Evaluation of severe traumatic brain injury referrals to the National Tertiary Neurosurgical Centre in the Republic of Ireland.

BACKGROUND: Transfer of all severe TBI patients to a neurosurgical unit (NSU) has been advocated irrespective of levels of complexity and prognostic factors. Previous publications have suggested that only 50% of severe TBI patients in Ireland were managed in NSUs. AIMS: This study aims to audit severe TBI referrals to the National Neurosurgical Centre, to evaluate reasons for nonacceptance, assess for differences in the transferred and not transferred cohorts and to analyse observed and expected mortality rates. METHODS: Data on all patients with TBI referred in 2021 were prospectively collected using an electronic referral system. Patients with severe TBI (GCS ≤ 8 and AIS ≥ 3) were included and dichotomised into transferred and not transferred cohorts. RESULTS: Of 118 patients referred with severe TBI, 45 patients (38.1%) were transferred to the neurosurgical centre. Patients in the transferred cohort were significantly younger (p < 0.001), had a higher GCS score (p < 0.001) and a lower proportion of bilaterally unreactive pupils (p < 0.001) compared to the not transferred cohort. 93% (68/73) of those not transferred were either >65 years old, or had bilaterally unreactive pupils, or both. Based on the IMPACT model, the observed to expected mortality ratios in the transferred and not transferred cohorts were 0.65 (95% CI 0.25-1.05) and 0.88 (95% CI 0.65-1.11) respectively. CONCLUSION: The observed mortality rate for severe TBI in Ireland was similar to or better than expected mortality rates when adjusted for important prognostic factors. 93% of severe TBI patients not transferred to a neurosurgical centre were either elderly or had bilaterally unreactive pupils or both. These patients have an extremely poor prognosis and recommendation for transfer cannot be made based on current available evidence.

Risk factor synergism in aneurysmal subarachnoid hemorrhage: a cross-sectional study.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) accounts for 5-10% of strokes but a disproportionately large amount of stroke-related morbidity. Several risk factors have been described, including smoking, hypertension, increasing age, and female sex. METHODS: This cross-sectional study examined all patients with aSAH within a nationally representative catchment from 01/01/2017 to 31/12/2020. Patients with aneurysmal SAH were identified from multiple sources, including a prospective database and death records. The population was estimated from projections from a door-to-door census and risk factors from stratified random sampled surveys conducted on a yearly basis. Poisson regression models were used to estimate the incidence and incidence rate ratios (IRRs) for risk factors with 95% confidence intervals (95% CIs). RESULTS: We identified 875 cases of aSAH in 11,666,807 patient-years of follow-up, which corresponded to a crude incidence of 7.5 per 100,000 patient-years (95% CI 7-8) and a standardized incidence of 6.1/100,000 (95% CI 5.6-6.5). Smoking was the strongest individual risk factor, with a standardized incidence of 24/100,000 (95% CI 20-27) in smokers compared with 2.6/100,000 (2.1-3.2) in non-smokers (age-adjusted IRR 9.2, 95% CI 6.3-13.6). Hypertension (age-adjusted IRR 3.1, 95% CI 2.2-4.3) and female sex (age-adjusted IRR 1.8, 95% CI 1.4-2.3) were also associated with increased incidence. The highest incidence was observed in hypertensive smokers (standardized incidence 63/100,000, 95% CI 41-84), who had a lifetime risk of aSAH of 6.7% (95% CI 5.4-8.1) after age 35. Compared with participants who were non-smokers without hypertension, the age-adjusted IRR in hypertensive smokers was 27.9 (95% CI 15.9-48.8). CONCLUSION: Smoking is the most prominent individual risk factor for aSAH. Smoking and hypertension appear to interact to increase the risk of aSAH synergistically.

Outcomes following poor-grade aneurysmal subarachnoid haemorrhage: a prospective observational study.

