Hereditary breast and ovarian cancer in Andalusian families: a genetic population study.

BACKGROUND: The BRCA1/2 mutation profile varies in Spain according to the geographical area studied. The mutational profile of BRCA1/2 in families at risk for hereditary breast and ovarian cancer has not so far been reported in Andalusia (southern Spain). METHODS: We analysed BRCA1/2 germline mutations in 562 high-risk cases with breast and/or ovarian cancer from Andalusian families from 2010 to 2015. RESULTS: Among the 562 cases, 120 (21.4%) carried a germline pathogenic mutation in BRCA1/2; 50 in BRCA1 (41.7%) and 70 in BRCA2 (58.3%). We detected 67 distinct mutations (29 in BRCA1 and 38 in BRCA2), of which 3 in BRCA1 (c.845C > A, c.1222_1223delAC, c.2527delA) and 5 in BRCA2 (c.293 T > G, c.5558_5559delGT, c.6034delT, c.6650_6654delAAGAT, c.6652delG) had not been previously described. The most frequent mutations in BRCA1 were c.5078_5080delCTG (10%) and c.5123C > A (10%), and in BRCA2 they were c.9018C > A (14%) and c.5720_5723delCTCT (8%). We identified 5 variants of unknown significance (VUS), all in BRCA2 (c.5836 T > C, c.6323G > T, c.9501 + 3A > T, c.8022_8030delGATAATGGA, c.10186A > C). We detected 76 polymorphisms (31 in BRCA1, 45 in BRCA2) not associated with breast cancer risk. CONCLUSIONS: This is the first study reporting the mutational profile of BRCA1/2 in Andalusia. We identified 21.4% of patients harbouring BRCA1/2 mutations, 58.3% of them in BRCA2. We also characterized the clinical data, mutational profile, VUS and haplotype profile.

Multiple cystic disease: K17 dysfunction?

Our patient is a 29-year-old woman without any previous disease who presented with different kinds of lesions on her face, neck, and chest. She first noticed the lesions 10 years ago and, since that time, they have become more numerous. She has no affected relatives. On physical examination, she had multiple cystic lesions on her neck, chest, and vulva, which were between 0.3 cm and 1 cm and skin-colored or yellowish (Figure 1). She presented with small, white papules on her face measuring approximately 0.2 cm, localized on her forehead and cheeks. Some of these papules had a blueish appearance (Figure 2). She also presented clinically typical eruptive syringomas on her upper and lower eyelids and neck and multiple facial milia. Finally, a sacrococcygeal pilonidal cyst was diagnosed and surgically removed. Her nails and teeth were clinically normal. Biopsies of each kind of lesion were performed, with the following results: (1) neck cystic lesion: steatocystoma; (2) small, white facial papule: eccrine hidrocystoma; (3) blueish facial papule: apocrine hidrocystoma; and (4) small neck papule: syringoma (Figure 3). With these findings, our diagnosis was steatocystoma multiplex with multiple eccrine and apocrine hidrocystomas, eruptive syringomas, and sacrococcygeal pilonidal cyst.

Incidence, factors related to presentation, course and mortality of metformin-associated lactic acidosis in the healthcare area of a tertiary hospital. / Incidencia, factores relacionados con la presentación, evolución y mortalidad de la acidosis láctica asociada a metformina en el área sanitaria de un hospital de tercer nivel.

OBJECTIVES: To determine the incidence of metformin-induced lactic acidosis during the period January 2014 to March 2017 in Aragon Healthcare Area III. To analyse the associated clinical and analytical factors and mortality. RESULTS: A total of 31 cases (61.3% males). Incidence: 79.76 cases/100,000 patients-year; mean age 75.39±9.34 years; 23 of them with levels of serum metformin (21.91±15.52 mcg/ ml); milligrams/day of metformin ingested: 1790.32±499; 96.8% of cases in the context of acute kidney failure; 11 cases with a history of chronic kidney disease (35.5%); 12 required intensive care (38.7%); 13 required purification treatment (41.9%; 3 haemodiafiltration, 10 haemodialysis). There was a significant correlation between daily milligrams of metformin ingested and drug levels; levels of metformin; and peak creatinine, pH and lactate. Mortality was 25.8%. There were only significant differences between the deceased and survivors regarding the duration of stay and final creatinine. Multivariate logistic regression did not detect any study variables associated with mortality. CONCLUSIONS: The incidence in our healthcare area is higher than in other series, with a 25.8% mortality rate. Virtually all cases were in the context of prerenal acute kidney failure. In 29% of cases, there was an overdose. Patients must be warned about the most common lactic acidosis-inducing situations, especially dehydration, if they continue taking the drug at such times.

