'The Year of Living Dangerously': Successful Rhodococcus Equi Therapy in an Immunosuppressed Patient with Minimal Toxicity by One Year of Continuous Intravenous Vancomycin Therapy Combined with Oral Levofloxacin And Rifampicin.

Background: Rhodococcus equi is a Gram-positive microorganism that causes infections, particularly in immunocompromised patients. Treatment duration can be prolonged. While vancomycin is an effective drug in this scenario, its use may lead to renal damage. Studies have shown that continuous vancomycin infusion appears to be a safe strategy in terms of adverse effects compared to bolus administration. Case description: We present the case of a 71-year-old female liver transplant recipient. After being diagnosed with a mediastinal infection caused by Rhodococcus equi with poor response to initial therapy, she required 12 months of continuous intravenous domiciliary infusion of vancomycin combined with oral levofloxacin and rifampicin. There was no drug-related complication throughout the follow-up. Conclusions: The use of continuous vancomycin infusion has emerged as a safer, more efficient, and cost-effective alternative to intermittent administration. We want to emphasise the uniqueness of this case, where despite the unprecedented treatment duration, no adverse effects occurred. LEARNING POINTS: Vancomycin therapy based on continuous infusion represents a safer and cheaper strategy than classic intermittent administration.The use of continuous infusion facilitates the management of complex infections with outpatient antimicrobial therapy.

Comparison of conventional dried blood spots and volumetric absorptive microsampling for tacrolimus and mycophenolic acid determination.

Therapeutic drug monitoring (TDM) of immunosuppressants is essential to avoid either rejection or toxicity after solid organ transplantations. Capillary microsampling approaches are an outstanding alternative to conventional venous sampling for TDM (easy and non-invasive collection, enabling self-sampling, and cost-saving shipment, processing and storage). Volumetric absorptive microsampling (VAMS) has gained importance in the last years, as it was meant to overcome the hematocrit (Hct) related issues commonly associated to DBS analysis. Despite all the benefits, microsampling techniques performance (including a thorough clinical validation) should be set up before their implementation in clinical practice. The aim of this study was to perform a clinical validation for both tacrolimus (TAC) and mycophenolic acid (MPA) in both DBS and Mitra™ VAMS. For the clinical validations, two different requirements were set up: analytical (following EMA and FDA guidelines) and clinical (following the Royal College of Pathologists of Australasia -RCPA- recommendations) acceptance criteria. For DBS, both analytical and clinical acceptance criteria were fulfilled for TAC, with 98.7% and 95% of the paired samples within the preset limits, respectively. For MPA, the analytical criterion was met (70.6% of paired specimens), although only half of the pairs were within the clinical limits. For VAMS, the clinical validation for both TAC and MPA showed good correlations but significant lower concentrations in VAMS compared to the routine matrices. After VAMS concentrations correction, the analytical requirement was fulfilled for both analytes (71.1% for TAC, 75% for MPA), although the more restrictive criteria recommended by the RCPA were not met for any analyte (half of the samples fell within the acceptance area). In addition, no significant Hct impact on the quantification was found in any case. Also, a preliminary home-sampling trial was set up, showing promising results. Moreover, a comparison between VAMS vs. DBS analytical and clinical performances was carried out, including a home-sampling trial, sample quality results and costs. Although the analytical performance for both VAMS and DBS was similar, DBS were superior regarding clinical criteria, sampling quality and cost.

Volumetric Absorptive Microsampling (VAMS) for assaying immunosuppressants from venous whole blood by LC-MS/MS using a novel atmospheric pressure ionization probe (UniSpray™).