BACKGROUND: Up to 35% of aneurysmal subarachnoid haemorrhage (aSAH) cases may present as poor grade, defined as World Federation of Neurosurgical Societies (WFNS) grades IV and V. In this study, we evaluate functional outcomes and prognostic factors. METHODS: This prospective study included all patients referred to a national, centralized neurosurgical service with a diagnosis of poor-grade aSAH between 01/01/2016 and 31/12/2019. Multivariable logistic regression models were used to estimate probability of poor functional outcomes, defined as a Glasgow Outcome Scale (GOS) of 1-3 at 3 months. RESULTS: Two hundred fifty-seven patients were referred, of whom 116/257 (45.1%) underwent treatment of an aneurysm, with 97/116 (84%) treated within 48 h of referral. Median age was 62 years (IQR 51-69) with a female predominance (167/257, 65%). Untreated patients tended to be older; 123/141 (87%) had WFNS V, 60/141 (45%) unreactive pupils and 21/141 (16%) circulatory arrest. Of all referred patients, poor outcome occurred in 169/230 (73.5%). Unreactive pupils or circulatory arrest conferred a universally poor prognosis, with mortality in 55/56 (98%) and 19/19 (100%), respectively. The risk of a poor outcome was 14.1% (95% CI 4.5-23.6) higher in WFNS V compared with WFNS IV. Age was important in patients without circulatory arrest or unreactive pupils, with risk of a poor outcome increasing by 1.8% per year (95% CI 1-2.7). In patients undergoing aneurysm securement, 48/101 (47.5%) had a poor outcome, with age, rebleeding, vasospasm and cerebrospinal fluid (CSF) diversion being important prognosticators. The addition of serum markers did not add significant discrimination beyond the clinical presentation. CONCLUSIONS: The overall outcomes of WFNS IV and V aSAH remain poor, mainly due to the devastating effects of the original haemorrhage. However, in patients selected for aneurysm securement, good outcomes can be achieved in more than half of patients. Age, pre-intervention rebleeding, vasospasm, and CSF diversion are important prognostic factors.

Predictive factors for pre-intervention rebleeding in aneurysmal subarachnoid haemorrhage: a systematic review and meta-analysis.

Rebleeding before intervention is a devastating complication of aneurysmal subarachnoid haemorrhage (aSAH). It often occurs early and is associated with poor outcomes. We present a systematic review and meta-analysis to identify potential predictors of rebleeding in aSAH. A database search identified studies detailing the occurrence of pre-intervention rebleeding in aSAH, and 809 studies were screened. The association between rebleeding and a variety of demographic, clinical, and radiological factors was examined using random effects meta-analyses. Fifty-six studies totalling 33,268 patients were included. Rebleeding occurred in 3,223/33,268 patients (11.1%, 95%CI 9.4-13), with risk decreasing by approximately 0.2% per year since 1981. Systolic blood pressure (SBP) during admission was higher in patients who rebled compared with those who did not (MD 7.4 mmHg, 95%CI 2.2 - 12.7), with increased risk in cohorts with SBP > 160 mmHg (RR 2.12, 95%CI 1.35-3.34), but not SBP > 140 mmHg. WFNS Grades IV-V (RR 2.05, 95%CI 1.13-3.74) and Hunt-Hess grades III-V (RR 2.12, 95%CI 1.38-3.28) were strongly associated with rebleeding. Fisher grades IV (RR 2.24, 95%CI 1.45-3.49) and III-IV (RR 2.05, 95%CI 1.17-3.6) were also associated with an increased risk. Awareness of potential risk factors for rebleeding is important when assessing patients with aSAH to ensure timely management in high-risk cases. Increased SBP during admission, especially > 160 mmHg, poorer clinical grades, and higher radiological grades are associated with an increased risk. These results may also aid in designing future studies assessing interventions aimed at reducing the risk of rebleeding.

S100B, GFAP, UCH-L1 and NSE as predictors of abnormalities on CT imaging following mild traumatic brain injury: a systematic review and meta-analysis of diagnostic test accuracy.

