Tumour Markers in the Differential Diagnosis of Patients With Isolated Involuntary Weight Loss.

BACKGROUND/AIM: Paraneoplastic syndrome symptoms include isolated involuntary weight loss (IIWL). The differential diagnosis of cancer from other diseases may require a significant number of tests. Tumour markers (TMs) can be used for the diagnosis and stratification of patients according to cancer risk. PATIENTS AND METHODS: This study included 606 patients (48% females) seen at the rapid diagnostic unit for IIWL. We determined the levels of TMs carcinoembryonic antigen, carbohydrate antigen 19-9, soluble fragments of cytokeratin 19, carbohydrate antigen 15-3, carbohydrate antigen 125, neuron specific enolase, alpha-fetoprotein, prostatic specific antigen using the multiparametric analyser COBAS 601. Two cut-off points were established, the upper reference limit described by the manufacturer and a high cut-off point suggested by Molina et al., to stratify patients according to cancer risk. RESULTS: Patients were classified according to TM levels as follows: I) all TMs below the upper reference limit; II) highest number of TMs between the two cut-offs; III) at least one TM above the higher cut-off. The odds ratio for malignancy was 4.3 for group II and 248 for group III. These results indicate that when at least one TM is above the higher cut-off, neoplasia is highly probable. CONCLUSION: TM determination allowed to establish cancer risk in patients with IIWL.

Etiologies and 12-month mortality in patients with isolated involuntary weight loss at a rapid diagnostic unit.

BACKGROUND: Numerous studies on involuntary weight loss (IWL) have been published since the 1980s, although most of them have included small samples of patients with specific symptoms. The aim of the present study was to determine the causes, demographic and clinical characteristics and mortality at 12 months in patients attended at a rapid diagnostic unit (RDU) for isolated IWL. METHODS: A single-center retrospective observational study including all patients presenting to the RDU for isolated IWL between 2005 and 2013. The following data were recorded: demographic and clinical variables, results of complementary tests (blood tests, x-rays, computed tomography scan and digestive endoscopy), main diagnosis and vital status at 12 months. RESULTS: Seven hundred and ninety-one patients met the criteria for IWL. Mean age was 67.9 years (SD 4.7), 50.4% were male and mean weight loss was 8.3 kg (SD 4.7). The cause for IWL was malignant disease in 23.6% of patients, non-malignant organic disease in 44.5%, psychiatric disorder in 29.0% and unknown in 3.2%. Overall mortality at 12 months was 18.6% (95%CI: 16.1-21.6). The mortality rate was highest in the group with malignancy (61.1%; 95%CI: 54.2-68.2). CONCLUSIONS: Almost a quarter of all patients attended at the RDU for IWL were diagnosed with cancer. Mortality at 12 months was higher in this group than in the other three. Malignancy should therefore be ruled out during the first visit for patients attended for IWL.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Coexistence of immune-mediated diseases in sarcoidosis. Frequency and clinical significance in 1737 patients.

OBJECTIVE: To analyze whether immune-mediated diseases (IMDs) occurs in sarcoidosis more commonly than expected in the general population, and how concomitant IMDs influence the clinical presentation of the disease. METHODS: We searched for coexisting IMDs in patients included in the SARCOGEAS-cohort, a multicenter nationwide database of consecutive patients diagnosed according to the ATS/ESC/WASOG criteria. Comparisons were made considering the presence or absence of IMD clustering, and odds ratios (OR) and their 95% confidence intervals (CI) were calculated as the ratio of observed cases of every IMD in the sarcoidosis cohort to the observed cases in the general population. RESULTS: Among 1737 patients with sarcoidosis, 283 (16%) patients presented at least one associated IMD. These patients were more commonly female (OR: 1.98, 95% CI: 1.49-2.62) and were diagnosed with sarcoidosis at an older age (49.6 vs. 47.5years, P<0.05). The frequency of IMDs in patients with sarcoidosis was nearly 2-fold higher than the frequency observed in the general population (OR: 1.64, 95% CI: 1.44-1.86). Significant associations were identified in 17 individual IMDs. In comparison with the general population, the IMDs with the strongest strength of association with sarcoidosis (OR>5) were common variable immunodeficiency (CVID) (OR: 431.8), familial Mediterranean fever (OR 33.9), primary biliary cholangitis (OR: 16.57), haemolytic anemia (OR: 12.17), autoimmune hepatitis (OR: 9.01), antiphospholipid syndrome (OR: 8.70), immune thrombocytopenia (OR: 8.43), Sjögren syndrome (OR: 6.98), systemic sclerosis (OR: 5.71), ankylosing spondylitis (OR: 5.49), IgA deficiency (OR: 5.07) and psoriatic arthritis (OR: 5.06). Sex-adjusted ORs were considerably higher than crude ORs for eosinophilic digestive disease in women, and for immune thrombocytopenia, systemic sclerosis and autoimmune hepatitis in men. CONCLUSION: We found coexisting IMDs in 1 out of 6 patients with sarcoidosis. The strongest associations were found for immunodeficiencies and some systemic, rheumatic, hepatic and hematological autoimmune diseases.

Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions.

BACKGROUND/AIM: There are two strategies for the interpretation of tumor markers (TM) in fluid effusions: i) high cut-off and ii) fluid/serum ratio (F/S) and low cut-off. The objective of this study is to compare these two strategies and to determine whether diagnostic accuracy improves by the identification of possible false positives using Adenosine deaminase (ADA), C reactive protein (CRP) and % of polymorphonuclear cells (%PN). PATIENTS AND METHODS: We studied 157 ascitic fluids, 74 of which were malignant. ADA, CRP and %PN were determined in ascitic fluid, and Carcinoembryonic antigen (CEA), Cancer antigen 72-4 (CA72-4), Cancer antigen CA19-9 and Cancer antigen 15-3 (CA15-3) in both fluid and serum. RESULTS: The strategy of high cut-off showed 59.5% sensitivity at 100% specificity. The F/S strategy showed 75.7% sensitivity at 95.2% specificity. Subclassifying cases with ADA, CRP and %PN negative showed 67.5% sensitivity at 100% specificity for high cut-off and for the F/S strategy was 81.7% sensitivity at 98.7% specificity. CONCLUSION: The strategy of F/S with negative ADA, CRP and %PN allow the best interpretation for TM in the ascitic fluid.

Diagnostic Accuracy of CYFRA21-1 in the Differential Diagnosis of Pleural Effusions.

BACKGROUND/AIM: Approximately 20% of pleural effusions are associated with cancer; about 50% require invasive procedures to perform diagnosis. Determination of the concentration of soluble cytokeratin 19-fragments (CYFRA21-1) may help identify patients with malignant effusions. However, pathologies other than cancer can increase its concentration. The identification of these possible false positives with routine tests CRP, ADA, % polymorphonuclear cells (PN) may improve diagnostic accuracy. This study aimed to determine the diagnostic accuracy of CYFRA21-1 in the detection of malignant pleural effusions and the possible false positives. MATERIALS AND METHODS: Analysis of CYFRA21-1, adenosine deaminase (ADA), C-reactive protein (CRP), and the percentage of polymorphonuclear leukocytes (PN%) in the fluid from 643 consecutive undiagnosed pleural effusions was performed. RESULTS: CYFRA21-1 showed 38.7% sensitivity and 97.3% specificity at 175 ng/ml cut-off. Effusions not suspicious of a false-positive showed 39.0% sensitivity and 98.2% specificity, while effusions suspicious of false positive showed lower sensitivity (36.4%) and specificity (95.0%). CONCLUSION: The diagnostic accuracy of CYFRA21-1 in pleural effusions can be improved by classification according to the possibility of false positives.

