Antiphospholipid antibodies and multiple organ failure in critically ill cancer patients

OBJECTIVES: To describe the clinical outcomes and thrombotic events in a series of critically ill cancer patients positive for antiphospholipid (aPL) antibodies. DESIGN: Retrospective case series study. SETTING: Medical-surgical oncologic intensive care unit (ICU). PATIENTS AND PARTICIPANTS: Eighteen patients with SIRS/sepsis and multiple organ failure (MOF) and positive for aPL antibodies, included over a 10-month period. INTERVENTIONS: None MEASUREMENTS AND RESULTS: aPL antibodies and coagulation parameters were measured up to 48 hours after the occurrence of acrocyanosis or arterial/venous thrombotic events. When current criteria for the diagnosis of aPL syndrome were applied, 16 patients met the criteria for "probable" and two patients had a definite diagnosis of APL syndrome in its catastrophic form (CAPS). Acrocyanosis, arterial events and venous thrombosis were present in eighteen, nine and five patients, respectively. Sepsis, cancer and major surgery were the main precipitating factors. All patients developed MOF during the ICU stay, with a hospital mortality rate of 72 percent (13/18). Five patients were discharged from the hospital. There were three survivors at 90 days of follow-up. New measurements of lupus anticoagulant (LAC) antibodies were performed in these three survivors and one patient still tested positive for these antibodies. CONCLUSIONS: In this small series of patients, we observed a high frequency of auto-antibodies and micro- and macro-vascular thrombotic events in critically ill cancer patients. The coexistence of sepsis or SIRS and aPL antibodies was often associated with MOF and death. More studies are necessary to determine the pathophysiological significance of antiphospholipid antibodies in severely ill cancer patients.

Soft tissue abscess and lymphadenitis due to Mycobacterium avium Complex as an expression of immune reconstitution inflammatory syndrome after a second scheme of highly active antiretroviral therapy

Immune reconstitution inflammatory syndrome (IRIS) is an atypical and unexpected reaction related to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infected patients. IRIS includes an atypical response to an opportunistic pathogen (generally Mycobacterium tuberculosis, Mycobacterium avium complex, cytomegalovirus and herpes varicella-zoster), in patients responding to HAART with a reduction of plasma viral load and evidence of immune restoration based on increase of CD4+ T-cell count. We reported a case of a patient with AIDS which, after a first failure of HAART, developed a subcutaneous abscess and supraclavicular lymphadenitis as an expression of IRIS due to Mycobacterium avium complex after starting a second scheme of HAART.

El síndrome inflamatorio de reconstitución inmune (SIRI) es una reacción atípica e inesperada relacionada con el tratamiento antirretroviral de gran actividad (TARGA) en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). El SIRI representa una respuesta inflamatoria frente a un patógeno oportunista (generalmente Mycobacterium tuberculosis, Complejo Mycobacterium avium, citomegalovirus y herpes varicela-zóster) en pacientes que responden a la TARGA con una marcada reducción de la carga viral en plasma y evidencia de una recuperación inmunológica expresada por el incremento de los niveles de linfocitos T CD4+. Presentamos el caso de un paciente con síndrome de inmunodeficiencia adquirida que desarrolló un absceso subcutáneo en muslo derecho y una adenitis supraclavicular izquierda como manifestación de SIRI por Complejo Mycobacterium avium luego del inicio de un segundo esquema de TARGA.

Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome

Sepsis is a systemic inflammatory response commonly caused by bacterial infection. We demonstrated that the outcome of sepsis induced by cecal ligation and puncture (CLP) correlates with the severity of the neutrophil migration failure towards infectious focus. Failure appears to be due to a decrease in the rolling and adhesion of neutrophil to endothelium cells. It seems that neutrophil migration impairment is mediated by the circulating inflammatory cytokines, such as TNF-alpha and IL-8, which induce the nitric oxide (NO) production systemically. It is supported by the fact that intravenous administration of these cytokines reduces the neutrophil migration induced by different inflammatory stimuli, and in severe sepsis the circulating concentrations of the cytokines and chemokines are significantly increased. Moreover, the neutrophil migration failure and the reduction in the rolling/adhesion were not observed in iNOS-/- mice and, aminoguanidine prevented this event. We also demonstrated that the failure of neutrophil migration is a Toll-4 receptor (TLR4) dependent mechanism, since it was not observed in TLR4 deficient mice. Furthermore, it was also observed that circulating neutrophils obtained from septic patients present failure of neutrophil chemotaxis toward fMLP, IL-8, and LTB4 and an increased in sera concentrations of NO3 and cytokines. In conclusion, we demonstrated that, in sepsis, failure of neutrophil migration is critical for the outcome and that NO is involved in the process.

Avances y promesas en la inmunoterapia de sepsis neonatal / Advances and promises in immunotherpy for neonatal sepsis

La sepsis neonatal es una infección sistémica en el primer mes de vida que, según su gravedad, presenta las 4 fases del síndrome de respuesta inflamatoria sistémica (SRIS) que caracteriza a esta enfermedad en los adultos. El uso de antibióticos sigue siendo el pilar en su tratamiento; sin embargo, la morbi-letalidad de la sepsis neonatal no ha disminuido significativamente y la aparición de cepas resistentes es alarmante, lo cual plantea la necesidad de alternativas terapéuticas. En esta búsqueda, se pretende regular la respuesta inflamatoria a la infección a través de 3 grandes grupos de citocinas: interleucinas, interferones y los factores de crecimiento, algunas de las cuales se comportan como pro-inflamatorias, y otras como anti-inflamatorias al neutralizar, bloquear o inhibir a las pro-inflamatorias. Hasta ahora, los 2 mayores avances en la terapia auxiliar de sepsis neonatales son la inmunoglobulina para uso intravenoso (IgIV), que tiene su principal indicación en los neonatos prematuros y de bajo peso, y los factores estimulantes de colonias de granulocitos y de macrófagos (G-CSF y GM-CSF), indicados en neonatos pretérmino o a término con neutropenia por sepsis. Una actitud de extrema reserva entre muchos médicos ha postergado de manera poco justificable su aplicación clínica. En fases preliminares de investigación se encuentran los antagonistas naturales de la endotoxina bacteriana, como la BPI, proteína producida por los granulocitos, y las inmunoadhesinas, moléculas híbridas de inmunoglubulina y un receptor específico que bloquean la unión de citocinas pro-inflamatorias con sus receptores celulares, modulando así la respuesta inflamatoria a la infección