Therapeutic drug monitoring (TDM) of immunosuppressants (IMS) is crucial to prevent rejection or toxicity after solid organ transplantation. Microsampling techniques (sampling <50 µL of blood) can be a good alternative to conventional venous sampling for TDM, due to their numerous advantages, including its easy and low-invasive sampling, enabling self-collection, and cost-saving shipment and storage. Furthermore, volumetric absorptive microsampling (VAMS) enables the collection of precise and accurate blood volumes, overcoming the hematocrit (Hct) effect related to dried blood spots, while offering the same benefits. In this work, an LC-MS/MS method for the determination of the 5 most common IMS (mycophenolic acid -MPA-, tacrolimus -TAC-, sirolimus -SIR-, everolimus -EVE- and cyclosporin A -CsA-) in venous blood collected with Mitra™ VAMS devices was developed and validated, employing a novel LC-MS/MS interface, Unispray™. The method was fully validated including linearity, limits of detection (LOD) and quantification (LLOQ), accuracy, precision, selectivity, carry-over, matrix effect, recovery, impact of Hct on recovery and autosampler and short-/long-term stability, satisfying acceptance criteria in all cases. LLOQs were 0.5 ng/mL for TAC, SIR and EVE, 20 ng/mL for CsA and 75 ng/mL for MPA. No impact of the Hct (range: 0.2 to 0.62 L/L) on recovery was found for any analyte. All compounds were stable in VAMS for at least 8 months at -20 °C. In addition, as part of the VAMS analytical method validation, we performed for the first time a broad statistical study to compare liquid venous blood concentrations from patients under TAC (n = 53) and MPA (n = 20) treatment to those observed when the same specimens were absorbed into VAMS. Our results showed that venous blood VAMS concentrations were correlated to those found in the original liquid venous blood, proving that the VAMS material itself will not bias blood drug concentrations. Therefore, the present method could be applied to evaluate possible correlations between venous blood and capillary blood collected with VAMS.

A multidrug LC-MS/MS method for the determination of five immunosuppressants in oral fluid.

Aim: This study aimed: to develop and validate an LC-MS/MS method for mycophenolic acid, tacrolimus, sirolimus, everolimus and cyclosporin A in oral fluid (OF), as an essential tool to study the usefulness of OF as an alternative matrix for immunossuppressants' therapeutic drug monitoring; and to find the best OF collector for these analytes. Materials & Methods: Chromatographic separation was achieved using an XBridge® Shield RP18 analytical column maintained at 65ºC, using 2 mM ammonium formate and 0.1% formic acid in water (A) and acetonitrile (B) as mobile phase. OF sample was extracted with solid phase extraction after sonication and protein precipitation. Results & Conclusions: Method validation met all the acceptance criteria. LODs were 0.05-1 ng/ml, and LOQs 0.1-5 ng/ml. Silanized tubes offered the best recoveries. The method was successfully applied to 31 OF specimens, describing everolimus detection in OF for the first time. Conclusion: The proposed method is sensitive enough for the detection of OF trough concentrations in patients receiving immunosuppressants when using an appropriate OF collector.

[Influence of donor age and recipient gender on survival in transplantation due to hepatocarcinoma]. / Influencia de la edad del donante y del sexo del receptor en la supervivencia de los pacientes trasplantados por hepatocarcinoma.

Hepatocarcinoma (HCC) is one of the most frequent indications for liver transplantation. Survival in patients undergoing transplantation due to HCC is similar to that in patients undergoing this procedure for other indications. However, the current shortage of donors has led to longer waiting lists with a consequent risk of tumor progression. The use of older donors in these patients could increase the donor pool and shorten the time spent on the waiting list. We analyzed the influence of donor age on survival in 78 patients with HCC who underwent transplantation in the Santiago de Compostela Hospital between 1994 and 2003.

Influencia de la edad del donante y del sexo del receptoren la supervivencia de los pacientes trasplantadospor hepatocarcinoma / Influence of donorage and recipient gender on survival in transplantarion due to hepatocarcinoma

En la actualidad el hepatocarcinoma (HCC) es una de las indicacionesmás frecuentes de trasplante hepático. La supervivenciade los pacientes trasplantados por HCC es similar aotras indicaciones. Sin embargo, la escasez de donante conllevaun aumento del tiempo en lista de espera, con el consiguienteriesgo de progresión tumoral. En estos pacientes, lautilización de donantes añosos podría aumentar el pool dedonantes y acortar el tiempo en lista de espera. En este estudioanalizamos la influencia de la edad del donante en la supervivenciade 78 pacientes con HCC trasplantados en elHospital Clínico de Santiago entre 1994 y 2003 (AU)

Hepatocarcinoma (HCC) is one of the most frequent indicationsfor liver transplantation. Survival in patients undergoingtransplantation due to HCC is similar to that in patientsundergoing this procedure for other indications.However, the current shortage of donors has led to longerwaiting lists with a consequent risk of tumor progression.The use of older donors in these patients could increase thedonor pool and shorten the time spent on the waiting list.We analyzed the influence of donor age on survival in 78 patientswith HCC who underwent transplantation in the Santiagode Compostela Hospital between 1994 and 2003 (AU)

Malaria infection through multiorgan donation: an update from Spain.

