A randomized, double-blind, single-dose study to assess bioequivalence of MB02 biosimilar after manufacturing iteration and reference bevacizumab.

To investigate and compare the pharmacokinetic (PK) profiles of MB02 products, before and after optimizing the manufacturing process, and reference bevacizumab to establish bioequivalence between them. In this randomized, double-blind, single dose, parallel study, 114 healthy male volunteers were randomized 1:1:1 to receive a 1 mg/kg intravenous dose of MB02-SP, MB02-DM, or US-bevacizumab. The follow-up period was 100 days. PK similarity between them was determined using the standard bioequivalence criteria (0.80-1.25) for the area under the serum concentration-time curve from time 0 extrapolated to infinity and the maximum observed serum concentration. Study results showed that the PK profiles of bevacizumab were similar. Statistical analysis demonstrated that for each pairwise comparison there were no differences. The 90% CIs for the ratios of geometric least squares means were fully contained within the predefined similarity acceptance limits and ranged from 0.899 to 1.12 for area under the curve and from 0.887 to 1.11 for maximum concentration. A total of 159 adverse events were reported by 76 subjects who received the study drug. The majority (90.6%) of the reported adverse events were grade 1 in severity, with 9.4% as grade 2 in severity. None were considered as grade 3, 4, or 5. Treatment-induced anti-drug antibodies incidence was 21.6%, 33.3%, and 23.7% for the treatment of MB02-SP, MB02-DM, and US-bevacizumab, respectively. No subjects showed treatment-induced neutralizing anti-drug antibodies. This study demonstrates the PK, safety, and immunogenicity similarity and bioequivalence of MB02-SP, MB02-DM, and the reference product bevacizumab.

[Nocardia nova brain abscess]. / Absceso cerebral por Nocardia nova.

Nocardia nova is an uncommon pathogen for human beings. We describe an immunocompetent patient who acquired multiple cerebral abscesses. A surgical drainage yielded a sulpha-trimethoprim susceptible N. nova strain. The patient recovered uneventfully after a prolonged treatment with sulpha-trimethoprim.

[Analysis of the number of patients needed to treat by coronary revascularisation in relation to the presence of myocardial viability in gated SPECT images: a prospective cohort study from a nuclear cardiology unit]. / Análisis del número de pacientes que es necesario tratar mediante revascularización coronaria en relación con la presencia de viabilidad miocárdica en las imágenes de la gated-SPECT: estudio de cohorte prospectivo desde una unidad de cardiología nuclear.

OBJECTIVE: To evaluate the number of patients needed to treat (NNT) to assess the magnitude of benefit of coronary revascularisation (CR) in patients with ischaemic cardiomyopathy (IC) in relation to the presence or absence of myocardial viability in myocardial perfusion gated-SPECT (single photon emission computed tomography) images. METHOD: We studied 198 consecutive patients with IC using rest gated-SPECT with technetium-based agents. The cardiac mortality was analysed in four groups: viable with CR (n = 50), viable with medical treatment (MT) (n = 90), non-viable with CR (n = 18), and non-viable with medical treatment (n = 40). RESULTS: During 2.3 +/- 1.2 years of follow-up, the cardiac mortality rate in patients with scintigraphic viability criteria undergoing revascularisation was 5.9/100 patients/year and 12.9/100 patients/year in those who received medical treatment. In patients without viability who underwent revascularisation, the cardiac mortality rate was 6.2/100 patients/year and in those who received MT it was 1.9/100 patients/year. In patients with myocardial viability the NNT was 4, while in patients without myocardial viability, the NNT was 24. CONCLUSIONS: In patients with scintigraphic viability criteria, the NNT to obtain one survival with CR was 6 times lower with respect to patients without viability, with lower cost and mortality.

Glomerular pathology in surviving pigs experimentally infected with African swine fever virus.

Twelve miniature pigs were inoculated with an attenuated African swine fever virus to study glomerular involvement in surviving pigs. In acute phase, kidneys were severely affected and displayed a glomerular capillary thrombosis with fibrin deposition in vascular lumen, detected by immunofluorescence. Fibrin-positive deposits were progressively cleared between one to three months after infection in surviving pigs. The histological picture in kidneys of surviving pigs, up to one post-infection year, showed a focal and segmental glomerulonephritis with hyalinosis, and IgM and C3 deposition was detected by immunofluorescence. Its pathogeny as an evolutive stage of acute glomerular injury is pointed out.

