Fibrinopeptide A and the phosphate content of fibrinogen in venous thromboembolism and disseminated intravascular coagulation

Concentrations of plasma fibrinopeptide A (FPA) were measured by radioimmunoassay in 50 patients with venous thromboembolism or disseminated intravascular coagulation or both. A consistent discrepancy was observed in values obtained with two anti-FPA antisera. Analysis of extracts from plasma of these patients by high-performance liquid chromatography (HPLC) revealed the presence of a phosphorylated and an unphosphorylated form of the A peptide. Differences in concentrations of FPA measured with the two antisera could be accounted for by their different reactivity with phosphorylated FPA (FPA-P). The differences were abolished by treatment with alkaline phosphatase. A good correlation was observed between the FPA-P content of free A- peptide material and of fibrinogen in plasma as determined by HPLC (r = .88, P less than .001, n = 11). In patients with elevated FPA levels, the mean FPA-P content of fibrinogen was significantly higher (P less than .002, n = 13) than in patients with normal FPA levels (n = 8) and in healthy controls (n = 14). Phosphorus in fibrinogen did not correlate with fibrinogen degradation products or fibrinogen levels and became normal on adequate anticoagulation. Therefore, blood-clotting activation may lead to a high phosphate content of fibrinogen and of free FPA in plasma.     

A comparison of the vasodilator responses to atrial peptides in the pulmonary and renal arteries of the pig in vitro.

Noradrenaline preconstricted pulmonary and renal artery segments from 20 large White pigs were examined in vitro for their responses to alpha-human atrial natriuretic peptide (alpha-hANP), rat-atriopeptin I (AP I) or rat-atriopeptin III (AP III) added in a cumulative manner. The role of the vascular endothelium in atrial peptide-induced relaxation was examined in the presence of indomethacin and propranolol by removal of the endothelium in one of a pair of arterial segments. Pulmonary artery was significantly (P less than 0.001) more sensitive than renal artery to alpha-hANP with a potency ratio of approximately 10. alpha-hANP appeared to be a more potent relaxant than AP III and AP I in pulmonary artery. Potency ratios were approximately 2 (AP III vs alpha-hANP; P less than 0.05) and 30 (API vs alpha-ANP; P less than 0.001). Removal of the endothelium increased the sensitivity of renal artery to a alpha-hANP, but made no difference to the pulmonary arterial relaxations. In man the highest circulating concentrations of ANP are found in the pulmonary artery. The demonstration of its potent relaxant effects at this site in the pig indicates a possible role in the modulation of pulmonary arterial tone.     

Outcome after salvage radiotherapy (brachytherapy +/- external) in patients with a vaginal recurrence from endometrial carcinomas.

BACKGROUND AND PURPOSE: The vagina is the site most commonly affected by loco-regional failure in endometrial carcinoma (EC). The aim of this study was to evaluate the efficacy of vaginal brachytherapy (BT) combined or not with whole pelvic external radiotherapy (RT) for the treatment of patients with vaginal recurrences from endometrial cancer. PATIENTS AND METHODS: Between 1986 and 1999 25 women were treated at the Institut Gustave Roussy (IGR) for a vaginal relapse (VR) from EC. Patient characteristics were as follows: median age 65 years (range 43-84), histologic type: adenocarcinoma (21 patients); endometrioid carcinoma (three patients); adenoacanthoma (one patient); FIGO staging for initial disease: Ia, three; Ib, eight; Ic, four; II, seven; IIIa, two; IVa, one. The initial tumor was treated by surgery alone in 18 patients, or surgery combined with RT and/or BT in seven patients. A VR occurred in a median interval of 21 months (range 2-89); 10/25 (40%) occurred within the first year following initial treatment. The recurrence was exclusively in the vagina in 18 patients and was associated with parametrial and or nodal involvement in seven patients; it was localized in the upper 1/3 of the vagina in nine patients, in the upper 2/3 or the entire vagina in 11 patients or in the lower 1/3 in five patients. The largest tumor diameter ranged from 10 to 70 mm (median: 25 mm). The treatment of the VR included low-dose rate endocavitary BT in all cases: three patients received endocavitary BT alone, or it was associated with external RT in 22 patients or delivered after surgical removal of the lesion in nine patients. Seven patients were submitted to further irradiation combining endocavitary and interstitial BT. RESULTS: Local control was achieved in 23 patients (92%). With a follow-up ranging from 4 to 154 months, 13 patients have died (ten due to metastasis, two of intercurrent disease and two due to local tumor progression) and ten patients are alive and disease free. The 3-year actuarial survival was 48%. Late radiation-related sequelae were observed in nine patients (mucous necrosis in one patient, moderate sclerosis in six patients) in an interval varying between 8 and 45 months. The majority of recurrences occurred in patients who had not previously received irradiation, which emphasizes the role of systematic prophylactic post-operative vaginal BT. Extra-vaginal extension (P < 0.001), the tumor size (P < 0.03) and the stage of initial disease (P < 0.01) appeared to have a significant impact on the prognosis. CONCLUSION: BT combined with external RT is an efficient treatment for VR from EC even in previously irradiated patients. Poor survival remains related to metastatic dissemination.     