During the last years, immigration has increased and, consequently, the pool of foreign donors and associated infectious diseases from exotic countries (especially from the tropics) has also increased. Only a few cases of malaria transmitted via different donation sources have been published. In the present report, a Plasmodium vivax transmitted through a multiorgan donation is reported. In conclusion, we discuss the features related with the diagnosis, the treatment, and the special characteristics of a case in which the liver and not any other organ is the reservoir of the plasmodium.

Dos casos de hipertensión portal segmentaria en relación con la enfermedad no pancreática / Two cases of segmental portal hypertension associated with pancreatic disease

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[Liver abnormalities in adult celiac disease. Clinicopathologic characterization and outcome after therapy]. / Alteraciones hepáticas en la enfermedad celíaca del adulto. Caracterización clínico-patológica y evolución.

BACKGROUND AND AIM: The clinical manifestations of adult celiac disease are highly varied and may include liver disease. The present study aimed to characterize liver abnormalities and outcome after a gluten-free diet in patients with celiac disease diagnosed in a hepatology clinic. MATERIAL AND METHOD: The clinical records of patients diagnosed with celiac disease during a 7-year period were reviewed. RESULTS: Of 1916 patients attending a first consultation at the clinic, 10 were finally diagnosed with celiac disease. All patients had been referred for evaluation of persistent elevation of liver enzyme levels. All patients were young (mean age 30 years, range 21-39 years) and there were more women than men (eight women, 80%). Six patients (60%) had additional manifestations attributable to undiagnosed celiac disease, sometimes since childhood. In all patients, elevation of liver enzyme levels was moderate and overall liver function was preserved. Liver biopsy was performed in five patients and all showed chronic periportal infiltrate. Immunohistochemical studies revealed that the infiltrate was mainly composed of CD8-positive T lymphocytes. In all patients, a gluten-free diet was followed by normalization of liver enzyme levels. CONCLUSIONS: Although celiac disease is not highly frequent, it should be considered in the differential diagnosis of patients with persistent abnormalities of liver markers. The most conspicuous histopathological change is periportal T-cell infiltrate. Liver abnormalities in celiac disease are generally mild and improve after a gluten-free diet.

Alteraciones hepáticas en la enfermedad celíaca del adulto. Caracterización clínico-patológica y evolución / Liver abnormalities in adult celiac disease. Clinicopathologic characterization and outcome after therapy

Introducción y objetivo: Las manifestaciones clínicas de la enfermedad celíaca del adulto son muy variadas y pueden incluir alteraciones hepáticas. El objetivo del presente estudio fue caracterizar las alteraciones hepáticas y su evolución con el tratamiento de los pacientes celíacos diagnosticados en una consulta de hepatología. Material y método: Revisión de los historiales clínicos de los pacientes adultos finalmente diagnosticados de enfermedad celíaca en un período de 7 años. Resultados: De un total de 1.916 pacientes adultos vistos por primera vez en dicha consulta, 10 pacientes fueron finalmente diagnosticados de enfermedad celíaca. Todos habían sido remitidos por elevación persistente de enzimas hepáticas. Todos eran jóvenes (edad media, 30 años; intervalo, 21-39 años) y con predominio de mujeres (8 casos; 80%); 6 pacientes (60%) habían presentado clínica atribuible a la enfermedad celíaca (no diagnosticada), a veces desde su infancia. En todos los casos la elevación de enzimas hepáticas era moderada y la función hepática de síntesis estaba conser vada. En la biopsia hepática (de los 5 pacientes en que fue realizada) se observó un infiltrado inflamatorio crónico periportal a expensas de linfocitos T mayoritariamente CD8+. La supresión del gluten de la dieta consiguió normalizar los valores de las enzimas hepáticas en todos los casos. Conclusiones: A pesar de que en general no es muy frecuente, se debe tener en cuenta la enfermedad celíaca en el diagnóstico diferencial de las alteraciones persistentes de la biología hepática en el adulto. El hallazgo histopatológico más constante es el infiltrado periportal por linfocitos T. La dieta sin gluten normaliza dichas alteraciones, que suelen ser escasamente graves

