MASP2 levels are elevated in thrombotic microangiopathies: association with microvascular endothelial cell injury and suppression by anti-MASP2 antibody narsoplimab.

Involvement of the alternative complement pathway (AP) in microvascular endothelial cell (MVEC) injury characteristic of a thrombotic microangiopathy (TMA) is well documented. However, the role of the lectin pathway (LP) of complement has not been explored. We examined mannose-binding lectin associated serine protease (MASP2), the effector enzyme of the LP, in thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome and post-allogeneic hematopoietic stem cell transplantation (alloHSCT) TMAs. Plasma MASP2 and terminal complement component sC5b-9 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Human MVEC were exposed to patient plasmas, and the effect of the anti-MASP2 human monoclonal antibody narsoplimab on plasma-induced MVEC activation was assessed by caspase 8 activity. MASP2 levels were highly elevated in all TMA patients versus controls. The relatively lower MASP2 levels in alloHSCT patients with TMAs compared to levels in alloHSCT patients who did not develop a TMA, and a significant decrease in variance of MASP2 levels in the former, may reflect MASP2 consumption at sites of disease activity. Plasmas from 14 of the 22 TMA patients tested (64%) induced significant MVEC caspase 8 activation. This was suppressed by clinically relevant levels of narsoplimab (1·2 µg/ml) for all 14 patients, with a mean 65·7% inhibition (36.8-99.4%; P < 0·0001). In conclusion, the LP of complement is activated in TMAs of diverse etiology. Inhibition of MASP2 reduces TMA plasma-mediated MVEC injury in vitro. LP inhibition therefore may be of therapeutic benefit in these disorders.

Comparison of a prepCheck-supported self-assessment concept with conventional faculty supervision in a pre-clinical simulation environment.

OBJECTIVES: This study aimed to evaluate the educational outcome of a digitally based self-assessment concept (prepCheck; DentsplySirona, Wals, Austria) for pre-clinical undergraduates in the context of a regular phantom-laboratory course. MATERIALS AND METHODS: A sample of 47 third-year dental students participated in the course. Students were randomly divided into a prepCheck-supervised (self-assessment) intervention group (IG; n = 24); conventionally supervised students constituted the control group (CG; n = 23). During the preparation of three-surface (MOD) class II amalgam cavities, each IG participant could analyse a superimposed 3D image of his/her preparation against the "master preparation" using the prepCheck software. In the CG, several course instructors performed the evaluations according to pre-defined assessment criteria. After completing the course, a mandatory (blinded) practical examination was taken by all course participants (both IG and CG students), and this assessment involved the preparation of a MOD amalgam cavity. Then, optical impressions by means of a CEREC-Omnicam were taken to digitalize all examination preparations, followed by surveying and assessing the latter using prepCheck. RESULTS: The statistical analysis of the digitalized samples (Mann-Whitney U test) revealed no significant differences between the cavity dimensions achieved in the IG and CG (P = .406). Additionally, the sum score of the degree of conformity with the "master preparation" (maximum permissible 10% of plus or minus deviation) was comparable in both groups (P = .259). CONCLUSION: The implemented interactive digitally based, self-assessment learning tool for undergraduates appears to be equivalent to the conventional form of supervision. Therefore, such digital learning tools could significantly address the ever-increasing student to faculty ratio.

[Left atrial appendage occlusion in elderly]. / Fermeture d'auricule gauche percutanée chez le sujet âgé.

Left atrial appendage occlusion (LAAO) is an alternative option to oral anticoagulation therapy in patients with non-valvular atrial fibrillation. According to French regulations, this procedure is currently reserved for patients with formal contraindications to VKA and direct thrombin inhibitors. LAAO procedures reduce ischemic and stroke risks compared to no treatment and also reduce bleeding events compared to VKA therapy in eligible patients. The peri-procedural complications risk has been reported to be limited in the different series published so far. Although elderly patients (>75 years) have either higher ischemic and bleeding risk than younger subjects, they hardly benefit from optimal anticoagulation. Thus, these subjects might greatly benefit from LAAO. Published studies reported excellent feasibility and efficiency of LAAO procedure in elderly patients. Yet there is a trend towards a higher incidence of peri-procedural complications (including tamponade), long-term safety is excellent and comparable to what is observed in patients<75 years. Therefore, interventional percutaneous LAAO is an attractive strategy in elderly patients with atrial fibrillation that should be incorporated in a multidisciplinary management.

[Intracoronary thrombectomy with the Export Aspiration Catheter before angioplasty in patients with ST-segment elevation myocardial infarction]. / Thromboaspiration par le cathéter Export avant angioplastie dans les syndromes coronariens aigus avec sus-décalage du ST.

