Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting.

BACKGROUND: Definitive diagnosis of acute ischemic stroke is challenging, particularly in telestroke settings. Although the prognostic utility of CT perfusion (CTP) has been questioned, its diagnostic value remains under-appreciated, especially in cases without an easily visible intracranial occlusion. We assessed the diagnostic accuracy of routine CTP in the acute telestroke setting. METHODS: Acute and follow-up data collected prospectively from consecutive suspected patients with stroke assessed by a state-wide telestroke service between March 2020 and August 2021 at 12 sites in Australia were analyzed. All patients in the final analysis had been assessed with multimodal CT, including CTP, which was post-processed with automated volumetric software. Diagnostic sensitivity and specificity were calculated for multimodal CT and each individual component (noncontrast CT [NCCT], CT angiogram [CTA], and CTP). Final diagnosis determined by consensus review of follow-up imaging and clinical data was used as the reference standard. RESULTS: During the study period, complete multimodal CT examination was obtained in 831 patients, 457 of whom were diagnosed with stroke. Diagnostic sensitivity for ischemic stroke increased by 19.5 percentage points when CTP was included with NCCT and CTA compared with NCCT and CTA alone (73.1% positive with NCCT+CTA+CTP [95% CI, 68.8-77.1] versus 53.6% positive with NCCT+CTA alone [95% CI, 48.9-58.3], P<0.001). No difference was observed between specificities of NCCT+CTA and NCCT+CTA+CTP (98.7% [95% CI, 98.5-100] versus 98.7% [95% CI, 96.9-99.6], P=0.13). Multimodal CT, including CTP, demonstrated the highest negative predictive value (75.0% [95% CI, 72.1-77.7]). Patients with stroke not evident on CTP had small volume infarcts on follow-up (1.2 mL, interquartile range 0.5-2.7mL). CONCLUSIONS: Acquisition of CTP as part of a telestroke imaging protocol permits definitive diagnosis of cerebral ischemia in 1 in 5 patients with normal NCCT and CTA.

Diagnostic value of clinical examination for identifying patients with large- and small-fibre neuropathy.

BACKGROUND: The diagnosis of polyneuropathy usually requires neurophysiological investigation, necessitating specialised testing and interpretation thereby increasing the time to final diagnosis. AIMS: To investigate the predictive value of the clinical examination in patients with potential neuropathies. METHODS: Patients were recruited based on their referral requesting neurophysiological testing. Two examiners tested ankle jerk reflexes and gradient to temperature sensation prior to the patient undergoing neurophysiology investigations, blinded to subsequent testing results. The neurophysiology investigations were either standard nerve conduction study (NCS) or thermal threshold testing (TTT) or both. These data were then analysed to determine the Kappa between examiners as well as sensitivity, specificity, and positive and negative likelihood ratios. RESULTS: There was a modest level of agreement between examiners for ankle jerk testing (Kappa = 0.6) but poor agreement for gradient temperature testing (Kappa = 0.3). Bilateral absence of ankle jerk reflexes was moderately associated with abnormal NCS, with the following characteristics: sensitivity 72%, specificity 91%, positive likelihood ratio 7.6 and negative likelihood ratio 0.3. The presence of a temperature gradient was poorly diagnostic for abnormal TTT: sensitivity 87%, specificity 14%, with positive and negative likelihood ratios close to 1. CONCLUSION: The absence of ankle jerks performed moderately well in identifying patients likely to have large-fibre neuropathy and could potentially be used to help decide who should be sent for NCS. Gradient temperature testing was much more subjective and did not change the likelihood of abnormal TTT.

Prevention of perioperative thromboembolism in patients with atrial fibrillation.

BACKGROUND: The aim of this retrospective study was to review the safety and efficacy of two regimens for the prophylaxis of perioperative thromboembolism in patients with atrial fibrillation. METHODS: From a database of 14 801 procedures, atrial fibrillation occurred in 1.9 per cent of patients. Those not on oral anticoagulation (n = 146) received low molecular weight heparin (LMWH) before and after surgery (nadroparine 40 units per kg). Patients on oral anticoagulation before surgery (n = 136) received intravenous unfractionated heparin (UFH) after surgery at a dose adequate to maintain the thrombin time at a therapeutic level. RESULTS: The incidence of perioperative arterial or venous thromboembolism was independent of pre-existing risk factors and occurred in 4.6 per cent of patients, without significant difference between the two regimens (P = 0.780). Logistic regression revealed that thromboembolism was significantly associated with increased perioperative mortality (odds ratio 9.5, (95 per cent confidence interval 2.5 to 35.8); P = 0.001). The rate of postoperative bleeding was 4.8 per cent in patients who had LMWH and 17.6 per cent in those who had UFH (P < 0.001). CONCLUSION: Postoperative anticoagulation with therapeutic UFH in patients with atrial fibrillation was associated with an increased rate of bleeding without reducing the risk of thromboembolism.

