High- and intermediate-risk susceptibility variants in melanoma families from the Mediterranean area: A multicentre cohort from the MelaNostrum Consortium.

BACKGROUND: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark-skinned individuals, are underrepresented. OBJECTIVES: We report a comprehensive pooled analysis of established high- and intermediate-penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium. METHODS: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country. RESULTS: We included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1; 95% CI 3.3-19.7), >3 affected members (OR 2.6; 95% CI 1.3-5.2) and occurrence of pancreatic cancer (OR 4.8; 95% CI 2.4-9.4) in the family (AUC 0.76, 95% CI 0.71-0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4; 95% CI 1.0-2.0 and OR 4.3; 95% CI 1.2-14.6, respectively). CONCLUSIONS: Variants in known high-penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk assessment.

[Perinatal outcome and five-year survival in children with prenatal diagnosis of hypoplastic left heart syndrome]. / Evolución perinatal y sobrevida a cinco años en niños con diagnóstico prenatal de síndrome de hipoplasia de ventrículo izquierdo.

Hypoplastic left heart syndrome (HLHS) is a congenital heart disease of low prevalence and high lethality. OBJECTIVE: to determine the perinatal outcome and survival at one and five years of fetuses with a prenatal diagnosis of HLHS. PATIENTS AND METHOD: Prospective cohort study of all the fetuses with HLHS from the Perinatal Reference Center (CERPO) born between January 2008 and December 2017. Demographic and clinical perinatal data were obtained from the CERPO database. At one and five years of age, a telephone survey was conducted to determine the surgical treatment and survival. RESULTS: 1,573 patients were admitted to the CERPO, 899 with congenital heart diseases (CHD), confirming the prenatal diagnosis of HLHS in 7% (110/1,573). The mean gestational age at diagnosis and the median at admission were 26+3 and 32+3 weeks, respectively. 89% were born alive, 90% at term, and 57% delivered by cesarean section. The median birth weight was 3,128 grams. 89% survive the prenatal period, 50% the early neonatal period, 33% the late neonatal period, 19% the first year, and 17% at 5 years. CONCLUSIONS: In this center, the one-year and five-year survival of fetuses with prenatal diagnosis of HLHS was 19% and 17%, respectively. It is important for prenatal counseling to consider publications based on local casuistry, that include patients with prenatal and postnatal diagnoses and those who underwent surgery, in order to provide more precise information to parents.

Experience in colorectal surgery at a quaternary care hospital in Bogotá, Colombia.

INTRODUCTION AND AIMS: Colorectal cancer is among the three most common cancers worldwide. Knowledge and identification of suboptimal outcome-associated factors enable comprehensive patient management. The aim of the present study was to present the results of the surgical management of colorectal cancer at a quaternary care university hospital. MATERIALS AND METHODS: An observational, analytic, cross-sectional study was conducted. Information was collected on a retrospective cohort of patients diagnosed with colorectal cancer from 2013 to 2017 at the Hospital Universitario Mayor Méderi, Bogotá, Colombia. RESULTS: Data on 452 patients, within the study period, were collected. A total of 48.5% of the patients were men, the overall complication rate was 24%, the surgical site infection (SSI) rate was 15.38%, anastomotic dehiscence occurred in 4.18% of the patients, bleeding required reoperation in 1.32%, and the intrahospital mortality rate was 7.47%. CONCLUSION: Colorectal cancer management at a university hospital was as beneficial as that provided by other types of hospitals, showing a direct association with complete R0 dissections; low complication rates, according to international reports; and reduced overall morbidity.

Dermoscopy comparative approach for early diagnosis in familial melanoma: influence of MC1R genotype.

