[Utility of the AGREE tool for the development and evaluation of clinical protocols: From theory to clinical practice]. / Utilidad del instrumento AGREE para la elaboración y la evaluación de protocolos clínicos: de la teoría a la práctica clínica.

INTRODUCTION AND OBJECTIVE: Clinical protocols are tools for the delivery of optimal and quality healthcare. However, there are often shortcomings in the quality of their design that invalidate their implementation. The aim of this study is to describe a systematic evaluation of clinical protocols, to analyse their quality in order to enable their implementation. MATERIALS AND METHODS: Descriptive study that included the clinical protocols assessed by the Committee of Reviewers of Clinical Practice Recommendations and Health Technologies of a tertiary hospital during 11years of its existence between 2013 and 2023. The AGREE instrument was used to assess the quality of the protocols received, calculating standardised scores by item and domain, and categorising them into: a)excellent (90-100%), b)good (70-89%), c)improvable (50-69%), d)very improvable (30-49%), e)deficient (10-29%), and f)very deficient: 0-9%. RESULTS: Of the 59 documents received by the Commission, 32 were subsidised for AGREE evaluation. The highest scoring domain was «Scope and objective¼, with excellent scores for 29 protocols; the remaining domains had scores ranging from 58.5%-100% for «Rigour in elaboration¼ and 0-100% for «Independence¼. By items, scores ranged from 85.7-100% for «Target users of the protocol are clearly defined¼ to 0-100% for the items «Potential costs of implementing recommendations¼ and «Conflict of interest¼. Of the 32 protocols, 9 were highly recommended, 22 were recommended with modifications/conditions and one was not recommended. CONCLUSIONS: The AGREE tool makes it possible to systematize both the drafting of clinical protocols by the authors and their evaluation by the Clinical Practice Recommendations and Health Technologies Review Committee. This makes it possible to have applicable and quality protocols in our hospital, which results in an improvement in the quality of healthcare.

Analysis of the expression of the Serpina1 gene in SARS-CoV-2 infection: study of a new biomarker.

INTRODUCTION: The SERPINA1 gene encodes the protein Alpha-1 Antitrypsin (AAT1). Possible imbalances between the concentrations of proteases and antiproteases (AAT1) can lead to the development of serious pulmonary and extrapulmonary pathologies. In this work we study the importance of this possible imbalance in patients with COVID-19. OBJECTIVES: To correlate the severity of the symptoms of SARS-COV-2 infection with the AAT1 concentrations at diagnosis of the disease. METHODS: An observational, prospective, cross-sectional, non-interventional, analytical study was carried out where 181 cases with COVID-19 admitted to the "Lozano Blesa" University Clinical Hospital of Zaragoza were selected. The concentration of AAT1 was studied in all of them and this was correlated with the clinical aspects and biochemical parameters at hospital admission. RESULTS: 141 cases corresponded to patients with severe COVID and 40 patients with mild COVID. AAT1 levels were positively correlated with the days of hospitalization, severity, C-Reactive Protein, ferritin, admission to Intensive Care, and death, and presented a negative correlation with the number of lymphocytes/mm3. AAT1 concentrations higher than 237.5 mg/dL allowed the patient to be classified as "severe" (S72%; E78%) and 311.5 mg/dL were associated with the risk of admission to Intensive Care or Exitus (S67%; E79%). CONCLUSIONS: Levels of the SERPINA1 gene expression product, AAT1, correlate with the severity of COVID-19 patients at diagnosis of the disease, being useful as a prognostic biomarker.

Recomendaciones para el tratamiento oral de pacientes adultos con enfermedad de Gaucher tipo 1 / Recommendations for oral treatment for adult patients with type 1 Gaucher disease