Background and aim: The clinical manifestations of adult celiac disease are highly varied and may include liver disease. The present study aimed to characterize liver abnormalities and outcome after a gluten-free diet in patients with celiac disease diagnosed in a hepatology clinic. Material and method: The clinical records of patients diagnosed with celiac disease during a 7-year period were reviewed. Results: Of 1916 patients attending a first consultation at the clinic, 10 were finally diagnosed with celiac disease. All patients had been referred for evaluation of persistent elevation of liver enzyme levels. All patients were young (mean age 30 years, range 21-39 years) and there were more women than men (eight women, 80%). Six patients (60%) had additional manifestations attributable to undiagnosed celiac disease, sometimes since childhood. In all patients, elevation of liver enzyme levels was moderate and overall liver function was preserved. Liver biopsy was performed in five patients and all showed chronic periportal infiltrate. Immunohistochemical studies revealed that the infiltrate was mainly composed of CD8-positive T lymphocytes. In all patients, a gluten-free diet was followed by normalization of liver enzyme levels. Conclusions: Although celiac disease is not highly frequent, it should be considered in the differential diagnosis of patients with persistent abnormalities of liver markers. The most conspicuous histopathological change is periportal T-cell infiltrate. Liver abnormalities in celiac disease are generally mild and improve after a gluten-free diet

Alteraciones hepáticas en la enfermedad celíaca del adulto. Caracterización clínico-patológica y evolución / Liver abnormalities in adult celiac disease. Clinicopathologic characterization and outcome after therapy

Introducción y objetivo: Las manifestaciones clínicas de la enfermedad celíaca del adulto son muy variadas y pueden incluir alteraciones hepáticas. El objetivo del presente estudio fue caracterizar las alteraciones hepáticas y su evolución con el tratamiento de los pacientes celíacos diagnosticados en una consulta de hepatología. Material y método: Revisión de los historiales clínicos de los pacientes adultos finalmente diagnosticados de enfermedad celíaca en un período de 7 años. Resultados: De un total de 1.916 pacientes adultos vistos por primera vez en dicha consulta, 10 pacientes fueron finalmente diagnosticados de enfermedad celíaca. Todos habían sido remitidos por elevación persistente de enzimas hepáticas. Todos eran jóvenes (edad media, 30 años; intervalo, 21-39 años) y con predominio de mujeres (8 casos; 80%); 6 pacientes (60%) habían presentado clínica atribuible a la enfermedad celíaca (no diagnosticada), a veces desde su infancia. En todos los casos la elevación de enzimas hepáticas era moderada y la función hepática de síntesis estaba conser vada. En la biopsia hepática (de los 5 pacientes en que fue realizada) se observó un infiltrado inflamatorio crónico periportal a expensas de linfocitos T mayoritariamente CD8+. La supresión del gluten de la dieta consiguió normalizar los valores de las enzimas hepáticas en todos los casos. Conclusiones: A pesar de que en general no es muy frecuente, se debe tener en cuenta la enfermedad celíaca en el diagnóstico diferencial de las alteraciones persistentes de la biología hepática en el adulto. El hallazgo histopatológico más constante es el infiltrado periportal por linfocitos T. La dieta sin gluten normaliza dichas alteraciones, que suelen ser escasamente graves

Background and aim: The clinical manifestations of adult celiac disease are highly varied and may include liver disease. The present study aimed to characterize liver abnormalities and outcome after a gluten-free diet in patients with celiac disease diagnosed in a hepatology clinic. Material and method: The clinical records of patients diagnosed with celiac disease during a 7-year period were reviewed. Results: Of 1916 patients attending a first consultation at the clinic, 10 were finally diagnosed with celiac disease. All patients had been referred for evaluation of persistent elevation of liver enzyme levels. All patients were young (mean age 30 years, range 21-39 years) and there were more women than men (eight women, 80%). Six patients (60%) had additional manifestations attributable to undiagnosed celiac disease, sometimes since childhood. In all patients, elevation of liver enzyme levels was moderate and overall liver function was preserved. Liver biopsy was performed in five patients and all showed chronic periportal infiltrate. Immunohistochemical studies revealed that the infiltrate was mainly composed of CD8-positive T lymphocytes. In all patients, a gluten-free diet was followed by normalization of liver enzyme levels. Conclusions: Although celiac disease is not highly frequent, it should be considered in the differential diagnosis of patients with persistent abnormalities of liver markers. The most conspicuous histopathological change is periportal T-cell infiltrate. Liver abnormalities in celiac disease are generally mild and improve after a gluten-free diet

Linfangioleiomiomatosis en una paciente menopáusica en tratamiento estrogénico / Lymphangioleiomiomatosis in a menopausic patient in estrogenic treatment

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