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Introduction Pressure-reactivity index (PRx) is a useful tool in brain monitoring of trauma patients, but the question remains about its critical values. Using our TBI database, we identified the thresholds for PRx and other monitored parameters that maximize the statistical difference between death/survival and favorable/unfavorable outcomes. We also investigated how these thresholds depend on clinical factors such as age, gender and initial GCS . Methods A total of 459 patients from our database were eligible. Tables of 2 × 2 format were created grouping patients according to survival/death or favorable/unfavorable outcomes and varying thresholds for PRx, ICP and CPP. Pearson’s chi square was calculated, and the thresholds returning the highest score were assumed to have the best discriminative value. The same procedure was repeated after division according to clinical factors. Results In all patients, we found that PRx had different thresholds for survival (0.25) and for favorable outcome (0.05). Thresholds of 70 mmHg for CPP and 22 mmHg for ICP were identified for both survival and favorable outcomes. The ICP threshold for favorable outcome was lower (18 mmHg) in females and patients older than 55 years. In logistic regression models, independent variables associating with mortality and unfavorable outcome were age, GCS, ICP and PRx. Conclusion The prognostic role of PRx is confirmed but with a lower threshold of 0.05 for favorable outcome than for survival (0.25). Results for ICP are in line with current guidelines. However, the lower value in elderly and in females suggests increased vulnerability to intracranial hypertension in these groups.

Defects in nuclear morphology often correlate with the onset of disease, including cancer, progeria, cardiomyopathy, and muscular dystrophy. However, the mechanism by which a cell controls its nuclear shape is unknown. Here, we use adhesive micropatterned surfaces to control the overall shape of fibroblasts and find that the shape of the nucleus is tightly regulated by the underlying cell adhesion geometry. We found that this regulation occurs through a dome-like actin cap that covers the top of the nucleus. This cap is composed of contractile actin filament bundles containing phosphorylated myosin, which form a highly organized, dynamic, and oriented structure in a wide variety of cells. The perinuclear actin cap is specifically disorganized or eliminated by inhibition of actomyosin contractility and rupture of the LINC complexes, which connect the nucleus to the actin cap. The organization of this actin cap and its nuclear shape-determining function are disrupted in cells from mouse models of accelerated aging (progeria) and muscular dystrophy with distorted nuclei caused by alterations of A-type lamins. These results highlight the interplay between cell shape, nuclear shape, and cell adhesion mediated by the perinuclear actin cap.

It has long been observed that many neuronal types position their nuclei within restricted cytoplasmic boundaries. A striking example is the apical localization of cone photoreceptors nuclei at the outer edge of the outer nuclear layer of mammalian retinas. Yet, little is known about how such nuclear spatial confinement is achieved and further maintained. Linkers of the Nucleoskeleton to the Cytoskeleton (LINC complexes) consist of evolutionary-conserved macromolecular assemblies that span the nuclear envelope to connect the nucleus with the peripheral cytoskeleton. Here, we applied a new transgenic strategy to disrupt LINC complexes either in cones or rods. In adult cones, we observed a drastic nuclear mislocalization on the basal side of the ONL that affected cone terminals overall architecture. We further provide evidence that this phenotype may stem from the inability of cone precursor nuclei to migrate towards the apical side of the outer nuclear layer during early postnatal retinal development. By contrast, disruption of LINC complexes within rod photoreceptors, whose nuclei are scattered across the outer nuclear layer, had no effect on the positioning of their nuclei thereby emphasizing differential requirements for LINC complexes by different neuronal types. We further show that Sun1, a component of LINC complexes, but not A-type lamins, which interact with LINC complexes at the nuclear envelope, participate in cone nuclei positioning. This study provides key mechanistic aspects underlying the well-known spatial confinement of cone nuclei as well as a new mouse model to evaluate the pathological relevance of nuclear mispositioning.

Statutory duty of candour was introduced in November 2014 for NHS bodies in England. Contained within the regulation were definitions regarding the threshold for what constitutes a notifiable patient safety incident. However, it can be difficult to determine when the process should be implemented. The aim of this survey was to evaluate the interpretation of these definitions by British neurosurgeons. All full (consultant) members of the Society of British Neurological Surgeons were electronically invited to participate in an online survey. Surgeons were presented with 15 cases and asked to decide in the case of each one whether they would trigger the process of duty of candour. Cases were stratified according to their likelihood and severity. In all, 106/357 (29.7%) members participated in the survey. Responses varied widely, with almost no members triggering the process of duty of candour in cases where adverse events were common (greater than 10% likelihood) and required only outpatient follow-up (7/106; 6.6%), and almost all members doing so in cases where adverse events were rare (less than 0.1% likelihood) and resulted in death (102/106; 96.2%). However, there was clear equipoise in triggering the process of duty of candour in cases where adverse events were uncommon (0.1-10% likelihood) and resulted in moderate harm (38/106; 35.8%), severe harm (57/106; 53.8%) or death (49/106; 46.2%). There is considerable nationwide variation in the interpretation of definitions regarding the threshold for duty of candour. To this end, we propose a framework for the improved application of duty of candour in clinical practice.