Biomarkers such as calcium channel binding protein S100 subunit beta (S100B), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neuron-specific enolase (NSE) have been proposed to aid in screening patients presenting with mild traumatic brain injury (mTBI). As such, we aimed to characterise their accuracy at various thresholds. MEDLINE, SCOPUS and EMBASE were searched, and articles reporting the diagnostic performance of included biomarkers were eligible for inclusion. Risk of bias was assessed using the QUADAS-II criteria. A meta-analysis was performed to assess the predictive value of biomarkers for imaging abnormalities on CT. A total of 2939 citations were identified, and 38 studies were included. Thirty-two studies reported data for S100B. At its conventional threshold of 0.1 µg/L, S100B had a pooled sensitivity of 91% (95%CI 87-94) and a specificity of 30% (95%CI 26-34). The optimal threshold for S100B was 0.72 µg/L, with a sensitivity of 61% (95% CI 50-72) and a specificity of 69% (95% CI 64-74). Nine studies reported data for GFAP. The optimal threshold for GFAP was 626 pg/mL, at which the sensitivity was 71% (95%CI 41-91) and specificity was 71% (95%CI 43-90). Sensitivity of GFAP was maximised at a threshold of 22 pg/mL, which had a sensitivity of 93% (95%CI 73-99) and a specificity of 36% (95%CI 12-68%). Three studies reported data for NSE and two studies for UCH-L1, which precluded meta-analysis. There is evidence to support the use of S100B as a screening tool in mild TBI, and potential advantages to the use of GFAP, which requires further investigation.

Prevalence of incidental intracranial findings on magnetic resonance imaging: a systematic review and meta-analysis.

BACKGROUND: As the volume and fidelity of magnetic resonance imaging (MRI) of the brain increase, observation of incidental findings may also increase. We performed a systematic review and meta-analysis to determine the prevalence of various incidental findings. METHODS: PubMed/MEDLINE, EMBASE and SCOPUS were searched from inception to May 24, 2021. We identified 6536 citations and included 35 reports of 34 studies, comprising 40,777 participants. A meta-analysis of proportions was performed, and age-stratified estimates for each finding were derived from age-adjusted non-linear models. RESULTS: Vascular abnormalities were observed in 423/35,706 participants (9.1/1000 scans, 95%CI 5.2-14.2), ranging from 2/1000 scans (95%CI 0-7) in 1-year-olds to 16/1000 scans (95%CI 1-43) in 80-year-olds. Of these, 204/34,306 were aneurysms (3.1/1000 scans, 95%CI 1-6.3), which ranged from 0/1000 scans (95%CI 0-5) at 1 year of age to 6/1000 scans (95%CI 3-9) at 60 years. Neoplastic abnormalities were observed in 456/39,040 participants (11.9/1000 scans, 95%CI 7.5-17.2), ranging from 0.2/1000 scans (95%CI 0-10) in 1-year-olds to 34/1000 scans (95%CI 12-66) in 80-year-olds. Meningiomas were the most common, in 246/38,076 participants (5.3/1000 scans, 95%CI 2.3-9.5), ranging from 0/1000 scans (95%CI 0-2) in 1-year-olds to 17/1000 scans (95%CI 4-37) in 80-year-olds. Chiari malformations were observed in 109/27,408 participants (3.7/1000 scans, 95%CI 1.8-6.3), pineal cysts in 1176/32,170 (9/1000 scans, 95%CI 1.8-21.4) and arachnoid cysts in 414/36,367 (8.5/1000 scans, 95%CI 5.8-11.8). CONCLUSION: Incidental findings are common on brain MRI and may result in substantial resource expenditure and patient anxiety but are often of little clinical significance.

Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity.

BACKGROUND: Interferon (IFN) signalling pathways, a key element of the innate immune response, contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy, and are often deregulated in cancer. The deubiquitylating enzyme USP18 is a major negative regulator of the IFN signalling cascade and is the predominant human protease that cleaves ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteins in vivo. METHODS: In this study, using advanced proteomic techniques, we have significantly expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line. USP18-dependent effects were explored further in CML and colorectal carcinoma cellular models. RESULTS: Novel ISGylation targets were characterised that modulate the sensing of innate ligands, antigen presentation and secretion of cytokines. Consequently, CML USP18-deficient cells are more antigenic, driving increased activation of cytotoxic T lymphocytes (CTLs) and are more susceptible to irradiation. CONCLUSIONS: Our results provide strong evidence for USP18 in regulating antigenicity and radiosensitivity, highlighting its potential as a cancer target.

Beyond magnification and illumination: preliminary clinical experience with the 4K 3D ORBEYE™ exoscope and a literature review.