BACKGROUND: MC1R polymorphisms interact with CDKN2A mutations modulating melanoma risk and contribute to a less suspicious clinical and dermoscopic appearance of melanomas. Different strategies, including dermoscopic comparative approach and digital monitoring, are used for the melanoma diagnosis in this context. OBJECTIVE: To analyse the diagnostic accuracy of the morphologic approach and comparative approach in dermoscopy, and to detect melanoma in familial melanoma (FamMM) patients according to different genetic backgrounds. METHODS: Two independent readers evaluated 415 lesions belonging to 25 FamMM: 26 melanomas (62% in situ, 36% early invasive) and 389 naevi, blinded for dermoscopic and histopathologic diagnosis, following two different steps. First step-Randomized: all lesions were randomly located in one single folder. Second step-Comparative approach: the lesions were clustered by patient. Sensitivity, specificity and number needed to excise (NNE) for melanoma diagnosis were calculated for both diagnostic strategies. Sensitivity and specificity were also assessed regarding the genetic background. RESULTS: The comparative approach showed lower sensitivity compared to the morphologic approach (69.2 and 73.1 vs. 76.9 both readers) but better specificity (95.9 and 95.1 vs. 84.3 and 90.2, respectively). NNE was better in the comparative approach. The readers had more difficulties diagnosing lesions from CDKN2A mutation carriers with red hair colour (RHC) MC1R variants. CONCLUSION: The comparative approach can be useful in high-risk patients to decrease the NNE. Early melanomas in CDKN2A carriers with RHC polymorphisms are more difficult to diagnose even with the comparative approach and benefit from the detection of changes during digital dermoscopy monitoring for early diagnosis.

Detection of cell-free circulating BRAFV 600E by droplet digital polymerase chain reaction in patients with and without melanoma under dermatological surveillance.

BACKGROUND: The p.V600E mutation in the BRAF protein is the most frequent mutation in cutaneous melanoma and is a recurrent alteration found in common benign naevi. Analysis of the cell-free BRAF c.1799T>A, p.V600E mutation (cfBRAFV 600E ) in plasma has emerged as a biomarker for monitoring prognosis and treatment response in patients with melanoma. OBJECTIVES: To quantify cfBRAFV 600E levels in plasma from patients with melanoma and from patients without melanoma undergoing regular follow-up of their melanocytic lesions, in order to assess the clinical significance of the test. METHODS: We quantified cfBRAFV 600E by droplet digital polymerase chain reaction in plasma from 146 patients without melanoma undergoing continuous dermatological screening, from 26 stage III and seven stage IV patients with BRAF-mutant melanoma, and from 32 patients with melanoma who were free of disease for 3 or more years. RESULTS: Among disease-free patients and individuals without melanoma, 52% presented a high naevus count (> 50) and 49% had clinically atypical naevi. cfBRAFV 600E was detected in 71% of patients with stage IV melanoma and 15% with stage III, and in 1·4% of individuals without melanoma. No cfBRAFV 600E mutation was detected in disease-free patients with melanoma. Individuals without melanoma had lower cfBRAFV 600E levels than patients with melanoma. We established a variant allelic frequency of 0·26% or 5 copies mL-1 of cfBRAFV 600E as the optimal cutoff value for identifying patients with melanoma with > 99% specificity. CONCLUSIONS: This study suggests that naevus-related factors do not influence the detection of cfBRAFV 600E in individuals without melanoma, and supports the clinical diagnostic value of plasma cfBRAFV 600E quantification in patients with melanoma. What's already known about this topic? The analysis of the BRAF c.1799T>A (p.V600E) mutation in cell-free (cf)DNA has emerged as a potential biomarker for monitoring prognosis and treatment response in patients with metastatic BRAFV600E melanoma. The BRAFV600E alteration is a common genetic alteration found in benign proliferations such as melanocytic naevi. No information exists about the impact of the number of common acquired naevi or the presence of clinically atypical naevi in cfBRAFV600E detection in an individual. What does this study add? The cfBRAFV600E mutation is detected in plasma from a reduced number of individuals without melanoma undergoing continuous dermatological follow-up. A high number of naevi or the presence of clinically atypical naevi are factors that do not influence cfBRAFV600E detection in an individual. Both total cfBRAF concentration and cfBRAFV600E frequency are effective biomarkers in patients with advanced melanoma but not in patients at early stages or with micrometastases. What is the translational message? Detection of cfBRAFV600E in an individual is not influenced by naevus-related factors. cfBRAFV600E is a robust and reliable biomarker that can be used in dermatological surveillance programmes.