Revisión de la evidencia científica sobre el tratamiento oral de pacientes adultos con enfermedad de Gaucher tipo 1 (EG1), con formato de guía clínica, según la normativa Agree II. Se describen las principales diferencias entre los 2 tratamientos orales disponibles actualmente para el tratamiento de esta entidad (miglustat y eliglustat).En esta revisión se recuerda que los criterios para iniciar el tratamiento oral en los pacientes con EG1 deben valorarse de forma individualizada. Si bien miglustat y eliglustat son inhibidores de la enzima glucosilceramida sintetasa, los 2 presentan diferentes mecanismos de acción y propiedades farmacológicas y nunca se deben considerar como equivalentes. Miglustat está indicado en pacientes con EG1 no grave que no pueden recibir otro tratamiento de primera línea, mientras que eliglustat está indicado en pacientes con EG1 con cualquier gravedad, en primera línea y sin necesidad de estabilización previa con tratamiento de reemplazo enzimático. Es importante enfatizar que para iniciar tratamiento con eliglustat debemos conocer el fenotipo metabólico CYP2D6 y que su asociación con fármacos metabolizados a través de los citocromos CYP2D6 y CYP3A4 –o bien que utilicen la glucoproteína P– se debe evaluar individualmente. Durante el embarazo se debe evitar el uso de eliglustat, pudiéndose emplear únicamente el tratamiento de reemplazo enzimático. A diferencia de miglustat, cuyos efectos adversos han limitado su utilización, eliglustat no solo ha demostrado una eficacia similar a la del tratamiento de reemplazo enzimático, sino que ha demostrado mejoría en la calidad de vida de los pacientes EG1. (AU)

This work is a review of the scientific evidence on the oral treatment of adult patients with Gaucher disease type 1 (GD1) with a clinical guideline format according to the Agree II regulations. It describes the main differences between the 2 oral treatments currently available for treating this disease (miglustat and eliglustat).This review reminds us that the criteria for starting oral treatment in patients with GD1 must be assessed individually. Although miglustat and eliglustat are both glucosylceramide synthase enzyme inhibitors, they have different mechanisms of action and pharmacological properties and should never be considered equivalent. Miglustat is indicated in patients with non-severe GD1 who cannot receive other first-line treatments, while eliglustat is indicated as first-line treatment for patients with GD1 of any severity without the need for prior stabilization with enzyme replacement therapy. It is important to emphasize that in order to start treatment with eliglustat, we must know the CYP2D6 metabolic phenotype and its association with drugs metabolized through the CYP2D6 and CYP3A4 cytochromes –or alternatively those that use P-Glycoprotein– must be evaluated on an individual basis. During pregnancy, the use of eliglustat should be avoided; only enzyme replacement therapy can be used. Unlike miglustat, whose adverse effects have limited its use, eliglustat has not only demonstrated similar efficacy to enzyme replacement therapy but has also been shown to improve the quality of life of patients with GD1. (AU)

Recommendations for oral treatment for adult patients with type 1 Gaucher disease.

This work is a review of the scientific evidence on the oral treatment of adult patients with Gaucher disease type 1 (GD1) with a clinical guideline format according to the Agree II regulations. It describes the main differences between the two oral treatments currently available for treating this disease (miglustat and eliglustat). This review reminds us that the criteria for starting oral treatment in patients with GD1 must be assessed individually. Although miglustat and eliglustat are both glucosylceramide synthase (GCS) enzyme inhibitors, they have different mechanisms of action and pharmacological properties and should never be considered equivalent. Miglustat is indicated in patients with non-severe GD1 who cannot receive other first-line treatments, while eliglustat is indicated as first-line treatment for patients with GD1 of any severity without the need for prior stabilization with enzyme replacement therapy (ERT). It is important to emphasize that in order to start treatment with eliglustat, we must know the CYP2D6 metabolic phenotype and its association with drugs metabolized through the CYP2D6 and CYP3A4 cytochromes-or alternatively those that use P-Glycoprotein must be evaluated on an individual basis. During pregnancy, the use of eliglustat should be avoided; only ERT can be used. Unlike miglustat, whose adverse effects have limited its use, eliglustat has not only demonstrated similar efficacy to ERT but has also been shown to improve the quality of life of patients with GD1.

A new and simple scoring system to predict overall survival after irradiation for metastatic spinal cord compression.

PURPOSE: To develop a model that predicts survival in patients irradiated for metastatic spinal cord compression (MSCC), hence assisting in the decision between a short and a long-course radiotherapy (RT) regimen. METHODS: 138 patients diagnosed with MSCC and treated with RT alone were included. Based on a multivariate analysis, a scoring system was developed. It included four prognostic variables: age, number of vertebrae, ECOG and histology. Total scores ranged between 14 and 24 points and patients were divided into two groups. RESULTS: The 6-month survival rate was 22% for patients with a score of 14-18 points; and 69% for patients with a score of 19-24 points (P < 0.001). The system exhibits a high specificity and positive predictive value and an appropriate discriminative ability. CONCLUSIONS: Patients with scores between 19 and 24 points were found to survive longer, thus a long-course RT appears to be more appropriate.

Survival after biochemical failure in prostate cancer treated with radiotherapy: Spanish Registry of Prostate Cancer (RECAP) database outcomes.

