Plaque rupture in the carotid artery is localized at the high shear stress region: a case report

BACKGROUND AND PURPOSE: Cerebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These ruptures are often observed at the upstream region of the plaque, where the wall shear stress (WSS) is considered to be highest. High WSS is known for its influence on many processes affecting tissue regression. Until now, there have been no serial studies showing the relationship between plaque rupture and WSS. Summary of Case- We investigated a serial MRI data set of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at 10-month follow up. The lumen, plaque components (lipid/necrotic core, intraplaque hemorrhage), and ulcer were segmented and the lumen contours at baseline were used for WSS calculation. Correlation of the change in plaque composition with the WSS at baseline showed that the ulcer was generated exclusively at the high WSS location. CONCLUSIONS: In this serial MRI study, we found plaque ulceration at the high WSS location of a protruding plaque in the carotid artery. Our data suggest that high WSS influences plaque vulnerability and therefore may become a potential parameter for predicting future events.     

Large variations in absolute wall shear stress levels within one species and between species

Wall shear stress (WSS), the frictional force between blood and endothelium, is an important determinant of vascular function. It is generally assumed that WSS remains constant at a reference value of 15 dyn/cm(2). In a study of small rodents, we realized that this assumption could not be valid. This review presents an overview of recent studies in large and small animals where shear stress was measured, derived from velocity measurements or otherwise, in large vessels. The data show that large variations exist within a single species (human: variation of 2-16 N/m(2)). Moreover, when we compared different species at the same location within the arterial tree, an inverse relationship between animal size and wall shear stress was noted. When we related WSS to diameter, a unique relationship was derived for all species studied. This relationship could not be described by the well-known r(3) law of Murray, but by the r(2) law introduced by Zamir et al. in 1972. In summary, by comparing data from the literature, we have shown that: (i) the assumption of a physiological WSS level of approximately 15 dyn/cm(2) for all straight vessels in the arterial tree is incorrect; (ii) WSS is not constant throughout the vascular tree; (iii) WSS varies between species; (iv) WSS is inversely related to the vessel diameter. These data support an "r(2) law" rather than Murray's r(3) law for the larger vessels in the arterial tree.     

The WHOQOL-100 has good psychometric properties in breast cancer patients

ObjectiveThis prospective follow-up study examines the psychometric properties of the World Health Organization Quality of Life assessment instrument (WHOQOL-100) for assessing quality of life in women suspected of having breast cancer and disease-free breast cancer survivors.Study Design and SettingThe WHOQOL-100 was tested at five points in time in women with a palpable lump in the breast or an abnormality on a screening mammography (N = 356) and breast cancer survivors (N = 140). Furthermore, all participants completed measures of anxiety (State Trait Anxiety Inventory) and depression (Center for Epidemiologic Studies Depression scale). Moreover, women who were diagnosed with breast cancer also completed the EORTC-QLQ-BR-23 at time points 2–5. Reliability (internal consistency; test–retest reliability) and construct validity were tested.ResultsConfirmatory factor analyses on the WHOQOL-100 items showed a good fit with models reflecting six factors (physical health, psychological health, level of independence, social relationships, environment, spirituality/religion/personal beliefs) or four factors (physical health, psychological health, social relationships, environment). Internal consistency was adequate. Test–retest correlations were high. The WHOQOL-100 correlated highly with related constructs and showed low correlations with unrelated constructs.ConclusionThe WHOQOL-100 is a reliable and valid instrument for measuring QOL in women suspected of having breast cancer and disease-free breast cancer survivors.     

Determinants of overall quality of life in women over the first year after surgery for early stage breast cancer

Purpose  

Scores on quality of life (QOL) domains and facets are probably subject to fluctuations across time due to the course of breast cancer treatment. Existing QOL studies have been cross-sectional. Therefore, this prospective follow-up study examined whether QOL domains (physical health, psychological health, social relationships, and environment) and QOL facets contributed differentially across time to overall QOL in women with early stage breast cancer.     

Gene therapy for the treatment of hip prosthesis loosening: adverse events in a phase 1 clinical study

Revision surgery for loosened hip prostheses is a heavy burden for elderly patients with comorbidity. As an alternative to surgery we performed a study to stabilize the prosthesis by percutaneous cement injection after removing inflammatory tissue with an intraarticular virus-directed enzyme prodrug approach. Twelve elderly patients with debilitating pain from a loosened hip prosthesis were included in a phase 1 dose-escalating clinical study. The patients were admitted to the hospital for 10 days for an intraarticular vector and prodrug injection, and subsequently for a percutaneous bone cement injection. This paper reports the adverse and serious adverse events of the study. After prodrug injection 9 of 12 patients had gastrointestinal adverse events (nausea, vomiting, and diarrhea), and 8 patients had hepatic adverse events (rise in aspartate aminotransferase and alanine aminotransferase). Five patients developed anemia (World Health Organization grade 1 or 2) from hematomas after cement injection. There were four serious adverse events in the first 6 months after vector injection, but these were not related to gene therapy as judged by an independent safety committee. There was no dose-limiting toxicity. However, the extensive comorbidity in these patients makes it difficult to fully establish the safety of the approach in this small and heterogeneous patient population.     

