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Javier Segovia

Publications and source records attributed to Javier Segovia.

14 recordsLinked to original sources

A review of critical periods for opportunistic infection in the new transplantation era.

BACKGROUND: The risk of opportunistic infection (OI) is considered to be maximum during the first six months after solid organ transplantation. The aim of this study was to know the incidence and risk factors for OI in the late period (>6 months) compared with the early period (<6 months) after solid organ transplantation. METHODS: We used the online database of the Spanish Network of Infection in Transplantation (RESITRA), which prospectively analyzed 2,702 solid organ transplantation recipients from August 2003 to February 2005. Univariate and multivariate analyses were performed to calculate the risk factors associated with the development of late OI. RESULTS: A total of 131 patients (6%) developed 176 infectious episodes in the late period. Although the incidence of infection and cytomegalovirus disease (0.4 per 1000 transplant days and 0.05 per 1000 transplant days, respectively) was lower than in the early period (3.5 per 1000 transplant days and 0.8 per 1000 transplant days; P<0.0001), the incidence of other OIs was similar in both periods (0.05 per 1000 transplant days versus 0.03 per 1000 transplant-days, P=0.5). Patients with the higher risk for developing late OI were those receiving early cytomegalovirus prophylaxis, patients who developed two or more episodes of acute rejection during the early period, patients with recurrent bacterial infection during the early period, patients with renal failure requiring dialysis, and patients with chronic graft malfunction. CONCLUSIONS: Our data suggest that in some high-risk patients, the critical period of risk for OI must be expanded beyond the first six months after transplant.

Adult↗

Similar efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS, myfortic) compared with mycophenolate mofetil (MMF) in de novo heart transplant recipients: results of a 12-month, single-blind, randomized, parallel-group, multicenter study.

BACKGROUND: Enteric-coated mycophenolate sodium (EC-MPS, myfortic) is an advanced formulation that delays the release of mycophenolic acid (MPA). Its efficacy and safety has been proven in several clinical trials in renal transplantation. METHODS: In a single-blind, multicenter trial, a total of 154 de novo heart transplant patients were randomized to either EC-MPS 1,080 mg twice daily or mycophenolate mofetil (MMF) 1,500 mg twice daily. Eligible patients included men or women aged 18 to 65 years, undergoing primary heart transplantation, who were treated with cyclosporine microemulsion and corticosteroids as basic immunosuppression. The primary study objective was to investigate the incidence of biopsy-proven and treated acute rejection, graft loss or death (defined as treatment failure) for EC-MPS vs MMF during the first 6 months of treatment in de novo heart transplant recipients. Secondary objectives included assessment of the overall safety and tolerability of EC-MPS vs MMF in the study population. RESULTS: The primary efficacy variable, treatment failure at 6 months, was similar for both treatments: 52.6% for EC-MPS and 57.9% for MMF (2-sided 95% confidence interval [CI]: -21.0% to 10.4%). At 12 months, treatment failure was 57.7% for EC-MPS and 60.5% for MMF (2-sided 95% CI: -18.4 to 12.7), and death and graft loss rate was 5.1% vs 9.2% for EC-MPS and MMF at 12 months, respectively (2-sided 95% CI: -12.2 to 4.1). The overall safety profile was similar for both groups. Significantly more patients on MMF had two or more study medication dose reductions during the treatment period. CONCLUSIONS: These 6- and 12-month results show that EC-MPS is therapeutically similar to MMF in de novo heart transplant recipients and has a comparable safety profile.

Adolescent↗

A randomized multicenter comparison of basiliximab and muromonab (OKT3) in heart transplantation: SIMCOR study.

BACKGROUND: Antilymphocytic antibodies have been long used for the prevention of acute rejection early after heart transplantation (HTx), but their adverse effects have limited their widespread use. Our aim was to evaluate the safety, tolerability, and efficacy of the novel anti-CD25 antibody basiliximab (BAS) compared with muromonab (OKT3). PATIENTS AND METHODS: In this multicenter study, 99 patients were randomly assigned to receive either BAS or OKT3 in the early post-HTx period. The primary endpoint was safety and tolerability. Specific safety variables were predefined for a better comparison of adverse effects. Secondary endpoints concerning anti-rejection efficacy were also evaluated. RESULTS: No adverse events related to study medication were found in the BAS group, whereas 23 were observed among patients receiving OKT3 (P<0.0001). The proportion of patients with predefined adverse events day 4 post-HTx was much higher with OKT3 than with BAS (43% vs. 4%; P<0.0001). Fever, acute pulmonary edema, hypotension, and other complications accounted for most of the difference. At 1-year follow-up, biopsy-proven rejection episodes grade>or=3A had occurred in 39.6% of BAS patients versus 40.4% of OKT3 patients (P=0.87). There were no differences in terms of severity and timing of acute rejection episodes. The number of infectious episodes, complications not related to study medication, and actuarial survival were similar in both groups. CONCLUSION: In this HTx study, induction therapy with BAS was safer and better tolerated than OKT3, without significant differences in efficacy outcomes.

