José M Ponseti

Publications (8)18.88 Total impact

• Article: A comparison of long-term post-thymectomy outcome of anti-AChR-positive, anti-AChR-negative and anti-MuSK-positive patients with non-thymomatous myasthenia gravis.

  José M Ponseti, Norma Caritg, Josep Gamez, Manuel López-Cano, Ramón Vilallonga, Manuel Armengol
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  ABSTRACT: A single-centre, non-randomized, non-controlled study was designed to compare the long-term post-thymectomy clinical outcome in anti-AChR-positive, anti-AChR-negative and anti-MuSK-positive patients with non-thymomatous myasthenia gravis (MG). A total of 331 consecutive patients with seropositive MG, 55 with seronegative MG and 10 with anti-MuSK-positive MG underwent extended transsternal thymectomy (T-3b according to Myasthenia Gravis Foundation of America). The primary endpoint was to assess differences in the rate of complete stable remission (CSR) in patients with and without anti-AChR and anti-MuSK antibodies. The mean follow-up was 218.3 (SD 128.1) months in the seropositive MG group, 149.8 (SD 131.1) in the seronegative group and 169.9 (SD 116) in the anti-MuSK-positive group. In the seropositive MG group, the probability of obtaining CSR at 5 years post-thymectomy was 51.1% for the seropositive group compared with 40 for the seronegative group (p = 0.05) and 20 for the anti-MuSK-positive group (p = 0.03). Differences between the seronegative and anti-MuSK-positive groups were not observed. The estimated median follow-up to obtain a CSR was 17.8 months (95% confidence interval [CI] 15.7 - 19.8 months) in seropositive MG patients, 22.1 (95% CI 16.7 - 27.4 months) in seronegative MG patients and 20.6 (95% CI 13.3 - 27.9 months) in anti-MuSK-positive MG patients (long-rank test, p = 0.07). Long-term post- thymectomy clinical outcome was better in patients with conventional anti-AChR antibodies than in those with seronegative disease. In seronegative anti-MuSK-positive MG, thymectomy seems to be less effective than in anti-MuSK-negative MG but this study cannot answer the question of whether thymectomy should be undertaken in anti-MuSK-positive patients.
  Expert opinion on biological therapy 02/2009; 9(1):1-8. · 3.22 Impact Factor
• Article: Influence of ectopic thymic tissue on clinical outcome following extended thymectomy in generalized seropositive nonthymomatous myasthenia gravis.

  José M Ponseti, Josep Gamez, Ramón Vilallonga, Carmen Ruiz, Jamal Azem, Manuel López-Cano, Manuel Armengol
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  ABSTRACT: We determined the effect of detecting ectopic thymic tissue in thymectomy specimens on the long-term outcome of patients with myasthenia gravis. A total of 83 consecutive patients with generalized seropositive nonthymomatous myasthenia gravis underwent transsternal extended thymectomy (T-3b according to Myasthenia Gravis Foundation of America). Ectopic thymic tissue was only accepted when Hassal's corpuscles in the excised cervicomediastinal fat were documented. The primary endpoint was to assess differences in time to obtain complete stable remission (CSR) according to the presence or absence of ectopic thymus. Thirty-five patients (42.2%) had ectopic thymic tissue. The mean follow-up was 88.4+/-36.3 months (range 20-144). By the Kaplan-Meier analysis method, the estimated median follow-up to obtain a CSR in the group without ectopic thymic tissue was 32.9 months (95% confidence interval [CI] 21.1-44.8 months) and 117.8 months (95% CI 98.0-137.6 months) for the group with ectopic thymic tissue (log-rank test, p=0.0002). The probability over time of obtaining CSR for the groups without and with ectopic thymic tissue was 65% vs 26% at 5 years. After stratification by hyperplasia or involution of the thymus as well as by post-thymectomy immunomodulating regimen (prednisone and prednisone-tacrolimus), the probability over time of obtaining CSR at 5 years was also significantly higher for patients without ectopic thymic tissue than for those with ectopic thymic tissue. The clinical outcome of patients with nonthymomatous seropositive myasthenia gravis is significantly affected by the presence of ectopic thymic tissue in the mediastinal fat.
  European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 09/2008; 34(5):1062-7. · 2.40 Impact Factor
• Article: Tacrolimus for myasthenia gravis: a clinical study of 212 patients.

