Contraction-Relaxation Coupling and Impaired Left Ventricular Performance in Coronary Surgery Patients

Background: Dependence of left ventricular (LV) relaxation on cardiac systolic load is a function of myocardial contractility. The authors hypothesized that, if a tight coupling would exist between LV contraction and relaxation, the changes in relaxation rate with an increase in cardiac systolic load would be related to the changes in LV contraction.

Methods: Coronary surgery patients (n = 120) with preoperative ejection fraction > 40% were included. High-fidelity LV pressure tracings (n = 120) and transgastric transesophageal echocardiographic data (n = 40) were obtained. Hearts were paced at a fixed rate of 90 beats/min. Effects on contraction were evaluated by analysis of changes in dP/dtmax and stroke area. Effects on relaxation were assessed by analysis of R (slope of the relation between [small tau, Greek] and end-systolic pressure). Correlations were calculated with linear regression analysis using Pearson's coefficient r.

Results: Baseline LV end-diastolic pressure was 10 +/- 3 mmHg (mean +/- SD). During leg raising, systolic LV pressure increased from 93 +/- 9 to 107 +/- 11 mmHg. The change in dP/dtmax was variable and ranged from -181 to +254 mmHg/s. A similar variability was observed with the changes in stroke area, which ranged from -2.0 to +5.5 cm2. Changes in dP/dtmax and in stroke area were closely related to individual R values (r = 0.87, P < 0.001; and r = 0.81, P < 0.001, respectively) and to corresponding changes in LV end-diastolic pressure (r = 0.81, P < 0.001; and r = 0.74, P < 0.001, respectively).     

Direct transoral approach to C2 for percutaneous vertebroplasty

Percutaneous vertebroplasty was performed via a transoral route in a 70-year-old woman with a C2 metastasis of thyroid origin involving anterior vertebral elements. Complete pain relief was obtained after an uncomplicated minimally invasive procedure. This preliminary experience demonstrates that a transoral approach under fluoroscopic control can provide safe access to the upper cervical spine at C2 level.     

Arteriovenous brain malformations: is functional MR imaging reliable for studying language reorganization in patients? Initial observations

PURPOSE: To determine whether the blood flow abnormalities frequently associated with arteriovenous malformations (AVMs) can alter functional magnetic resonance (MR) imaging evaluation of language lateralization and whether reorganization of language function occurs in patients with brain AVMs. MATERIALS AND METHODS: Eleven patients with left-hemisphere brain AVMs and 10 age-matched control subjects were examined with 1.5-T blood oxygen level-dependent (BOLD) functional MR imaging. Verbal fluency, sentence repetition, and story listening tasks were performed. The functional MR imaging laterality index in the frontal and temporal lobes was defined as the (L - R)/(L + R) ratio, where L and R are the numbers of activated pixels in the left and right hemispheres, respectively. Statistical analyses were performed with Wilcoxon signed rank, Fisher exact, and Kruskal-Wallis tests. RESULTS: Control subjects had left-sided language dominance, although symmetric pixel counts were observed in the frontal lobes in two subjects and in the temporal lobes in one subject. Six patients had left-sided language dominance similar to that observed in control subjects. Five of these patients had AVMs outside frontal or temporal language areas, without flow abnormalities. Five patients had abnormally right-sided asymmetric indexes (below mean control subject value - 2 SDs), which suggested language reorganization (P <.05). Results of Wada examination and/or postembolization functional MR imaging performed in two of these patients showed that the abnormal laterality indexes were at least partly due to severe flow abnormalities that impaired detection of BOLD MR imaging signal intensity. CONCLUSION: These data suggest that flow abnormalities may interfere with language lateralization assessment with functional MR imaging.     