Transfusión intrauterina: tratamiento de anemia fetal severa en el Centro de Referencia Perinatal Oriente / Intrauterine transfusion: treatment of severe fetal anemia at the Oriente Perinatal Reference Center

RESUMEN INTRODUCCIÓN: La anemia fetal es una importante causa de morbilidad y mortalidad perinatal. En la actualidad la principal herramienta terapéutica es la transfusión fetal intrauterina, permitiendo una mejoría en el pronóstico y sobrevida en fetos con anemia severa. El objetivo de este estudio fue reportar los resultados obtenidos en el Centro de Referencia Perinatal Oriente (CERPO). MÉTODO: Se realizó un análisis descriptivo retrospectivo de los casos de anemia fetal que requirieron transfusión intrauterina en CERPO entre los años 2003-2019. RESULTADOS: Se incluyeron 17 embarazos, con un total de 27 procedimientos. La sobrevida perinatal fue de 82%, con un 18% de mortalidad perinatal. Se reporta una tasa de mortalidad de 3,7% asociado al procedimiento. CONCLUSIÓN: Los resultados observados son similares a lo publicado, con una tasa de complicaciones similar a lo reportado en la literatura internacional y nacional.

SUMMARY INTRODUCTION: Fetal anemia is an important cause of perinatal morbidity and mortality. At present, the main therapeutic tool is intrauterine fetal transfusion, allowing an improvement in the prognosis and survival in fetuses with severe anemia. The objective of this study was to report the results obtained in Centro de Referencia Perinatal Oriente (CERPO). METHOD: A retrospective descriptive analysis of the cases of fetal anemia that required intrauterine transfusion in CERPO between 2003-2019. RESULTS: There were 17 pregnancies included, with a total of 27 procedures. Perinatal survival was 82%, with 18% perinatal mortality; a mortality rate of 3.7% is reported per procedure. CONCLUSION: The observed results agree with previous reports.

POT1 germline mutations but not TERT promoter mutations are implicated in melanoma susceptibility in a large cohort of Spanish melanoma families.

BACKGROUND: Germline mutations in telomere-related genes such as POT1 and TERT predispose individuals to familial melanoma. OBJECTIVES: To evaluate the prevalence of germline mutations in POT1 and TERT in a large cohort of Spanish melanoma-prone families (at least two affected first- or second-degree relatives). METHODS: Overall, 228 CDKN2A wild-type melanoma-prone families were included in the study. Screening of POT1 was performed in one affected person from each family and TERT was sequenced in one affected patient from 202 families (26 families were excluded owing to DNA exhaustion/degradation). TERT promoter sequencing was extended to an additional 30 families with CDKN2A mutation and 70 patients with sporadic multiple primary melanoma (MPM) with a family history of other cancers. RESULTS: We identified four families with potentially pathogenic POT1 germline mutations: a missense variant c.233T>C (p.Ile78Thr); a nonsense variant c.1030G>T (p.Glu344*); and two other variants, c.255G>A (r.125_255del) and c.1792G>A (r.1791_1792insAGTA, p.Asp598Serfs*22), which we confirmed disrupted POT1 mRNA splicing. A TERT promoter variant of unknown significance (c.-125C>A) was detected in a patient with MPM, but no germline mutations were detected in TERT promoter in cases of familial melanoma. CONCLUSIONS: Overall, 1·7% of our CDKN2A/CDK4-wild type Spanish melanoma-prone families carry probably damaging mutations in POT1. The frequency of TERT promoter germline mutations in families with melanoma in our population is extremely rare.

Acquired erythropoietic uroporphyria secondary to myelodysplastic syndrome with chromosome 3 alterations: a case report.

Congenital erythropoietic porphyria is a rare autosomal recessive disease caused by a deficiency of uroporphyrinogen III synthase, owing to mutations in UROS in chromosome 10. Occasionally, patients show a mild, late-onset disease, without germline UROS mutations, associated with haematological malignancies. We report a 65-year-old patient with photosensitivity, overexcretion of porphyrins and thrombocytopenia. Bone marrow analysis gave a diagnosis of myelodysplastic syndrome (MDS) with the presence of a derivative chromosome 3, possibly due to an inversion including 3q21 and 3q26 break points. After allogeneic stem-cell transplantation, complete remission of MDS and uroporphyria was achieved. To our knowledge, this is the first reported case of acquired erythropoietic uroporphyria associated with MDS, with chromosome 3 alterations.

