PICO questions and DELPHI methodology for improving the management of patients with acute hepatic porphyria.

BACKGROUND: Acute hepatic porphyrias (AHPs) are a group of rare diseases that encompasses acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and 5-aminolaevulinic acid dehydratase deficiency porphyria. Symptoms of AHP are nonspecific which, together with its low prevalence, difficult the diagnosis and follow-up of these patients. MATERIAL AND METHODS: This project used DELPHI methodology to answer PICO questions related to management of patients with AHPs. The objective was to reach a consensus among multidisciplinary porhyria experts providing answers to those PICO questions for improving diagnosis and follow-up of patients with AHP. RESULTS: Ten PICO questions were defined and grouped in four domains: 1. Biochemical diagnosis of patients with AHP. 2. Molecular tests for patients with AHP. 3. Follow-up of patients with AHP. 4. Screening for long-term complications of patients with AHP. CONCLUSIONS: PICO questions and DELPHI methodology have provided a consensus on relevant and controversial issues for improving the management of patients with AHP.

Systemic phenotype of sarcoidosis associated with radiological stages. Analysis of 1230 patients.

BACKGROUND: To analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe. METHODS: The SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al. RESULTS: We analyzed 1230 patients (712 female, mean age 47 yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (n = 98), stage I (n = 395), stage II (n = 500), stage III (n = 195) and stage IV (n = 42). Women were overrepresented in patients presenting with extrathoracic/extrapulmonary disease, while the diagnosis was made at younger ages in patients presenting with BHL, and at older ages in those presenting with pulmonary fibrosis (q values <0.05). Multivariable adjusted analysis showed that patients presenting with pulmonary involvement (especially those with stages II and III) had a lower frequency of concomitant systemic involvement in some specific extrathoracic clusters (cutaneous-adenopathic/musculoskeletal, ENT and neuro-ocular/OCCC) but a higher frequency for others (hepatosplenic), in comparison with patients with extrapulmonary involvement (stages 0 and I). The presence of either BHL or fibrotic lesions did not influence the systemic phenotype of patients with pulmonary involvement. CONCLUSIONS: The key determinant associated with a differentiated systemic phenotype of sarcoidosis at diagnosis was interstitial pulmonary involvement rather than the individual Scadding radiological stage.

Clinical characteristics of adult patients with inborn errors of metabolism in Spain: A review of 500 cases from university hospitals.

Patients with inborn errors of metabolism (IEMs) have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification. The most prevalent group of IEMs was amino acid disorders, with 108 (21.6%) patients diagnosed with phenylketonuria. Lysosomal storage disorders were the second group, in which 32 (6.4%) and 25 (5%) patients had Fabry disease and Gaucher disease respectively. The great clinical heterogeneity, the significant delay in diagnosis after symptom onset, the existence of some degree of physical dependence in a great number of patients, the need for a multidisciplinary and coordinated approach, and the lack of specific drug treatment are common features in this group of conditions.

The role of 18FDG, 18FDOPA PET/CT and 99mTc bone scintigraphy imaging in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes that stain positively for CD68 marker but not express CD1a and S100 proteins. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. Multisystemic involvement leads to a wide variety of clinical manifestations that results in a poor prognosis although recent advances in treatment. We present the clinical, nuclear medicine findings and therapeutic aspects of a serie of 6 patients with histopathological diagnosis of ECD, who have undergone both bone scintigraphy (BS) and 18F-fluorodeoxyglucose (18FDG)-PET/CT scans in our institution. A complementary 18F-fluorodopa (18FDOPA)-PET/CT was performed in one case. Three different presentations of the disease were observed in our casuistic: most indolent form was a cutaneous confined disease, presented in only one patient. Multifocal involvement with central nervous system (CNS) preservation was observed in two patients. Most aggressive form consisted in a systemic involvement with CNS infiltration, presented in three patients. In our experience neurological involvement, among one case with isolate pituitary infiltration, was associated with mortality in all cases. 18FDG-PET/CT and BS were particularly useful in despite systemic involvement; locate the site for biopsy and the treatment response evaluation. By our knowledge, 18FDOPA-PET/CT not seems useful in the initial staging of ECD. A baseline 18FDG-PET/CT and BS may help in monitoring the disease and could be considered when patients were incidentally diagnosed and periodically 18FDG-PET/CT must be performed in the follow up to evaluate treatment response.

