Incidence and predictors of poor functional outcome despite complete recanalisation following endovascular thrombectomy for acute ischaemic stroke.

BACKGROUND: Numerous ischaemic stroke patients experience poor functional outcome despite successful recanalisation following endovascular thrombectomy (EVT). We aimed to identify the incidence and predictors of futile complete recanalisation (FCR) in a national stroke registry. METHODS: Patients who achieved complete recanalisation (mTICI 3) following EVT, between October 2015 and March 2020, were included from a United Kingdom national stroke registry. Modified Rankin Scale of 4-6 at discharge was defined as a 'poor/futile outcome'. Backward stepwise multivariable logistic regression analysis was performed with FCR as the dependent variable, incorporating all baseline characteristics, procedural time metrics and post-procedural events. RESULTS: We included 2132 of 4383 patients (48.8%) with complete recanalisation post-EVT, of which 948 patients (44.4%) developed FCR. Following multivariable regression analysis adjusted for potential confounders, patients with FCR were associated with multiple baseline patient, imaging and procedural factors: age (p=0.0001), admission NIHSS scores (p=0.0001), pre-stroke disability (p=0.007), onset-to-puncture (p=0.0001) and procedural times (p=0.0001), presence of diabetes (p=0.005), and use of general anaesthesia (p=0.0001). Although not predictive of outcome, post-procedural events including development of any intracranial haemorrhage (ICH) (p=0.0001), symptomatic ICH (sICH) (p=0.0001) and early neurological deterioration (END) (p=0.007) were associated with FCR. CONCLUSION: Nearly half of patients in this national registry experienced FCR following EVT. Significant predictors of FCR included increasing age, admission NIHSS scores, pre-stroke disability, onset-to-puncture and procedural times, presence of diabetes, atrial fibrillation, and use of general anaesthesia. Post procedural development of any ICH, sICH, and END were associated with FCR.

Prescribing costs of hypoglycaemic agents and associations with metabolic control in Wales; a national analysis of primary care data.

AIMS: There has been a dramatic increase in hypoglycaemic agent expenditure. We assessed the variability in prescribing costs at the practice level and the relationship between expenditure and the proportion of patients achieving target glycaemic control. METHODS: We utilized national prescribing data from 406 general practices in Wales. This was compared against glycaemic control (percentage of patients achieving a HbA1c level < 59 mmol/mol in the preceding 12 months). Analyses were adjusted for the number of patients with diabetes in each general practice and the Welsh Index of Multiple Deprivation. RESULTS: There was considerable heterogeneity in hypoglycaemic agent spend per patient with diabetes, Median = £289 (IQR 247-343) range £31.1-£1713. Higher total expenditure was not associated with improved glycaemic control B(std)  = -0.01 (95%CI -0.01, 0.002) p = 0.13. High-spend practices spent more on SGLT2 inhibitors (16 vs. 9% p < 0.001) and GLP-1 agonists (13 vs. 11% p < 0.001) and less on insulin (34 vs. 42% p < 0.001), biguanides (9 vs. 11% p = 0.001) and sulphonylureas (2 vs. 3% p < 0.001) than low spend practices. There were no differences in the pattern of drug prescribing between high spend practices with better glycaemic control (mean 68% of patients HbA1c <59 mmol/mol) and those with less good metabolic control (mean 58% of patients HbA1c <59 mmol/mol). CONCLUSIONS: Spend on hypoglycaemic agents is highly variable between practices and increased expenditure per patient is not associated with better glycaemic control. Whilst newer, more expensive agents have additional benefits, in individuals where these advantages are more marginal widespread use of these agents has important cost implications.

Dissociable effects of complement C3 and C3aR on survival and morphology of adult born hippocampal neurons, pattern separation, and cognitive flexibility in male mice.

Adult hippocampal neurogenesis (AHN) is a form of ongoing plasticity in the brain that supports specific aspects of cognition. Disruptions in AHN have been observed in neuropsychiatric conditions presenting with inflammatory components and are associated with impairments in cognition and mood. Recent evidence highlights important roles of the complement system in synaptic plasticity and neurogenesis during neurodevelopment and in acute learning and memory processes. In this work we investigated the impact of the complement C3/C3aR pathway on AHN and its functional implications for AHN-related behaviours. In C3-/- mice, we found increased numbers and accelerated migration of adult born granule cells, indicating that absence of C3 leads to abnormal survival and distribution of adult born neurons. Loss of either C3 or C3aR affected the morphology of immature neurons, reducing morphological complexity, though these effects were more pronounced in the absence of C3aR. We assessed functional impacts of the cellular phenotypes in an operant spatial discrimination task that assayed AHN sensitive behaviours. Again, we observed differences in the effects of manipulating C3 or C3aR, in that whilst C3aR-/- mice showed evidence of enhanced pattern separation abilities, C3-/- mice instead demonstrated impaired behavioural flexibility. Our findings show that C3 and C3aR manipulation have distinct effects on AHN that impact at different stages in the development and maturation of newly born neurons, and that the dissociable cellular phenotypes are associated with specific alterations in AHN-related behaviours.