Intervenciones en hernias inguinocrurales: bilateralidad y recidiva hemiaria. Servicio de Cirugía del Hospital Naval de Viña del Mar / Reoperations in femoral and inguinal hernias: bilaterality and relapse. Surgery Service in the Navy Hospital Viña del Mar

Introducción: En nuestro país la hernioplastia inguinocrural es una de las intervenciones quirúrgicas más frecuentes, pero hay escasos estudios acerca de los resultados a largo plazo. Materiales y método: Estudio observacional de cohorte retrospectiva utilizando base de datos, fichas clínicas y electrónicas, con el objeto de analizar las causas de reintervenciones en hernioplastias inguinocrurales desde el año 2000 hasta el 2010, con seguimiento hasta junio del 2015. Resultados y discusión: Se realizaron 1.765 intervenciones con los códigos de hernia inguinal y femoral, de los cuales 100 casos requirieron reintervención: 84 hombres y 16 mujeres, con edad promedio de 62 años para la primera cirugía. En un tercio se encontró HTA, y en el 38% de los hombres uropatía obstructiva, sin ser estadísticamente significativo (p = 0,6). Se demostró intervención por hernia contralateral en el 38% de los casos, con aparición predominante dentro de los 3 primeros años desde la primera cirugía; en el 37% se demostró recidiva herniaria. Los pacientes que recidivaron equivalen al 2,7% del total de cirugías realizadas, pero al considerar las recidivas solo con técnica de Lichtenstein, esta fue del 1,7% con respecto al total de hernioplastias realizadas, presentándose dentro de los 3 primeros años. En 5 casos se demostró doble recidiva y en 2 casos triple recidiva. Cinco pacientes presentaron complicaciones: 2 hematomas, un seroma, una inguinodinia crónica y un paciente falleció por obstrucción intestinal postoperatoria. Conclusión: Nuestros resultados son similares a casuísticas nacionales y metaanálisis reportados en cuanto a tipo de pacientes, comorbilidades asociadas y porcentaje de recidiva a largo plazo, con menor tasa de complicaciones.

Introduction: In our country, hernioplasty for inguinocrural hernia is one of the most frequent surgical procedures, but there are scanty studies bring over of the long-term results. Materials and method: Observational retrospective cohort study, using clinical data base of patient's clinical history, in order to analyze the cause of reoperations on our inguinocrural hernioplasty data base, from the year 2000 to the year 2010, and with a follow up until June 2015. Results and discussion: In total they were performed 1,765 interventions coded crural and inguinal hernia, 100 cases required reoperation, 84 men and 16 women with an average age of 62 years for the first surgery. In a third hypertension was found, and in 38% of men, obstructive uropathy, not statistically significant (P=.6). Reoperation for contralateral hernia was performed in 38% of the cases, with predominant appearance within the first three years after the first surgery; in 37% of the cases, hernia recurrence was demonstrated. Patients, who recurred, were equivalent to 2.7% of all surgeries performed, but considering Lichtenstein technique, it was only 1.7% of all hernioplasties, occurring within the first three years. In 5 cases, we found double recurrence, and triple recurrence in two. Five patients had complications: two bruising, seroma, chronic inguinal pain and one death by postoperative intestinal obstruction. Conclusion: Our results were similar to those reported in our country in relation to the type of patients, comorbidities and recurrence at long-term, but with a lower rate of complications.

Successful Short Desensitization Treatment Protocol with Narrowband UVB Phototherapy (TL-01) in Polymorphic Light Eruption.

INTRODUCTION: Polymorphic light eruption (PLE) is a common idiopathic photodermatosis that typically presents with pruritic papular or papulovesicular lesions on sun-exposed skin between spring and autumn. In many subjects PLE is mild, and can usually be prevented by the use of broad-spectrum topical sunscreens and a gradual increase in sunlight exposure. However, in some individuals, sunlight exposure results in florid PLE and they often benefit from prophylactic desensitization treatment using phototherapy in early spring, an artificial method that induces a "hardening" phenomenon. OBJECTIVE: To describe and evaluate the efficacy of a short desensitization protocol, based on a one-month-treatment, administered twice a week with narrow band UVB in subjects with severe polymorphic light eruption (PLE). METHODS: A retrospective, open planned and non-randomized study to assess the efficacy of UVB phototherapy in prevention of polymorphic light eruption. RESULTS: Fifteen subjects diagnosed with severe PLE were treated with the standard protocol in our Photobiology Unit between 2014 and 2015. The effect of hardening was sustained during follow up in 87.5% of desensitization treatments. A statistically significant association (p<0.05) between the years of duration of the PLE and the response to treatment was found. CONCLUSIONS: The effect of hardening was maintained in the vast majority of subjects, obtaining a good benefit with no PLE episodes during all the summer. We demonstrate that our standard protocol is effective, and produces a successful outcome for the majority of PLE subjects. Our protocol is shorter than those currently applied, being favourable both for the patient and the physician.

