Prehospital use of cervical collars in trauma patients: a critical review

Abstract The cervical collar has been routinely used for trauma patients for more than 30 years and is a hallmark of state-of-the-art prehospital trauma care. However, the existing evidence for this practice is limited: Randomized, controlled trials are largely missing, and there are uncertain effects on mortality, neurological injury, and spinal stability. Even more concerning, there is a growing body of evidence and opinion against the use of collars. It has been argued that collars cause more harm than good, and that we should simply stop using them. In this critical review, we discuss the pros and cons of collar use in trauma patients and reflect on how we can move our clinical practice forward. Conclusively, we propose a safe, effective strategy for prehospital spinal immobilization that does not include routine use of collars

CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells

Melanomas frequently metastasize to the brain. Despite recent progress in the treatment of melanoma brain metastasis, therapy resistance and relapse of disease remain unsolved challenges. CCT196969 is a SRC family kinase (SFK) and Raf proto-oncogene, serine/threonine kinase (RAF) inhibitor with documented effects in primary melanoma cell lines in vitro and in vivo. Using in vitro cell line assays, we studied the effects of CCT196969 in multiple melanoma brain metastasis cell lines. The drug effectively inhibited proliferation, migration, and survival in all examined cell lines, with viability IC50 doses in the range of 0.18–2.6 μM. Western blot analysis showed decreased expression of p-ERK, p-MEK, p-STAT3 and STAT3 upon CCT196969 treatment. Furthermore, CCT196969 inhibited viability in two B-Raf Proto-Oncogene (BRAF) inhibitor resistant metastatic melanoma cell lines. Further in vivo studies should be performed to determine the treatment potential of CCT196969 in patients with treatment-naïve and resistant melanoma brain metastasis.publishedVersio

Severe traumatic brain injury in Norway: Impact of age on outcome

Objective: The aim of this study was to investigate the influence of age on mortality and 3-month outcome in a Norwegian cohort of patients with severe traumatic brain injury (TBI). Methods: Norwegian residents ≥ 16 years of age who were admitted with a severe TBI to the country’s 4 major trauma centres in 2009 and 2010 were included, as were adults (16– 64 years) and elderly patients (≥ 65 years). Results: Half of the adult subjects and 84% of the elderly subjects were injured by falls. One-third of the adults and half of the elderly subjects were admitted to a local hospital before being transported to a regional trauma hospital. Subdural haematomas were more frequent in the elderly subjects. One-quarter of adults and two-thirds of the elderly subjects died within 3 months. At 3 months, 41% of the adult survivors were still in-patients, mainly in rehabilitation units (92%). Of the surviving elderly subjects, 14% were in-patients and none were in rehabilitation units. There was no difference in functional level for survivors at the 3-month follow-up. Conclusion: Old age is associated with fall-induced severe TBI and high mortality rates. Less intensive treatment strategies were applied to elderly patients in the present study despite high rates of haemorrhage. Few surviving elderly patients received rehabilitation at 3 months post-injury.publishedVersio

Prospective Study of Surgery for Traumatic Brain Injury in Addis Ababa, Ethiopia: Surgical Procedures, Complications, and Postoperative Outcomes

Under embargo until: 2022-06-02Background Traumatic brain injury (TBI) is an important cause of trauma-related mortality and morbidity in Ethiopia. There are significant resource limitations along the entire continuum of care, and little is known about the neurosurgical activity and patient outcomes. Methods All surgically treated TBI patients at the 4 teaching hospitals in Addis Ababa, Ethiopia were prospectively registered from October 2012 to December 2016. Data registration included surgical procedures, complications, reoperations, discharge outcomes, and mortality. Results A total of 1087 patients were included. The most common procedures were elevation of depressed skull fractures (49.5%) and craniotomies (47.9%). Epidural hematoma was the most frequent indication for a craniotomy (74.7%). Most (77.7%) patients were operated within 24 hours of admission. The median hospital stay for depressed skull fracture operations or craniotomies was 4 days. Decompressive craniectomy was only done in 10 patients. Postoperative complications were seen in 17% of patients, and only 3% were reoperated. Cerebrospinal fluid leak was the most common complication (7.9%). The overall mortality was 8.2%. Diagnosis, admission Glasgow Coma Scale (GCS) score, surgical procedure, and complications were significant predictors of discharge GCS score (P < 0.01). Age, admission GCS score, and length of hospital stay were significantly associated with mortality (P ≤ 0.005). Conclusions The injury panorama, surgical activity, and outcome are significantly influenced by patient selection due to deficits within both prehospital and hospital care. Still, the neurosurgical services benefit a large number of patients in the greater Addis region and are qualitatively comparable with reports from high-income countries.acceptedVersio

