The Novel Variant NP_00454563.2 (p.Glu259Glyfs*77) in Gene PKP2 Associated with Arrhythmogenic Cardiomyopathy in 8 Families from Malaga, Spain.

INTRODUCTION AND OBJECTIVES: Arrhythmogenic cardiomyopathy (ACM) is a hereditary heart disease defined by the progressive replacement of the ventricular myocardium with fibroadipose tissue, which can act as a substrate for arrhythmias, sudden death, or even give rise to heart failure (HF). Sudden death is frequently the first manifestation of the disease, particularly among young patients. The aim of this study is to describe a new pathogenic variant in the PKP2 gene. METHODS: A descriptive observational study that included eight initially non-interrelated families with a diagnosis of ACM undergoing follow-up at our HF and Familial Cardiomyopathies Unit, who were carriers of the NM_004572.3:c.775_776insG; p.(Glu259Glyfs*77) variant in the PKP2 gene. The genetic testing employed next-generation sequencing for the index cases and the Sanger method for the targeted study with family members. We compiled personal and family histories, demographic and clinical characteristics, data from the additional tests at the time of diagnosis, and arrhythmic events at diagnosis and during follow-up. RESULTS: We included 47 subjects, of whom 8 were index cases (17%). Among the evaluated family members, 16 (34%) were carriers of the genetic variant, 3 of whom also had a diagnosis of ACM. The majority were women (26 patients; 55.3%), with a mean age on diagnosis of 48.9 ± 18.6 years and a median follow-up of 39 [24-59] months. Worthy of note are the high incidences of arrhythmic events as the form of presentation and in follow-up (21.5% and 20.9%, respectively), and the onset of HF in 25% of the sample. The most frequent ventricular involvements were right (four patients, 16.7%) and biventricular (four patients, 16.7%); we found no statistical differences in any of the variables analysed. CONCLUSIONS: This variant is a pathogenic variant of gene PKP2 that has not previously been described and is not present in the control groups associated with ACM. It has incomplete penetrance, a highly variable phenotypic expressivity, and was identified in eight families of our geographical area in Malaga (Andalusia, Spain), suggesting a founder effect in this area and describe the clinical and risk characteristics.

Estructura diagnóstica y funcional de una consulta de alta resolución de nódulo tiroideo / Diagnostic and functional structure of a high-resolution thyroid nodule clinic

La aparición de un nódulo tiroideo se ha convertido en un hecho cotidiano en la práctica clínica diaria. Habitualmente, la adecuada evaluación del nódulo tiroideo requiere la realización de diversas pruebas diagnósticas y múltiples citas médicas, con la consiguiente demora diagnóstica. La instauración de una consulta de alta resolución de nódulo tiroideo evita en gran medida estos inconvenientes, condensando en una única cita todas las pruebas necesarias para la correcta evaluación del nódulo tiroideo. En este trabajo revisamos cuál debe ser la estructura diagnóstica y funcional de una consulta de alta resolución de nódulo tiroideo

Appearance of a thyroid nodule has become a daily occurrence in clinical practice. Adequate thyroid nodule assessment requires several diagnostic tests and multiple medical appointments, which results in a substantial delay in diagnosis. Implementation of a high-resolution thyroid nodule clinic largely avoids these drawbacks by condensing in a single appointment all tests required for adequate evaluation of thyroid nodule. This paper reviews the diagnostic and functional structure of a high-resolution thyroid nodule clinic

Diagnostic and functional structure of a high-resolution thyroid nodule clinic.

Appearance of a thyroid nodule has become a daily occurrence in clinical practice. Adequate thyroid nodule assessment requires several diagnostic tests and multiple medical appointments, which results in a substantial delay in diagnosis. Implementation of a high-resolution thyroid nodule clinic largely avoids these drawbacks by condensing in a single appointment all tests required for adequate evaluation of thyroid nodule. This paper reviews the diagnostic and functional structure of a high-resolution thyroid nodule clinic.