Late-onset cutaneous porphyria in a patient heterozygous for a uroporphyrinogen III synthase gene mutation.

Deficiency of uroporphyrinogen III synthase (UROS) causes congenital erythropoietic porphyria (CEP). The disease, originating from the inheritance of mutations within the UROS gene, presents a recessive form of transmission. In a few patients, a late-onset CEP-like phenotype without UROS mutations appears to be associated with a myelodysplastic syndrome. We report a 60-year-old man with late-onset signs of cutaneous porphyria and accumulation in urine, plasma and faeces of type I porphyrin isomers characteristic of CEP. Analysis of DNA from peripheral leucocytes, skin and bone marrow aspirate showed that he was a heterozygous carrier of a Cys73Arg (c.217 T>C) mutation within UROS. Sequencing of cDNA from peripheral blood confirmed heterozygosity and expression of the normal allele. Measurement of UROS enzymatic activity in erythrocytes showed values ~70% of normal, indirectly indicating expression of the normal allele. Differently from other cases of late-onset uroporphyria, the patient did not present thrombocytopenia or any evidence of a myelodysplastic syndrome. Five years of clinical follow-up showed persistence of skin signs and increased excretion of porphyrins, independently of lifestyle factors or changes in medication regimes. We hypothesize acquired mosaicism (in the bone marrow) affecting the UROS gene. Thus, unstable cellular clones initiated overproduction of isomer I porphyrins leading to a CEP phenotype. This could be explained either by a clonal expansion of the porphyric (Cys73Arg) allele or by loss of function of the normal allele. Cellular turnover would facilitate release of uroporphyrins into circulation and subsequent skin lesions. This is the first case of a CEP heterozygous carrier presenting clinical manifestations.

Sobrecarga y Burnout en cuidadores informales del adulto mayor / Overload and Burnout among aged informal caregivers / Sobrecarga e Burnout com cuidadores informais do idoso

Objetivo: Conocer las condiciones personales, de sobrecarga y su relación con el Síndrome de Burnout en el cuidador informal del adulto mayor. Método: Estudio correlacional y transversal. Muestreo no probabilístico, por conveniencia. Muestra: 52 cuidadores informales de ancianos de ambos sexos. Se utilizó cédula de datos personales, la escala de Zarit y el cuestionario Maslach Burnout Inventory. El procesamiento de datos se realizó con el Statistical Package for the Social Sciences versión 20. Resultados: La media de edad de los cuidadores fue de 44 años, 58% están casados, 50% tienen escolaridad media superior, 45% son hijos de los seniles (35% son las hijas), el 27% trabajan como profesionistas, 73% tienen de 1 a 6 años cuidando al anciano; 42% dedica de 6-15 horas a su cuidado; 58% padece sobrecarga, con significancia (r = 0.442, p = 001) con las horas diarias dedicadas al cuidado. El Síndrome de Burnout mostró bajo riesgo en todas las dimensiones: Agotamiento Emocional 67%, Deshumanización 80% y Realización Personal 73%, aunque más del 20% lo padece en alguna dimensión. Conclusiones: La sobrecarga y el síndrome de Burnout en los cuidadores familiares se encontraron bajos. El factor relacionado con la sobrecarga y él Burnout fue el tiempo diario dedicado al cuidado. Con base en los resultados, se propone establecer programas preventivos de entrenamiento acerca del cuidado dirigidos a familiares de ancianos; con el fin de contribuir al bienestar de los cuidadores.