OBJECTIVES: We aimed to assess the safety and feasibility of thrombectomy with the Export Aspiration Catheter (EAC) before angioplasty, and its ability to improve angiographic results in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Distal embolization of atherothrombotic material often occurs during angioplasty in STEMI, compromising optimal myocardial reperfusion. METHODS: We performed a thrombus-aspiration with EAC prior to angioplasty in 64 consecutive patients with STEMI. Successful thrombectomy was defined as an improvement of TIMI flow grade > or =1. RESULTS: Successful thrombectomy (increase of TIMI flow > or =1) was achieved in 40 patients (62.5%). Mean TIMI flow grade increased from 0.7 +/- 1 to 1.9 +/- 1.2 (P < 0.0001) after thrombectomy. TIMI flow grade 3 was observed more frequently after EAC compared with guidewire alone (51.5 vs. 9%, P = 0.0062). Direct stenting was performed in most of patients (N=41, 64%). Distal embolization and noreflow/slowflow phenomenon occurred in 8 patients (12.5%). No vessel injury after EAC thrombectomy was reported. After treatment with balloon angioplasty and/or stenting, final TIMI flow grade 3 was achieved in 54 patients (84.5%). By multivariate analysis, ischemic time <6 h was a significant independent predictor of successful thrombectomy (P = 0.0437). CONCLUSIONS: Our series suggests that EAC thrombectomy prior to angioplasty in the setting of STEMI is safe and feasible. It might reduce the culprit coronary lesion's thrombus burden, leading to improved flow restoration and myocardial reperfusion. Further large randomized studies are warranted to confirm these preliminary results and to assess the impact of thrombus-aspiration on infarct size as well as on clinical outcomes.

[Isolated anomalous origin of a septal artery from a third coronary ostium. Apropos of a case]. / Naissance anormale isolée d'une artère septale par un troisième ostia coronaire. A propos d'un cas.

The authors report the case of a patient undergoing coronary angiography for angina who had an anomalous origin of the septal perforator artery from a separate ostium. Anomalies of the coronary arteries may consist not only of anomalous trajectories and coronary fistulae but also of anomalous origins of the main coronary arteries. The anomalous origin of a septal artery from a separate ostium is very rare accounting for 0.5% of cases in the medical literature. In some cases, this artery provides a collateral circulation for occluded main coronary vessels, thereby preserving left ventricular contractility.

[Complete atrioventricular block disclosing Fabry's disease]. / Bloc auriculo-ventriculaire complet révélateur de maladie de Fabry.

Fabry's disease is a hereditary sex-linked sphinglopidosis characterised by abnormal cellular lipid overload in most organs due to deficiencies in enzymes implicated in the catabolism of certain neutral glycolipids. There are two main clinical forms; cardiovascular manifestations usually congestive cardiac failure, and renal manifestations progressing to renal failure and death due to uraemic coma. The authors report a case presenting with juvenile, symptomatic complete infrahisian atrioventricular block. They describe the different cardiovascular complications of Fabry's disease from a review of the medical literature.

[Occlusion of a coronary endoprosthesis after a negative stress test]. / Occlusion d'endoprothèse coronaire au décours d'une épreuve d'effort négative.

The frequency of early occlusion of coronary stents has fallen with the use of a powerful association of platelet antiaggregants (ticlopidine and aspirin) in the first month. The authors report the case of coronary stent occlusion after a negative exercise stress test, 11 days after implantation in a centre of cardiac rehabilitation. According to the literature, this type of complication would appear to be rare and related to the small size of the stent and the conditions of implantation (acute phase). It would be useful to compile a registry of complications related to coronary angioplasty during rehabilitation to determine their prevalence and, if necessary, change the protocols of physical training of these patients.

[Iatrogenic lesions of the left main coronary artery]. / Lésions iatrogéniques du tronc commun coronaire gauche.

Reoccurrence of ischemic events several months after a percutaneous transcutaneous coronary angioplasty is usually due to a restenosis. Coronary angiography rarely shows a new stenosis on another site or on the left main coronary artery. In this series, we report 5 cases of left main coronary artery stenosis which have occurred from 3 to 12 months after a prior percutaneous angioplasty. This phenomenon which has previously been described after direct cannulation of the coronaries ostia during aortic valve replacement in the 70'. This complication is related to intimal damage caused by traumatic manipulation of the left main, which can be either already minimally altered or normal. This complication is rare after percutaneous transcutaneous coronary angioplasty (0.2-1.7%) according to various series. We compare our cases to the published cases in the literature.

[Morphological study by transesophageal echocardiography and clinical aspects of ruptured chordae tendineae in the elderly]. / Etude morphologique par échocardiographie transoesophagienne et aspects cliniques de la rupture de cordages mitral chez le sujet âgé.