Long-term patency of polytetrafluoroethylene vascular grafts in coronary artery surgery.

Patients undergoing coronary revascularization may not have suitable autologous vessels for coronary artery grafting and therefore may need vascular prostheses. We present a case report of a patient undergoing coronary artery bypass with polytetrafluoroethylene vascular grafts. Follow-up has been 53 months, and the grafts remain patent.

The Spanish Monostrut Study Group: a ten-year experience with 8,599 implants.

BACKGROUND: The Monostrut valve is a pyrolytic carbon, tilting-disc prosthesis with no welds. After the first implantation in Spain in May 1983, the Spanish Monostrut Study Group was established to evaluate prospectively the performance of the valve using uniform protocols. METHODS: During a 10-year period, 8,599 Monostrut valves were implanted in 7,317 patients in 22 centers. Mean age was 53.3 +/- 11 years. Of the total group, 3,229 underwent aortic valve replacement, 2,806 had mitral valve replacement, and 1,282 had double valve replacement. Follow-up was 96% complete, with a mean period of 4.3 years and a total of 29,155 patient-years. RESULTS: The operative mortality rate was 7.2%. The 10-year probability of freedom from valve-related complications and linearized rates (event/100 patient-years in parentheses) were as follows: structural deterioration, 100% (0); nonstructural dysfunction, 96% +/- 0.5% (0.51); thromboembolism, 82.9% +/- 1.5% (1.32); anticoagulant-related hemorrhage, 87.6% +/- 1.4% (0.98); and prosthetic valve endocarditis, 96.1% +/- 0.5% (0.48). There were five obstructive valve thromboses (0.017/100 patient-years). Actuarial freedom from reoperation was 95% +/- 0.5% at 10 years. Actuarial freedom from all valve-related morbidity was 70.2% +/- 1.6%; freedom from all valve-related morbidity and mortality (including operative and sudden deaths) was 62.6% +/- 2% (70.1% +/- 2% for aortic valve replacement, 56.9% +/- 2% for mitral valve replacement, and 59.8% +/- 3% for double valve replacement; p < 0.0001). Clinically, 5,988 patients (94%) are in New York Heart Association class I-II. CONCLUSIONS: The Monostrut valve has shown no structural failures and a low rate of valve-related complications over a 10-year period in a large patient population.

[Coronary endarterectomy]. / Endarterectomía coronaria.

The technique of coronary endarterectomy, in coronary artery surgery, has been controversial and alternatively indicated or contraindicated by different authors. In this paper coronary endarterectomy is reviewed, including its definition, history and development of different techniques. Early and late results of the main papers in the literature are commented on as well as our results. The surgical technique of endarterectomy in the different coronary artery territories is described with the primary indications and contraindications. Coronary endarterectomy is a valid and well established technique that can provide possibilities of revascularization in patients with extended and diffused coronary artery obstructions, which are unable to be treated with conventional coronary artery bypass grafts. Operative mortality and morbidity are slightly higher, but long-term results, as far as survival and functional class are concerned, are similar to standard coronary artery surgical procedures.

[Primary cardiac hemangioma. A case report and review of the literature]. / Hemangioma cardíaco primario. Presentación de un caso y revisión de la literatura.

A 26-years-old woman, without symptoms, was diagnosed of cardiac tumor by means of two-dimensional echocardiography, magnetic resonance imaging and angiocardiography. The tumor was removed underwent open-heart operation and cardiopulmonary bypass. Histologic study was suggestive of a capillary hemangioma. We present our experience with this case and a review of the literature.

Prognosis of left-sided infective endocarditis in patients transferred to a tertiary-care hospital--prospective analysis of referral bias and influence of inadequate antimicrobial treatment.

