Factors influencing quality of anticoagulation control and warfarin dosage in patients after aortic valve replacement within the 3 months of follow up.

Warfarin dosage estimation using the pharmacogenetic algorithms has been shown to improve the quality of anticoagulation control in patients with atrial fibrillation. We sought to assess the genetic, demographic and clinical factors that determine the quality of anticoagulation in patients following aortic valve replacement (AVR). We studied 200 consecutive patients (130 men) aged 63 ± 12.3 years, undergoing AVR, in whom warfarin dose was established using a pharmacogenetic algorithm. The quality of anticoagulation within the first 3 months since surgery was expressed as the time of international normalized ratio (INR) in the therapeutic range (TTR). The median TTR in the entire cohort was 59.6% (interquartile range, 38.7 - 82.7). Ninety-nine (49.5%) patients with TTR ≥ 60% did not differ from those with poor anticoagulation control (TTR < 60%) with regard to demographic and cardiovascular risk factors. Coronary artery disease (n = 84, 42%) and previous stroke (n = 5, 2.5%) predicted higher TTR, while possession of CYP2C9*2 variant allele (n = 49, 25%) was associated with lower TTR (P = 0.01). In turn, VKORC1 c.-1639A, CYP2C9*2 and *3 variants were independently associated with actual warfarin dose (P < 0.0001). In AVR patients better anticoagulation control is observed in patients with coronary artery disease and history of stroke, which might result in part from previous lifestyle modification and therapy. Possession of CYP2C9*2 and/or CYP2C9*3 allele variants is associated with lower TTR values and warfarin dose variations in AVR patients, the latter affected also by VKORC1 c.-1693G>A polymorphism.

Impaired fibrinolysis is associated with the severity of aortic stenosis in humans.

BACKGROUND: A role of fibrinolysis in the pathogenesis of aortic valve stenosis (AS) is unknown, although fibrinolytic proteins have been detected in aortic stenotic valves. OBJECTIVE: To investigate whether impaired fibrinolysis could be associated with AS. METHODS AND RESULTS: We studied 74 patients with AS (43 male, 31 female, aged 62.7 ± 10.7 years) without documented atherosclerotic valvular disease scheduled for isolated valve replacement and 68 controls. The plasma fibrin clot lysis time (CLT) in the presence of tissue factor (TF) and tissue plasminogen activator (tPA), along with plasma plasminogen activator inhibitor-1 (PAI-1) were determined. Valvular expression of fibrin and PAI-1 together with macrophages and mast cells (MC) was evaluated by immunostaining. Patients with AS compared with controls were characterized by a prolonged CLT (median, 110 [54-153] vs. 92.5 [58-115] min, P = 0.0007) and increased plasma PAI-1 (78.6 [35.5-149] vs. 38.5 [18-61] ng mL(-1) , P < 0.0001). CLT was correlated with maximal (r = 0.43, P = 0.0002) and mean (r = 0.38, P = 0.001) transvalvular pressure gradients, and aortic valve area (r = -0.59, P < 0.0001). In AS patients, the CLT was positively correlated with the valve leaflet thickness (r = 0.67, P = 0.003), the degree of valve calcification (r = 0.65, P < 0.00001), valvular fibrin (r = 0.54, P = 0.007) and PAI-1 expression (r = 0.48, P = 0.007). Double-immunostaining revealed colocalization of valvular PAI-1 with MC (87 ± 17% cells) and macrophages (48 ± 11% cells) within stenotic valves. CONCLUSIONS: Hypofibrinolysis might be a marker of severe AS and be implicated in AS progression.

Mast cells in human stenotic aortic valves are associated with the severity of stenosis.

Aortic valve stenosis (AS) is characterized by extensive calcification of the aortic valve leaflets and infiltration of inflammatory cells. Activated mast cells (MCs) may participate in the induction of fibrosis and calcification with ensuing valve stiffening. We sought to investigate whether the number of MCs within stenotic aortic valves is associated with the severity of AS. We studied 43 patients (19 men, 24 women) with dominant AS (age, 64.2 ± 5.9 years; mean transvalvular pressure gradient, 62.11 ± 24.47 mmHg) without atherosclerotic vascular disease, undergoing elective aortic valve replacement. MCs were detected in the excised valves by immunostaining. Aortic valves from five healthy subjects obtained on autopsy served as negative controls. The number of tryptase- and chymase-positive MCs was increased in AS valves compared with the control valves (6.9 [2.3-18.9]/mm(2) vs. 0.7 [0-2.2]/mm(2), P = 0.0001 and 3.2 [2.1-9.4]/mm(2) vs. 0.3 [0-1.9]/mm(2), P = 0.002, respectively). MCs that colocalized with macrophages and neovessels were detected mainly in the calcified regions of the leaflets. The number of MCs positively correlated with maximal (r = 0.73, P < 0.0001) and mean (r = 0.78, P < 0.0001) gradients and maximal aortic jet velocity (r = 0.68, P = 0.0005). An inverse correlation with aortic valve area (r = -0.71, P = 0.0001) was also observed. Multivariate regression analysis revealed that MC number and valve thickness were significantly associated with mean transvalvular gradient (R (2) = 0.74, P < 0.000001) in AS patients. Increased MC number within human stenotic aortic valves is associated with the severity of AS.

Evidence-based recommendations for the use of negative pressure wound therapy in chronic wounds: steps towards an international consensus.