Avascular necrosis of the femoral head after single steroid intra-articular injection.

Femoral head avascular bone necrosis (AVN) is the loss of blood supply to the bone tissue of femoral head that results in cellular death. This condition causes a significant limitation in patient daily life activities and has a poor functional outcome. Long-term steroid intake was established as a cause of AVN. However, few cases reported femoral head AVN post-single steroid intra-articular injection. We review all cases of AVN that results from single intra-articular steroid injection and present a case of femoral head AVN developed in a 78-year-old male. The patient, who was not known to have any medical illness, presented complaining of mild left hip pain for 4 months with long distant ambulation and weight standing. He was diagnosed to have left hip joint osteoarthritis for which he received intra-articular steroid injection 2 months prior visiting our orthopedics center. MRI of the pelvis revealed AVN of the femoral head. He underwent total hip arthroplasty. The pathological examination confirmed the diagnosis of AVN. To best of our knowledge, this is the fifth case of AVN of femoral head AVN after single intra-articular steroid injection. We reviewed all cases of AVN of femoral head after single steroid injection. Intra-articular steroid injection can cause femoral head AVN, and the patient receiving these injections should be aware about this rare but significant complication that results in poor functional outcome and significant morbidity.

Safety and efficacy of adjunctive intra-arterial antithrombotic therapy during endovascular thrombectomy for acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Half of patients who achieve successful recanalization following endovascular thrombectomy (EVT) for acute ischemic stroke experience poor functional outcome. We aim to investigate whether the use of adjunctive intra-arterial antithrombotic therapy (AAT) during EVT is safe and efficacious compared with standard therapy (ST) of EVT with or without prior intravenous thrombolysis. METHODS: Electronic databases were searched (PubMed/MEDLINE, Embase, Cochrane Library) from 2010 until October 2023. Data were pooled using a random-effects model and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using ROBINS-I and ROB-2. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes were successful recanalization (modified Thrombolysis In Cerebral Infarction (TICI) 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: 41 randomized and non-randomized studies met the eligibility criteria. Overall, 15 316 patients were included; 3296 patients were treated with AAT during EVT and 12 020 were treated with ST alone. Compared with ST, patients treated with AAT demonstrated higher odds of functional independence (46.5% AAT vs 42.6% ST; OR 1.22, 95% CI 1.07 to 1.40, P=0.004, I2=48%) and a lower likelihood of 90-day mortality (OR 0.71, 95% CI 0.61 to 0.83, P<0.0001, I2=20%). The rates of sICH (OR 1.00, 95% CI 0.82 to 1.22,P=0.97, I2=13%) and successful recanalization (OR 1.09, 95% CI 0.84 to 1.42, P=0.52, I2=76%) were not significantly different. CONCLUSION: The use of AAT during EVT may improve functional outcomes and reduce mortality rates compared with ST alone, without an increased risk of sICH. These findings should be interpreted with caution pending the results from ongoing phase III trials to establish the efficacy and safety of AAT during EVT.

Acute subdural haematoma in the elderly: to operate or not to operate? A systematic review and meta-analysis of outcomes following surgery.

OBJECTIVES: Acute subdural haematoma (ASDH) is a devastating pathology commonly found on CT brain scans of patients with traumatic brain injury. The role of surgical intervention in the elderly has been increasingly questioned due to its associated morbidity and mortality. Therefore, a systematic review and meta-analysis of the literature to quantify the mortality and functional outcomes associated with surgical management of ASDH in the elderly was performed. DESIGN/SETTING: A multidatabase literature search between January 1990 and May 2020, and meta-analysis of proportions was performed to quantify mortality and unfavourable outcome (Glasgow Outcome scale 1-3; death/ severe disability) rates. PARTICIPANTS: Studies reporting patients aged 60 years or older. INTERVENTIONS: Craniotomy, decompressive craniectomy, conservative management. OUTCOME MEASURES: Mortality and functional outcomes (discharge, long-term follow-up (LTFU)). RESULTS: 2572 articles were screened, yielding 21 studies for final inclusion and 15 for meta-analysis. Pooled estimates of mortality were 39.83% (95% CI 32.73% to 47.14%; 10 studies, 308/739 patients, I2=73%) at discharge and 49.30% (95% CI 42.01% to 56.61%; 10 studies, 277/555 patients, I2=63%) at LTFU. Mean duration of follow-up was 7.1 months (range 2-12 months). Pooled estimate of percentage of poor outcomes was 81.18% (95% CI 75.61% to 86.21%; 6 studies, 363/451 patients, I2=45%) at discharge, and 79.25% (95% CI 72.42% to 85.37%; 8 studies, 402/511 patients, I2=66%) at LTFU. Mean duration of follow-up was 6.4 months (range 2-12 months). Potential risk factors for poor outcome included age, baseline functional status, preoperative neurological status and imaging parameters. CONCLUSIONS: Outcomes following surgical evacuation of ASDH in patients aged 60 years and above are poor. This constitutes the best level of evidence in the current literature that surgical intervention for ASDH in the elderly carries significant risks, which must be weighed against benefits. PROSPERO REGISTRATION NUMBER: CRD42020189508.