The aims of this study were to compare the characteristics of adult patients with left-sided infective endocarditis (LSIE) diagnosed and treated in a tertiary-care hospital with those of patients referred from a second-level community hospital, and to establish the accuracy of diagnosis and adequacy of treatment in referred patients and the influence of this factor on outcome. A prospective observational cohort study was conducted at Hospital Universitari Vall d'Hebron, a 1000-bed teaching hospital in Barcelona (Spain) and a referral centre for cardiac surgery. One hundred and fourteen of 337 (34%) episodes of LSIE treated in our hospital occurred in transferred patients. As compared with patients diagnosed in our hospital, transferred patients acquired LSIE within the healthcare system less often (16.7% vs. 38.1%, p <0.001), were in better health (Charlson index 3 (interquartile range (IQR)) 1-4) vs. 4 (IQR 2-6), p <0.001), had more complications (94.7% vs. 78.9%, p <0.001), underwent more operations (69.3% vs. 22.1%, p <0.001), and experienced similar mortality (22.8% vs. 31.4%, p 0.100). Only 52 of 114 (45.6%) referred patients received an antimicrobial regimen included in the American, European or Spanish guidelines at the hospital of origin. After adjustment for congestive heart failure and staphylococcal infection in multivariate logistic regression, inadequate or no antimicrobial treatment at origin was a risk factor for in-hospital mortality (OR 3.3, 95% CI 1.1-10.0, p 0.030). Errors in the initial antimicrobial treatment prescribed for LSIE are associated with greater mortality.

Enoxaparin as bridging anticoagulant treatment in cardiac surgery.

OBJECTIVE: To assess enoxaparin as bridging anticoagulant treatment in cardiac surgery. METHODS: Prospective registry of those patients who underwent cardiac surgery in our centre between December 2003 and June 2004 and required long-term anticoagulation. Subcutaneous enoxaparin was used as bridging anticoagulant treatment according to a pre-established protocol. The global thromboembolic risk was carefully assessed in all patients. All patients were followed up for 3 months. RESULTS: Of 140 patients who were included (mean (SD) age 66 (11); 49% female), 51 were already receiving long-term acenocumarol treatment before the index intervention. 50% of the patients were at high or very high risk for thromboembolic events in the postoperative period. The mean (SD) number of days between surgery and the first dose of anticoagulant was 2.01 (7) for acenocumarol and 1 (1.01) for enoxaparin. The mean (SD) daily dose of enoxaparin was 1.1 (0.27) mg/kg. Six thromboembolic events (4.3%; 95% CI 1.6 to 9.1) occurred, but only four of them were plausibly related to enoxaparin (2.9%; 95% CI 0.8 to 7.1). Six major haemorrhagic events (4.3%; 95% CI 1.6 to 9.1) occurred, but only three were plausibly related to enoxaparin (2.1%; 95% CI 0.4 to 6.1). CONCLUSIONS: These findings show a reasonable rate of adverse events using enoxaparin as bridging anticoagulant treatment in cardiac surgery. Randomised studies are necessary to evaluate the real efficacy and safety of enoxaparin as bridging anticoagulant treatment in cardiac surgery.

Clinical performance of the omniscience prosthetic heart valve with Dacron sewing ring.

The Omniscience prosthetic heart valve has been clinically evaluated in 44 patients operated on between January and July, 1981. There were 23 aortic valve replacements (AVR), 18 mitral valve replacements (MVR) and 3 double valve replacements (DVR). Mean age was 48 +/- 11 years. Preoperatively, 61% patients were in New York Heart Association (NYHA) functional class IV, 36% in class III and 2% in class II. The hospital mortality rate was 4.5%. Actuarial freedom from thromboembolic events was 97.4 +/- 2.6% (3 1/2 years of follow-up). Postoperatively, 93% of the patients were in NYHA class I and 7% in class II. There were 7 cases of periprosthetic leak requiring reoperation (6 AVR, 1 MVR) for an overall incidence of 6.3% per patient year. In all these cases the causative factor was considered to be the Dacron sewing ring. All patients survived the reoperation. The actuarial survival rate was 93.9 +/- 5.9% for AVR and 93.7 +/- 6.1% for MVR. These data would suggest that the Omniscience prosthesis represents an acceptable device for heart valve replacement, except for the high incidence of periprosthetic leakage, related to the Dacron sewing ring. Recent modification of the valve-construction including a Teflon sewing ring may avoid the relatively high rates of periprosthetic leakage following implantation of this mechanical valve.