Inflammatory processes involved in the alteration of liver function biomarkers in adult hospitalized patients treated with parenteral nutrition

IntroductionLiver damage has been associated with the accumulation of phytosterols (PS) in patients treated with parenteral nutrition (PN). We aimed to study the association of inflammatory markers with liver function biomarker (LFB) alterations in patients treated with PN containing PS.Materials and methodsProspective observational study. Simple linear and stepwise multiple linear regression tests and interactions were performed.ResultsNineteen patients were included. In the multivariable model, determinations based on LFBs as dependent and phytosterols (and their fractions) as independent variables showed an association between increases in gamma-glutamyltransferase (GGT) and lanosterol (p < 0.001), stigmasterol (p < 0.001), interleukin-10 (IL-10) × total phytosterols (Phyt) (p < 0.009), tumor necrosis factor-α (TNF-α) × Phyt (p < 0.002), IL-10 × sitosterol (p < 0.002), TNF-α × sitosterol (p < 0.001), IL-10 × campesterol (p < 0.033), IL-10 (p < 0.006 and p < 0.015), TNF-α (p < 0.048 and p < 0.027). Increases in alanine aminotransferase (ALT) were associated with Phyt (p < 0.006), lanosterol (p < 0.016), C-reactive protein (CRP) × campesterol (p < 0.001), interleukin-6 (IL-6) × stigmasterol (p < 0.030), CRP (p < 0.08), and IL-6 (p < 0.042). Alkaline phosphatase (AP) increases were associated with CRP (p < 0.002).DiscussionInflammation in the presence of plasmatic PS seems to have a synergistic effect in impairing liver function, mainly altering GGT but also ALT

Effect of Fish Oil Parenteral Emulsion Supplementation on Inflammatory Parameters after Esophagectomy

(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (omega-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of omega-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) administered parenterally with enteral nutrition support. (Methods) Randomization was 1:1:1 in three groups: Group A received a LE mixture of 0.4 g/kg/day of fish oil and 0.4 g/kg/day of LCT/MCT 50:50, Group B received 0.8 g/kg/day of fish oil LE, and Group C received 0.8 g/kg/day of LCT/MCT 50:50. Variables were measured at recruitment time and day +1, +3, and +5. Inflammatory variables studied were Interlukin-6, C-reactive protein (CRP), tumoral necrosis factor-alpha (TNF-alpha), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of omega-3LE in the immediate postoperative period did not modulate the earlier inflammatory response. Statistically significant differences were found in IL-6 and CRP overall temporal evolution but were not found when studying the type of LE administered or in patients needing critical care. Administration of omega-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) omega-3FA has no impact on the early inflammatory postoperative response assessed for a short period but was safe. More studies for longer periods are needed

Case report : Challenges in immune reconstitution following hematopoietic stem cell transplantation for CTLA-4 insufficiency-like primary immune regulatory disorders

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is a T-cell hyperactivation disorder that can manifest with both immunodeficiency and immune dysregulation. Approximately one-third of patients may present mild symptoms and remain stable under supportive care. The remaining patients may develop severe multiorgan autoimmunity requiring lifelong immunosuppressive treatment. Hematopoietic stem cell transplantation (HSCT) is potentially curable for patients with treatment-resistant immune dysregulation. Nevertheless, little experience is reported regarding the management of complications post-HSCT. We present case 1 (CTLA-4 haploinsufficiency) and case 2 (CTLA-4 insufficiency-like phenotype) manifesting with severe autoimmunity including cytopenia and involvement of the central nervous system (CNS), lung, and gut and variable impairment of humoral responses. Both patients underwent HSCT for which the main complications were persistent mixed chimerism, infections, and immune-mediated complications [graft-versus-host disease (GVHD) and nodular lung disease]. Detailed management and outcomes of therapeutic interventions post-HSCT are discussed. Concretely, post-HSCT abatacept and human leukocyte antigen (HLA)-matched sibling donor lymphocyte infusions may be used to increase T-cell donor chimerism with the aim of correcting the immune phenotype of CTLA-4 haploinsufficiency

Infección por Citomegalovirus en el Trasplante Alogénico de Progenitores Hematopoyéticos en la era del tratamiento anticipado: consideraciones actuales sobre la definición de grupos de riesgo y el diagnóstico