INTRODUCTION: The clinical course in patients with prostate cancer (PCa) after biochemical failure (BF) has received limited attention. This study analyzes survival time from recurrence, patterns of progression, and the efficacy of salvage therapies in patients treated with radical or postoperative radiotherapy (RT). METHODS: This is a multicenter retrospective comparative study of 1135 patients diagnosed with BF and treated with either radical (882) or postoperative (253) RT. Data correspond to the RECAP database. Clinical, tumor, and therapeutic characteristics were collected. Descriptive statistics, survival estimates, and comparisons of survival rates were calculated. RESULTS: Time to BF from initial treatment (RT or surgery) was higher in irradiated patients (51 vs 37 months). At a median follow-up of 102 months (14-254), the 8-year cause-specific survival (CSS) was 80.5%, without significant differences between the radical (80.1%) and postoperative (83.4%) RT groups. The 8-year metastasis-free survival rate was 57%. 173 patients (15%) died of PCa and 29 (2.5%) of a second cancer. No salvage therapy was given in 15% of pts. Only 5.5% of pts who underwent radical RT had local salvage treatment and 71% received androgen deprivation (AD) ± chemotherapy. The worst outcomes were in patients who developed metastases after BF (302 pts; 26.5%) and in cases with a Gleason > 7. CONCLUSIONS: In PCa treated with radiotherapy, median survival after BF is relatively long. In this sample, no differences in survival rates at 8-years have been found, regardless of the time of radiotherapy administered. AD was the most common treatment after BF. Metastases and high Gleason score are adverse variables. To our knowledge, this is the first study to compare outcomes after BF among patients treated with primary RT vs. those treated with postoperative RT and to evaluate recurrence patterns, treatments administered, and causes of death. The results allow avoiding overtreatment, improving quality of life, without negatively affecting survival.

Computerized registry of patients with hemorrhagic hereditary telangiectasia (RiHHTa Registry) in Spain: Objectives, methods, and preliminary results. / Registro informatizado de la telangiectasia hemorrágica hereditaria (Registro RiHHTa) en España: objetivos, métodos y resultados preliminares.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is a rare disease with autosomal dominant inheritance that causes systemic vascular affectation. MATERIAL AND METHOD: After development a multicentric Spanish national registry, called RiHHTa, main clinical manifestations and diagnostic procedures of the first patients introduced are described. RESULTS: 141 patients were included, of which 91 (64.5%) were women. The mean age at diagnosis was 42 years. Mutations in the ACVRL1 gene predominated over the ENG gene. The initial symptom was recurrent epistaxis in 130 (92.2%) patients and in three (2.1%), brain abscess. Pulmonary arteriovenous (AV) fistula were detected in 36 (45%) of the 79 patients who underwent thoracic CT angiography. The contrast echocardiography detected very few bubbles (grade I) or none, in 36 (45%) of these 79 affected patients. In 43 (67.2%) of the 64 patients with an abdominal CT angiography, hepatic vascular malformations were detected, mostly telangiectasias, AV and arterio-portal fistula, and extrahepatic in 14 (10%) subjects. More than half of the patients were screened for the presence of brain arteriovenous malformations which was found in 3.9% of them. The upper part of the intestinal tube was the most (95%) affected region. CONCLUSION: The RiHHTa Registry allows improving the management of patients with HHT. An inadequate use of thoracic CT angiography and the usefulness of abdominal CT angiography has been detected in order to define subtypes of hepatic vascular involvement and detect extrahepatic vascular involvement.

The pathophysiology of Fabry disease. / Fisiopatología de la enfermedad de Fabry.

Fabry disease is a lysosomal condition with systemic clinical expression, caused by the tissue deposit of globotriaosylceramide, due to a deficit in its degradation. As with most lysosomal diseases, the presence of a mutation in a gene does not explain the pathophysiological disorders shown by patients. We conducted a comprehensive review of the pathogenic mechanisms that occur in Fabry disease.

Infrastructures, treatment modalities, and workload of radiation oncology departments in Spain with special attention to prostate cancer.