Síndrome de hiperemesis cannabinoide / Cannabinoid hyperemesis síndrome

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Dèficit de vitamina D i raquitisme nutricional / Déficit de vitamina D y raquitismo nutricional / Vitamin D deficiency and nutritional rickets

Fonament: En les darreres dècades s'ha posat de manifest un ressorgiment del dèficit de vitamina D. A més, s'ha postulat un possible paper en processos patològics independents de la mineralització esquelètica. Tot això ha provocat un canvi en la pràctica clínica que ha fet que se sol·licitin nivells de vitamina D de forma més freqüent. Això ha augmentat la detecció d'infants amb nivells deficitaris de vitamina D sense tenir clar quina actuació s'ha de tenir en aquests casos. Objectiu: Recordar les darreres recomanacions clíniques sobre vitamina D i proposar una actuació consensuada. Mètode. Revisió bibliogràfica dels articles publicats durant els darrers anys, així com de recomanacions de diferents societats científiques. Resultats: En els darrers anys s'ha publicat una àmplia bibliografia sobre diferents aspectes de la vitamina D en què es descriuen un augment del seu dèficit i la seva relació amb aspectes no relacionats amb la salut esquelètica, i es fan recomanacions per millorar-ne el cribratge, la prevenció i el tractament del dèficit. Conclusions: Actualment no hi ha proves suficients per recomanar la determinació de vitamina D en infants sense factors de risc, ni per prescriure-la per aconseguir beneficis sense evidència clara a la literatura. Estaria indicat fer una suplementació universal fins als 12 mesos de vida. Si hi ha factors de risc, cal fer la suplementació almenys en períodes de màxim creixement. El tractament s'ha de fer en casos de dèficit de vitamina D simptomàtic o amb alteracions analítiques acompanyants. En cas de raquitisme, cal estudiar la família i posteriorment fer el seguiment, assegurant la provisió adequada de vitamina D

Fundamento: En las últimas décadas se ha puesto de manifiesto un resurgimiento del déficit de vitamina D. Además, se ha postuladoun posible papel en procesos patológicos independientes de lamineralización esquelética. Todo esto ha provocado un cambio en la práctica clínica, que ha conllevado que se soliciten niveles devitamina D de forma más frecuente, y que ha aumentado la detecciónde niños con niveles deficitarios de vitamina D sin tener claroqué actuación se debe llevar a cabo en estos casos. Objetivo: Recordar las últimas recomendaciones clínicas sobre vitaminaD y proponer una actuación consensuada. Método. Revisión bibliográfica de los artículos publicados durantelos últimos años así como recomendaciones de diferentes sociedades científicas.Resultados: En los últimos años se ha publicado una amplia bibliografíasobre diferentes aspectos de la vitamina D en la que se describen un aumento de su déficit y su relación con aspectos norelacionados con la salud esquelética, y se realizan recomendacionespara mejorar el cribado, la prevención y el tratamiento de su déficit.Conclusiones: Actualmente no existen pruebas suficientes para recomendar determinación de vitamina D en niños sin factores de riesgo, ni prescribir vitamina D para conseguir beneficios sin evidencia clara en la literatura. Estaría indicado realizar suplementación universal hasta los 12 meses de vida. Si existen factores de riesgo, la suplementación debe realizarse al menos en períodos de máximo crecimiento, i plantear tratamiento en casos de déficit de vitamina D sintomático o con alteraciones analíticas acompañantes. En caso de raquitismo, hay que estudiar a la familia y posteriormente realizar seguimiento, asegurando la provisión adecuada de vitamina D

Background: In recent decades a resurgence of vitamin D deficiency has been revealed. In addition, a possible role in pathological processes independent of skeletal mineralization has been postulated. It has led to a change in clinical practice, making vitamin D levels request more frequently, which has increased detection of children with deficient vitamin D levels without being clear what action should be taken in these cases. Objective: To remember the latest clinical recommendations on vitamin D and to propose a consensual action. Method. Bibliographical review of articles published during last years as well as recommendations from different scientific societies. Results: There is a wide bibliography on different aspects of vitamin D in recent years which describe an increase in its deficit, its relation to aspects not related to skeletal health and make recommendations to improve the screening, prevention and treatment of its deficit. Conclusions: There is no sufficient evidence to recommend vitamin D determination in children without risk factors, nor to prescribe vitamin D to achieve benefits. It would be desirable to perform universal supplementation until 12 months of age. If risk factors exist, supplementation is needed at least during maximum growth periods. Cases of symptomatic vitamin D deficiency or with anaylitical alterations should be treated. In case of rickets, it is recommended to study the family and then ensuring an adequate vitamin D supply

Evaluation of two strategies for the interpretation of tumour markers in pleural effusions.