BACKGROUND: The operating microscope (OM) is an invaluable tool in neurosurgery but is not without its flaws. The ORBEYE™ (Olympus, Tokyo, Japan) is a 4K 3D exoscope aspiring to offer similar visual fidelity but with superior ergonomics. 2D visualisation was a major limitation of previous models which newer 3D exoscopes attempt to overcome. Here, we present our initial experience using a 4K 3D exoscope for neurosurgical procedures. OBJECTIVE: To evaluate the feasibility of the ORBEYE™ exoscope in performing neurosurgery and review of the literature. METHODS: All patients undergoing neurosurgery performed by a single surgeon, using the ORBEYE™, were assessed. Descriptive statistics and data relating to complications and operative time were recorded and analysed. An anecdotal literature review was performed for the experience of other authors using 4K 3D exoscopes in neurosurgery and compared to our subjective experience with the ORBEYE™. RESULTS: 18 patients underwent surgery using the ORBEYE™. There were no 30-day post-operative complications observed. Our experience and that of other authors suggests that the ORBEYE™ offers comparable visualisation to the traditional OM, with superior ergonomics and an enhanced experience for assistants and observers. CONCLUSION: Neurosurgery can be performed safely and effectively with the ORBEYE™, with improved ergonomics and educational benefit. There appears to be a short learning curve provided one has experience with endoscopic surgery and the use of a foot pedal.

Blood-brain barrier permeability imaging as a predictor for delayed cerebral ischaemia following subarachnoid haemorrhage. A narrative review.

BACKGROUND: Aneurysmal subarachnoid haemorrhage is associated with significant morbidity and mortality due to the myriad of complications contributing to early brain injury and delayed cerebral ischaemia. There is increasing interest in the exploration of the association between blood-brain barrier integrity and risks of delayed cerebral ischaemia and poor outcomes. Despite recent advances in cerebral imaging, radiographic imaging of blood-brain barrier disruption, as a biomarker for outcome prediction, has not been adopted in clinical practice. METHODS: We performed a narrative review by searching for articles describing molecular changes or radiological identification of changes in BBB permeability following subarachnoid haemorrhage (SAH) on MEDLINE. Preclinical studies were analysed if reported structural changes and clinical studies were included if they investigated for radiological markers of BBB disruption and its correlation with delayed cerebral ischaemia. RESULTS: There is ample preclinical evidence to suggest that there are structural changes in BBB permeability following SAH. The available clinical literature has demonstrated correlations between permeability imaging and outcomes following aneurysmal subarachnoid haemorrhage (aSAH). CONCLUSION: Radiological biomarkers offer a potential non-invasive prognostication tool and may also allow early identifications of patients who may be at risk of DCI.

Complications of cranioplasty following decompressive craniectomy for traumatic brain injury: systematic review and meta-analysis.

BACKGROUND: Decompressive craniectomy (DC) is a common neurosurgical intervention for severe traumatic brain injury (TBI), as well as malignant stroke, malignancy and infection. DC necessitates subsequent cranioplasty. There are significant demographic differences between TBI and non-TBI patients undergoing cranioplasty, which may influence their relative risk profiles for infection, aseptic bone flap resorption (aBFR) and re-operation. OBJECTIVE: Perform a meta-analysis to determine the relative infection, aBFR and re-operation risk profiles of TBI patients as compared to other indications for DC. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, EMBASE and Google Scholar were searched until 26/11/2020. Studies detailing rates of infection, re-operation and/or aBFR in specific materials and the post-TBI population were included, while studies in paediatrics or craniosynostosis repair were excluded. RESULTS: Twenty-six studies were included. There was no difference in relative risk of infection between TBI and non-TBI cohorts (RR 0.81, 95% CI 0.57-1.17), with insignificant heterogeneity (I2 = 33%). TBI was a risk factor for aBFR (RR 1.54, 95% CI 1.25-1.89), with no significant heterogeneity (I2 = 13%). TBI was a risk factor for re-operation in the autologous sub-group (RR 1.49, 95% CI 1.05-2.11) but not in the alloplastic sub-group (RR = 0.86, 95% CI 0.34-2.18). Heterogeneity was insignificant (I2 = 11%). CONCLUSION: TBI is a risk factor for aBFR and re-operation following cranioplasty. Use of an alloplastic graft for primary cranioplasty in these patients may partially mitigate this increased risk.