End-stage renal failure and cardiac mortality after heart transplantation

BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality after the first year of heart transplantation. End-stage renal failure (ESRF) is more frequent because of long-term survival. Impact of ESRF on cardiac mortality in heart transplant patients is unappreciated. The hypothesis of accelerated CAD in uremic patients has been suggested. METHODS: In Pitié La Salpêtrière hospital, 1211 heart transplants have been performed between 1982 and 2001. Thirty-three patients have reached ESRF. A case-control study was performed to identify risk factors responsible for ESRF and to appreciate the impact of ESRF on cardiac mortality. RESULTS: In cases at 6 months, serum creatinine tended to be higher (159 +/- 31 micromol/L vs. 141 +/- 44 micromol/L, p = 0.06) and cyclosporine (CSA) dosage (mg/kg) was significantly lower (5.4 +/- 1.8 mg/kg vs. 7.7 +/- 2.7 mg/ kg, p = 0.002). Mean triglyceride level after transplantation until dialysis was significantly lower in cases (2.18 +/- 0.82 mmol/L vs. 1.48 +/- 0.62 mmol/L, p = 0.002). In cases and controls, cardiac mortality was responsible for 67% (10 of 15) and 38% (three of eight) of all deaths, respectively. High triglyceride level (> or = 2 mmol/L) was associated with cardiac mortality [p < 0.03, hazard ratio (HR) = 3.89]. Kaplan Meier cardiac free survival rates were significantly lower in cases than in controls (p < 0.03). CONCLUSION: These data suggest that CSA nephrotoxicity could result from individually determined susceptibility and that hypertriglyceridemia may have a negative impact on renal function and cardiac mortality. The risk of cardiac mortality is increased in heart transplant patients with ESRF. The hypothesis of accelerated atherosclerosis in ESRF patients after heart transplantation leading to higher cardiac mortality incidence needs further study.     

Late incidence and determinants of stroke after aortic and mitral valve replacement

Background

Stroke is a devastating complication in patients with prosthetic valves, but characterization of its late occurrence from a large cohort is lacking.

Methods

Three thousand one hundred eighty-nine adult patients who underwent a total of 3,576 operations for left-heart valve replacement were managed with contemporary anticoagulation guidelines and prospectively followed in a dedicated clinic. Total follow-up was 20,096 patient years. Bootstrapped survival analysis was used to determine the impact of patient and valve related factors on the incidence of stroke.

Results

Most strokes were embolic. Linearized embolic stroke rates were 1.3% ± 0.2% per year for aortic bioprostheses, 1.4% ± 0.2% per year for aortic mechanical valves, 1.3% ± 0.3% per year for mitral bioprostheses, and 2.3% ± 0.4% per year for mitral mechanical valves (p = 0.002, vs other implant types). Age more than 75 years, female gender, and smoking were independent risk factors after aortic and mitral valve replacement. Atrial fibrillation, coronary disease, and tilting-disc mechanical prostheses were independent predictors of embolic stroke after aortic valve replacement. Preoperative left ventricular (LV) dysfunction was an independent risk factor in patients with mitral prostheses. Primary operative indication, diabetes, redo status, or the presence of two prosthetic valves were not associated with an increased hazard. The addition of acetyl salicylic or dipyridamole to warfarin anticoagulation did not significantly lower embolic stroke risk in patients with mechanical prostheses.

Conclusions

Approximately 20% of patients with valve prostheses have an embolic stroke by 15 years after valve replacement. Some risk factors such as the avoidance of smoking, mitral mechanical prostheses, aortic tilting-disc valves, and proceeding to mitral surgery before LV dysfunction occurs are potentially modifiable.     

Robotic aortic valve replacement: case report

We have developed a technique that enables robotic aortic valve replacement with port access via a small right anterior thoracotomy and minimally invasive aortic cross clamping. The procedure is performed under video guidance with all the annular sutures placed with the robot. In the case we report, the patient's postoperative course was extremely simple and pain was minimal. We believe that this is the first reported aortic valve replacement using robotic technology and that it opens a new field of application for robotic assisted surgery.     

Expression of minichromosome maintenance MCM6 protein in meningiomas is strongly correlated with histologic grade and clinical outcome