Objective: To explore the personal conditions associated with work overload and the Syndrome of Burnout among aged informal caregivers. Method: Correlational and transversal study using by-convenience not-probabilistic sampling. Sample: 52 aged informal caregivers of both sexes. A personal data form, the Zarit scale, and the Maslach Burnout Inventory questionnaire were all used. Data were processed with the Statistical Package for the Social Sciences version 20. Results: The care providers average age was 44 years old, 58% reported being married, 50% said they had a mid-high level education, 45% were sons of the elderly (35% were daughters), 27% said they worked as professionals, 73% stated they had a 1- 6 year-experience taking care of elders, 42% said that they usually devote between 6 and 15 hours daily to their care activities, and 58% turned out to be suffering from a work overload (r = .442, p=.001). A low Burnout Syndrome risk was found in all the corresponding dimensions: Emotional Fatigue 67%, Dehumanization 80%, and Personal Accomplishment 73%, though more than 20% of the respondents were shown to be suffering from the syndrome in at least one dimension. Conclusions: Work overloads and the Burnout Syndrome among the aged family caregivers were found to be low. An important factor associated with the work overload and the Burnout Syndrome was the time per day devoted to the care. Based on the results, it is suggested to establish preventive training programs related to caring and aimed at the aged family caregivers with the objective of contributing to the wellbeing of these specific caregivers.

Objetivo: Conhecer as condições pessoais, de sobrecarga e sua relação com a síndrome de Burnout no cuidador informal do idoso. Método: Estudo correlacional e transversal. Amostragem não probabilística por conveniência. Amostra: 52 cuidadores informais de idosos de ambos os sexos. Utilizou-se a cédula de dados pessoais, a escala de Zarit e o questionário Maslach Burnout Inventory. O processamento de dados realizou-se com o Statistical Package for the Social Sciences versão 20. Resultados: A média de idade dos cuidadores foi de 44 anos, 58% são casados, 50% são de escolaridade de ensino médio, 45% são filhos dos idosos (35% são as filhas), 27% trabalham como profissionais, 73% cuidam o idoso de 1 a 6 anos, 42% dedica ao cuidado de 6 a 15 horas, 58% padece de sobrecarga com significância (r=.442, p=001) pelo cuidado dedicado diariamente. A síndrome de Burnout mostrou um risco baixo em todas as dimensões: esgotamento emocional 67%, desumanização 80% e realização pessoal 73%, ainda que mais do 20% padeça em alguma dimensão. Conclusões: A sobrecarga e a síndrome de Burnout nos cuidadores familiares encontram-se baixos. O fator relacionado com a sobrecarga e o Burnout foi pelo cuidado dedicado diariamente. Com base nos resultados, propõem-se estabelecer programas preventivos de treino em volta do cuidado dirigido a familiares de idosos, com o fim de contribuir para o bem-estar dos cuidadores.

Determination of minimal erythema dose and anomalous reactions to UVA radiation by skin phototype.

BACKGROUND: Phototesting is a technique that assesses the skin's sensitivity to UV radiation by determining the smallest dose of radiation capable of inducing erythema (minimal erythema dose [MED]) and anomalous responses to UV-A radiation. No phototesting protocol guidelines have been published to date. METHODOLOGY: This was a multicenter prospective cohort study in which 232 healthy volunteers were recruited at 9 hospitals. Phototests were carried out with solar simulators or fluorescent broadband UV-B lamps. Each individual received a total of 5 or 6 incremental doses of erythemal radiation and 4 doses of UV-A radiation. The results were read at 24hours. RESULTS: At hospitals where solar simulators were used, the mean (SD) MED values were 23 (8), 28 (4), 35 (4), and 51 (6) mJ/cm(2) for skin phototypes i to iv, respectively. At hospitals where broadband UV-B lamps were used, these values were 28 (5), 32 (3), and 34 (5) mJ/cm(2) for phototypes ii to iv, respectively. MED values lower than 7, 19, 27, and 38 mJ/cm(2) obtained with solar simulators were considered to indicate a pathologic response for phototypes I to IV, respectively. MED values lower than 18, 24, and 24mJ/cm(2) obtained with broadband UV-B lamps were considered to indicate a pathologic response for phototypes ii to iv, respectively. No anomalous responses were observed at UV-A radiation doses of up to 20J/cm(2). CONCLUSIONS: Results were homogeneous across centers, making it possible to standardize diagnostic phototesting for the various skin phototypes and establish threshold doses that define anomalous responses to UV radiation.