Background Low back pain is a common musculoskeletal disorder defined as pain and soreness, muscle tension, or stiffness in the lumbosacral area of the spine which does not have a specific cause. Low back pain results in high health costs and incapacity to work causing an economic burden to society. The optimal management of non-specific low back pain appears to be undecided. Recently published guidelines support the use of acupuncture for treating non-specific low back pain and it has become a popular alternative treatment modality for patients with low back pain. Methods A comprehensive systematic literature search was conducted through Medline using Ovid and Medical Subject Headings for randomized controlled trials published in the last 10 years. The outcomes scored were subjective pain scores and functional outcome scores. Results Eighty two randomized studies were identified, of which 7 met our inclusion criteria. Three studies found a significant difference in pain scores when comparing acupuncture, or sham acupuncture, with conventional therapy or no care. Two studies demonstrated a significant difference between acupuncture treatment and no treatment or routine care at 8 weeks and 3 months. Three studies demonstrated no significant difference between acupuncture and minimal/sham acupuncture with no difference in pain relief or function over 6 to 12 months. Conclusions This review provides some evidence to support acupuncture as more effective than no treatment, but no conclusions can be drawn about its effectiveness over other treatment modalities as the evidence is conflicting.

Background Syndrome of the trephined is a well-recognised phenomenon that occurs in patients following a craniectomy. It is associated with several symptoms, including headaches, motor impairments, cognitive disorders and reduced consciousness. Treatment for the syndrome usually involves replacing the skull defect. Case Study A 71-year-old male underwent a left-sided craniectomy after being diagnosed with biopsy-confirmed invasive squamous cell carcinoma with associated skull erosion. Subsequently, he developed a severe case of syndrome of the trephined (SoT,) resulting in having to lie flat to prevent the motor component of the Glasgow Coma Score (GCS) falling from M5/6 (E3/4 Vt M5/6) to M1 (E3/4 Vt M1) on sitting to 30 degrees. Unfortunately, due to ongoing chest sepsis and physical frailty, he was unable to undergo a cranioplasty. Therefore, to aid in clinical stabilisation, the treating physicians and clinical engineering teams designed and manufactured a prosthesis on-site, allowing rapid patient treatment. The prosthesis led to the patient being able to sit up to 30 degrees without the motor component of the GCS falling from M6 to M1 (E4 VT M6). Conclusion Clinical improvements were demonstrated with definitive neurological improvement after applying the external cranial plate in clinical outcome measures and radiographically. Furthermore, we have shown that rapid prototyping technology provides a flexible solution to synthesise bespoke medical prostheses with the correct expertise and regulatory framework.

In a trial comparing decompressive craniectomy with medical therapy in patients with traumatic brain injury and raised intracranial pressure refractory to medical therapy, decompressive craniectomy resulted in lower mortality and higher rates of vegetative state and severe disability. After traumatic brain injury (TBI), intracranial pressure can be elevated owing to a mass effect from intracranial hematomas, contusions, diffuse brain swelling, or hydrocephalus. 1 Intracranial hypertension can lead to brain ischemia by reducing the cerebral perfusion pressure. 2 Intracranial hypertension after TBI is associated with an increased risk of death in most studies. 3 , 4 The monitoring of intracranial pressure and the administration of interventions to lower intracranial pressure are routinely used in patients with TBI, despite the lack of level 1 evidence. 5 Decompressive craniectomy is a surgical procedure in which a large section of the skull is removed and the underlying . . .

In an international trial involving 450 patients with acute subdural hematoma, craniotomy (bone flap replaced) and decompressive craniectomy (bone flap left out) yielded similar disability-related outcomes at 12 months.

The benefit of statins in patients with acute aneurysmal subarachnoid haemorrhage is unclear. We aimed to determine whether simvastatin 40 mg could improve the long-term outcome in patients with this disorder. In this international, multicentre, randomised, double-blind trial, we enrolled patients aged 18–65 years with confirmatory evidence of an aneurysmal subarachnoid haemorrhage and presenting less than 96 h from ictus from 35 acute neurosurgical centres in nine countries. Patients were randomly allocated (1:1) to receive either simvastatin 40 mg or placebo once a day for up to 21 days. We used a computer-generated randomisation code to randomise patients in every centre by blocks of ten (five simvastatin, five placebo). Participants and investigators were masked to treatment assignment. The primary outcome was the distribution of modified Rankin Scale (mRS) score obtained by questionnaire at 6 months. Analyses were done on the intention-to-treat population. This trial has been completed and is registered with Current Controlled Trials, number ISRCTN75948817. Between Jan 6, 2007, and Feb 1, 2013, apart from the period between May 15, 2009, and Feb 8, 2011, when recruitment was on hold, 803 patients were randomly assigned to receive either simvastatin 40 mg (n=391) or placebo (n=412). All patients were included in the intention-to-treat population. 782 (97%) patients had outcome data recorded at 6 months, of whom 560 (72%) were classed as having a favourable outcome, mRS 0–2 (271 patients in the simvastatin group vs 289 in the placebo group). The primary ordinal analysis of the mRS, adjusted for age and World Federation of Neurological Surgeons grade on admission, gave a common odds ratio (OR) of 0·97, 95% CI 0·75–1·25; p=0·803. At 6 months, we recorded 37 (10%) deaths in the simvastatin group compared with 35 (9%) in the placebo group (log-rank p=0·592). 70 (18%) serious adverse events were reported in the simvastatin group compared with 74 (18%) in the placebo group. No suspected unexpected serious adverse reactions were reported. The STASH trial did not detect any benefit in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid haemorrhage. Despite demonstrating no safety concerns, we conclude that patients with subarachnoid haemorrhage should not be treated routinely with simvastatin during the acute stages. British Heart Foundation.