Histologically unstable asymptomatic carotid plaques have altered expression of genes involved in chemokine signalling leading to localised plaque inflammation and rupture.

BACKGROUND: Many studies have evaluated histological and gene expression profiles in TIA/stroke patients after onset of symptoms, but there is limited understanding as to how these plaque related features interact before symptom onset. In particular, no studies have evaluated differential gene expression in histologically unstable (vs stable plaques) in neurologically asymptomatic patients. METHODS: Nine asymptomatic patients had their plaques scored blindly by two independent Histopathologists using the AHA plaque scoring system. RNA extracted from the plaques was hybridised onto a whole genome microarray. Analysis was performed using GenomeStudio (v1.0) and the DAVID bioinformatics resource (v6.7). RESULTS: Three plaques were histologically unstable (Grade 2/3), while six were stable (Grade 0/1). 346 differentially expressed genes (>1.3 fold, P < 0.05) were identified (293 down-regulated and 53 up-regulated) between stable and unstable plaques. Genes related to chemokine and protein signalling (pro-inflammatory/pro-apoptotic) were identified to have high enrichment scores (>1.3) and were significantly up-regulated in unstable (asymptomatic) plaques. CONCLUSION: The findings confirm the intuitively held belief that changes in chemokine and protein signalling may be associated with acute plaque disruption and precede the onset of symptoms. Once validated, these genes could therefore become targets for innovative medical treatments in the future or could help identify asymptomatic patients with histologically unstable plaques that would benefit from surgical intervention.

Botulinum toxin vs glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis.

OBJECTIVE: The objective of this review was to analyse systematically the prospective randomized controlled trials on the effectiveness of botulinum toxin (BTX) and glyceryltrinitrate (GTN) for the pharmacological management of chronic anal fissure (CAF). METHOD: A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of BTX and GTN for the management of CAF were selected according to specific criteria and analysed to generate summative data. RESULTS: Six studies encompassing 355 patients with CAF were retrieved from electronic databases. Only three randomized controlled trials on 180 patients qualified for the meta-analysis according to inclusion criteria. There were 90 patients in BTX and 90 in the GTN group. BTX and GTN were equally effective in healing/improving the CAF. There was no statistically significant difference between the two pharmacotherapies [RR 1.29 (0.98-1.70) 95% CI, z = -1.83, P = 1.93, Fig. 1]. However, there was statistically significant heterogeneity among the trials (Q = 4.03, df = 1, P = 0.042). On fixed effect model, GTN was associated with higher incidence of total side effects [fixed effect model RR 0.14 (0.05-0.40) 95% CI, z = -3.71, P = 0.0002] and headache [RR 0.07 (0.02-0.20) 95% CI, z = -5.05, P = 0.0007] among patients of CAF. CONCLUSION: Botulinum toxin is as effective as GTN for the management of CAF but it is associated with a lower complication rate. BTX can be recommended as a first-line therapy for chemical sphincterotomy in patients of CAF. However, a major and multi-centre randomized controlled trial is required to support this treatment approach in order to establish stronger evidence.

Literature review of cranial nerve injuries during carotid endarterectomy.

OBJECTIVE: In the recent prospective randomised trials on carotid endarterectomy (CEA), the incidence of cranial nerve injuries (CNI) are reported to be higher than in previously published studies. The objective of this study is to review the incidence of post CEA cranial nerve injury and to discover whether it has changed in the last 25 years after many innovations in vascular surgery. METHODS: Generic terms including carotid endarterectomy, cranial nerve injuries, post CEA complications and cranial nerve deficit after neck surgery were used to search a variety of electronic databases. Based on selection criteria, decisions regarding inclusion and exclusion of primary studies were made. The incidence of CNI before and after 1995 was compared. RESULTS: We found 31 eligible studies from the literature. Patients who underwent CEA through any approach were included in the study. All patients had cranial nerves examined both before and after surgery. The total number of patients who had CEA before 1995 was 3521 with 10.6% CNI (352 patients) and after 1995, 7324 patients underwent CEA with 8.3% CNI (614 patients). Cranial nerves XII, X and VII were most commonly involved (rarely IX and XI). Statistical analysis showed that the incidence of CNI has decreased (X(2) = 5.89 + 0.74 = 6.63 => p-value = 0.0100). CONCLUSION: CNI is still a significant postoperative complication of carotid endarterectomy. Despite increasing use of CEA, the incidence of CNI has decreased probably because of increased awareness of the possibility of cranial nerve damage.