Ruptured mitral chordae tendinae is a classical complication of myxomatous mitral valves or Barlow's syndrome. This complication is controversial in non-myxomatous mitral valve. Of 91 consecutive patients with mitral valve prolapse examined over an 18 months period by transthoracic and transesophageal echocardiography, 42 (18 women and 24 men) with an average age of 76 +/- 8 years (60-93 years) had ruptured mitral chordae tendinae. The thickness of the anterior mitral leaflet measured at the distal third of the valve by transesophageal echocardiography enabled the identification of two groups of patients; group I: > 3 mm (24 patients), average 4.8 +/- 0.8 mm and group II: < or = 3 mm (18 patients), average 2.6 +/- 0.3 mm. The diameter of the mitral ring and left atrium, the length of the anterior mitral leaflet, the left ventricular end diastolic dimensions and fractional shortening, were measured by transthoracic 2D echocardiography (mitral ring) and M mode (other parameters). Ruptured chordae were detected in only 13 cases (31%) by transthoracic echocardiography; 38% were asymptomatic and a chance finding at transesophageal echocardiography. No significant difference was observed between the two groups with respect to age, gender presence of hypertension, dimensions of the cardiac chambers, fractional shortening or localisation of the prolapse related to the ruptured chordae. Fifty-eight per cent of patients in group I were in NYHA functional classes 3-4 as compared to 16% in group II (p < 0.02). The size of the left atrium was significantly greater in group I, 51 +/- 8 mm vs 38 +/- 7 mm (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Medical treatment after implantation of intracoronary stents]. / Traitement médical après implantation de stents intracoronaires.

RATIONALE FOR ANTITHROMBOSIS THERAPY: Introducing a foreign body into the coronaries raises the risk of thrombosis in the acute phase and for the 4 following weeks. The objective of antithrombotic therapy is to inhibit platelet adhesion and aggregation or to induce hypocoagulability. AT IMPLANTATION: High-dose heparin is given in a bolus following pretreatment with aspirin. ASPIRIN-TICLOPIDINE COMBINATION: The risk of subacute thrombosis is low, about 1%, and the rate of vascular complications is minimal. Treatment is simple and compatible with short hospitalization.

[Different types of coronary stents]. / Les différents types de stent coronaire.

GENERAL CHARACTERISTICS: Several criteria are used for coronary stent design: biocompatibility, i.e. the capacity to resist thrombotic events and corrosion, flexibility, radial force sufficient to resist elastic recoil, percentage of the lesion covered, radio-opacity, minimal shortening at opening, absence of effect on collateral branches, possibility to use small calibre probe guides, and cost. TWO CATEGORIES: Both tubular stents (self-expanding stents and balloon stents) and filamentary stents (made of stainless steel or tantalum) are used, THE IDEAL STENT: There is no one ideal stent. Choice is dictated by the characteristics of the lesion and by the status of the artery to treat.

[Why so many stents?]. / Pourquoi autant de stents?

BETTER THAN ANGIOPLASTY: Prolonging inflation with a perfusion balloon decreases the risk of acute coronary occlusion after angioplasty. The longer the artery remains patent, the greater the chances of 0% residual stenosis. This is what the sent allows. Stent act on both mechanisms of stenosis: elastic recoil and fibrous remodeling of the arterial plaque. TARGETTED ACTION: Stents improve angioplasty prevention of acute stenosis. They have a real action on preventing degeneration of the saphenous graft and lead to a significant reduction in the rate of restenosis of the dilated site. There are however two specific complications: subacute occlusion and greater incidence of vascular events. Stents are particularly indicated for the treatment of restenosis and chronic occlusions. TWO IMPROVEMENTS: Risks related to the implantation of a foreign body in the vascular system have been reduced with the use of ticlopidine and high-pressure stent implantation. POSITIVE RESULTS: Stents have produced better angiographic results. They limit restenosis and the number of revascularizations required in treated patients. Several questions concerning indications remain open.

[High-risk left main coronary stenting supported by percutaneous Impella Recover LP 2.5 assist device]. / Assistance ventriculaire gauche percutanée avec le système Impella Recover LP 2,5 au cours d'une angioplastie à haut risque du tronc commun coronaire gauche.

Percutaneous coronary interventions (PCI) of complex coronary lesions in patients with severely depressed left ventricular (LV) function may increasingly constitute an alternative to surgical revascularization. The availability of hemodynamic support devices offers a promising option to reduce PCI-related complications in such high-risk procedures. We report the case of a successful distal left main coronary artery T-stenting supported by the Impella Recover LP 2.5 assist device in a patient with severe LV dysfunction.