[Drug-drug interactions in multicentre polypathological polymedicated patients]. / Interacciones medicamentosas en pacientes pluripatológicos.

OBJECTIVE: To determine the prevalence of relevant drug-drug interactions (DDIs) and associated predictor factors in a sample of patients with multiple complex chronic diseases (polypathological patients) receiving multiple drug therapy. Our secondary objective was to determine the acceptance of a drug interaction reporting program with recommendations addressed to the prescribing physicians. SUBJECTS AND METHODS: A cross-sectional study performed in three primary care centres assigned to a teaching hospital. All patients with 2 or more chronic diseases and treated simultaneously with 5 or more drugs were recruited in the study. DDIs were detected by using Drug-Reax System((R)) (Micromedex) program, the Drug Data Base (Bot) Spanish General Council of Official Colleges of Pharmacists or literature search when needed. Those DDIs which, according to the opinion of the pharmacist investigators, required any intervention were considered relevant. Acceptance of the reported DDI recommendations was evaluated by means of a survey addressed by primary care physicians ("acceptable," pertinent recommendation to modify treatment). RESULTS: A total of 283 polypathological polymedicated patients were included. Mean age was 74.5 years (range 43-100 years). Mean number of diseases per patient was 2.5 and prescriptions 9.7). Out of a total of 2748 drug prescriptions, 1053 DDIs in 250 patients (96.5%) were identified. Of these, 45% were filtered as relevant DDIs. The presence of ischemic heart disease, two or more hospital admissions and having received 7 or more prescriptions were associated with the presence of DDIs. 177 informs containing 473 recommendations about DDIs were sent to primary care physicians from our Pharmacy Department. 339 recommendations were answered by primary care physicians, and 84% were favourably accepted. CONCLUSIONS: Almost every polypathological polymedicated patient is exposed to at least one DDI and about a 60% would require any intervention. Appropriate filtering and personalising recommendations in a collaborative way may represent an adequate manner to improve the risk-benefit ratio of the drug prescriptions.

Kaposiform hemangioendothelioma.

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular neoplasm that mainly occurs during childhood. It generally originates on the skin, usually affecting deeper tissue by infiltrative growth. It appears as one or multiple masses, and in most cases is associated to consumptive coagulopathy (Kasabach-Merritt syndrome), and lymphangiomatosis. Although visceral involvement is very uncommon, several cases with bone, retroperitoneal, or mediastinal involvement have been described. These tumors tend to be locally invasive, but are not known to produce distant metastases. The development of KHE in adolescents or in adults is very rare, but cases have also been described. Several factors are associated with the outcome of patients with KHE: accessibility to surgical excision, location (cutaneous versus visceral), size of tumoral mass, clinical response to interferon and glucocorticoids, and the absence of lymphangiomatosis and Kasabach-Merritt syndrome, may result in partial remissions. On the other hand, bulk visceral masses lead to a 40-50% mortality rate, mainly due to progressive failure of the infiltrated organ(s), in spite of interferon, glucocorticoids, and combined chemotherapy. In conclusion, the onset of a consumptive coagulopathy following the presence of a vascular tumor, in children as well as in older patients, should spark suspicion of KHE, among other entities.

[Risk factors associated to mortality and functional deterioration in pluripathologic patients with heart failure]. / Factores de riesgo asociados a la mortalidad y al deterioro funcional en la insuficiencia cardíaca del paciente pluripatológico.