Human urotensin II-induced aorta ring contractions are mediated by protein kinase C, tyrosine kinases and Rho-kinase: inhibition by somatostatin receptor antagonists.

Human urotensin II-(1-11) and its N-terminally shortened analogues, human urotensin II-(4-11)-OH and human urotensin II-(4-11)-NH2 are potent vasoconstrictor peptides in isolated rat thoracic aorta. Human urotensin II-induced tonic aorta ring contractions are inhibited by the Ca2+ channel antagonists, verapamil, nitrendipine and diltiazem; D609 (Tricyclodecan-9-yl-xanthogenate, K), selective inhibitor of phosphatidylcholine-specific phospholipase C and partially by phospholipase C inhibitor U-73122 [1-[6-((17ss-3 Methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-25-dione] and a selective inhibitor of phosphatidyl-inositol-specific phospholipase C-ET-18-OCH3 (Edelfosine,1-O-octadecyl-2O-methyl-rac-glycero-3-phosphorylcholine); protein kinase C inhibitors, chelerythrine and NPC-15437 [S-2,6-diamino-N-[[1-(1-oxotridecyl)-2-piperidinyl]methyl]-hexanamide dihydrochloride]; tyrosine kinase inhibitors, genistein and tyrphostin B42 and Rho-kinase inhibitor HA-1077 [1-(5-isoquinolinylsulfonyl)-homopiperazine dihydrochloride]. This indicates that human urotensin II-induced tonic contractions of the rat aorta are mediated by phospholipase C, protein kinase C, tyrosine kinases and Rho-kinase related pathways. In the high K+ medium, human urotensin II induces dose-dependent phasic oscillations of aortic rings. These are inhibited by Ca2+ channel antagonists, the phospholipase C inhibitor, U-73122 and protein kinase C inhibitors, chelerythrine and NPC-15437, indicating that human urotensin II-induced phasic oscillations of the rat aorta are mediated by phospholipase C and protein kinase C-dependent pathways. Given their close structural similarity, several somatostatin analogues, importantly containing DCys5 and DTrp7 and expressing different degrees of somatostatin receptor antagonist activity, were tested for possible inhibitory effects on human urotensin II-induced contractions of the rat aorta rings. Pre-incubation of rat aorta rings in the presence of somatostatin analogues, which are preferentially sst2 specific binders: PRL-2882; PRL-2903 and PRL-2915 at micro-molar concentrations significantly blocked the development of human urotensin II-induced tonic contractions. Somatostatin receptor antagonists dose-dependently inhibited human urotensin II-induced Ca2+ transients in rat thoracic aorta rings. These somatostatin receptor antagonists displayed moderate affinities for recombinant rat and human urotensin II receptor binding sites. The data support the suggestion that urotensin II receptor and somatostatin type 2/5 receptors display similar surface topologies and that analogues of somatostatin could provide useful lead compounds for the development of more potent urotensin II receptor antagonists.

Characterization of riboflavin-modified dentin collagen matrix.

Crosslinking is considered a possible approach to increasing the mechanical and structural stability and biodegradation resistance of the dentin collagen matrix. The aim of this study was to investigate the mechanical and chemical variations and collagen degradation resistance associated with crosslinking of the dentin collagen matrix with UVA-activated riboflavin. Dentin collagen matrix specimens were treated with 0.1 and 1% riboflavin for 2 min and photo-activated with 7 mW/cm(2) UVA (368 nm) for 2 min. The structural change of the dentin collagen network with collagenase exposure was investigated by AFM and SEM at different time-points. The variations in surface/bulk mechanical properties and biodegradation resistance were characterized by nano-indentation, conventional mechanical testing, and hydroxyproline liberation at different time-points. Chemical changes associated with riboflavin/collagen-matrix interaction were analyzed by micro-Raman spectroscopy. UVA-activated riboflavin increased the mechanical properties, mechanical stability, and biodegradation resistance of the dentin collagen matrix. Higher collagen-network structural resistance against collagenolytic challenges was found with crosslinking. micro-Raman spectroscopy showed a strong dependency, in both intensity and wave-number, of certain Raman bands (1242-1667 cm(-1)) with crosslinking indicating the collagen/riboflavin interactions. UVA-activated riboflavin (1%) more efficiently crosslinked the dentin collagen matrix within a relatively clinically acceptable time-frame compared with 0.1% riboflavin.