MRI Detection of Carotid Intraplaque Hemorrhage and Postintervention Cognition.

BACKGROUND AND PURPOSE: Cognitive improvement has been reported after carotid revascularization and attributed to treating stenosis and correcting hypoperfusion. This study investigated the effect of carotid intraplaque hemorrhage on postintervention cognition. MATERIALS AND METHODS: In this institutional review board-approved single-center study, consecutive patients scheduled for carotid surgery were recruited for preoperative carotid MR imaging (MPRAGE) and pre- and postintervention cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status. Pre- and postintervention scores were compared using t tests and multivariable linear regression. RESULTS: Twenty-three participants were included, with endarterectomy performed in 20 (87%) and angioplasty/stent placement, in 3 (13%). Overall, statistically significant improvements occurred in the pre- versus postintervention mean Total Scale score (92.1 [SD, 15.5] versus 96.1 [SD, 15.8], P = .04), immediate memory index (89.4 [SD, 18.2] versus 97.7 [SD, 14.9], P < .001), and verbal index (96.1 [SD, 14.1] versus 103.0 [SD, 12.0], P = .002). Intraplaque hemorrhage (+) participants (n = 11) had no significant improvement in any category, and the attention index significantly decreased (99.4 [SD, 18.0] versus 93.5 [SD, 19.4], P = .045). Intraplaque hemorrhage (-) participants (n = 12) significantly improved in the Total Scale score (86.4 [SD, 11.8] versus 95.5 [SD, 12.4], P = .004), immediate memory index (82.3 [SD, 14.6] versus 96.2 [SD, 14.1], P = .002), delayed memory index (94.3 [SD, 14.9] versus 102.4 [SD, 8.0], P = .03), and verbal index (94.3 [SD, 13.2] versus 101.5 [SD, 107.4], P = .009). Postintervention minus preintervention scores for intraplaque hemorrhage (+) versus (-) groups showed statistically significant differences in the Total Scale score (-0.4 [SD, 6.8] versus 8.0 [SD, 8.5], P = .02), attention index (-5.9 [SD, 8.5] versus 4.3 [SD, 11.9], P = .03), and immediate memory index (4.2 [SD, 6.7] versus 12.2 [SD, 10.2], P = .04). CONCLUSIONS: Cognitive improvement was observed after carotid intervention, and this was attributable to intraplaque hemorrhage (-) plaque. MR imaging detection of intraplaque hemorrhage status may be an important determinant of cognitive change after intervention.

Vessel Wall Enhancement on Black-Blood MRI Predicts Acute and Future Stroke in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a known risk factor for ischemic stroke though angiographic imaging is often negative. Our goal was to determine the relationship between vessel wall enhancement (VWE) in acute and future ischemic stroke in CAA patients. MATERIALS AND METHODS: This was a retrospective study of patients with new-onset neurologic symptoms undergoing 3T vessel wall MR imaging from 2015 to 2019. Vessel wall enhancement was detected on pre- and postcontrast flow-suppressed 3D T1WI. Interrater agreement was evaluated in cerebral amyloid angiopathy-positive and age-matched negative participants using a prevalence- and bias-adjusted kappa analysis. In patients with cerebral amyloid angiopathy, multivariable Poisson and Cox regression were used to determine the association of vessel wall enhancement with acute and future ischemic stroke, respectively, using backward elimination of confounders to P < .20. RESULTS: Fifty patients with cerebral amyloid angiopathy underwent vessel wall MR imaging, including 35/50 (70.0%) with ischemic stroke and 29/50 (58.0%) with vessel wall enhancement. Prevalence- and bias-corrected kappa was 0.82 (95% CI, 0.71-0.93). The final regression model for acute ischemic stroke included vessel wall enhancement (prevalence ratio = 1.5; 95% CI, 1.1-2.2; P = .022), age (prevalence ratio = 1.02; 95% CI, 1.0-1.05; P = .036), time between symptoms and MR imaging (prevalence ratio = 0.9; 95% CI, 0.8-0.9; P < .001), and smoking (prevalence ratio = 0.7; 95% CI, 0.5-1.0; P = .042) with c-statistic = 0.92 (95% CI, 0.84-0.99). Future ischemic stroke incidence with cerebral amyloid angiopathy was 49.7% (95% CI, 34.5%-67.2%) per year over a total time at risk of 37.5 person-years. Vessel wall enhancement-positive patients with cerebral amyloid angiopathy demonstrated significantly shorter stroke-free survival with 63.9% (95% CI, 43.2%-84.0%) versus 32.2% (95% CI, 14.4%-62.3%) ischemic strokes per year, chi-square = 4.9, P = .027. The final model for future ischemic stroke had a c-statistic of 0.70 and included initial ischemic stroke (hazard ratio = 3.4; 95% CI, 1.0-12.0; P = .053) and vessel wall enhancement (hazard ratio = 2.5; 95% CI, 0.9-7.0; P = .080). CONCLUSIONS: Vessel wall enhancement is associated with both acute and future stroke in patients with cerebral amyloid angiopathy.

