Incidence of thrombotic stent occlusion during the first three months after sirolimus-eluting stent implantation in 500 consecutive patients

Sirolimus-eluting stents have been used in our institution for all percutaneous interventions, without clinical or anatomic exclusion criteria, as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital registry. We analyzed the incidence of (sub)acute stent thrombosis after sirolimus-eluting stent implantation in an unselected population of 510 consecutive patients. At 3-month follow-up, (sub)acute stent thrombosis was diagnosed in 2 patients (0.4%) 6 hours and 11 days after the procedure, respectively. These cases occurred in diabetic women with complex coronary lesions. Intravascular ultrasound examination showed inadequate stent expansion and uncovered distal dissection as possible mechanical explanations for the thrombosis.     

Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy)

Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.     

Fluvastatin reduces the 4-year cardiac risk in patients with multivessel disease

BACKGROUND: To evaluate the impact of the extent of coronary disease (single- or multivessel) and of fluvastatin treatment on the incidence of long-term cardiac atherosclerotic complications in the Lescol Intervention Prevention Study (LIPS). METHODS: A total of 1063 patients with single-vessel disease and 614 patients with multivessel disease were randomized to receive fluvastatin (40 mg bid) or placebo for at least 3 years following a first successful percutaneous coronary intervention. The incidence of cardiac atherosclerotic events (cardiac death, non-fatal myocardial infarction, and coronary re-interventions not related to restenosis) was evaluated. RESULTS: Patients with multivessel disease tended to be older and presented a higher prevalence of associated risk factors and cardiovascular antecedents. The presence of multivessel disease markedly increased the risk of cardiac atherosclerotic events compared with single-vessel disease among patients allocated to placebo (RR 1.67 [95% CI: 1.24-2.25]; p<0.001). In patients treated with fluvastatin, however, no significant differences in long-term outcomes were observed between patients with multivessel disease and patients single-vessel disease (RR 1.28 [95% CI: 0.90-1.81]; p=0.2). CONCLUSIONS: Multivessel coronary disease impaired the 4-year outcomes after percutaneous intervention. However, the hazardous effect of multivessel disease was significantly reduced by long-term fluvastatin treatment.     

Inhibition of indoleamine 2,3-dioxygenase in mixed lymphocyte reaction affects glucose influx and enzymes involved in aerobic glycolysis and glutaminolysis in alloreactive T-cells

Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity. T-cell proliferation and differentiation to effector cells require increased glucose consumption, aerobic glycolysis and glutaminolysis. The effect of IDO on the above metabolic pathways was evaluated in alloreactive T-cells. Mixed lymphocyte reaction (MLR) in the presence or not of the IDO inhibitor, 1-methyl-dl-tryptophan (1-MT), was used. In MLRs, 1-MT decreased tryptophan consumption, increased cell proliferation, glucose influx and lactate production, whereas it decreased tricarboxylic acid cycle activity. In T-cells, from the two pathways that could sense tryptophan depletion, i.e. general control nonrepressed 2 (GCN2) kinase and mammalian target of rapamycin complex 1, 1-MT reduced only the activity of the GCN2 kinase. Additionally 1-MT treatment of MLRs altered the expression and/or the phosphorylation state of glucose transporter-1 and of key enzymes involved in glucose metabolism and glutaminolysis in alloreactive T-cells in a way that favors glucose influx, aerobic glycolysis and glutaminolysis. Thus in alloreactive T-cells, IDO through activation of the GCN2 kinase, decreases glucose influx and alters key enzymes involved in metabolism, decreasing aerobic glycolysis and glutaminolysis. Acting in such a way, IDO could be considered as a constraining factor for alloreactive T-cell proliferation and differentiation to effector T-cell subtypes.     

Diuretic-induced hyponatremia and osteoporotic fractures in patients admitted to the emergency department

Objective

Hyponatremia is a complication of diuretic treatment and has been recently identified as a novel factor associated with osteoporosis and fractures. The impact of diuretic-associated electrolyte disorders on osteoporotic fractures (OF) has rarely been studied systematically.

Design and setting

We conducted a study in patients presenting to the emergency department at the University Hospital Bern. In this retrospective case series analysis of prospectively gathered data, over a 2-year period we identified 10,823 adult (≥50 years) outpatients with a measured baseline serum sodium, at admission to the hospital. OF patients were compared to a control group without fractures using standard statistical methods.

