androgens as they express the relevant receptors.

Trigeminal schwannomas.

Trigeminal schwannomas are the second most common intracranial schwannoma. They may occur sporadically or in association with neurofibromatosis type 2. The vast majority are benign in nature although malignancies have been reported. They may present with a range of symptoms because of their variable locations in areas with multiple differing functional activities. There is little understanding of the natural history of these tumours, and the choice of treatment includes surgery, stereotactic radiosurgery and fractionated radiotherapy. This article reviews the management options and outcomes. The incidence of recurrence and the time interval following treatment to recurrence is unpredictable.