[spa] El Citomegalovirus (CMV) es un virus herpes con capacidad de permanecer latente tras la primoinfección y reactivarse durante estados de inmunosupresión. La respuesta inmune celular mediada por los linfocitos T CD8 citotóxicos es la encargada, de manera predominante, del control de la infección por este virus. Los pacientes que reciben un trasplante alogénico de progenitores hematopoyéticos (TPH) presentan un estado de inmunosupresión severa y prolongada. La reconstitución del sistema inmune ocurre de manera escalonada y la de los linfocitos T tiene lugar a partir del tercer mes post-TPH. Complicaciones como la enfermedad injerto contra receptor (EICR) y su tratamiento contribuyen a agravar la inmunosupresión. Por ello, las complicaciones infecciosas son frecuentes, en especial la infección por CMV que afecta al 60% de los pacientes con una mortalidad asociada del 2% (directamente relacionada con la afección de algún órgano) y una mortalidad indirecta, derivada del tratamiento y de la propia infección, cercana al 10%. La presencia de una serología positiva (IgG) en el receptor del TPH es el principal factor de riesgo para presentar infección por CMV, especialmente cuando el donante es seronegativo (alto riesgo). Otros factores de riesgo son la presencia de linfopenia, EICR y su tratamiento, así como fármacos utilizados en la profilaxis de EICR que provoquen linfopenia. En el primer trabajo se demuestra que el tratamiento con corticoides a altas dosis (debido a la presencia de EICR) aumenta la incidencia de infección e infección recurrente por CMV, lo que impacta sobre todo en los pacientes de riesgo intermedio serológico (donante y receptor IgG positivos) y la equipara a la incidencia de los de alto riesgo serológico (donante negativo/receptor positivo), situándola en torno al 80%. En los pacientes de alto riesgo, el tratamiento con corticoides alarga la duración del tratamiento. Además, se evidencia que el tratamiento con corticoides enlentece la reconstitución inmune de manera global y tiene un efecto negativo sobre la inmunidad CMV específica, disminuyendo su eficacia. La administración de ciclofosfamida post-TPH, estrategia eficaz en disminuir la incidencia de EICR, debido al efecto que ejerce sobre la reconstitución inmune post-TPH, provoca un cambio en la epidemiología de la infección, como se describe en el tercer trabajo. La linfopenia profunda que ocurre en el primer mes explicaría la mediana de reactivación más precoz. El retraso en la reconstitución de los linfocitos T CD4, que se iniciaría a los 6 meses post-TPH, explica la mayor incidencia de enfermedad orgánica y, sobre todo, de infección refractaria al tratamiento antiviral. El segundo trabajo se centra en la utilidad de la PCR-RT (cuantificación de DNA viral) como técnica diagnóstica para la manifestación más frecuente de enfermedad por CMV, la gastrointestinal (asociada a mortalidad). Los síntomas derivados del daño causado por el CMV en tejido gastrointestinal son indistinguibles de los provocados por la EICR intestinal. Para llegar al diagnóstico se debe realizar biopsia endoscópica con estudio anatomopatológico y tinción inmunohistoquímica (gold standard). Se demuestra que la PCR-RT en tejido intestinal presenta la misma sensibilidad, especificidad y valores predictivos positivos y negativos que la inmunohistoquímica, lo que la convierte en una técnica fiable. Además, la PCR-RT, gracias a la cuantificación del DNA viral, permite realizar un diagnóstico precoz en base a un punto de corte definido, e iniciar tratamiento antiviral precozmente, así como evaluar la respuesta al mismo, según la evolución de la carga viral. Identificar los factores de riesgo que presenta cada paciente para desarrollar infección por CMV así como el uso de nuevas herramientas disponibles, permite diseñar estrategias individualizadas de tratamiento que sean eficaces en el control de la infección y minimizar la toxicidad asociada para mejorar la supervivencia global de los pacientes.[eng] Cytomegalovirus (CMV) is a herpes virus with the ability to reactivate from a latent phase during immunosuppression. The cellular immune response mediated by cytotoxic CD8 T-lymphocytes is predominantly responsible for the control of CMV infection. Patients who receive an allogeneic stem cell transplant (SCT) experience severe and prolonged immunosuppression. Immune reconstitution after transplant is a stepwise process and T cell recovery begins after the third month after SCT. Complications such as graft-versus-host disease (GVHD) and its treatment contribute to increased immunosuppression. Therefore, infectious complications are frequent, especially CMV infection that affects 60% of patients A positive serology (IgG) in the recipient is the main risk factor for CMV infection, especially when the donor is seronegative (high risk). Other risk factors are the presence of lymphopenia, GVHD and its treatment, and T cell depletion. Our studies show that treatment with high-dose steroids increases the incidence of CMV infection and recurrent infection, especially for intermediate-risk serological patients (IgG-positive donor and recipient). In high-risk patients, steroid treatment prolonged the duration of antiviral treatment. In addition, steroid treatment delays global immune reconstitution and impairs CMV-specific immunity. The administration of post-SCT cyclophosphamide, used for GVHD prophylaxis, changes the CMV infection’s epidemiology. Deep lymphopenia occurring in the first month would explain the earlier median time to CMV infection and the delay in the CD4 T lymphocyte’s recovery (after 6 months post-SCT), explains the higher incidence of CMV disease and refractory CMV infection. We focused on the usefulness of RT-PCR as a diagnostic technique for the CMV gastrointestinal disease. The symptoms derived from CMV gastrointestinal disease are indistinguishable from those caused by GVHD. An endoscopic biopsy with histological study and inmunohistochemistry staining (gold standard) is needed for diagnosis. It has been shown that RT-PCR has the same sensitivity, specificity and predictive values than immunohistochemistry, so PCR is useful and reliable for CMV gastrointestinal disease. Furthermore, PCR-RT (quantification of viral DNA), allows an early diagnosis based on a defined cut-off so would initiate antiviral treatment more promptly. PCR-RT could also be useful for monitoring the response and define the duration of the treatment