Is postdilatation useful after implantation of the Edwards valve?

Background: Few data are available about postdilatation (PD) for the treatment of significant paravalvular aortic regurgitation (AR) after transcatheter aortic valve implantation of the Edwards valve. Methods and Results : A total of 470 patients, aged 83.4 ± 6.4 yrs, with logistic European System for Cardiac Operative Risk Evaluation 21.9 ± 12.3, undergoing transcatheter aortic valve implantation with the Edwards valve were evaluated. PD was performed using the balloon delivery system when significant paravalvular AR was identified. The diameter of the valve was measured from cine acquisition at three different levels. PD was performed in 49 (10.4%) patients with grade 2, 3, or 4 AR as 42.1%, 55.3%, and 2.6%, respectively. After PD, a reduction of at least 1 degree of AR was achieved in 81.5% of cases. Residual AR grades 2, 3, and 4 were observed in 36.8%, 10.5%, and 0%, respectively. A significant increase in the prosthesis diameter was observed at the three valve levels (absolute Δ 3.5%–5.4%, P.< 0.01). For the 23 mm valve, mid level of valve increased from 23.0 ± 0.4 to 24.1 ± 0.5 mm (P < 0.01) and for the 26 mm, from 25.2 ± 0.9 to 26.6 ± 0.9 mm (P < 0.01). Occurrence of annulus rupture (4.1% vs. 1.7%, P = 0.24), cerebrovascular accidents (2.0% vs. 2.1%, P = 0.72), need for new pacemaker (8.2% vs. 5.5%, P = 0.31), and 30‐day composite endpoint (24.5% vs. 20.2%, P = 0.48) were not significantly different between PD and non‐PD groups. Conclusions : PD for the treatment of significant paravalvular leak proved to be a feasible treatment allowing a significant increase in valve size and decrease in PVL without increase in stroke rates. This promising approach needs further confirmation. © 2014 Wiley Periodicals, Inc.     

Cardiovascular magnetic resonance predictors of clinical outcome in patients with suspected acute myocarditis

Background

The natural history of acute myocarditis (AM) remains highly variable and predictors of outcome are largely unknown. The objectives were to determine the potential value of various cardiovascular magnetic resonance (CMR) parameters for the prediction of adverse long-term outcome in patients presenting with suspected AM.

Methods

In a single-centre longitudinal prospective study, 203 routine consecutive patients with an initial CMR-based diagnosis of AM (typical Late Gadolinium Enhancement, LGE) were followed over a mean period of 18.9 ± 8.2 months. Various CMR parameters were evaluated as potential predictors of outcome. The primary endpoint was defined as the occurrence of at least one of the combined Major Adverse Clinical Events (MACE) (cardiac death or aborted sudden cardiac death, cardiac transplantation, sustained documented ventricular tachycardia, heart failure, recurrence of acute myocarditis, and the need for hospitalization for cardiac causes).

Results

The vast majority of patients (N = 143,70 %) presented with chest pain, mild to moderate troponin elevation and ST-segment or T wave abnormalities. Various CMR parameters were evaluated on initial CMR performed 3 ± 2 days after acute clinical presentation (LV functional parameters, presence/extent of edema on T2 CMR, and extent of late gadolinium enhancement lesions). Out of the 203 patients, 22 experienced at least one major cardiovascular event (10.8 %) during follow-up for a total of 31 major cardiovascular events. Among all CMR parameters, the only independent CMR predictor of adverse clinical outcome by multivariate analysis was an initial alteration of LVEF (p = 0.04).

Conclusions

In routine consecutive patients without severe hemodynamic compromise and a CMR-based diagnosis of AM, various CMR parameters such as the presence and extent of myocardial edema and the extent of late gadolinium-enhanced LV myocardial lesions were not predictive of outcome. The only independent CMR predictor of adverse clinical outcome was an initial alteration of LVEF.     

Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival

Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2^−ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2^−ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.     

Behavior of Serous Borderline Ovarian Tumors With and Without Micropapillary Patterns: Results of a French Multicenter Study

Background  

Behavior of serous borderline ovarian tumors with micropapillary patterns (MP-SBOT) is thought to be worse than those without micropapillary patterns, but few cohort studies have compared epidemiological characteristics, surgical management, and recurrence rates between these two groups.