Neumonitis intersticial como reacción adversa a inhibidores de mTOR / Interstitial pneumonitis as an adverse reaction to mTOR inhibitors

Introducción: Los inhibidores de mTOR (del inglés mammalian target of rapamycin), sirolimus y everolimus, utilizados como tratamiento inmunosupresor en el trasplante de órganos sólidos, pueden producir efectos adversos graves, como la neumonitis intersticial. Incidencia y presentación clínica: La incidencia de neumonitis intersticial se ha estimado entre el 4 % y el 11 %, aunque podría ser mayor. La mayoría de los casos publicados se ha producido en pacientes trasplantados renales en tratamiento con sirolimus. La presentación clínica es heterogénea, lo que dificulta el diagnóstico. Se acostumbra a observar alteraciones en la tomografía axial computarizada torácica, como opacidades en vidrio deslustrado. La fisiopatología es poco conocida. Sin embargo, se ha observado una mayor incidencia en pacientes con función renal alterada y en pacientes que habían recibido inhibidores de calcineurina previamente. La relación entre aparición de neumonitis y concentraciones plasmáticas de inhibidores de mTOR no está bien definida. Tratamiento: La suspensión del fármaco y la administración de dosis altas de corticoides parecen ser efectivos. Otras alternativas terapéuticas, aunque más discutidas, son la reducción de la dosis del inhibidor de mTOR y el cambio de sirolimus a everolimus. Conclusión: Se debe sospechar de neumonitis iatrogénica en pacientes trasplantados en tratamiento con inhibidores de mTOR y con síntomas respiratorios. Faltan datos concluyentes en cuanto a estrategias de tratamiento. Parece que everolimus podría ser mejor tolerado que sirolimus (AU)

Introduction: mTOR (mammalian target of rapamycin) inhibitors sirolimus and everolimus, used as immunosuppressants in solid organ transplantation, may cause severe adverse effects, such as interstitial pneumonitis. Incidence and clinical presentation: The estimated incidence of interstitial pneumonitis is 4-11% although it may be higher. Most reported cases have occurred in renal transplant recipients treated with sirolimus. Clinical presentation is heterogeneous, which makes diagnosis difficult. Abnormalities, such as ground glass opacities, are often found in computerised axial tomography scans of the chest. Physiopathology is not well-known. However, patients with abnormal renal function and those with previous calcineurin inhibitor treatment display a higher incidence. The relationship between pneumonitis and mTOR inhibitor plasma concentrations is not well defined. Treatment: Drug discontinuation and administration of high doses of corticosteroids seems to be an effective treatment. mTOR inhibitor dose reduction and replacing sirolimus with everolimus are other alternatives, but they are still under discussion. Conclusion: Iatrogenic pneumonitis must be suspected when a transplant recipient being treated with mTOR inhibitors presents respiratory symptoms. There is lack of conclusive data on treatment strategies. It appears that everolimus may be tolerated better than sirolimus (AU)

Interstitial pneumonitis as an adverse reaction to mTOR inhibitors.

INTRODUCTION: mTOR (mammalian target of rapamycin) inhibitors sirolimus and everolimus, used as immunosuppressants in solid organ transplantation, may cause severe adverse effects, such as interstitial pneumonitis. INCIDENCE AND CLINICAL PRESENTATION: The estimated incidence of interstitial pneumonitis is 4-11% although it may be higher. Most reported cases have occurred in renal transplant recipients treated with sirolimus. Clinical presentation is heterogeneous, which makes diagnosis difficult. Abnormalities, such as ground glass opacities, are often found in computerised axial tomography scans of the chest. Physiopathology is not well-known. However, patients with abnormal renal function and those with previous calcineurin inhibitor treatment display a higher incidence. The relationship between pneumonitis and mTOR inhibitor plasma concentrations is not well defined. TREATMENT: Drug discontinuation and administration of high doses of corticosteroids seems to be an effective treatment. mTOR inhibitor dose reduction and replacing sirolimus with everolimus are other alternatives, but they are still under discussion. CONCLUSION: Iatrogenic pneumonitis must be suspected when a transplant recipient being treated with mTOR inhibitors presents respiratory symptoms. There is lack of conclusive data on treatment strategies. It appears that everolimus may be tolerated better than sirolimus.

Respuesta: Desensibilización frente a tolerancia clínica / Reply: Desensitization versus clinical tolerance

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Prescribing of zoledronic acid in a tertiary outpatient hospital setting.

BACKGROUND: Zoledronic acid (ZA) is an intravenous bisphosphonate approved for the prevention and treatment of cancer skeletal-related events. OBJECTIVE: Our aim was to analyze the prescription patterns of ZA in the cancer outpatient clinic. METHOD: We performed a retrospective chart review of all patients who received at least 1 dose of ZA from January 2009 until December 2010 in our institution. The patients' follow-up period was defined from the administration of the first dose until February 2011. RESULTS: The sample comprised 345 patients: 31.9 % had breast cancer, 14.5 % prostate cancer, 29.0 % multiple myeloma, and 24.6 % other solid tumors. A total of 4,546 doses were administered; 2,749 (60.5 %) without intravenous chemotherapy. 71.1 % of patients with breast cancer, 86 % with prostate cancer, 60 % with multiple myeloma and 44.6 % with other solid tumors, received ZA without intravenous chemotherapy throughout bisphosphonate treatment. Doses were adjusted in one-third of cases. Administration every 4-weeks was the most frequent schedule. Median duration of treatment varied between 15.0 months for breast cancer and 4.2 months for other solid tumors. CONCLUSION: Most of ZA prescriptions in cancer outpatients followed the labeled indications. The percentage of ZA doses administered without intravenous chemotherapy was 60.5 %.

Eficacia y tolerabilidad de un protocolo de desensibilización a clopidogrel / Efficacy and tolerability of a clopidogrel desensitization protocol

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