Estudio radiológico de un caso de pseudotumor sarcoideo renal bilateral / Bilateral kidney pseudotumor due to sarcoidosis: a radiological study case

OBJETIVO: Describir un caso de pseudotumor renal bilateral secundario a sarcoidosis en un paciente de 75 años en seguimiento por carcinoma de próstata y con historia de paquimeningitis hipertrófica. MÉTODOS: Se realizó ecografía-doppler abdominal, TC tóraco-abdomino-pélvico y biopsia renal guiada por TC, estudios analíticos, determinación de ECA y tratamiento de prueba con esteroides. RESULTADOS: En las pruebas de imagen se identificaron masa renales bilaterales y adenopatías mediastínicas calcificadas, insuficiencia renal y aumento de la ECA en la analítica y granulomas no caseificantes en la biopsia renal. Tanto la clínica neurológica como la función renal mejoraron con esteroides. CONCLUSIONES: La afectación renal pseudotumoral por sarcoidosis es una patología rara que debe incluirse en el diagnóstico diferencial de las masas renales, principalmente en pacientes con sospecha de enfermedad inflamatoria/autoinmune. Los hallazgos radiológicos del "sarcoide renal" son inespecíficos. Puede obtenerse biopsia guiada por TC/ecografía para diagnóstico histológico a partir de las masas renales(AU)

OBJECTIVE: To report one case of bilateral kidney pseudotumor due to sarcoidosis in a 75 year-old man with prostatic carcinoma and hypertrophic pachymeningitis. METHODS: Renal Doppler, body CT, CT-guided renal biopsy, blood analysis including angiotensin converting enzyme (ACE), blood levels and test-treatment (corticosteroid response) were performed. RESULTS: The radiological studies performed showed bilateral kidney masses and pulmonary calcified hilar adenopathies. Blood analysis showed renal failure and increased ACE levels. Renal biopsy showed non-caseating granulomas. Neurological symptoms and renal failure improved with corticosteroid therapy. CONCLUSION: Bilateral kidney pseudotumor due to sarcoidosis is a rare pathology. Sarcoidosis must be included in the differential diagnosis work up of patients with inflammatory or autoimmune disease and bilateral kidney pseudotumors. Radiological findings of kidney sarcoidosis are quite unspecific. Histological diagnosis with CT guided biopsy or US guided biopsy of kidney masses may be performed(AU)

Bilateral kidney pseudotumor due to sarcoidosis: a radiological study case.

OBJECTIVE: To report one case of bilateral kidney pseudotumor due to sarcoidosis in a 75 year-old man with prostatic carcinoma and hypertrophic pachymeningitis. METHODS: Renal Doppler, body CT, CT-guided renal biopsy, blood analysis including angiotensin converting enzyme (ACE), blood levels and test-treatment (corticosteroid response) were performed. RESULTS: The radiological studies performed showed bilateral kidney masses and pulmonary calcified hilar adenopathies. Blood analysis showed renal failure and increased ACE levels. Renal biopsy showed non-caseating granulomas. Neurological symptoms and renal failure improved with corticosteroid therapy. CONCLUSION: Bilateral kidney pseudotumor due to sarcoidosis is a rare pathology. Sarcoidosis must be included in the differential diagnosis work up of patients with inflammatory or autoimmune disease and bilateral kidney pseudotumors. Radiological findings of kidney sarcoidosis are quite unspecific. Histological diagnosis with CT guided biopsy or US guided biopsy of kidney masses may be performed.

Experiencia clínica en una consulta de alta resolución de nódulo tiroideo / Clinical experience in a high-resolution thyroid nodule clinic

Fundamentos y objetivos El hallazgo de un nódulo tiroideo es un hecho muy frecuente en la práctica clínica habitual. El manejo del nódulo tiroideo necesita un abordaje multidisciplinar que puede ser facilitado con la creación de unidades de alta resolución de nódulo tiroideo. Describimos la experiencia clínica y los resultados obtenidos en una consulta de alta resolución y acto único de nódulo tiroideo. Material y métodos Se han evaluado todos los pacientes derivados a la consulta de nódulo tiroideo del Hospital Virgen de la Victoria (Málaga) desde el año 2005 al 2007. Se han seguido las guías de práctica clínica de nódulo tiroideo para la recomendación de punción aspirativa con aguja fina (PAAF) y cirugía tiroidea. Se realizó análisis estadístico con programa SPSS. Resultados Durante el periodo de estudio, la consulta de nódulo tiroideo atendió a 658 pacientes (edad media 48,6 años, 89,8% mujeres). Mediante ecografía se confirmó la existencia de nódulo tiroideo en el 85,5% de los pacientes. Con un diámetro medio de 1,96cm, un 74,2% de nódulos fueron sólidos, un 55,8% hipoecoicos, y un 4,7% presentaron microcalcificaciones. Se realizó la PAAF a 475 pacientes. El 76,5% de las citologías fueron benignas, el 19,1% sospechosas, el 2,1% malignas y el 2,3% insuficientes. Se derivó a cirugía al 23,3% de los pacientes (principalmente por tamaño nodular o sospecha de malignidad). Se confirmó la existencia de patología maligna (principalmente carcinoma papilar) en el 24,9% de los nódulos intervenidos. La sensibilidad/especificidad de la citología (considerando la biopsia como el gold standard) fue del 81,8 y el 94,7%, respectivamente. Conclusiones La instauración de una consulta monográfica de nódulo tiroideo permite la optimización de recursos y reduce la demora diagnóstica, obteniendo unos resultados clínicos ampliamente satisfactorios (AU)