OBJECTIVES: Incidence, clinical features, and outcome of heart failure in patients with other chronic pathologies have been scarcely evaluated. The aim of the present study was to prospectively assess these issues, and the prognostic and factors associated to functional deterioration in a cohort of pluripathologic patients (PP) with heart failure (HF), attended in areas of Internal Medicine of a tertiary teaching hospital in the south of Spain. METHODS: Prospective observational study of all patients, attended in Internal Medicine areas of a tertiary teaching hospital, during June 2003. Patients were stratified in two cohorts: PP with HF as main category (PP-HF), and PP with no HF. Patients with two or more chronic diseases, distributed into seven categories (defined by a panel of experts) were considered PP. Incidence of PP-HF, functional evaluation (at baseline, at admission, and at discharge), and burden of hospital care (by means of urgent and programmed assistances, as well as episodes of hospitalization) in the last 12 months were analyzed. Chi-square, Fisher, "t" Student or U-Mann-Whitney and Rho de Spearman test were used for group comparisons. A multivariate analysis of predictors of survival and functional deterioration (fall in Barthel's scale > or = 10 points between baseline-discharge values) was performed in the PP-HF cohort. A p < 0.05 was considered significant. RESULTS: 132 pluripathologic patients (55 in PP-HF, and 77 in PP cohort) were included, from a global cohort of 339. Global incidence of PP-HF was 38,9/100 admissions. Mean age of PP-HF patients was 78, 50.9% were females; mortality rate and mean hospital stay were 23.6% and 12.2 days, respectively. Patients of PP-HF cohort compared to those of PP, were older (78 +/- 9.5 vs 73 +/- 10.8; p < 0.005), and suffered more chronic diseases (p = 0.0001). Functional abilities (at baseline, at admission, and at discharge), mean hospital stay, mortality, and burden of care in the previous 12 months were similar. Better functional abilities (OR: 1.136 [0.94-1.842]; p = 0.055), and less associated chronic diseases (OR: 0.072 [0.006-0.943], p = 0.045) were independently associated to survival; while older age (OR: 1,217 [1.016-1.457]; p = 0.03), and a poorer functional status at baseline (OR:1.80 [1.019-1.144]; p = 0.01) were associated to functional deterioration. CONCLUSIONS: Heart failure prevalent disease in pluripathologic patients. Specific factors associated to survival were gender and less chronic conditions; while those associated to functional deterioration during hospital stay were age and a poor functional status at baseline.

[Decreased activity of 11-beta-hydroxysteroid dehydrogenase in patients with Cushing's syndrome]. / Disminución de la actividad de la 11-beta-hidroxiesteroide deshidrogenasa en pacientes con síndrome de Cushing.

BACKGROUND: To study 11 beta-hydroxysteroid dehydrogenase activity in Cushing's syndrome. PATIENTS AND METHOD: Measurements of free cortisol, cortisone, tetrahydrocortisol and tetrahydrocortisone in 24 h urine samples of patients with Cushing's syndrome and controls. RESULTS: The cortisol to cortisone and tetrahydrocortisol to tetrahydrocortisone relationship was significant (in controls, r = 0.70; p < 0.0001, and r = 0.75; p < 0.0001) respectively, but it was not in patients with Cushing's syndrome. CONCLUSIONS: 11 beta-hydroxysteroid dehydrogenase activity is decreased in patients with Cushing's syndrome.

[Study of the gene of hemochromatosis in first degree relatives of patient with porphyria cutanea tarda]. / Estudio del gen de la hemocromatosis en familiares en primer grado de una paciente con porfiria cutánea tarda.

BACKGROUND: Porphyria cutanea tarda (PCT) is characterized by a deficiency of uroprophyrinogen decarboxylase (URO-D). The activity of this enzyme is decreased in the presence of iron-dependent disorders. A relationship between the hepatic hemosiderosis, which is present in most patients with PCT, and the status of the hemochromatosis gene has been observed. Particularly, two mutations of the gene have been described, one of them (Cys282Tyr) is related to the iron overload and might influence on the development of the clinical signs of PCT. PATIENTS AND METHODS: We have measured the transferrin saturation percentage and observed the status of the hemochromatosis gene in a patient diagnosed with PCT and in five of their relatives. RESULTS: The proband and one sister had a marked increase of uroporphyrins and iron overload, and both had the mutation Cys282Tyr, which was also present in the mother. CONCLUSIONS: This is the first study measuring iron overload and hemochromatosis gene mutations in relatives, and not in patients with PCT. We think that the study of this family justifies the systematic investigation of these parameters in all first degree relatives of patients with PCT, to identify subjects at risk, who can benefit from prophylactic measures and early therapy.