TREATMENT OF ANEMIA AND IMPROVEMENT OF QUALITY OF LIFE AMONG PATIENTS WITH CROHN'S DISEASE: experience using ferric carboxymaltose

Objectives - Anemia is the most common hematological alteration in patients with Crohn's disease, and is frequently related to intestinal inflammatory activity. Its cause is multifactorial and mostly associated with absolute iron deficiency (iron deficiency anemia) and/or functional iron deficiency (inflammation anemia or anemia of chronic disease). It may also be identified through other causes, such as folic acid or vitamin B12 deficiency and secondary to adverse effects from medications (salicylic derivatives and immunosuppressive drugs). In the present study, patients with active Crohn's disease and anemia were evaluated and treated with intravenous ferric carboxymaltose. We discuss the therapeutic schemes (doses), safety, results and improvement of quality of life. Methods - In the present prospective study, 10 consecutive patients with Crohn's disease, with moderate to severe activity, with anemia (Hb: 6.7 to 10 g/dL), who were attended between March 2014 and March 2015, were evaluated. Six (60%) were men and four were women, all with moderate or severe anemia (hemoglobin <10 g/dL). They were treated with a maximum of three intravenous infusions of 1000 mg of ferric carboxymaltose, of at least 15 minutes in duration. It was also sought to correlate the inflammatory Crohn's disease activity degree (measured using the Crohn's Disease Activity Index, CDAI) and C-reactive protein level with the severity of anemia. The primary outcome was an increase in Hb of ≥2 g/dL and the secondary outcome was the normalization of anemia (Hb ≥12 g/dL for women and ≥13 g/dL for men) and the improvement in quality of life seen 12 weeks after the last application of carboxymaltose. Results - Among the 10 patients studied, parenteral iron supplementation was administered in three cases during hospitalization and the others received this on an outpatient basis. The total iron dose ranged from 1,000 to 2,000 mg, with an average of 1,650 mg. Crohn's disease activity measured using CDAI and C-reactive protein correlated with the intensity of anemia. An increase of 2 g/dL occurred in eight (80%) patients after 12 weeks and normalization of anemia was found in seven (70%) patients. Improvements in quality-of-life scores were found for all (100%) patients after 12 weeks. Carboxymaltose was well tolerated. Three patients presented adverse reactions (two with nausea and one with headache) of mild intensity. Conclusions - Anemia is a frequent complication for Crohn's disease patients. Intravenous iron therapy has been recommended for Crohn's disease patients, because for these patients, oral iron absorption is very limited. This is because of the inflammatory state and "blocking" of iron entry into enterocytes through hepcidin action on ferroportin, along with the elevated rates of gastrointestinal adverse events that compromise adherence to treatment and possibly aggravate the intestinal inflammatory state. The degree of Crohn's disease activity, as measured using CDAI and C-reactive protein, correlates with the severity of anemia. Carboxymaltose is a safe drug, which can be administrated in high doses (up to 1,000 mg per application per week) and corrects anemia and iron stocks over a short period of time, with consequent improvement in quality of life.

Objetivos - Anemia é a alteração hematológica mais comum em portadores de doença de Crohn, estando frequentemente relacionada à atividade inflamatória intestinal. Sua causa é multifatorial, está associada na maioria das vezes com deficiência absoluta de ferro (anemia ferropriva) e/ou deficiência funcional de ferro (anemia da inflamação ou anemia de doença crônica), podendo também ser identificada outras causas como deficiência de ácido fólico ou vitamina B12 e secundária a efeitos adversos de medicamentos (derivados salicílicos e imunossupressores). Neste trabalho, avaliamos portadores de doença de Crohn em atividade com anemia que foram tratados com carboximaltose férrica endovenosa, e discutimos os esquemas terapêuticos (doses), a segurança e os resultados, assim como a melhora da qualidade de vida. Métodos - Neste estudo prospectivo, avaliamos 10 consecutivos pacientes portadores de doença de Crohn de moderada a grave atividade com anemia (Hb: 6,7 a 10 g/dL) que foram atendidos no período de março de 2014 a março de 2015. Eram seis (60%) do sexo masculino e quatro do sexo feminino, todos com anemia moderada ou grave (hemoglobina <10g/dL), tratados com no máximo três infusões de 1000 mg de carboximaltose férrica por via endovenosa em, pelo menos, 15 minutos. Procurou-se também correlacionar o grau de atividade inflamatória da doença de Crohn (mensuração realizada com o IADC-índice de atividade da doença de Crohn) e dosagem da proteína C reativa com a gravidade da anemia. O desfecho primário foi aumento da Hb de ≥2 g/dL e desfecho secundário a normalização da anemia (Hb ≥12 g/dL para mulheres e ≥13 g/dL para homens) e melhora na qualidade de vida após 12 semanas da aplicação da última dose de carboximaltose férrica. Resultados - Dos 10 pacientes estudados, em 3 a suplementação parenteral de ferro foi realizada durante internação hospitalar, o restante em regime ambulatorial. A dose total de ferro administrada variou de 1.000 a 2.000 mg, sendo a média de 1.650 mg. A atividade da doença de Crohn mensurada pelo IADC e pelo PCR se correlacionou com a intensidade da anemia. O aumento de 2 g/dL ocorreu em oito (80%) pacientes após 12 semanas e a normalização da anemia foi observada em sete (70%). Melhora do escore de qualidade de vida foi observada em todos (100%) após 12 semanas. A carboximaltose férrica foi bem tolerada, três pacientes apresentaram reações adversas (2 - náusea e 1 - cefaléia) de leve intensidade. Conclusões - Anemia é uma complicação frequente em portadores de doença de Crohn. A terapia com ferro por via endovenosa tem sido a recomendada em portadores de doença de Crohn, pois nestes pacientes a absorção do ferro oral é bastante limitada devido ao estado inflamatório e "bloqueio" da entrada de ferro nos enterócitos por ação da hepcidina sobre a ferroportina, além das elevadas taxas de eventos adversos gastrointestinais que comprometem a adesão ao tratamento e podem agravar o estado inflamatório intestinal. O grau de atividade da doença de Crohn mensurado pelo IADC e PCR se correlaciona com a severidade da anemia. A carboximaltose férrica é uma droga segura, pode ser administrada em altas doses (até 1.000 mg por aplicação por semana), corrige a anemia e os estoques de ferro em curto espaço de tempo, com consequente melhora da qualidade de vida.