Targets in the Tumour Matrisome to Promote Cancer Therapy Response.

The extracellular matrix (ECM) is composed of complex fibrillar proteins, proteoglycans, and macromolecules, generated by stromal, immune, and cancer cells. The components and organisation of the matrix evolves as tumours progress to invasive disease and metastasis. In many solid tumours, dense fibrotic ECM has been hypothesised to impede therapy response by limiting drug and immune cell access. Interventions to target individual components of the ECM, collectively termed the matrisome, have, however, revealed complex tumour-suppressor, tumour-promoter, and immune-modulatory functions, which have complicated clinical translation. The degree to which distinct components of the matrisome can dictate tumour phenotypes and response to therapy is the subject of intense study. A primary aim is to identify therapeutic opportunities within the matrisome, which might support a better response to existing therapies. Many matrix signatures have been developed which can predict prognosis, immune cell content, and immunotherapy responses. In this review, we will examine key components of the matrisome which have been associated with advanced tumours and therapy resistance. We have primarily focussed here on targeting matrisome components, rather than specific cell types, although several examples are described where cells of origin can dramatically affect tumour roles for matrix components. As we unravel the complex biochemical, biophysical, and intracellular transduction mechanisms associated with the ECM, numerous therapeutic opportunities will be identified to modify tumour progression and therapy response.

Intramolecular Force Mapping at Room Temperature.

Acquisition of dense, three-dimensional, force fields with intramolecular resolution via noncontact atomic force microscopy (NC-AFM) has yielded enormous progress in our ability to characterize molecular and two-dimensional materials at the atomic scale. To date, intramolecular force mapping has been performed exclusively at cryogenic temperatures, due to the stability afforded by low temperature operation, and as the carbon monoxide functionalization of the metallic scanning probe tip, normally required for submolecular resolution, is only stable at low temperature. In this paper we show that high-resolution, three-dimensional force mapping of a single organic molecule is possible even at room temperature. The physical limitations of room temperature operation are overcome using semiconducting materials to inhibit molecular diffusion and create robust tip apexes, while challenges due to thermal drift are overcome with atom tracking based feedforward correction. Three-dimensional force maps comparable in spatial and force resolution to those acquired at low temperature are demonstrated, permitting a quantitative analysis of the adsorption induced changes in the geometry of the molecule at the picometer level.

WITHDRAWN: Middle Meningeal Artery Embolization for Chronic Subdural Hematoma-A New Treatment Paradigm?

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.wneu.2023.01.069. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Meningioma in the elderly.

Meningiomas are the most common primary intracranial neoplasm, accounting for approximately 40% of all primary brain tumors. The incidence of meningioma increases with age to 50 per 100,000 in patients older than 85. As the population ages, an increasing proportion of meningioma patients are elderly. Much of this increase is accounted for by an increase in incidental, asymptomatic diagnoses, which have a low risk of progression in the elderly. The first-line treatment of symptomatic disease is resection. Fractionated radiotherapy (RT) or stereotactic radiosurgery (SRS) can be considered as primary treatment where surgery is not feasible, or as adjuvant therapy in cases of subtotal resection or high grade histopathology. The role of RT/SRS, particularly following gross total resection of atypical meningioma, is unclear and requires further evaluation. There is an increased risk of perioperative and postoperative morbidity in the elderly and therefore management decisions must be tailored to individual circumstances. Good functional outcomes can be achieved in selected patients and age alone is not a contraindication to intervention. The immediate postoperative course is an important determinant of prognosis. Therefore, careful preoperative evaluation and avoidance of complications are necessary to optimize outcomes.

A single centre retrospective analysis of short- and medium-term outcomes using the Woven EndoBridge (WEB) device and identification of the device-to-aneurysm volume ratio as a potential predictor of aneurysm occlusion status.