Background and objectives: The finding of a thyroid nodule is a very common occurrence inclinical practice. Management of thyroid nodules requires a multidisciplinary approach that may be eased by a high-resolution thyroid nodule clinic. We report our clinical experience and outcomes in a high-resolution thyroid nodule clinic. Patients and methods: All patients referred to Virgen de la Victoria Hospital (Málaga) from 2005to 2007 were evaluated following thyroid nodule guidelines. Statistical analysis was performed using SPSS software. Results: In the study period, 658 patients (mean age 48.6 years, 89.8% females) were seen atthe thyroid nodule clinic. Thyroid nodules were discovered in 85.5% of patients. Mean nodule diameter was 1.96 cm. Of these nodules, 74.2% were solid, 55.8% hypoechogenic, and 4.7% showed microcalcifications. Fine needle aspiration (FNA) was performed in 475 patients (76.5% of all cytological samples were benign, 19.1% had suspected malignancy, 2.1% were malignant, and 2.3% inadequate). Referral for surgery was required in 23.3% of patients (mainly because of nodule size or suspected malignancy). Malignancy was confirmed in 24.9% of nodules. Sensitivity and specificity of cytology (considering biopsy as gold standard) were 81.8% and 94.7%respectively.Conclusions: Implementation of a high-resolution thyroid nodule clinic decreases delay in diagnosis and optimizes available resources, thus providing for satisfactory clinical outcomes (AU)

[Clinical experience in a high-resolution thyroid nodule clinic]. / Experiencia clínica en una consulta de alta resolución de nódulo tiroideo.

BACKGROUND AND OBJECTIVES: The finding of a thyroid nodule is a very common occurrence in clinical practice. Management of thyroid nodules requires a multidisciplinary approach that may be eased by a high-resolution thyroid nodule clinic. We report our clinical experience and outcomes in a high-resolution thyroid nodule clinic. PATIENTS AND METHODS: All patients referred to Virgen de la Victoria Hospital (Málaga) from 2005 to 2007 were evaluated following thyroid nodule guidelines. Statistical analysis was performed using SPSS software. RESULTS: In the study period, 658 patients (mean age 48.6 years, 89.8% females) were seen at the thyroid nodule clinic. Thyroid nodules were discovered in 85.5% of patients. Mean nodule diameter was 1.96 cm. Of these nodules, 74.2% were solid, 55.8% hypoechogenic, and 4.7% showed microcalcifications. Fine needle aspiration (FNA) was performed in 475 patients (76.5% of all cytological samples were benign, 19.1% had suspected malignancy, 2.1% were malignant, and 2.3% inadequate). Referral for surgery was required in 23.3% of patients (mainly because of nodule size or suspected malignancy). Malignancy was confirmed in 24.9% of nodules. Sensitivity and specificity of cytology (considering biopsy as gold standard) were 81.8% and 94.7% respectively. CONCLUSIONS: Implementation of a high-resolution thyroid nodule clinic decreases delay in diagnosis and optimizes available resources, thus providing for satisfactory clinical outcomes.

Influence of high homocysteine and low folate plasmatic levels in medium-term prognosis after acute coronary syndromes.