  José M Ponseti, Josep Gamez, Jamal Azem, Manuel López-Cano, Ramón Vilallonga, Manuel Armengol
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  ABSTRACT: Tacrolimus is a macrolide T cell immunomodulator that is used in myasthenia gravis (MG) patients to affect muscle contraction (ryanodine receptor by modulating intracellular calcium-release channels and increasing muscular strength), glucocorticoid receptors (increasing intracellular concentration of steroids and blocking the steroid export mechanism), and an increase in T cell apoptosis. In this study, we report the results of low-dose tacrolimus (0.1 mg/kg/day) treatment in 212 MG patients. There were 110 thymectomized, cyclosporine- and prednisone-dependent patients; 68 thymectomized patients who started tacrolimus early postoperatively (24 h after operation); and 34 patients over 60 years old with nonthymomatous generalized MG or in whom thymectomy was contraindicated. The mean follow-up time was 49.3 +/- 18.1 months. Muscular strength showed an increase of 23% after 1 month of treatment and 29% at the end of the study. The acetylcholine receptor antibodies decreased significantly from a mean of 33.5 nmol/L at base line to 7.8 nmol/L at the final visit. In the thymectomy group with combined prednisone and tacrolimus stratified by histology of the thymus, the mean probability to attain complete stable remission at 5 years was 80.8% in patients with hyperplasia, 48.1% in thymic involution, and 9.3% in patients with thymoma. In 4.9% of patients, tacrolimus was withdrawn because of major adverse effects. Our results suggest that a low dose of tacrolimus is effective for MG and could be included to the armamentarium for this autoimmune disease. The present results should be interpreted considering the limitations of a retrospective clinical study. Confirmation of these results in randomized studies is desirable.
  Annals of the New York Academy of Sciences 07/2008; 1132:254-63. · 3.15 Impact Factor
• Article: Post-thymectomy combined treatment of prednisone and tacrolimus versus prednisone alone for consolidation of complete stable remission in patients with myasthenia gravis: a non-randomized, non-controlled study.

  José M Ponseti, Josep Gamez, Jamal Azem, José M Fort, Manuel López-Cano, Ramón Vilallonga, Martín Buera, Manuel Armengol
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  ABSTRACT: Thymectomy is a standard treatment of myasthenia gravis (MG). Immunomodulating agents are frequently given during the post-thymectomy latency period until complete remission is fully consolidated. A single-centre, non-randomized, non-controlled study was conducted to compare rates of complete stable remission (CSR) to post-thymectomy early treatment with prednisone alone or prednisone combined with tacrolimus, in 80 patients with MG. Thirty-nine consecutive patients underwent elective transsternal extended thymectomy in 1997-1999 and received prednisone alone (1.5 mg/kg/day) postoperatively, whereas 41 patients operated on in 2000-2002 received prednisone combined with tacrolimus (0.1 mg/kg per day b.i.d. starting 24 hours after thymectomy). The mean follow-up was 59 months (SD 32.9) in the prednisone group and 35.9 months (SD 17.1) in the tacrolimus group (p = 0.003). CSR was achieved in 47.5% of patients in the tacrolimus group and in 41.0% in the prednisone group (p = 0.60). The estimated median follow-up to obtain a CSR in non-thymomatous MG was 38.2 months (95% confidence interval [CI] 30.1-46.4 months) for the tacrolimus group and 64.6 months (95% CI 50.9-78.2 months) for the prednisone group, and in patients with hyperplasia, 32.2 months (95% CI 23-41.5 months) and 62.9 months (95% CI 45.7-80.1 months), respectively (log-rank test, p = 0.03). The behavior of the two study groups stratified by thymic histology were significantly different (log-rank test, p = 0.006). Post-thymectomy administration of tacrolimus combined with prednisone was more effective than prednisone alone for the consolidation of CSR in a substantially shorter period of time in patients with MG.
  Current Medical Research and Opinion 07/2007; 23(6):1269-78. · 2.38 Impact Factor
• Article: Experience with starting tacrolimus postoperatively after transsternal extended thymectomy in patients with myasthenia gravis.