Efficacy of Ferric Carboxymaltose in Anaemia of Malignancy - A Pilot Study.

Anaemia is an important problem in malignancy. It may be due to chronic causes like malnutrition, marrow infiltration, associated renal or endocrine disorders and it may be complicated with blood loss. Measures like blood transfusion, erythropoietin injections often pose a logistical problem. Parenteral iron injections have proved to be useful in fighting anaemia in some chronic conditions e.g. patients on hemodialysis. Aims and Objectives: Primarily to see the observable change in hemoglobin (Hb) level with ferric carboxymaltose (FCM) in treating patients of malignancy on anti-cancer treatment. Materials and Methods: Twenty seven patients were enrolled for this study who were suffering from various malignancies. The baseline Hb level was estimated and FCM injection was administered as per the schedule of 500 mg intravenously (IV) weekly once. The overall results of increase in Hb level was noted during the middle of the treatment (chemotherapy or radiotherapy) and later 3-4 weeks after treatment completion. The results were analysed using SPSS and the mean values of initial Hb and after treatment were analysed. Level of significance (p value) was noted using t test. Results: In 27 patients the mean initial Hb level was 8.09 g/dl before treatment which increased to 10.28 g/dl after FCM treatment (p <0.0001). Conclusion: Treatment with FCM definitely led to a significant increase in Hb level in patients of malignancy undergoing treatment. However, further detailed study is needed to establish its definite role in improving the body iron parameters.

Establishment of cell suspension cultures of two Costa Rican Jatropha species (Euphorbiaceae) / Establecimiento de suspensiones celulares de dos especies Jatropha (Euphorbiaceae) de Costa Rica

J. curcas has been studied in different countries and some interesting agronomic, pharmacological and industrial properties have been reported. More recently, it has been considered an important alternative source for biofuel production. The objective of this study was to establish a long-term method for the maintenance of calli and cell suspension cultures of the local species J. curcas and J. gossypifolia, in order to allow future studies for novel compounds with pharmaceutical or industrial applications. For this, friable calli were successfully induced from hypocotyl segments of J. curcas and J. gossypifolia that were cultured in semisolid MS media supplemented with 1.5mg/L, and 0.5mg/L of 2,4-D, respectively. Cell suspension cultures of J. curcas were established using 1g of 35 and 60-day calli, in 50mL of liquid MS media supplied with 1.5mg/L of 2,4-D; sucrose and maltose were additionally evaluated as carbon sources. After 35 days, cell suspension cultures initiated with 35-day calli, showed greater cell growth with a maximum biomass of 194.9g/L fresh weight, 6.59g/L dry weight and 17.3% packed volume. The exponential phase ended at day 35 for cultures initiated with 35-day calli, and at day 21 for cultures initiated with 60-day calli. Higher biomass production was obtained with sucrose. Cell cultures were established with 35-day calli in MS media with the same 2,4-D concentration used for calli induction and 30g/L sucrose. This medium was considered optimum for the maintenance and growth of cell suspensions for both species, with sub-cultures every 20 days. The biotechnological potential for the production of bioactive compounds in these species for pharmacological, agricultural and industrial applications is being evaluated.

J. curcas es un importante recurso alternativo de biocombustible. Por otro lado, propiedades de interés agronómico, farmacológico e industrial han sido reportadas para esta especie. El objetivo de este estudio fue el establecimiento y mantenimiento a largo plazo de callos y cultivos celulares en suspensión de J. curcas y J. gossypifolia, con el objetivo de permitir futuros estudios para nuevos compuestos con aplicaciones farmaceúticas e industriales. Los callos friables fueron exitosamente inducidos a partir de segmentos de hipocótilos J. curcas and J. gossypifolia cultivados en medio MS semisólido suplementado con 1.5mg/L y 0.5mg/L of 2,4-D, respectivamente. Los cultivos celulares en suspensión de J. curcas fueron establecidos utilizando 1g de callos de 35 y 60 días de edad en 50mL de medio MS líquido adicionado con 1.5mg/L de 2,4-D. Después de 35 días, los cultivos en suspensión celular iniciados con callos de 35 días, mostraron mayor crecimiento celular con una biomasa máxima de 194.9g/L de peso fresco y 6.59g/L de peso seco y 17.3% de volumen empacado. La fase exponencial finalizó al día 35 en los cultivos iniciados con callos de 35 días, y al día 21 en los cultivos iniciados con callos de 60 días. Dos fuentes de carbono fueron evaluadas: sacarosa y maltosa. La producción de mayor biomasa fue obtenida con sacarosa. Los cultivos celulares se establecieron con callos de 35 días cultivados en medio MS con la misma concentración de 2,4-D utilizada para la inducción de callos y 30g/L de sacarosa. Este medio fue considerado el óptimo para el mantenimiento y crecimiento de suspensiones celulares en ambas especies con subcultivos cada 20 días. El potencial biotecnológico para la producción de compuestos bioactivos en estas especies, para aplicaciones farmacológicas, agrícolas e industriales está siendo evaluado.