BACKGROUND: To test prospectively whether moderate hyperhomocysteinemia and low folate levels could have an influence in the prognosis of 155 patients who presented with an acute coronary syndrome. METHODS AND RESULTS: After a mean follow-up of 13.4+/-7.4 months, patients with low folate levels had higher percentages of cardiovascular death and major cardiovascular events (33% vs. 5%, p<0.001; 44% vs. 22%, p<0.05) and patients with high homocysteine levels had a higher percentage of major cardiovascular events (31% vs. 14.5%, p<0.03). Kaplan-Meier survival estimates analysis showed that patients with low folate levels had a significantly higher probability of cardiovascular death and lower free-of-events survival (log rank statistic: 21.17, p<0.001 and 6.59, p=0.01). Patients with high homocysteine levels had a lower free-of-events survival (log rank statistic: 4.95, p=0.02). Different survival multivariate analysis model showed that the presence of low folate levels was an independent predictor of cardiovascular death (hazard ratio 8.85, 95% confidence interval 2.6-29.3, p<0.000) and high homocysteine levels was identified as independent predictor of major cardiovascular events (hazard ratio 2.34, 95% confidence interval 1.07-5.12, p<0.03). CONCLUSIONS: Low folate levels and moderate hyperhomocysteinemia were identified as independent predictors of cardiovascular events in the follow-up.

[Synchronous chromophobe renal carcinoma and centrocytic lymphoma]. / Carcinoma renal cromófobo y linfoma centrocítico sincrónicos.

OBJECTIVES: To report a case of synchronic neoplasia--chromophobe renal cell carcinoma and low grade non Hodgkin lymphoma--in a 38-year-old male patient, because, although association of these two neoplasias is known, the fact of renal neoplasia being a chromophobe carcinoma is rarely referred to in medical bibliography (3 cases described after Med-Line search). METHODS/RESULTS: The diagnostic study included ultrasound and CT scan in a patient presenting with in non specific abdominal symptoms and neck adenopathy; patient underwent left radical nephrectomy and excision of neck adenopathy. Histologic and immuno-histochemical studies revealed the coexistence of chromophobe type renal cell carcinoma and diffuse centrocytic lymphoma. CONCLUSIONS: Column in the association between chromophobe histological type renal cell carcinoma and non Hodgkin lymphoma is very rare. Presence of these two tumors in the same patient may pose problems for clinical staging, prognostic predictions, and treatment. Then, due to the fact that it is not usual and that a local stage renal carcinoma presents with neck adenopathies, when they appear possible coexistence of these tumors should be suspected.

Carcinoma renal cromófobo y linfoma centrocítico sincrónicos / Synchronic chromophobe renal cell carcinoma and centrocytic lymphoma

OBJETIVO: Comunicar un caso de diagnóstico neoplásico sincrónico: carcinoma renal de tipo cromófobo y linfoma no Hodgkin de bajo grado, en un paciente varón de 38 años de edad, ya que, aunque la asociación de estas dos neoplasias es conocida, el que la neoplasia renal corresponda a un carcinoma de tipo cromófobo es un hecho escasamente referido en la literatura (3 casos descritos, según búsqueda bibliográfica Med-Line). MÉTODOS/RESULTADOS: El estudio diagnóstico se realizó mediante ecografía y tomografía, en un paciente con clínica abdominal inespecífica y adenopatías cervicales, practicándose posteriormente una nefrectomía radical izquierda y la resección de una adenopatía cervical. El estudio histológico e inmunohistoquímico correspondiente puso de manifiesto la coexistencia de un carcinoma renal de tipo "cromófobo" y un linfoma centrocítico difuso. CONCLUSIONES: La asociación entre el carcinoma renal subtipo histológico cromófobo y el linfoma no Hodgkin es muy infrecuente. La presencia de estos dos tumores en un mismo paciente puede plantear problemas de estadiaje, predicción pronóstica y tratamiento. Por tanto, dado que no es habitual que un carcinoma renal en estadio local presente adenopatías cervicales, en estos casos debería sospecharse esta posible coexistencia (AU)

Recidiva paratesticular de carcinoma renal / Paratesticular metastasis from renal cell carcinoma

OBJETIVO: Describir las características clínicas e histopatológicas que presenta la recidiva de un carcinoma de células renales en el testículo, ya que la rareza de esta forma de presentación puede suponer dificultades diagnósticas y, consecuentemente, de estadiaje y tratamiento de la enfermedad. MÉTODOS/RESULTADOS: Presentamos un caso de metástasis paratesticular de carcinoma renal en un paciente de 65 años, diagnosticado, tras nefrectomía, 3 años antes. El estudio histológico muestra las típicas características citohistológicas e inmunohistoquímicas de esta neoplasia: nidos de células epiteliales claras con positividad inmunohistoquímica para Vimentina, Citoqueratinas y EMA. CONCLUSIÓN: Aunque el carcinoma de células renales metastatiza raramente al área testicular, el estudio histológico constituye un método fundamental para el diagnóstico definitivo y el planteamiento terapéutico de la enfermedad (AU)