Results

Four hundred and eighty (5%) patients had 547 OF. The OF group had a higher mean age (73 vs. 68 years, p < 0.0001), smaller proportion of men (37% vs. 58%, p < 0.0001), higher hospitalisation rate (83% vs. 62%, p < 0.0001) and longer hospital stay (8 vs. 6 days, p < 0.0001). Any diuretic agent (p < 0.0001), loop diurietics (p = 0.02), spironolactone (p = 0.02) and amiloride (p < 0.01) were used significantly more in OF patients, but not thiazides (p = 0.68). The prevalence of hyponatremia increased significantly (p < 0.0001) with the number of diuretics taken. Advanced age (odds ratio [OR] 1.04, p < 0.0001), hyponatremia (OR 1.46, p = 0.011) higher serum creatinine (OR 1.53, p = 0.0001), furosemide use alone (OR 1.40, p = 0.01) and co-treatment with amiloride (OR 2.22, p = 0.02) were associated with a higher risk for OF.

Conclusions

This study highlights the clinical association of hyponatremia during the use of certain diuretics (i.e. furosemide or in combination, i.e. amiloride) with an increased risk of osteoporosis associated fractures. Although evidence-based data is currently lacking a pragmatic approach concerning hyponatremia monitoring and correction appears reasonable in selected groups of patients.     

Effects of ankle–foot braces on medial gastrocnemius morphometrics and gait in children with cerebral palsy

PurposeIn children with cerebral palsy (CP), braces are used to counteract progressive joint and muscle contracture and improve function. We examined the effects of positional ankle–foot braces on contracture of the medial gastrocnemius (MG) and gait in children with CP while referencing to typically developing children.MethodsSeventeen independently ambulant children with CP and calf muscle contracture (age 10.4 ± 3.0y) and 17 untreated typically developing peers (age 9.5 ± 2.6y) participated. Children with CP were analysed before and 16 ± 4 weeks after ankle–foot bracing. MG muscle belly length and thickness, tendon and fascicle length, as well as their extensibility were captured by 2D ultrasound and 3D motion capturing during passive, manually applied stretches. In addition, 3D gait analysis was conducted.ResultsPrior to bracing, the MG muscle–tendon unit in children with CP was 22 % less extensible. At matched amounts of muscle–tendon unit stretch, the muscle belly and fascicles in CP were 7 % and 14 % shorter while the tendon was 11 % longer. Spastic fascicles displayed 32 % less extensibility than controls. Brace wear increased passive dorsiflexion primarily with the knees flexed. During gait, children walked faster and foot lift in swing improved. MG muscle belly and tendon length showed little change, but fascicles further shortened (−11 %) and muscle thickness (−8 %) decreased.ConclusionsUse of ankle–foot braces improves function but may lead to a loss of sarcomeres in series, which could explain the shortened fascicles. To potentially induce gastrocnemius muscle growth, braces may also need to extend the knee or complementary training may be necessary to offset the immobilizing effects of braces.     

Impact of baseline renal function on mortality after percutaneous coronary intervention with sirolimus-eluting stents or bare metal stents

Renal impairment is an important predictor of mortality after percutaneous coronary intervention and may increase the restenosis rate. However, the relation between restenosis and the risk of death in patients who have renal impairment remains unclear. We evaluated the incidences of repeat revascularization and mortality in patients who had renal impairment and those who did not and who received sirolimus-eluting stents or bare stents. A total of 1,080 consecutive patients treated for 1 year had available data to calculate baseline creatinine clearance. Patients received bare stents (first 6 months, n = 543) or sirolimus-eluting stents (last 6 months, n = 537) and were grouped according to the presence or absence of renal impairment (creatinine clearance <60 ml/min). Patients who had renal impairment had a higher mortality rate at 1 year (7.6% vs 2.5%, hazard ratio 3.14, 95% confidence interval 1.68 to 5.88, p <0.01), with no differences in mortality between patients who received bare stents and those who received sirolimus-eluting stents (hazard ratio 0.91, 95% confidence interval 0.49 to 1.68, p = 0.8). The incidence of target vessel revascularization decreased significantly in patients who were treated with sirolimus-eluting stents and did not have renal impairment (hazard ratio 0.59, 95% confidence interval 0.39 to 0.90, p = 0.01) and in those who had decreased renal function (hazard ratio 0.37, 95% confidence interval 0.15 to 0.90, p = 0.03). Thus, sirolimus-eluting stents compared with conventional stents decreased clinical restenosis in patients who had renal impairment. However, this benefit was not paralleled by a decrease in the risk of death in this population. It seems unlikely that restenosis could be a contributing factor that influenced the increased mortality of patients who had impaired renal function.     