BACKGROUND: The Woven EndoBridge (WEB) is a potential treatment option in patients with wide-necked bifurcation aneurysms (WNBAs). We analysed our WEB device outcomes (occlusion rates and complications) and studied factors that may predict aneurysm occlusion status at short- and medium-term follow-up. METHODS: 74 patients with ruptured and unruptured aneurysms underwent treatment with the WEB device over a 5-year period. Simple hypothesis tests assessed differences between treated ruptured and unruptured aneurysms. Univariable binary logistic regression was used to assess the effect of age, gender, and aneurysm location on the likelihood of adequate occlusion at six months. Aneurysm dimentions including device-to-aneurysm volume (DAV) ratios were compared between adequately and inadequately occluded aneurysms. RESULTS: The mean age at the time of the procedure was 58.2 years (SD 12.2; range 34-88) and the male to female ratio was 1:2.7. Middle cerebral artery (MCA) was the most commonly treated aneurysm. There was no significant difference in occlusion rates between ruptured and unruptured aneurysms. The six- and 18-month angiographic follow-up data was available for 61 and 32 patients respectively with adequate occlusion rates of 78.7% (48/61) and 78.1% (25/32). Procedure-related complications occurred in 6 patients (8.1%). Baseline DAV ratio was found to be significantly higher in aneurysms that were adequately occluded at both short- (p-value 0.015) and medium-term (p-value 0.047) follow-up. CONCLUSIONS: WEB devices are a safe and effective endovascular treatment option for WNBAs. WEB device selection incorporating the peri-procedural DAV ratio may help improve the accuracy of device sizing thereby improving the successful occlusion rate.

LITTing up Gliomas-Is the Future Bright?

Background: Laser interstitial thermal therapy (LITT) represents an attractive therapeutic strategy for several intracranial pathologies; however, there is a paucity of literature regarding its efficacy for the treatment of gliomas. Methods: MEDLINE, EMBASE, Scopus, and Web of Science were searched from inception until March 19, 2021. Studies specifically relating to the use of LITT in treatment of glioma were eligible for inclusion. A meta-analysis of means was performed to assess the progression-free survival (PFS) and overall survival (OS) following LITT and descriptive statistics relating to patients undergoing LITT were collated and a meta-analysis of proportions was also performed to assess the rate of complications. Results: In total, 17 studies were included for the meta-analysis, comprising 401 patients with 408 gliomas of which 88 of 306 (28.8%) were grade 1 or 2 and 218 of 306 (71.2%) were grade 3 or 4. Of these, 256 of 408 (62.8%) were primary presentation and 152 of 408 (37.2%) were recurrent. The pooled mean OS was 13.58 months (95% confidence interval [CI] 9.77-17.39) and the PFS was 4.96 months (95% CI 4.19-5.72). The OS and PFS of recurrent glioblastoma were 12.4 months (95% CI 9.61-16.18) and 4.84 months (95% CI 0.23-9.45), respectively. Complications occurred in 114 of 411 (24%; 95% CI 14-41), of which 44 (11%) were transient deficits. Conclusions: There is an increasing body of evidence demonstrating the use of LITT in the surgical management of deep-seated gliomas in patients of poor performance status. However, further studies are required to interrogate the clinical effectiveness of LITT in the setting of gliomas as well as assessing the survival benefit versus standard treatment alone.

Management of Chronic Subdural Hematoma: A Systematic Review and Component Network Meta-analysis of 455 Studies With 103 645 Cases.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical condition with a high risk of recurrence after treatment. OBJECTIVE: To assess and compare the risk of recurrence, morbidity, and mortality across various treatments for CSDH. METHODS: A systematic review and meta-analysis was performed. PubMed/MEDLINE, EMBASE, SCOPUS, and Web of Science were searched from January 01, 2000, to July 07, 2021. The primary outcome was recurrence, and secondary outcomes were morbidity and mortality. Component network meta-analyses (CNMAs) were performed for surgical and medical treatments, assessing recurrence and morbidity. Incremental risk ratios (iRRs) with 95% CIs were estimated for each component. RESULTS: In total, 12 526 citations were identified, and 455 studies with 103 645 cases were included. Recurrence occurred in 11 491/93 525 (10.8%, 95% CI 10.2-11.5, 418 studies) cases after surgery. The use of a postoperative drain (iRR 0.53, 95% CI 0.44-0.63) and middle meningeal artery embolization (iRR 0.19, 95% CI 0.05-0.83) reduced recurrence in the surgical CNMA. In the pharmacological CNMA, corticosteroids (iRR 0.47, 95% CI 0.36-0.61) and surgical intervention (iRR 0.11, 95% CI 0.07-0.15) were associated with lower risk. Corticosteroids were associated with increased morbidity (iRR 1.34, 95% CI 1.05-1.70). The risk of morbidity was equivalent across surgical treatments. CONCLUSION: Recurrence after evacuation occurs in approximately 10% of cSDHs, and the various surgical interventions are approximately equivalent. Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials.