Prediction of Carotid Intraplaque Hemorrhage Using Adventitial Calcification and Plaque Thickness on CTA.

BACKGROUND AND PURPOSE: Carotid intraplaque hemorrhage is associated with stroke, plaque thickness, stenosis, ulceration, and adventitial inflammation. Conflicting data exist on whether calcification is a marker of plaque instability, and no data exist on adventitial calcification. Our goal was to determine whether adventitial calcification and soft plaque (a rim sign) help predict carotid intraplaque hemorrhage. MATERIALS AND METHODS: This was a retrospective cohort study of 96 patients who underwent carotid MRA and CTA within 1 month, from 2009 to 2016. We excluded occlusions (n = 4) and near occlusions (n = 0), leaving 188 carotid arteries. Intraplaque hemorrhage was detected by using MPRAGE. Calcification, adventitial pattern, stenosis, maximum plaque thickness (total, soft, and hard), ulceration, and intraluminal thrombus on CTA were recorded. Atherosclerosis risk factors and medications were recorded. We used mixed-effects multivariable Poisson regression, accounting for 2 vessels per patient. For the final model, backward elimination was used with a threshold of P < .10. Receiver operating characteristic analysis determined intraplaque hemorrhage by using the area under the curve. RESULTS: Our final model included the rim sign (prevalence ratio = 11.9, P < .001) and maximum soft-plaque thickness (prevalence ratio = 1.2, P = .06). This model had excellent intraplaque hemorrhage prediction (area under the curve = 0.94), outperforming the rim sign, maximum soft-plaque thickness, NASCET stenosis, and ulceration (area under the curve = 0.88, 0.86, 0.77, and 0.63, respectively; P < .001). Addition of the rim sign performed better than each marker alone, including maximum soft-plaque thickness (area under the curve = 0.94 versus 0.86, P < .001), NASCET stenosis (area under the curve = 0.90 versus 0.77, P < .001), and ulceration (area under the curve = 0.90 versus 0.63, P < .001). CONCLUSIONS: The CTA rim sign of adventitial calcification with internal soft plaque is highly predictive of carotid intraplaque hemorrhage.

Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain.

BACKGROUND: Opioids are used increasingly in the management of moderate-to-severe chronic non-cancer pain (CNCP). Opioid-induced bowel disorders (OBD) markedly impact health-related quality of life (HRQoL) and frequently limit medically indicated opioid pharmacotherapy. We assessed the risk factors, and effect of OBD on HRQoL in CNCP patients. We also estimated the likely prevalence of narcotic bowel syndrome (NBS). These effects have been reported in cancer patients but not in CNCP previously. METHODS: Ambulatory CNCP patients (n = 146) taking regularly scheduled opioids were invited to complete the Bowel-Disease-Questionnaire and a pain-sensitive HRQoL instrument. The Rome-II criteria were used to define bowel disorders. Narcotic bowel syndrome was defined as presence of daily severe to very-severe abdominal pain of more than 3 months duration requiring more than 100 mg of morphine equivalent per day. KEY RESULTS: Ninety-eight patients (69%) returned the survey. Respondents had taken opioids for 10 days to 10 years (median 365 days) at a median daily dose of 127.5 mg morphine-equivalent (range 7.5-600 mg). Constipation prevalence was 46.9% (95% CI 36.8-57.3), nausea 27% (95% CI 17.2-35.3), vomiting 9% (95% CI 17.2-35.3), and gastro-esophageal reflux disease 33% (95% CI 23.5-42.9). Chronic abdominal pain was reported by 58.2% (95% CI 53.2-73.9) and 6.4%, (95% CI 2.4-13.5) fulfilled the criteria of NBS. Prevalence of constipation increased with duration of treatment. Health-related quality of life was low in patients with chronic abdominal pain. CONCLUSION & INFERENCES: Bowel disorders including chronic abdominal pain and NBS are common in patients taking opioids for CNCP. Decreased HRQoL in patients with CNCP is driven by chronic abdominal pain.