[Clinical and angiographic outcomes after implantation of drug-eluting stents in bifurcation lesions with the crush stent technique]. / Résultats immédiats et à long terme après angioplastie coronaire avec stents actifs de lésions de bifurcation par la technique du << crush stenting >>

The most common approach in the treatment of bifurcation lesions is stenting only the main branch (MB) with provisional T-stenting of the side branch (SB). However, some bifurcation lesions may have extensive disease within a large SB requiring stenting of this vessel. The "crush" technique, which has been proposed as an alternative approach to other strategies to treat complex bifurcations, is a relatively simple technique that ensures complete coverage of the SB ostium. Previous series have reported its safety and feasibility, but limited data are available about the long-term outcomes. We report our experience on 21 consecutive patients (pts) treated with the "crush" technique with drug-eluting stents (DES) between November 2005 and March 2007. Clinical follow-up was 18+/-7 months for 19 pts (90%), and angiographic follow-up was completed in 66% of pts (N=14), at a mean time of 8.5+/-4 months. Mean pt age was 70+/-11 years; 33% (N=7) had diabetes mellitus, and mean preoperative logistic EUROSCORE predicted 11% mortality rate. The left anterior descending artery/diagonal and the distal left main were the most frequent bifurcation locations (52 and 43% of cases respectively), with a type 1,1,1 of the Medina classification of bifurcation lesions in 62% of pts, and an angulation MB-SB below 50 degrees in 66% of cases. Final kissing balloon dilation was performed in 90% of pts (N=20). Stent diameter and length were similar between MB and SB. The procedure was successfull in 100% of cases in the MB and 95% of cases in the SB. Procedure-related CK elevation above 2 ULN was seen in two pts (9.5%), without ECG modification. One pt had subacute stent thrombosis 5 days after his procedure. At the end of follow-up, target vessel revascularization (TVR) was required in four pts (19%), and target lesion revascularisation (TLR) in three pts (14%) whom had focal restenosis in the SB ostium (one pt) and in the MB and SB ostia (one pt). Sudden death occurred in one pt 14 months after his procedure. In conclusion, when an effective strategy for stenting both branches is planned, the "crush" technique with final kissing balloon can be safely used by experienced operators to treat complex bifurcation lesions with DES. The safety profile and TLR rate in our small series of "crush" stenting were similar to that of other studies reported thus far.

Soluble CD23 potentiates interleukin-1-induced secretion of interleukin-6 and interleukin-1 receptor antagonist by human monocytes.

The low-affinity receptor for IgE (CD23) is cleaved into biologically active soluble fragments (sCD23), some of which have been reported to exhibit pleiotropic activities. However, it is not known whether the sCD23 fragments contribute to the induction and/or regulation of pro-inflammatory cytokine production. In this study, this possibility was tested using interleukin (IL)-1-stimulated human whole blood as an ex vivo model of cytokine cascade production. We show that human recombinant 25-kDa sCD23 significantly enhanced the production of IL-6 in whole blood stimulated by IL-1, but had only little or no effect in the absence of IL-1. The potentiating effect of sCD23 was concentration dependent within the range of plasma levels occurring during various inflammatory processes in man. These results prompted us to study whether sCD23 and IL-1 together also enhance the production of regulating factors exhibiting anti-cytokine activities. Our data indicate that sCD23 augments the release of IL-1 receptor antagonist induced by IL-1. Finally, examining the effect of sCD23 on human peripheral monocytes stimulated by IL-1, we confirmed the capacity of sCD23 to potentiate cytokine production. We suggest that sCD23 can modulate monocyte functions, thereby contributing to the amplification and regulation of immune and inflammatory processes.

Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction.

BACKGROUND: When administered in conjunction with primary coronary stenting for the treatment of acute myocardial infarction, a platelet glycoprotein IIb/IIIa inhibitor may provide additional clinical benefit, but data on this combination therapy are limited. METHODS: We randomly assigned 300 patients with acute myocardial infarction in a double-blind fashion either to abciximab plus stenting (149 patients) or placebo plus stenting (151 patients) before they underwent coronary angiography. Clinical outcomes were evaluated 30 days and 6 months after the procedure. The angiographic patency of the infarct-related vessel and the left ventricular ejection fraction were evaluated at 24 hours and 6 months. RESULTS: At 30 days, the primary end point--a composite of death, reinfarction, or urgent revascularization of the target vessel--had occurred in 6.0 percent of the patients in the abciximab group, as compared with 14.6 percent of those in the placebo group (P=0.01); at 6 months, the corresponding figures were 7.4 percent and 15.9 percent (P=0.02). The better clinical outcomes in the abciximab group were related to the greater frequency of grade 3 coronary flow (according to the classification of the Thrombolysis in Myocardial Infarction trial) in this group than in the placebo group before the procedure (16.8 percent vs. 5.4 percent, P=0.01), immediately afterward (95.1 percent vs. 86.7 percent, P=0.04), and six months afterward (94.3 percent vs. 82.8 percent, P=0.04). One major bleeding event occurred in the abciximab group (0.7 percent); none occurred in the placebo group. CONCLUSIONS: As compared with placebo, early administration of abciximab in patients with acute myocardial infarction improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at six months, left ventricular function, and clinical outcomes.