Colistin Use in Patients with Chronic Kidney Disease: Are We Underdosing Patients?

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.

Granulomatosis linfomatoide: una neoplasia infrecuente de mal pronóstico / Lymphomatoid Granulomatosis: A Rare Tumor with Poor Prognosis

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Carcinoma gástrico con estroma linfoide: 3 entidades clínico-patológicas / Gastric carcinoma with lymphoid stroma: 3 clinicopathological entities

Los carcinomas gástricos con estroma linfoide son un grupo heterogéneo de neoplasias mal caracterizadas que históricamente no se han clasificado en entidades clínico-patológicas distintas. Conocer los criterios diagnósticos e identificarlos tiene una importancia relevante tanto clínica como pronóstica. Analizamos 13 casos de pacientes con carcinomas gástricos con estroma linfoide. Con criterios histopatológicos, inmunofenotípicos y moleculares, se definieron 3 subtipos (patrón 1, 2 y 3). Realizamos inmunohistoquímica para caracterizar las poblaciones linfoides (CD3, CD4, CD8 y CD20), para analizar la expresión de virus de Epstein-Barr (VEB) y la expresión de proteínas reparadoras del ADN. El objetivo de este estudio es definir criterios útiles que permitan distinguir estas inusuales lesiones y estudiar el inmunofenotipo de las poblaciones linfoides (AU)

Gastric carcinomas with lymphoid stroma comprise a heterogeneous group of incompletely characterized neoplasms that have not as yet been classified as different clinico-pathological entities. We analysed 13 cases of gastric carcinoma with lymphoid stroma in order to establish diagnostic criteria for their identification. We defined 3 different subtypes (patterns 1, 2 and 3) based on histopathologic, immunophenotypic and molecular criteria. Immunohistochemistry was performed to identify lymphoid populations (CD 3, CD4, CD8 and CD20), the presence of Epstein-Barr Virus (EBV) and the expression of DNA mismatch repair proteins. Our aim is to define criteria that are helpful in the differential diagnosis of these unusual lesions and to clarify the immunophenotype of their lymphoid population (AU)

Utilidad del tratamiento con infliximab en la enterorragia severa asociada a la enfermedad de Crohn. Experiencia de tres casos / Utility of infliximab therapy in severe enterorrhagia associated with Crohn's disease. Report of three cases

La hemorragia digestiva baja severa es una complicación poco frecuente en la enfermedad de Crohn. Presentamos 3 pacientes con enfermedad de Crohn, de diferente localización que desarrollaron una enterorragia severa, con necesidad transfusional múltiple y que respondieron favorablemente a la administración de infliximab, consiguiendo el cese de la hemorragia que comprometía la vida del paciente y evitando una resección quirúrgica de urgencia que parecía inevitable para la resolución del episodio hemorrágico. Sobre la base de esta experiencia clínica y tras revisar la literatura comparando infliximab con otras opciones farmacológicas, consideramos este fármaco, como primera opción terapéutica a emplear en pacientes con enfermedad de Crohn, que presenten una hemorragia digestiva severa, evitando la cirugía en algunos casos, si conseguimos que la hemorragia ceda por rápida cicatrización de las profundas ulceraciones mucosas, responsables del cuadro hemorrágico (AU)

Severe lower gastrointestinal (GI) bleeding is an infrequent complication in Crohn's disease. We report the cases of three patients with Crohn's disease, localized in distinct areas, who developed severe enterorrhagia requiring multiple transfusions. All three patients responded favorably to infliximab administration, which resolved the life-threatening hemorrhages and avoided emergency surgical resection, which had seemed inevitable. Based on this clinical experience and a review of the literature comparing infliximab with other pharmacological options, we believe that this drug should be the treatment of choice in patients with Crohn's disease who develop severe lower gastrointestinal bleeding. This strategy can, in some cases, avoid surgery if the bleeding stops due to rapid healing of the deep mucosal lesions causing the hemorrhagic episode (AU)

[Utility of infliximab therapy in severe enterorrhagia associated with Crohn's disease. Report of three cases]. / Utilidad del tratamiento con infliximab en la enterorragia severa asociada a la enfermedad de Crohn. Experiencia de tres casos.

Severe lower gastrointestinal (GI) bleeding is an infrequent complication in Crohn's disease. We report the cases of three patients with Crohn's disease, localized in distinct areas, who developed severe enterorrhagia requiring multiple transfusions. All three patients responded favorably to infliximab administration, which resolved the life-threatening hemorrhages and avoided emergency surgical resection, which had seemed inevitable. Based on this clinical experience and a review of the literature comparing infliximab with other pharmacological options, we believe that this drug should be the treatment of choice in patients with Crohn's disease who develop severe lower gastrointestinal bleeding. This strategy can, in some cases, avoid surgery if the bleeding stops due to rapid healing of the deep mucosal lesions causing the hemorrhagic episode.