ACE inhibitor effects on platelet function in stages I-II hypertension.

Angiotensin II enhances platelet aggregation through activation of the G protein-linked pathway present in platelets. Studies of several angiotensin-converting enzyme (ACE) inhibitors have demonstrated marked differences on platelets. Therefore this prospective, randomized, double-blind, crossover study compared the ex vivo effects of equivalent antihypertensive doses of captopril, enalapril, and fosinopril on platelet aggregation and thromboxane B2 (TxB2) formation in subjects with stage I-II essential hypertension. Nineteen male subjects with a baseline mean seated blood pressure of 141 +/- 3/100 +/- 1 mm Hg were enrolled. The decline in mean arterial pressure after 4 weeks of stable dosing was 10 +/- 1, 12 +/- 1, and 11 +/- 1 mm Hg for captopril, enalapril, and fosinopril, respectively (p = NS). There was no significant change in adenosine diphosphate (ADP)-, epinephrine-, or thrombin-stimulated platelet aggregation from baseline or between ACE inhibitors. Compared with baseline, fosinopril decreased TxB2 concentrations 27.5-67.6% with all stimuli after 1 and 5 min. Captopril also decreased TxB2 formation, but this effect was stimulus and time dependent. Enalapril consistently increased TxB2 concentrations, independent of stimuli or time. We conclude that different ACE inhibitors have distinct effects on platelet TxB2 formation without significant effects on platelet aggregation. Fosinopril may be a direct antagonist ofTxA2 synthase, suggesting benefit in syndromes of platelet activation or vascular occlusion.

Molecular analyses of the lactococcin A gene cluster from Lactococcus lactis subsp. lactis biovar diacetylactis WM4.

The genes responsible for bacteriocin production and immunity in Lactococcus lactis subsp. lactis biovar diacetylactis WM4 were localized and characterized by DNA restriction fragment deletion, subcloning, and nucleotide sequence analysis. The nucleotide sequence of a 5.6-kb AvaII restriction fragment revealed a cluster with five complete open reading frames (ORFs) in the same orientation. DNA and protein homology analyses, combined with deletion and Tn5 insertion mutagenesis, implicated four of the ORFs in the production of and immunity to lactococcin A. The last two ORFs in the cluster were the lactococcin A structural and immunity genes, lcnA and lciA. The two ORFs immediately upstream of lcnA and lciA were designated lcnC and lcnD, and the proteins that they encoded showed similarities to proteins of signal sequence-independent secretion systems. lcnC encodes a protein of 716 amino acids that could belong to the HlyB family of ATP-dependent membrane translocators. LcnC contains an ATP binding domain in a conserved C-terminal stretch of approximately 200 amino acids and three putative hydrophobic segments in the N terminus. The lcnD product, LcnD, of 474 amino acids, is essential for lactococcin A expression and shows structural similarities to HlyD and its homologs. On the basis of these results, a secretion apparatus that is essential for the full expression of active lactococcin A is postulated.

Potential savings from the adoption of nurse practitioner technology in the Canadian health care system.

An investigation is reported of the potential for reducing aggregate medical costs by the introduction of nurse practitioners into the Canadian health care system to an extent consistent with demonstrated safety and effectiveness. A cost model is developed for this purpose and estimates of its parameters are provided. The cost model is coupled with a demographic projection model and potential cost reductions are simulated over the period 1980-2050, under alternative assumptions. Results suggest that savings could have been in the range 10-15% in 1980 for medical services as a whole, and 16-24% for ambulatory services. The estimated savings percentages are quite insensitive to projected changes in the age structure of the Canadian population.