AIM: The purpose of the study was to describe infrastructures, treatment modalities, and workload in radiation oncology (RO) in Spain, referred particularly to prostate cancer (PC). METHODS: An epidemiologic, cross-sectional study was performed during 2008-2009. A study-specific questionnaire was sent to the 108 RO-registered departments. RESULTS: One hundred and two departments answered the survey, and six were contacted by telephone. Centers operated 236 treatment units: 23 (9.7 %) cobalt machines, 37 (15.7 %) mono-energetic linear accelerators, and 176 (74.6 %) multi-energy linear accelerators. Sixty-one (56.4 %) and 33 (30.5 %) departments, respectively, reported intensity-modulated radiation therapy (IMRT) and image-guided RT (IGRT) capabilities; three-dimensional-conformal RT was used in 75.8 % of patients. Virtual simulators were present in 95 departments (88.0 %), 35 use conventional simulators. Fifty-one departments (47.2 %) have brachytherapy units, 38 (35.2 %) perform prostatic implants. Departments saw a mean of 24.9 new patients/week; the number of patients treated annually was 102,054, corresponding to 88.4 % of patients with a RT indication. In 56.5 % of the hospitals, multidisciplinary teams were available to treat PC. CONCLUSIONS: Results provide an accurate picture of current situation of RO in Spain, showing a trend toward the progressive introduction of new technologies (IMRT, IGRT, brachytherapy).

Respuesta precoz a idursulfasa en un paciente de 31 años de edad con síndrome de Hunter / Early response to idursulfase in a 31-year old male patient with Hunter syndrome

La respuesta al tratamiento de sustitución enzimática [TSE] en el síndrome de Hunter [MPS II] se produce en la mayoría de los pacientes de forma temprana tras su inicio y persiste durante los primeros 12 a 18 meses. Sin embargo, casi todos los pacientes con MPS II tienen formas graves de la enfermedad y fallecen de manera prematura. Más del 90% de los sujetos fallecen antes de los 25 años y solamente una minoría sobrevive por encima de los 30. Existe información muy limitada acerca de la respuesta temprana al TSE entre pacientes adultos con síndrome de Hunter. Notificamos el caso de un varón de 31 años con MPS II, con una invalidez articular grave, pero una discapacidad cognitiva leve, que recibió tratamiento con idursulfasa durante seis meses. El modelo de respuesta observado fue similar al esperado en pacientes más jóvenes. La mejoría observada en la movilidad articular sugiere que pacientes de mayor edad, con afectación articular, pueden beneficiarse de la terapia con Idursulfasa incluso cuando el tratamiento se inicia en estadios más tardíos de la enfermedad(AU)

The response to Enzyme Replacement Therapy (ERT) in Hunter syndrome (MPS II) occurs early in most of the patients after its initiation and continues during the first 12-18 months. However, almost all the patients with MPS II have severe forms of the disease and death occurs prematurely. More than 90% of subjects die before 25 years, and only a minority will survive after the age of 30. There is very limited information on early response to ERT among adult patients with Hunter's syndrome. We report the case of a 31 year-old male with MPS II, with a remarkably severe joint disability, but mild cognitive impairment, who was treated with idursulfase for six months. The pattern of response observed, was similar to what can be expected in younger patients. The amelioration in joint mobility observed in this case suggests that older patients with advanced articular involvement may benefit from idursulfase, even when therapy is started in later stages of the disease(AU)

[Early response to idursulfase in a 31-year old male patient with Hunter syndrome]. / Respuesta precoz a idursulfasa en un paciente de 31 años de edad con síndrome de Hunter.

The response to Enzyme Replacement Therapy (ERT) in Hunter syndrome (MPS II) occurs early in most of the patients after its initiation and continues during the first 12-18 months. However, almost all the patients with MPS II have severe forms of the disease and death occurs prematurely. More than 90% of subjects die before 25 years, and only a minority will survive after the age of 30. There is very limited information on early response to ERT among adult patients with Hunter's syndrome. We report the case of a 31 year-old male with MPS II, with a remarkably severe joint disability, but mild cognitive impairment, who was treated with idursulfase for six months. The pattern of response observed, was similar to what can be expected in younger patients. The amelioration in joint mobility observed in this case suggests that older patients with advanced articular involvement may benefit from idursulfase, even when therapy is started in later stages of the disease.

[Rare complication in a patient with giant cell arteritis]. / Paciente con complicación poco frecuente de arteritis de células gigantes.

Giant cell arteritis (temporal arteritis) is a chronic vasculitis that usually affects older people. Although this is a systemic disease, it most often affects the cranial arteries. The most frequent complication of this disorder is visual loss. We report the case of a patient who suffered several rare complications, including tongue necrosis, as a result of being diagnosed with giant cell arteritis following the start of treatment.

Signo del tres invertido y pirosis / No disponible

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