Immunotolerance in liver transplantation: a primer for the clinician.

The use of immunosuppressive medications for solid organ transplantation is associated with cardiovascular, metabolic, and oncologic complications. On the other hand, the development of graft rejection is associated with increased mortality and graft dysfunction. Liver transplant recipients can withdraw from immunosuppression without developing graft injury while preserving an adequate antimicrobial response - a characteristic known as immunotolerance. Immunotolerance can be spontaneously or pharmacologically achieved. Contrary to the classic dogma, clinical studies have elucidated low rates of true spontaneous immunotolerance (no serologic or histological markers of immune injury) among liver transplant recipients. However, clinical, serologic, and tissue biomarkers can aid in selecting patients in whom immunosuppression can be safely withdrawn. For those who failed an immunosuppression withdrawal trial or are at high risk of rejection, pharmacological interventions for immunotolerance induction are under development. In this review, we provide an overview of the mechanisms of immunotolerance, the clinical studies investigating predictors and biomarkers of spontaneous immunotolerance, as well as the potential pharmacological interventions for inducing it.

Perioperative management of patients with antiphospholipid syndrome: a single-center experience.

The objective was to describe the management and risk factors for complications of antiphospholipid syndrome (APS) patients who underwent a surgical procedure in a single center. We reviewed medical records of all patients with primary or secondary APS who underwent an elective surgery during a 6-year period. Demographical data, management of anticoagulation and complications were recorded. We identified 43 patients, mean age 37.9 ± 8.9 years, who underwent a total of 48 elective surgeries. All patients had history of at least one thrombotic event and were under vitamin K antagonists. Before surgery, all patients received bridging therapy with intravenous infusion of heparin or low molecular weight heparin (LMWH). Among the LMWH group, 36 had a full anticoagulation regimen and nine prophylactic doses. In 62% of the surgeries, we identified an optimal management of periprocedural anticoagulation according to guidelines. Overall six patients had severe bleeding and three thrombotic complications (full anticoagulation regimen n = 2 and prophylactic dose group n = 1). Patients with optimal management of anticoagulation experienced less thrombotic and hemorrhagic complications (7 vs. 33%; OR 0.14, 95% CI 0.02-0.81; p = 0.040) and patients with INR ≤1.5 at surgery had fewer episodes of major bleeding (6 vs. 29%; OR 0.19, 95% CI 0.02-0.98; p = 0.050). All three thrombotic events occurred in patients with INR ≤1.5. Proper management of anticoagulation based on guidelines is associated with less complications in patients with APS. Notwithstanding the proper use of bridging therapy, some patients may develop thrombotic complications.

Sarcoidosis: a single hospital-based study in a 24-year period.

BACKGROUND: Clinical presentation of sarcoidosis varies according to race and geographical area. We describe the clinical spectrum and outcome of sarcoidosis in Mexican patients compared with other populations. METHODS: We reviewed the medical charts of 21 patients with sarcoidosis seen at a referral hospital in 1989-2012; organ involvement was assessed using the ACCESS instrument. We compared our results with the ACCESS and Latin American studies. We used descriptive statistics and reported odd ratios with 95% CI. RESULTS AND CONCLUSION: Fifty-two percent were women; median age was 31 years; median time to diagnosis, 5.5 months. Frequency of organ involvement was: constitutional symptoms 62%, lungs 66.6%, skin 42.8%, bone marrow 23.4%, lymph node 19%, liver 19%, and eye 19%. After one year of follow-up, 47.5% of patients were asymptomatic without treatment, 38% asymptomatic on treatment, and 14.2% symptomatic on treatment. In our patients, pulmonary involvement was lower (66.6 vs. 94.9%; p = 0.001) and cutaneous (42.8 vs. 15.8%; p = 0.003) and bone marrow (23.4 vs. 4.7%; p = 0.001) were higher than in the ACCESS cohort. Data regarding Latin American populations was scarce. The clinical spectrum of sarcoidosis in our population differed from other studies, with a higher frequency of cutaneous sarcoidosis and less pulmonary involvement.

Tratamiento del síndrome de sjögren primario con ciclosporina-A: efectos clínicos y biológicos / Treatment of primary sjogren syndrome with ciclosporine-A: clinical an biological effects

Objetivo: Evaluar el efecto de la ciclosporina A (CsA) en el tratamiento del síndrome de Sjögren primario (SSP). Métodos: Se incluyeron nueve pacientes con SSP. Se les suministró CsA (2 mg/kg de peso) durante seis meses. Todos los pacientes fueron evaluados clínicamente cada mes. Se realizó la prueba de Schirmer y la respuesta a CsA se registró por medio de la escala visual análoga durante y después del tratamiento. En suero se determinó el factor reumatoide y los niveles de inmunoglobulinas por nefelometría y los anticuerpos anti-Ro y anti-La por análisis inmunoenzimático. En sobrenadantes de células mononucleares cultivadas por 24 y/o 48 horas. Se cuantificó la producción espontánea de IL-10 e inmunoglobulinas. La IL-10 intracelular en las subpoblaciones CD4+, CD8+, CD19+ y CD14+ fue detectada mediante citometría de flujo. Resultados: El tratamiento fue bien tolerado y sin efectos colaterales. Las manifestaciones oculares mejoraron notablemente en cinco pacientes, en forma moderada en dos, en una no hubo respuesta y en otra no fue evaluable. Las manifestaciones orales mejoraron notablemente en tres pacientes, moderadamente en cinco y en otra no hubo respuesta. Los niveles de inmunoglobulinas tanto en suero como en sobrenadante, se normalizaron en los cinco pacientes que presentaron hipergamaglobulinemia al inicio del estudio. Los niveles de IL-10 disminuyeron en siete pacientes a expensas de las células CD19+. Conclusiones: El tratamiento del SSP con CsA mostró efectos benéficos en la xerostomía y xeroftalmia, aunado a la corrección de los parámetros biológicos estudiados. Por ello la CsA podría ser una alternativa terapéutica promisoria para pacientes con SSP.