Adolescent↗

Treatment of allograft vasculopathy in heart transplantation.

Cardiac allograft vasculopathy remains one of the main causes of morbidity and mortality after heart transplantation, although its impact is becoming somewhat smaller as prophylactic measures are implemented. Advances in the understanding of the molecular and cellular mechanisms involved in the genesis and development of cardiac allograft vasculopathy are opening ways for new diagnostic and therapeutic strategies. Successful prophylaxis of the early stages of the disease has been demonstrated with the use of newer immunosuppressive agents, such as sirolimus and everolimus, that will probably be included in future protocols. For most patients with established cardiac allograft vasculopathy, currently available revascularisation methods and retransplantation are not appropriate options. Antiproliferative agents could provide significant improvement in terms of symptom relief and prognosis, but their definite value must be proven in well-designed trials.

Coronary Artery Disease↗

[Ischemia-reperfusion injury during experimental heart transplantation. Evaluation of trimetazidine's cytoprotective effect].

INTRODUCTION AND OBJECTIVES: The objectives of this study were to analyze the ischemia-reperfusion injury due to free radicals that occurs during heart transplantation and to determine the potential cytoprotective effect of trimetazidine. MATERIAL AND METHOD: A total of 21 orthotopic heart transplantations were performed in pigs. We divided the experimental animals into 2 groups: in group A (n=11),standard myocardial protection was used; in group B (n=10), trimetazidine was added to the cardioplegic solution used to protect the donor heart and to the solution administered to the recipient prior to release of the aortic clamp (trimetazidine, 10(-5) mol/L), and recipients were pretreated with trimetazidine, 2.5 mg/kg. Blood samples were taken from the recipients coronary sinus at three times: at baseline, during ischemia, and during reperfusion. We measured the levels of malondialdehyde, a marker of lipid peroxidation, and of several antioxidants: glutathione peroxidase, glutathione reductase, superoxide dismutase, alpha-tocopherol, and retinol. The total antioxidant status was also determined. RESULTS: Malondialdehyde production and enzymatic antioxidant activity rose during ischemia and reperfusion, while the retinol level decreased. The increases in malondialdehyde level and glutathione peroxidase activity that occurred between baseline and reperfusion were significantly higher in group A. CONCLUSIONS. The degree of lipid peroxidation and the level of activity of intracellular antioxidant mechanisms increased progressively throughout transplantation. Trimetazidine had a cytoprotective effect. It ameliorated free radical-induced reperfusion injury and modified the response pattern of several defense mechanisms.

Animals↗

Re-innervation after heart transplantation: a multidisciplinary study.

BACKGROUND: Several authors have demonstrated the existence and implications of re-innervation in the transplanted heart. Our aim was to study this phenomenon using 3 different techniques and to analyze the correlation among them. METHODS: The study population consisted of 55 patients who had undergone heart transplantation 0.5 to 160 months earlier. We used a control group of 10 healthy individuals for comparison. To detect re-innervation, we used 1) planar and single photon emission computed tomography (SPECT) scintigraphic imaging of cardiac sympathetic activity with 123I-metaiodobenzylguanidine (MIBG), 2) analysis of heart-rate variability based on 24-hour Holter recordings; and 3) immunohistochemical study of endomyocardial biopsy specimens with anti-S100 antibody. RESULTS: The SPECT images showed evidence of sympathetic re-innervation in 17 patients (31%), predominantly in the anterior and in the septal regions of the left ventricle. Sympathetic activity increased during the post-transplant time course (r = 0.32; p = 0.017), although it did not reach normal values. We found a correlation between the low-frequency component of heart-rate variability (a marker of sympathetic activity) and the degree of MIBG uptake according to scintigraphy (r = 0.32; p = 0.015). Immunostaining study demonstrated the existence of nerve fibers in 36 patients (65%) who had greater values of heart-rate variability parameters reflecting parasympathetic activity. CONCLUSIONS: The 3 techniques evidenced re-innervation after heart transplantation. A correlation exists between sympathetic activity detected using MIBG scintigraphy and analysis of heart-rate variability. Patients in whom endomyocardial biopsy specimen reveals the presence of nerve fibers show more parasympathetic activity in the heart-rate variability analysis.

3-Iodobenzylguanidine↗