Contenido de sodio en pan elaborado en panaderia de distribución nacional y comparado con una panadería local en la ciudad de Chillán de Chile / Comparison of sodium content in bread from a bakery with national distribution and a local bakery of Chillán city, Chile

Introduction: The Chilean Ministry of Health (MINSAL) and the Chilean Federation of Bakers (FECHIPAN) agreed to progressively decrease sodium content in bread from 800 to 500 mg/100 g bread in 100 bakeries in 2011 and in 100% of bakeries in 2014. Objective: To analyze and compare the sodium content in bread from a bakery with national distribution (A) and a local bakery (B). Materials and methods: A total of 100 samples were analyzed in each bakery 50 each of the two types of bread known as marraqueta and hallulla (types of bread rolls). Analysis was performed at different times of the day and at different days of the week. Sodium content was determined by the AOAC (2005) method using atomic absorption spectrophotometry and compared with the sodium content declared in the nutrition label in bakery A. Differences between content for type of bread, bakery and time of sampling were established by ANOVA and Student's t-test with the STATA 12.0 software at a p<0.05 level of significance. Results: Total sodium in bread (mg/100 g unit) was estimated as 619.6±127.7 mg for hallulla and 641.0±93.3 for marraqueta. There were no significant differences in sodium content in both bakeries (p=0.971) and type of bread (p=0.177). Sodium content was higher on Wednesdays (p<0.0001, p=0.016) and at 17 hours (p<0.000001, p=0.028) in hallulla and marraqueta, respectively. Total sodium content in both bakeries varied between 412.5 and 954.5 mg/100 g. Conclusions: Bread from both bakeries showed similar sodium contents although they exceeded the MINSAL-FECHIPAN agreement by 26% to 80%.

Introducción: El Ministerio de Salud de Chile (MINSAL) y la Federación de Panaderos de Chile (FECHIPAN) acordaron reducir progresivamente el contenido de sodio en el pan de 800 mg a 500 mg/100 g pan, en 100 panaderías el 2011 y en 100% de ellos el año 2014. Objetivo: Analizar el contenido de sodio en pan de una panadería de distribución nacional (A) comparada con una de tipo local (B). Materiales y métodos: Se analizaron 100 muestras de pan por panadería, 50 de marraqueta y 50 de hallulla, en diferentes horas y días de la semana. El contenido de sodio se determinó con el método AOAC (2005) mediante espectrofotometría de absorción atómica y se comparó con el contenido de sodio declarado en el etiquetado nutricional de la panadería A. Se utilizó ANOVA y T-student para establecer diferencias del contenido de sodio por tipo de pan, panadería y hora de extracción, utilizando el software STATA 12.0 con un nivel de significancia p<0,05. Resultados: El sodio total en el pan (mg/100 g pan) se estimó en 619,6±127,7 mg para hallulla y 641±93,3 para marraqueta, sin diferencias significativas para su contenido en ambas panaderías (p=0,971) y tipo de pan (p=0,177). El sodio fue mayor el día miércoles (p<0,0001 - p=0.016) y a las 17 horas (p<0,000001 - p=0.028) en pan hallulla y marraqueta respectivamente. Con variabilidad en el contenido de sodio total en ambas panaderías entre 412,5 a 954,5 mg/100 g. Conclusiones: El pan de ambas panaderías presenta similar contenido de sodio pero excediéndose 26% a 80% del acuerdo MINSAL-FECHIPAN.

Dermoscopic criteria associated with BRAF and NRAS mutation status in primary cutaneous melanoma.