  José M Ponseti, Jamal Azem, José M Fort, Manuel López-Cano, Ramón Vilallonga, Josep Gamez, Manuel Armengol
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  ABSTRACT: Thymectomy is a standard treatment of myasthenia gravis (MG). Immunomodulating agents are frequently given during the post-thymectomy latency period until complete remission is fully consolidated, but serious side effects is a relevant clinical problem for patients on long-term immunomodulating treatment. To assess the effectiveness of starting tacrolimus in the immediate postoperative period in MG patients undergoing transsternal extended thymectomy, with complete stable remission (CSR) as the primary outcome of the study. Forty-eight MG patients received tacrolimus, 0.1 mg/kg per day b.i.d. (started 24 h after thymectomy) and prednisone 1.5 mg/kg/day. Histologically, 34 patients had hyperplasia, 20 thymic involution, and 14 thymoma. Of the 48 patients, 40 completed 1 year of tacrolimus therapy, 38 completed 2 years, 27 completed 3 years, 21 completed 4 years, and 9 more than 5 years. Mean dose of tacrolimus was 4.9 mg/day (range 2-8 mg/day) with a mean plasma drug concentration of 7.6 ng/mL (range 7-9 ng/mL). Prednisone could be withdrawn after the first year in 93.7% of patients and at 2 years in 100%. The mean follow-up was 24.4 months, SD 17.3 (range 6-60 months). Improvement of muscular strength and decrease of anti-AChR antibodies were statistically significant (p < 0.001) shortly after operation. CSR was obtained in 33.4% of patients, pharmacological remission in 62.6%; 4% of patients had minimal symptoms. None of the patients with thymoma achieved CSR. The estimated median follow-up to obtain a CSR was 37.9 months (95% confidence interval [CI] 26.4-49.5 months). The overall crude CSR rate was 33.4%, with 47% for non-thymoma patients. The probability to achieve CSR at 3 years was 67% for the non-thymomatous group. Long-term immune-directed treatment with tacrolimus to improve the effectiveness of thymectomy in MG is feasible and was associated with a high rate of CSR in patients without thymoma.
  Current Medical Research and Opinion 05/2006; 22(5):885-95. · 2.38 Impact Factor
• Article: Ileostomy-site adenocarcinoma after proctocolectomy for ulcerative colitis.

  Jamal Azem, Manuel López-Cano, José M Ponseti, Eloi Espín, José L Sánchez, Manuel Armengol
  International Journal of Colorectal Disease 12/2005; 20(6):549-50. · 2.38 Impact Factor
• Article: Benefits of FK506 (tacrolimus) for residual, cyclosporin- and prednisone-resistant myasthenia gravis: one-year follow-up of an open-label study.

  José M Ponseti, Jamal Azem, José M Fort, Agustín Codina, J Bruno Montoro, Manuel Armengol
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  ABSTRACT: Thirteen patients with myasthenia gravis, unresponsive to prednisone and cyclosporin after thymectomy, received KF506 (tacrolimus) for 12 months, at starting doses of 0.1 mg/kg per day b.i.d. and then adjusted to achieve plasma concentrations between 7 and 8 ng/mL. The doses of prednisone were progressively reduced and finally discontinued. Anti-acetylcholine antibodies and myasthenia gravis score for disease severity decreased significantly and muscular strength increased by 37%. All patients achieved pharmacological remission, 11 were asymptomatic and two had minimal weakness of eyelid closure. Tacrolimus was well tolerated and appears a suitable approach after unsuccessful treatment with conventional immunosuppressants in patients with disabling myasthenia.
  Clinical Neurology and Neurosurgery 05/2005; 107(3):187-90. · 1.58 Impact Factor
• Article: [Tacrolimus (FK506) in the treatment of prednisone-resistant myasthenia gravis. Preliminary results of 20 cases].

  José M Ponseti, José M Fort, Eloy Espin, Manuel Armengol
  Medicina Clínica 03/2002; 118(3):117. · 1.38 Impact Factor