Permeability of the Blood-Brain Barrier after Traumatic Brain Injury: Radiological Considerations.

Traumatic brain injury (TBI) is a leading cause of death and disability, especially in young persons, and constitutes a major socioeconomic burden worldwide. It is regarded as the leading cause of mortality and morbidity in previously healthy young persons. Most of the mechanisms underpinning the development of secondary brain injury are consequences of disruption of the complex relationship between the cells and proteins constituting the neurovascular unit or a direct result of loss of integrity of the tight junctions (TJ) in the blood-brain barrier (BBB). A number of changes have been described in the BBB after TBI, including loss of TJ proteins, pericyte loss and migration, and altered expressions of water channel proteins at astrocyte end-feet processes. There is a growing research interest in identifying optimal biological and radiological biomarkers of severity of BBB dysfunction and its effects on outcomes after TBI. This review explores the microscopic changes occurring at the neurovascular unit, after TBI, and current radiological adjuncts for its evaluation in pre-clinical and clinical practice.

Disruption of pancreatic stellate cell myofibroblast phenotype promotes pancreatic tumor invasion.

In pancreatic ductal adenocarcinoma (PDAC), differentiation of pancreatic stellate cells (PSCs) into myofibroblast-like cancer-associated fibroblasts (CAFs) can both promote and suppress tumor progression. Here, we show that the Rho effector protein kinase N2 (PKN2) is critical for PSC myofibroblast differentiation. Loss of PKN2 is associated with reduced PSC proliferation, contractility, and alpha-smooth muscle actin (α-SMA) stress fibers. In spheroid co-cultures with PDAC cells, loss of PKN2 prevents PSC invasion but, counter-intuitively, promotes invasive cancer cell outgrowth. PKN2 deletion induces a myofibroblast to inflammatory CAF switch in the PSC matrisome signature both in vitro and in vivo. Further, deletion of PKN2 in the pancreatic stroma induces more locally invasive, orthotopic pancreatic tumors. Finally, we demonstrate that a PKN2KO matrisome signature predicts poor outcome in pancreatic and other solid human cancers. Our data indicate that suppressing PSC myofibroblast function can limit important stromal tumor-suppressive mechanisms, while promoting a switch to a cancer-supporting CAF phenotype.

Common Trajectories for Freehand Frontal Ventriculostomy: A Systematic Review.

BACKGROUND: Freehand ventriculostomy is one of the most commonly performed neurosurgical procedures. While a variety of approaches have been described, frontal via Kocher's point is the most common. Multiple trajectories have been described, but no consensus exists as to the most efficacious. Our objective was to assess the literature regarding trajectories for frontal ventriculostomy and their associated success rates and complications. METHODS: We performed a systematic review of the literature, querying the PubMed/MEDLINE database with the search term "(EVD OR extra-ventricular drain OR ventriculostomy OR external ventricular drain) AND (hand OR freehand OR bedside)" and reported the characteristics and findings of both simulation and clinical studies according to trajectory and catheter position. Final catheter tip position was graded on the Kakarla scale. RESULTS: A total of 198 abstracts were screened; 40 full papers were assessed. Sixteen were included, 11 of which were clinical studies and 5 of which were simulation studies. Six studies coronally targeted the ipsilateral medial epicanthus (IMC), 4 utilized an orthogonal trajectory (P), and 1 targeted the naison (N). Ideal placement (Kakarla grade 1) was achieved in 954 of 1391 (68.58%) procedures when the IMC was targeted versus 243 of 354 (70.43%) when P was targeted. Potentially harmful (Kakarla grade 3) placement was observed in 142 of 1391 (10.21%) procedures when the IMC was targeted and 20 of 345 (5.80%) when P was targeted. All 5 simulation studies found the IMC target to be inferior. CONCLUSIONS: The IMC is the most prevalent trajectory for frontal ventriculostomy but no target is demonstrably superior. More robust clinical research is required to determine the optimal trajectory.