Learning curves of robot-assisted laparoscopic surgery compared with conventional laparoscopic surgery: an experimental study evaluating skill acquisition of robot-assisted laparoscopic tasks compared with conventional laparoscopic tasks in inexperienced users

BACKGROUND: Laparoscopic surgery can be demanding, resulting in longer operating time and a longer time before reaching proficiency compared with open surgery. Robotic assistance allows stereoscopic vision and improves dexterity, potentially leading to faster and safer laparoscopic surgery and a shortening of the learning curve. METHODS: Duration and accuracy were measured in inexperienced participants, performing basic and advanced laparoscopic tasks using both conventional laparoscopy and the daVinci Surgical System. RESULTS: Eight participants performed 176 laparoscopic tasks. Robotic assistance resulted in faster and more accurate performance of laparoscopic tasks. However, conventional laparoscopy showed faster skill acquisition. CONCLUSIONS: Robotic assistance resulted in faster and more accurate performance of laparoscopic tasks. However, learning curves favored conventional laparoscopy. These data suggest robotic assistance might be most beneficial in inexperienced subjects. The relatively flat learning curve in robot-assisted laparoscopy suggests robotic assistance might be less (or marginally) beneficial in experienced surgeons. This could explain why robotic assistance has failed to show clear benefit in several clinical studies. Extensive conventional laparoscopic training might lead to faster, safer, and less expensive surgery, further marginalizing the role for robotic assistance in laparoscopic surgery.     

Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer.

PURPOSE: To evaluate potential detrimental effects of exemestane on bone and lipid metabolism. PATIENTS AND METHODS: Postmenopausal women with early breast cancer were randomly assigned to exemestane 25 mg daily or placebo for 2 years in a double-blind setting. Primary objective was to evaluate the effect of exemestane on bone mineral density. Secondary objectives were effects on bone biomarkers, plasma lipids, coagulation factors, and homocysteine. Planned size was 128 patients. RESULTS: One hundred forty-seven patients were enrolled. All patients completed their 24-month visit except for those discontinuing treatment at an earlier stage. The mean annual rate of bone mineral density loss was 2.17% v 1.84% in the lumbar spine (P = .568) and 2.72% v 1.48% in the femoral neck (P = .024) in the exemestane and placebo arm, respectively. The mean change in T-score after 2 years was -0.21 for exemestane and -0.11 on placebo in the hip, and -0.30 and -0.21, respectively, in the lumbar spine. Exemestane significantly increased serum level and urinary excretion of bone resorption, but also bone formation markers. Except for a modest reduction in high-density lipoprotein cholesterol (P < .001) and apolipoprotein A1 (P = .004), exemestane had no major effect on lipid profile, homocysteine levels, or coagulation parameters. CONCLUSION: Exemestane modestly enhanced bone loss from the femoral neck without significant influence on lumbar bone loss. Except for a 6% to 9% drop in plasma high-density lipoprotein cholesterol, no major effects on serum lipids, coagulation factors, or homocysteine were recorded. Bone mineral density should be assessed according to the US Preventive Services Task Force guidelines.     

Lipopolysaccharide analogs improve efficacy of acellular pertussis vaccine and reduce type I hypersensitivity in mice

Pertussis is an infectious disease of the respiratory tract that is caused by the gram-negative bacterium Bordetella pertussis. Although acellular pertussis (aP) vaccines are safe, they are not fully effective and thus require improvement. In contrast to whole-cell pertussis (wP) vaccines, aP vaccines do not contain lipopolysaccharide (LPS). Monophosphoryl lipid A (MPL) and Neisseria meningitidis LpxL2 LPS have been shown to display immune-stimulating activity while exerting little endotoxin activity. Therefore, we evaluated whether these LPS analogs could increase the efficacy of the aP vaccine. Mice were vaccinated with diphtheria-tetanus-aP vaccine with aluminum, MPL, or LpxL2 LPS adjuvant before intranasal challenge with B. pertussis. Compared to vaccination with the aluminum adjuvant, vaccination with either LPS analog resulted in lower colonization and a higher pertussis toxin-specific serum immunoglobulin G level, indicating increased efficacy. Vaccination with either LPS analog resulted in reduced lung eosinophilia, reduced eosinophil numbers in the bronchoalveolar lavage fluid, and the ex vivo production of interleukin-4 (IL-4) by bronchial lymph node cells and IL-5 by spleen cells, suggesting reduced type I hypersensitivity. Vaccination with either LPS analog increased serum IL-6 levels, although these levels remained well below the level induced by wP, suggesting that supplementation with LPS analogs may induce some reactogenicity but reactogenicity considerably less than that induced by the wP vaccine. In conclusion, these results indicate that supplementation with LPS analogs forms a promising strategy that can be used to improve aP vaccines.     

Hypocalcaemia may reduce the beneficial effect of magnesium treatment in aneurysmal subarachnoid haemorrhage.

To assess whether magnesium treatment in patients with subarachnoid haemorrhage (SAH) is associated with hypocalcaemia and whether hypocalcaemia in these patients is associated with an increased risk of delayed cerebral ischemia (DCI) and poor outcome. All 137 patients randomized in the clinically controlled "Magnesium in Aneurysmal Subarachnoid Haemorrhage" trial were included. The relationship between mean serum magnesium and mean serum calcium during treatment was assessed with linear regression. The relationship between hypocalcaemia (serum calcium < 2.0 mmol/L) during treatment and the occurrence of DCI and poor outcome was studied with the Cox proportional hazards method and logistic regression, respectively. There was a statistically significant inverse relation between elevated serum magnesium and hypocalcaemia (B = -0.27; 95% CI, -0.33 to -0.20; p < 0.001). Patients with hypocalcaemia during study treatment had an increased frequency of DCI (HR 2.1; 95% CI, 1.0 to 4.3), and an increased risk for poor outcome (OR 2.9; 95% CI, 1.4 to 6.4), but this effect attenuated in the multivariable analysis (OR 1.9; 95% CI, 0.8 to 4.7). In conclusion, prolonged elevated serum magnesium is associated with hypocalcaemia. Hypocalcaemia is associated with an increased risk of DCI and poor outcome and may therefore reduce the potential beneficial effect of magnesium treatment in SAH.