Prospective Study of Surgery for Traumatic Brain Injury in Addis Ababa, Ethiopia: Trauma Causes, Injury Types, and Clinical Presentation

Under embargo until: 2022-04-27Background Traumatic brain injury (TBI) is a public health problem in Ethiopia. More knowledge about the epidemiology and neurosurgical management of TBI patients is needed to identify possible focus areas for quality improvement and preventive efforts. Methods This prospective cross-sectional study (2012–2016) was performed at the 4 teaching hospitals in Addis Ababa, Ethiopia. All surgically treated TBI patients were included, and data on clinical presentation, injury types, and trauma causes were collected. Results We included 1087 patients (mean age 29 years; 8.7% females; 17.1% 50 km from the hospitals, whereas 46% of road traffic accident victims came from the urban area. Delayed admission was associated with higher Glasgow Coma Scale scores and nonsevere TBI (P < 0.01). Conclusions The injury panorama, delayed admission, and small number of operations performed for severe TBI are linked to a substantial patient selection bias both before and after hospital admission. Our results also suggest that there should be a geographical framework for tailored guidelines, preventive efforts, and development of prehospital and hospital services.acceptedVersio

Is intracranial volume a risk factor for IDH-mutant low-grade glioma? A case-control study

Purpose Risk of cancer has been associated with body or organ size in several studies. We sought to investigate the relationship between intracranial volume (ICV) (as a proxy for lifetime maximum brain size) and risk of IDH-mutant low-grade glioma. Methods In a multicenter case–control study based on population-based data, we included 154 patients with IDH-mutant WHO grade 2 glioma and 995 healthy controls. ICV in both groups was calculated from 3D MRI brain scans using an automated reverse brain mask method, and then compared using a binomial logistic regression model. Results We found a non-linear association between ICV and risk of glioma with increasing risk above and below a threshold of 1394 ml (p < 0.001). After adjusting for ICV, sex was not a risk factor for glioma. Conclusion Intracranial volume may be a risk factor for IDH-mutant low-grade glioma, but the relationship seems to be non-linear with increased risk both above and below a threshold in intracranial volume.publishedVersio

CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells

Melanomas frequently metastasize to the brain. Despite recent progress in the treatment of melanoma brain metastasis, therapy resistance and relapse of disease remain unsolved challenges. CCT196969 is a SRC family kinase (SFK) and Raf proto-oncogene, serine/thre onine kinase (RAF) inhibitor with documented effects in primary melanoma cell lines in vitro and in vivo. Using in vitro cell line assays, we studied the effects of CCT196969 in multiple melanoma brain metastasis cell lines. The drug effectively inhibited proliferation, migration, and survival in all examined cell lines, with viability IC50 doses in the range of 0.18–2.6 μM. Western blot analysis showed decreased expression of p-ERK, p-MEK, p-STAT3 and STAT3 upon CCT196969 treatment. Furthermore, CCT196969 inhibited viability in two B Raf Proto-Oncogene (BRAF) inhibitor resistant metastatic melanoma cell lines. Further in vivo studies should be performed to determine the treatment potential of CCT196969 in patients with treatment-naïve and resistant melanoma brain metastasis

Inhibition of extracellular vesicle-derived miR-146a-5p decreases progression of melanoma brain metastasis via Notch pathway dysregulation in astrocytes

Melanoma has the highest propensity of all cancers to metastasize to the brain with a large percentage of late-stage patients developing metastases in the central nervous system (CNS). It is well known that metastasis establishment, cell survival, and progression are affected by tumour-host cell interactions where changes in the host cellular compartments likely play an important role. In this context, miRNAs transferred by tumour derived extracellular vesicles (EVs) have previously been shown to create a favourable tumour microenvironment. Here, we show that miR-146a-5p is highly expressed in human melanoma brain metastasis (MBM) EVs, both in MBM cell lines as well as in biopsies, thereby modulating the brain metastatic niche. Mechanistically, miR-146a-5p was transferred to astrocytes via EV delivery and inhibited NUMB in the Notch signalling pathway. This resulted in activation of tumour-promoting cytokines (IL-6, IL-8, MCP-1 and CXCL1). Brain metastases were significantly reduced following miR-146a-5p knockdown. Corroborating these findings, miR-146a-5p inhibition led to a reduction of IL-6, IL-8, MCP-1 and CXCL1 in astrocytes. Following molecular docking analysis, deserpidine was identified as a functional miR-146a-5p inhibitor, both in vitro and in vivo. Our results highlight the pro-metastatic function of miR-146a-5p in EVs and identifies deserpidine for targeted adjuvant treatment.publishedVersio