AIM: Negative Pressure Wound Therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer-reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this communication the results of the study of evidence in chronic wounds including pressure ulcers, diabetic foot ulcers (DFU), venous leg ulcers (VLU), and ischaemic lower limb wounds are reported. METHODS: Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% agreement. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. RESULTS: The primary treatment goal of NPWT in most chronic wounds is to achieve wound closure (either by secondary intention or preparing the wound for surgical closure). Secondary goals commonly include: to reduce wound dimensions, and to improve the quality of the wound bed. Thirteen evidence based recommendations were developed in total to address these treatment goals; 4 for pressure ulcers, 4 for DFU, 3 for ischaemic lower limb wounds and 2 for VLU. CONCLUSION: The present evidence base is strongest for the use of NPWT in non-ischaemic DFU and weakest in VLU. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

Evidence-based recommendations for negative pressure wound therapy: treatment variables (pressure levels, wound filler and contact layer)--steps towards an international consensus.

Negative pressure wound therapy (NPWT) is becoming a commonplace treatment in many clinical settings. New devices and dressings are being introduced. Despite widespread adoption, there remains uncertainty regarding several aspects of NPWT use. To respond to these gaps, a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In a previous communication, we have reviewed the evidence base for the use of NPWT within trauma and reconstructive surgery. In this communication, we present results of the assessment of evidence relating to the different NPWT treatment variables: different wound fillers (principally foam and gauze); when to use a wound contact layer; different pressure settings; and the impact of NPWT on bacterial bioburden. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence and drafting of the recommendations by a global expert panel. Evidence and recommendations were graded according to the Scottish Intercollegiate Guidelines Network (SIGN) classification system. In general, there is relatively weak evidence on which to base recommendations for any one NPWT treatment variable over another. Overall, 14 recommendations were developed: five for the choice of wound filler and wound contact layer, four for choice of pressure setting and five for use of NPWT in infected wounds. With respect to bioburden, evidence suggests that reduction of bacteria in wounds is not a major mode of action of NPWT.

Evidence-based recommendations for the use of Negative Pressure Wound Therapy in traumatic wounds and reconstructive surgery: steps towards an international consensus.

Negative pressure wound therapy (NPWT) has become widely adopted over the last 15 years and over 1000 peer reviewed publications are available describing its use. Despite this, there remains uncertainty regarding several aspects of usage. In order to respond to this gap a global expert panel was convened to develop evidence-based recommendations describing the use of NPWT. In this paper the results of the study of evidence in traumatic wounds (including soft tissue defects, open fractures and burns) and reconstructive procedures (including flaps and grafts) are reported. Evidence-based recommendations were obtained by a systematic review of the literature, grading of evidence, drafting of the recommendations by a global expert panel, followed by a formal consultative consensus development program in which 422 independent healthcare professionals were able to agree or disagree with the recommendations. The criteria for agreement were set at 80% approval. Evidence and recommendations were graded according to the SIGN (Scottish Intercollegiate Guidelines Network) classification system. Twelve recommendations were developed in total; 4 for soft tissue trauma and open fracture injuries, 1 for burn injuries, 3 for flaps and 4 for skin grafts. The present evidence base is strongest for the use of NPWT on skin grafts and weakest as a primary treatment for burns. In the consultative process, 11/12 of the proposed recommendations reached the 80% agreement threshold. The development of evidence-based recommendations for NPWT with direct validation from a large group of practicing clinicians offers a broader basis for consensus than work by an expert panel alone.

[Coronary bypass grafting after failed percutaneous angioplasty (PTCA)]. / Pilne pomostowanie tetnic wiencowych po powiklanych angioplastykach wiencowych (PTCA).

Between January 1991 and September 1997, in the Cardiovascular Surgery Department of the Institute of Cardiology of Jagiellonian University Medical School, 23 patients underwent emergency CABG due to acute myocardial ischaemia in result of failed PTCA. Over the same period of time invasive cardiologists performed 1883 PTCAs out of which 23 (1.2%) were emergency cardiosurgical procedures, and in 38 patients, stents were implanted in the damaged coronary arteries. The patients' age ranged from 37 to 67 years (median 52.2). In all patients good left ventricular function was preserved, median ejection fraction being 64%. Two patients required IABP to support left ventricular function. 1-4 bypass grafts were implanted (median 1.9 per patient). In one patient, internal mammary artery was collected and then implanted into anterior interventricular branch. The most common complication was myocardial infarction which occurred in 12 patients (52%). In ten patients low output was observed postoperatively. One operated patient (a female died (4.3%). The mean time of hospitalization was 11 days. Emergency myocardial revascularisation procedures performed after failed PTCA, bring higher risk of mortality and dangerous postoperative complications.

[Surgical treatment of coronary artery disease in the opinion of "first-contact" physicians and their patients]. / Leczenie chirurgiczne choroby wiencowej w opinii lekarzy pierwszego kontaktu i ich pacjentów.

A group of physicians working at regional dispensaries in Cracow and its surroundings, and their patients were inquired about surgical treatment of coronary artery disease using specially prepared questionnaires. In comparison with a similar study, performed in 1987, a significant improvement of acquirement was stated in both groups. It may be connected with development of coronary surgery during the last years. However, the respondents emphasized a deficiency of easy accessible medical information on this topic.