The 2007 World Health Organization histologic grading of meningiomas is associated with recurrence and clinical outcome. However, distinction of grade I from grade II (atypical) meningiomas can be challenging. In the World Health Organization classification, there are 4 parameters on the basis of which grade II status can be determined: mitotic rate, cytoarchitectural features, brain invasion, and/or histologic subtype. Furthermore, this classification fails to detect grade I recurrent meningiomas, for which other prognostic criteria would be needed. The aim of this study was to evaluate the respective value of several markers involved in cell cycle as effective tools to predict recurrence. This retrospective study was based on a series of 59 meningiomas (grade I: 32 of 59, grade II: 27 of 59, all harboring ≥4 mitoses/1.6 mm), analyzed with the following immunohistochemical markers: MCM6, Ki-67, PHH3, cyclin D1, and p53. We found a significant correlation between histologic grade and mean labeling index for MCM6 (grade I: 21.8% vs. grade II: 65.8%; P<0.001), Ki-67 (3.2% vs. 16.9%; P<0.001), PHH3 (0.7‰ vs. 2.8‰; P<0.001), cyclin D1 (50.4% vs. 70.0%; P=0.005), and p53 (17.3% vs. 32.4%; P=0.017). Histologic grading and mitotic index were correlated with progression-free survival (P=0.010 and P=0.020, respectively). A nearly linear correlation was found between progression-free survival and staining for MCM6 (P<0.001), Ki-67 (P=0.003), and PHH3 (P=0.037) but not for cyclin D1 (P=0.400) and p53 (P=0.758). The interobserver agreement coefficients for MCM6, Ki-67, PHH3, cyclin D1, and p53 were, respectively, 0.97 (95% confidence interval, 0.95-0.98), 0.93 (0.89-0.96), 0.81 (0.70-0.88), 0.90 (0.83-0.94), and 0.84 (0.73-0.90). In conclusion, because of its strong level of expression and sharp difference in labeling index between indolent and recurrent tumors, MCM6 is the most efficient marker to identify tumors with a high risk of recurrence.     

Functional hypoparathyroidism in postmenopausal women with fragility fracture

IntroductionSecondary hyperparathyroidism sometimes is lacking despite authentic vitamin D insufficiency (VDI) and the concept of functional hypoparathyroidism with a protective role on bone status has been proposed. Therefore, we tested the hypothesis that its prevalence was very low in a population of women with a peripheral fragility fracture.MethodsWe conducted our study in postmenopausal women, admitted for such a fracture in our Fracture Liaison Service. All had bone mineral density (BMD), biochemical assessment and a medical visit.ResultsTwo hundred and thirty seven women (72.9 ± 11.6-year-old) were included and 90.4% had VDI (25[OH]D ≤ 30 ng/mL). Yet, 87.9% of the latter had normal PTH levels less or equal to 64 ng/L. In this population with VDI (n = 214), we found no PTH plateau level related to 25(OH)D. Since a recent study reported an increase in the risk of fracture only when 25(OH)D was below 15 ng/mL, we then used this value as a new threshold. We observed a significant difference in hip BMD between patients with 25(OH)D either less or equal to or greater than 15 ng/mL. However, 81.2% of the formers were still with normal PTH with no difference in BMD whether PTH level was above or within normal range.ConclusionIn a population of postmenopausal women with a fragility fracture, we found that 25(OH)D less or equal to 15 ng/mL was associated with significantly lower hip BMD. Even using this low threshold, we found a high prevalence of functional hypoparathyroidism and it was not associated with any difference in hip or spine BMD. Overall, our results do not support the hypothesis of a protective effect of this biological profile.     

Prognostic Value of BRAF V600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes

Purpose

BRAF ^V600 mutations are frequent in melanomas, and BRAF^V600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ??2?mm according to BRAF ^V600 mutations and other previously reported prognostic criteria.

Methods

This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF ^V600 mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60?% melanoma cells.

Results

BRAF mutations (p.V600E and p.V600K in 83 and 14?% of cases, respectively) were detected in 40?% of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3?%, with a median OS of 1.4 and 2.8?years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P?=?0.005, hazard ratio 2.2, 95?% confidence interval 1.3?C3.9) and BRAF status (P?=?0.005, hazard ratio 1.9, 95?% confidence interval 1.2?C3.1).

Conclusions

BRAF ^V600 status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.     

Inter-observer variation in the diagnosis of coronal articular fracture lines in the lunate facet of the distal radius

Background

Several studies support the use of CT for diagnosing coronal fractures of the distal radius but the inter-observer reliability of these observations is less well studied. We tested the null hypothesis that radiographs alone and the combination of radiographs and two-dimensional computed tomography scans (2DCT) have the same inter-observer variation for the diagnosis of coronal articular fracture lines in the distal radius.

Methods

Using a web-based survey, 63 surgeons were randomized to evaluate 16 fractures of the distal radius on radiographs alone or radiographs and 2DCT for the presence or absence of a coronal fracture line of the lunate facet and, if present, the stability of the fracture. The kappa multirater measure was calculated to estimate agreement between observers.

Results

The inter-observer variation in diagnosis of a coronal fracture line was fair with both radiographs and 2DCT, as was the diagnosis of instability of the volar lunate facet fracture when present.

Conclusion

Two-dimensional computed tomography does not improve observer agreement on the diagnosis of coronal plane articular fracture lines in the lunate facet of the distal radius.