[Occult renal disease and drug prescription in primary care]. / Insuficiencia renal oculta y prescripción de fármacos en atención primaria.

OBJECTIVE: To study the prevalence of chronic kidney disease (CKD) [glomerular filtration rate (GFR) <60ml/min/1.73m(2)] and occult kidney disease (OKD) (normal serum creatinine values with GFR <60) in elderly patients. DESIGN: Retrospective, observational study. SETTING: Four primary care centres in the province of Huesca, Spain. PARTICIPANTS: About 4014 patients older than 65 years were randomly selected. MAIN MEASUREMENTS: GFR was calculated for all subjects using the four-variable modified MDRD equation. We registered all drugs prescriptions to the patients during a period of twelve months focusing on the potential nephrotoxic drugs. RESULTS: After exclusions, GFR was estimated in 3286 patients (1424 men of 75.49+/-6.6 years and 1862 women of 76.29+/-7.04 years; P=.001). The prevalence of CKD was 21.2%. A total of 10.1% of patients (12.8% of women and 6.44% of men) had OKD. We recorded the complete drug prescription in 269 patients. Mean of all different drugs that were prescribed by patient-year was 10.69+/-5.92 (men 9.55+/-5.57 and women 11.11+/-6; P=.05)]. A large number of patients were treated with potentially dangerous drugs, particularly the non-steroidal anti-inflammatory drugs with 165 cases (61.34%), and 72% were exposed to drugs that can lead to hyperkalaemia. CONCLUSIONS: We conclude that GFR estimation by clinical laboratories in the setting of primary care can contribute to prevent the adverse effects of inappropriate drug prescriptions.

Comparison of Epstein-Barr virus presence in Hodgkin lymphoma in pediatric versus adult Argentine patients.

CONTEXT: In developed countries and high socioeconomic groups, Hodgkin lymphoma has an initial peak in young adulthood, whereas in undeveloped countries and low socioeconomic groups, it shows an early childhood peak. In developing countries, 90% of children are infected with the Epstein-Barr virus (EBV) by the age of 6 years, but in developed countries, only 30% to 40% are seropositive by that age. Early childhood EBV infection in 75% of Argentine patients was demonstrated. OBJECTIVE: To explore the epidemiology of Hodgkin lymphoma and its relationship with EBV in Argentine patients. METHODS: The presence of EBV was assessed by Epstein-Barr encoded RNA in situ hybridization and latent membrane protein 1 immunohistochemistry. We studied 92 pediatric and 42 adult Hodgkin lymphoma cases from a public center as well as 39 adult cases from a private center. RESULTS: The mixed cellularity Hodgkin lymphoma had a prevalence of 52% in the pediatric group, while similar frequencies of both nodular sclerosis Hodgkin lymphoma (47%) and mixed cellularity Hodgkin lymphoma (44%) were observed in adults. As for Epstein-Barr encoded RNAs, 55% of the pediatric cases and 31% of the adult cases were positive. Among adult EBV+ cases, 38% were from the public hospital, and 23% were from the private center. EBV was present in 77% of the pediatric mixed cellularity Hodgkin lymphoma cases when compared with the other histologic subtypes of Hodgkin lymphoma. EBV was mainly detected in mixed cellularity cases (39% in the adult group). CONCLUSION: Our findings strengthen the argument that EBV is involved in the pathogenesis of Hodgkin lymphoma in most children younger than 10 years. Our findings of EBV prevalence, along with both childhood and second-decade peaks as well as comparable frequencies for Hodgkin lymphomas of mixed cellularity and nodular sclerosis, distinguish our population from others in developing countries.

La derivación temprana al nefrólogo mejora los resultados a largo plazo en la enfermedad renal crónica / Early referral to nephrologists of patients with chronic kidney disease: an opportunity to improve the outcome

La enfermedad renal crónica es una patología creciente en todo el mundo y cada vez es mayor la prevalencia de pacientes en diálisis, lo que ocasiona un costo muy elevado. En los últimos años han cobrado relevancia los adecuados cuidados en la etapa prediálisis. Para ello es fundamental detectar la enfermedad en sus primeras fases, lo que puede permitir adoptar las medidas necesarias para su tratamiento o, en su caso, retrasar su progresión y prevenir las complicaciones asociadas. A pesar de todo siguen siendo muchos los pacientes que son vistos por primera vez por un especialista en nefrología en etapas avanzadas de la enfermedad como consecuencia de su derivación tardía. Los factores que ocasionan este fenómeno son numerosos e implican tanto a los médicos, como a los pacientes y al sistema sanitario. Las consecuencias negativas de la derivación tardía ya han sido demostradas en cuanto a morbilidad, mortalidad y costos, pero todavía no está demostrado cuál es el mejor momento de iniciar la diálisis en función del filtrado glomerular. Es imprescindible la elaboración y difusión de guías clínicas junto con la colaboración entre nefrólogos y médicos generales para disminuir el impacto de la derivación tardía.