Inferior mesenteric arteriovenous fistula: Case report and world-literature review

Arteriovenous fistulas between the inferior mesenteric artery and vein are rare, with only 26 primary and secondary cases described in the literature. Secondary fistulas occur following operations of the left hemicolon and manifest as abdominal pain, abdominal mass, gastrointestinal bleeding, colonic ischemia and portal hypertension. Symptom intensities are flow-dependent, and can range from minimal symptoms to severe heart failure due to left to right shunt. Diagnosis is usually established by radiological or intraoperative examination. Treatment options include embolization and/or surgical resection. Therapeutic decisions should be adapted to the unique characteristics of the fistula on an individual basis. A new case of a primary arteriovenous fistula is described and discussed along with a complete review of the literature. The patient in this report presented with signs and symptoms of colonic ischemia without portal hypertension. The optimal treatment for this patient required a combination of embolization and surgical operation. The characteristics of these rare inferior mesenteric arteriovenous fistulas are examined and some considerations concerning diagnostic and therapeutic strategies that should be followed are presented.     

Sirolimus-eluting stents for the treatment of in-stent restenosis

The treatment of in-stent restenosis (ISR) remains one of the major therapeutic challenge for the interventional cardiologist. All percutaneous mechanical approaches have shown disappointing results and the recurrence of ISR was reported to be unacceptably high. Currently, the only proven effective therapy available for the treatment of ISR, at least for the most complex lesions, is vascular brachytherapy. However, this therapy is limited by potential side effects and logistic requirements. The introduction of drug-eluting stents, that carry and release antiproliferative agents, have demonstrated to virtually eliminate ISR in de novo lesions. In the light of this promising results for de novo lesions, sirolimus-eluting stents (SES) were recently used for the treatment of ISR in 2 pilot studies. In Sao Paulo, 25 patients with ISR treated with SES (1.4 stent per lesion) presented 4% ISR and no clinical events at 1 year. In Rotterdam, 16 patients with severe ISR were treated with 26 SES. Intravascular ultrasound evaluation demonstrated successful inhibition of neointimal hyperplasia with 1.1% volume obstruction of the stent, which is similar to the Sao Paulo series (0.8%). At 9 months clinical follow-up, 3 patients had experienced 4 major adverse cardiac events (2 deaths and 1 acute myocardial infarction necessitating repeat target vessel angioplasty). With the results presently available, SES implantation can be considered safe and potentially efficacious in the treatment of ISR. However, multicenter, long-term randomized studies are warranted in order to evaluate this new treatment concept.     

Differences between measured and resultant joint moments during voluntary and artificially elicited isometric knee extension contractions

OBJECTIVE: Examine two hypotheses: (a) during isometric knee extension contractions the moment measured at the dynamometer is different from the resultant moment in the same plane around the knee joint and (b) during isometric contractions, at the same given resultant moment the knee angle while loading is different from the knee angle while unloading. DESIGN: Comparative study in which the geometrical and the kinetic differences between joint and dynamometer were determined. BACKGROUND: It is usually assumed that the moment measured by the dynamometer is equivalent to the resultant joint moment. The non-rigidity of the dynamometer-leg system can influence the equivalence of these two moments. METHOD: Twenty seven subjects performed isometric maximal knee extension contractions and contractions induced by electrostimulation on a dynamometer. The kinematics of the leg were recorded using 8 cameras (120 Hz). RESULTS: The resultant moment at the knee joint and the moment measured by the dynamometer are different. During a knee extension effort the knee angle changes significantly. At identical resultant knee joint moments the knee angles are different when comparing the loading and the unloading phases. CONCLUSIONS: The differences between the measured and the resultant joint moments might influence the estimation of parameters as: muscle forces, moment-angle relationship and strain and hysteresis of tendons and aponeuroses. RELEVANCE: Torque dynamometers have been often used to estimate muscle forces, to examine neuromuscular processes and to determine the mechanical properties of tendons and aponeuroses.