BACKGROUND: Pleural effusions present a diagnostic challenge. Approximately 20% are associated with cancer and some 50% require invasive procedures to perform diagnosis. Determination of tumour markers may help to identify patients with malignant effusions. Two strategies are used to obtain high specificity in the differential diagnosis of malignant pleural effusions: a) high cut-off, and b) fluid/serum (F/S) ratio and low cut-off. The aim of this study is to compare these two strategies and to establish whether the identification of possible false positives using benign biomarkers - ADA, CRP and % of polymorphonuclear cells - improves diagnostic accuracy. METHODS: We studied 402 pleural effusions, 122 of them malignant. Benign biomarkers were determined in pleural fluid, and CEA, CA72-4, CA19-9 and CA15-3 in pleural fluid and serum. RESULTS: Establishing a cut-off value for each TM for a specificity of 100%, a joint sensitivity of 66.5% was obtained. With the F/S strategy and low cut-off points, sensitivity was 77% and specificity 98.2%, Subclassifying cases with negative benign biomarkers, both strategies achieved a specificity of 100%; sensitivity was 69.9% for single determination and 80.6% for F/S ratio. CONCLUSIONS: The best interpretation of TM in the differential diagnosis of malignant pleural effusions is obtained using the F/S ratio in the group with negative benign biomarkers.

Adolescent amb amenorrea secundària i galactorrea / Adolescent with secondary amenorrhea and galactorrhea

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Pseudohypoparathyroidism vs. tricho-rhino-phalangeal syndrome: patient reclassification.

OBJECTIVES: Given that tricho-rhino-phalangeal syndrome (TRPS) and pseudohypoparathyroidism/pseudopseudohypoparathyroidism (PHP/PPHP) are very rare monogenic disorders that share some features (distinctive facies, short stature, brachydactyly and, in some patients, intellectual disability) that lead to their misdiagnosis in some cases, our objective was to identify clinical, biochemical or radiological signs that could help to distinguish these two syndromes. METHODS AND RESULTS: We report on two cases, which were referred to the Endocrinology and Pediatric Endocrinology Services for obesity. Clinical evaluation initially suggested the diagnosis of PHP-Ia [phenotype suggestive of Albright hereditary osteodystrophy (AHO) with parathyroid hormone (PTH) resistance] and PPHP (phenotype resembling AHO, without PTH resistance), but (epi)genetic analysis of the GNAS locus ruled out the suspected diagnosis. Further clinical re-evaluation prompted us to suspect TRPS, and this was confirmed genetically. CONCLUSION: TRPS was mistakenly identified as PHP/PPHP because of the coexistence of obesity and brachydactyly, with PTH resistance in one of the cases. Specific traits such as sparse scalp hair and a pear-shaped nose, present in both cases, can be considered pathognomonic signs of TRPS, which could help us to reach a correct diagnosis.

Imatge radiològica amb petites densitats radioopaques abdominals en nen immigrant / No disponible

No disponible

Nadó amb criptorquídia i hipospàdies / No disponible

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Cuatro casos de exantema periflexural asimétrico. ¿se diagnostica poco esta entidad clínica? / Four cases of asymmetric periflexural exanthema. An underdiagnosed entity?