BACKGROUND: The identification of BRAF mutations in melanoma led to the development and implementation of new and effective therapies. Few clinical and histological features have been associated with this mutational status. OBJECTIVES: The main objective of this study was to investigate clinical, histopathological and dermoscopic characteristics of primary melanomas according to BRAF or NRAS mutational status. METHODS: An observational retrospective study including melanoma dermoscopy images assessed for somatic mutations in BRAF and NRAS. RESULTS: Seventy-two patients were included, 30 women (42%) and 42 men (58%), mean age was 59 ± 15.51 years. BRAF-mutated melanomas were more frequently located on the trunk (n = 18, 64% for BRAF-mutated vs. n = 11, 29% for wild-type melanomas, P = 0.013). Histological ulceration was associated with the presence of BRAF mutations [odds ratio (OR) 3.141; 95% confidence interval (CI) 1.289-7.655; P = 0.002]. The Breslow index tended to be thicker in BRAF-mutated compared with wild-type (P = 0.086). BRAF mutations were present in 28 (39%) patients and only four cases were positive for NRAS mutations (6%), BRAF and NRAS mutations being mutually exclusive. The presence of dermoscopic peppering was associated with MAPK mutations (BRAF and NRAS) (OR 1.68; 95% CI 1.089-2.581; P = 0.015). Dermoscopic ulceration was also associated with BRAF mutations excluding acral and facial melanomas (OR 2.64; 95% CI 1.032-6.754). CONCLUSIONS: This study showed a correlation between BRAF and NRAS status and dermoscopic findings of 'peppering' as an expression of regression and melanophages in the dermis, suggesting a morphological consequence of immune behaviour in BRAF-mutated melanomas.

Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population.

BACKGROUND: Cutaneous melanoma tumour is classified into clinicohistopathological subtypes that may be associated with different genetic and host factors. Variation in the MC1R gene is one of the main factors of risk variation in sporadic melanoma. The relationship between MC1R variants and the risk of developing a specific subtype of melanoma has not been previously explored. OBJECTIVES: To analyse whether certain MC1R variants are associated with particular melanoma subtypes with specific clinicohistopathological features. METHODS: An association study was performed between MC1R gene variants and clinicopathological subtypes of primary melanoma derived from 1679 patients. RESULTS: We detected 53 MC1R variants (11 synonymous and 42 nonsynonymous). Recurrent nonsynonymous variants were p.V60L (30·0%), p.V92M (11·7%), p.D294H (9·4%), p.R151C (8·8%), p.R160W (6·2%), p.R163Q (4·2%) p.R142H (3·3%), p.I155T (3·8%), p.V122M (1·5%) and p.D84E (1·0%). Melanoma subtypes showed differences in the total number of MC1R variants (P = 0·028) and the number of red hair colour variants (P = 0·035). Furthermore, an association between p.R163Q and lentigo maligna melanoma was detected under a dominant model of heritance (odds ratio 2·16, 95% confidence interval 1·07-4·37; P = 0·044). No association was found between p.R163Q and Fitzpatrick skin phototype, eye colour or skin colour, indicating that the association was independent of the role of MC1R in pigmentation. No association was observed between MC1R polymorphisms and other melanoma subtypes. CONCLUSIONS: Our findings suggest that certain MC1R variants could increase melanoma risk due to their impact on pathways other than pigmentation, and may therefore be linked to specific melanoma subtypes.

Benefits of oral Polypodium Leucotomos extract in MM high-risk patients.

BACKGROUND: UV radiation and the presence of melanocytic nevi are the main risk factors of sporadic melanoma (MM). Protection of skin by an oral photoprotective agent would have substantial benefits. OBJECTIVE: We investigated the possible role of an oral Polypodium leucotomos (PL) extract to improve systemic photoprotection in patients at risk of skin cancer analyzing the ability to decrease UV-induced erythema. We also studied the interaction among MC1R polymorphisms and CDKN2A status with the minimal erythematous dose (MED) and their influence in the response after oral PL. METHODS: A total of 61 patients (25 with familial and/or multiple MM, 20 with sporadic MM and 16 with atypical mole syndrome without history of MM) were exposed to varying doses of artificial UVB radiation without and after oral administration of a total dose of 1080 mg of PL. RESULTS: Oral PL treatment significantly increased the MED mean in all group patients (0.123 to 0.161 J/cm(2) , p<0.05). Although not significant, we noticed a stronger effect of PL on the MED of patients with familial MM compared to those with MM (U=273, p=0.06). Among the patients with familial MM, those exhibiting a mutated CDKN2A and/or polymorphisms in MC1R had the bigger differences in response to treatment with PL. LIMITATIONS: Reduced number of patients. No control population. CONCLUSIONS: Administration of PL leads to a significant reduction of sensitivity to UVR (p<0.05) in all patients. Dark-eye patients and patients with higher UVR sensibility (lower basal MED) would be the most benefited from oral PL treatment.