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.

Chronic atrazine exposure increases the expression of genes associated with GABAergic and glutamatergic systems in the brain of male albino rat.

The herbicide atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is widely used to destroy grasses and broadleaf weeds in crops and some fruits. Studies in rodents have shown that acute, repeated or chronic exposure to ATR is associated with alterations in the nigrostriatal dopaminergic pathway, whereas its effects on GABAergic and glutamatergic pathways have only recently been reported. Sprague-Dawley male rats were exposed daily to 1 or 10 mg ATR/kg of BW for 13 months to evaluate the ATR effects on GABAergic and glutamatergic systems. At the end of the ATR treatment, the levels of mRNA of several genes involved in the production, vesiculation, reuptake, and receptors of GABA and Glu in the striatum (STR), nucleus accumbens (NAcc), prefrontal cortex (PFC), ventral midbrain (vMID) and hippocampus (HIPP) were evaluated by absolute qPCR. For the GABAergic genes, increased expression of GAD67 and Slc32a1 in STR and/or vMID in rats exposed to 1 and/or 10 mg ATR were detected. With regard to the expression of genes involved in the glutamatergic system, Slc17a6 and Grin1 in HIPP of rats exposed to 1 and/or 10 mg ATR, increased as was Gria1 in STR and PFC in the group exposed to 1 mg ATR. In the same fashion, Slc1a3 expression and MGLUR1 increased in STR of rats exposed to 1 and 10 mg ATR groups. The expression of the glutaminases gls (variants 1 and 2) was greater in STR, NAcc, HIPP, and PFC of rats exposed to 1 and/or 10 mg ATR. These findings show that the GABAergic and, especially glutamatergic systems are targets of ATR exposure.

Shape Changes in the Mirror Nuclei

We studied the proton-rich T_{z}=-1 nucleus ^{70}Kr through inelastic scattering at intermediate energies in order to extract the reduced transition probability, B(E2;0^{+}→2^{+}). Comparison with the other members of the A=70 isospin triplet, ^{70}Br and ^{70}Se, studied in the same experiment, shows a 3σ deviation from the expected linearity of the electromagnetic matrix elements as a function of T_{z}. At present, no established nuclear structure theory can describe this observed deviation quantitatively. This is the first violation of isospin symmetry at this level observed in the transition matrix elements. A heuristic approach may explain the anomaly by a shape change between the mirror nuclei ^{70}Kr and ^{70}Se contrary to the model predictions.

Recomendaciones del Grupo Español de Fotobiología de la AEDV en referencia al manejo de las unidades de fototerapia durante la pandemia por SARS-CoV-2 / Management of Phototherapy Units During the COVID-19 Pandemic: Recommendations of the AEDV's Spanish Photobiology Group

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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.

Recomendaciones sobre exposición solar y fotoprotección del Grupo Español de Fotobiología de la AEDV adecuadas al periodo de desconfinamiento durante la pandemia por SARS-CoV-2 / Recommendations on Sun Exposure and Photoprotection Following Easing of the COVID-19 Pandemic Lockdown: Spanish Photobiology Group of the Spanish Academy of Dermatology and Venerology (AEDV)

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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.

Photoonycholysis: new findings.

First described in 1961, photoonycholysis (PO) is a rare nail alteration that may result from drug intake, from topical aminolevulinate photodynamic therapy or from photosensitive conditions such as porphyria or pseudoporphyria. Spontaneous PO is rare. This review updates the numerous causes of PO and highlights some new ways producing this condition. Four different types of PO are clearly recognized without relationship with the responsible drug. An updated list of potential inducing drug is provided. Some practical points on PO have been raised. The inability to reproduce photoonycholysis experimentally should be emphasized, and the pathogenesis of PO still needs to be clarified.

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.

Inducción de fototolerancia con ultravioleta B de banda estrecha en urticaria solar / Inducing Light Tolerance With Narrowband UV-B Therapy in Solar Urticaria

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