Introducción. Diagnosticar una enfermedad que cursacon exantema no siempre es fácil, es preciso la valoraciónde los antecedentes, las manifestaciones iniciales, las propiascaracterísticas del exantema y la clínica extracutáneaacompañante.En el caso del exantema periflexural asimétrico de lainfancia, las características cutáneas son el elemento clavepara establecer el diagnóstico.A pesar de que es una enfermedad antigua, probablementees poco reconocida por el pediatra en el momentode establecer los diagnósticos. Su benignidad clínica probablementeha hecho que se infravalore y no se hagandiagnósticos precisos de la misma y se incluya dentro deexantemas inespecíficos y viriasis.Observación clínica. Se presentan cuatro casos diagnosticadosdurante la primavera, de niñas en edades entre18 meses y 3 años con mínimas manifestaciones prodrómicasde 1-2 días de duración con febrícula y manifestacionescatarrales mínimas de vías respiratorias. El exantema fuediagnosticado entre la primera y la cuarta semana de evolución,con duración total entre 4 y 6 semanas. La distribuciónfue unilateral con alguna zona de confluencia y en uncaso con extensión a la espalda. Los estudios serológicosfueron negativos.Comentarios. El perfecto conocimiento de esta enfermedadfavorecerá el diagnóstico y su diferenciación conotras entidades clínicas, como la dermatitis de contacto, lapitiriasis rosada, otros exantemas, sudamina o reaccionesmedicamentosas.La infravaloración del diagnóstico puede ser debida avarios factores: el desconocimiento de la enfermedad; labenignidad evolutiva, que provoca que tampoco preocupeen exceso el establecimiento exacto del diagnóstico; la variabilidadsegún el momento de la visita, junto a la inexperiencia.Además, se acostumbra a desviar el caso al dermatólogopensando que se trata sólo de una enfermedadcutánea.Probablemente se trata de una reacción cutánea a diferentesetiologías

Background. The diagnosis of exanthematic diseases isnot easy; a careful evaluation of the prior history, the initialsymptoms, the characteristics of the exanthem, andthe extracutaneous manifestations must be performed. Inthe case of asymmetric periflexural exathem, the cutaneousfeatures are diagnostic. This disease has been recognizedfor a long time, although general pediatricians usuallyare not familiar with its features. Its benign clinical coursehas probably resulted in its underdiagnosis, as it is usuallyincluded in the diagnosis of non-specific extanthems andviral illnesses.Case reports. We describe four girls diagnosed withasymmetric periflexural exanthem during the spring. Theage at diagnosis was between 18 months and 3 years, thepatients had very mild prodromes, with 1 – 2 days of lowgradefever and upper respiratory symptoms. The exanthemwas diagnosed between the first and the fourthweek, and the total duration of symptoms was 4 to 6weeks. All cases had unilateral involvement, with someconfluent areas and, in one case, spread to the back. Allserology studies were negative.Comments. The better knowledge of this disease willfacilitate its diagnosis and its differentiation from otherclinical entities, such as contact dermatitis, pityriasis roseaor other viral exanthems, sweat rashes, and drug reactions.The probable underdiagnosis of this entity is due to thelack of knowledge of it clinical features and its benignclinical course. Often times, these cases are referred todermatology specialists. While the etiology of this diseaseis unclear, it is thought to represent a cutaneous reactionto different causes

Acanthosis nigricans as an adverse effect of highly active antiretroviral therapy in an adolescent girl with human immunodeficiency virus infection.

We report an 11-year-old girl with acanthosis nigricans that appeared after 4 years of treatment with didanosine, stavudine and amprenavir. Laboratory studies showed hyperglycemia, hyperinsulinemia and hypertriglyceridemia. Withdrawal of amprenavir resulted in disappearance of acanthosis nigricans and improvement of metabolic abnormalities.

3,4-methylenedioxymethamphetamine (MDMA) intoxication in an infant chronically exposed to cocaine.

Accidental ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) was detected in an infant admitted at the Pediatric Emergency Department by drug testing in urine. Concentrations of MDMA and its principal metabolite 4-hydroxy-3-methoxymethamphetamine (HMMA) in the infant's hydrolyzed urine were 11.7 mg/L and 34.4 mg/L, respectively. Apparent febrile convulsions and cardiovascular side effects resolved within 1 day after treatment with benzodiazepines. Chronic exposure to cocaine was evidenced by segmental hair analysis. Continuous maternal denial of the presence of any drug in the household made diagnosis of accidental ingestion of MDMA and chronic exposure to cocaine problematic. Periodic clinical and laboratory follow-ups were requested to check eventual long-term effects of exposure to illicit drugs and discontinuation of the child from exposure to dangerous environments.