Hamartoma mesenquimático de la pared costal en la infancia: tres casos / Mesenchymal hamartoma of the wall in infancy. Three cases

El Hamartoma Mesenquimático de la Pared Costal (HMPC) es un tumor congénito infrecuente, detectado generalmente por la deformidad torácica que produce, o por trastornos respitarorios relacionados a su rápido crecimiento inicial. Si bien es benigno, una biopsiaque toma sólo áreas inmaduras puede llevar a una diagnóstico erróneo de sarcoma. Por su gran tamaño, que obligan a la resección de varias costillas, y eventualmente bilateralidad, puede dejar secuelas de difícil manejo en la mecánica de la pared torácica. Se presentan tres casos de HMPC, uno de ellos bilateral, diagnosticados a las edades de 1;30; y 120 días. Sus características radiológicas y macroscópicas son ilustradas, Microscopicamente coexisten áreas de tejido mesenquimatoso embrionario, con diferenciación zonal fibroblástica, cartilaginosa y osteoide, y característicamente extensas áreas de quiste óseo aneurismático. El seguimiento de nuestros pacientes y la revisión de la bibliografía confirman el caracter benigno de esta entidad. La edad de aparición, la ubicación costal, y el especto radiológico, permiten el diagnóstico preoperatorio adecuado con alto grado de certeza.

Xantogranuloma nodular: variedad multinodular / Nodular xanthogranuloma: multinodular variety

Se presenta el caso de un niño de quince meses de edad con lesiones nodulares múltiples asintomáticas en cuero cabelludo, que fueron aumentando en número desde los seis meses de vida con crecimiento acelerado en los últimos tres meses, resultando lesiones de más de 10 mm de diaámetro, hecho que motivó la consulta. En el resto del examen físico se hallaron también tres máculas café con leche en el tronco, de aproximadamente 5 mm de diámetro, con antecedentes familiares de las mismas. Los diferentes diagnósticos diferenciales de esta patología, su variedad macronodular y su posible asociación con neurofibromatosis motivaron la presente comunicación

Acropustulosis infantil / Infantile acropustulosis

Se presenta un caso de Acropustulosis Infantil, descripto originariamente por Kahn en 1976 y publicado en 1979. Los autores trataron exitosamente durante tres semanas con D.D.S. un síndrome caracterizado por vesicopústulas intensamente pruriginosas en las manos y en los pies, resistente al empleo de corticosteroides tópicos

Macroglobulinosis cutis / Macroglobulinosis cutis

Presentamos un paciente de 74 años con una forma específica cutánea de macroglobulinemia de Waldenstrom, denominada macroglobulinosis cutis, la cual es de observación excepcional. Las lesiones cutáneas resultaron de gran ayuda para diagnosticar la enfermedad de base. Fue tratado con ciclos de clorambucil, prednisona y plasmaféresis, evolucionando de manera satisfactoria

Linfangitis cronica hipertrofica desarrollada sobre linfangiectasia adquirida circunscripta / Chronic hypertrofic lymphangytis on adquired circumscribed lymphangyectasia

Se presenta un caso de linfangitis crónica hipertrófica sobre linfangiectasia adquirida circunscripta. Se realiza una revisión bibliográfica sobre las diferentes causas y se establecen diagnósticos diferenciales clínicos e histológicos

Epitelioma basocelular: localización en aréola mamaria / basal cell epithelioma: localization in mammary areola

Se presenta un paciente de 68 años de edad, sexo masculino, con un Epitelioma Basocelular de localización inusual en aréola mamaria, cuyo aspecto clínico simulaba una enfermedad de Paget

Carcinomas ecrinos: actualización a propósito de la observación de un carcinoma ecrino epidermotropo y un carcinoma ecrino trabecular / Eccrine carcinoma: report apropos of the observation of epidermatropic eccrine carcinoma and trabecular eccrine carcinoma

Presentamos dos variedades de carcinoma ecrino tipo básico, basándonos en rasgos histopatológicos que confirman su estirpe ecrina. Adoptamos los nombres de carcinoma ecrino epidermotropo y carcinoma ecrino trabecular, pues ellos describen las características microscópicas. Se actualiza la clasificación de estas neoplasias y se consideran nuevos elementos diagnósticos.