Correction: Velasco-Amo et al. Use of traC Gene to Type the Incidence and Distribution of pXFAS_5235 Plasmid-Bearing Strains of Xylella fastidiosa subsp. fastidiosa ST1 in Spain. Plants 2022, 11, 1562.

In the original publication [...].

Development of a novel in vitro model to study the modulatory role of the respiratory complex I in macrophage effector functions.

Increasing evidence demonstrate that the electron transfer chain plays a critical role in controlling the effector functions of macrophages. In this work, we have generated a Ndufs4-/- murine macrophage cell lines. The Ndufs4 gene, which encodes a supernumerary subunit of complex I, is a mutational hotspot in Leigh syndrome patients. Ndufs4-/- macrophages showed decreased complex I activity, altered complex I assembly, and lower levels of maximal respiration and ATP production. These mitochondrial respiration alterations were associated with a shift towards a pro-inflammatory cytokine profile after lipopolysaccharide challenge and improved ability to phagocytose Gram-negative bacteria.

The mitochondrial succinate dehydrogenase complex controls the STAT3-IL-10 pathway in inflammatory macrophages.

The functions of macrophages are tightly regulated by their metabolic state. However, the role of the mitochondrial electron transport chain (ETC) in macrophage functions remains understudied. Here, we provide evidence that the succinate dehydrogenase (SDH)/complex II (CII) is required for respiration and plays a role in controlling effector responses in macrophages. We find that the absence of the catalytic subunits Sdha and Sdhb in macrophages impairs their ability to effectively stabilize HIF-1α and produce the pro-inflammatory cytokine IL-1ß in response to LPS stimulation. We also arrive at the novel result that both subunits are essential for the LPS-driven production of IL-10, a potent negative feedback regulator of the macrophage inflammatory response. This phenomenon is explained by the fact that the absence of Sdha and Sdhb leads to the inhibition of Stat3 tyrosine phosphorylation, caused partially by the excessive accumulation of mitochondrial reactive oxygen species (mitoROS) in the knockout cells.

Heterogeneous attitudes and behaviors in relation to participation in the ecotourism: Do customer segments play a role?

The potential of ecotourism is expanding year on year. Given the broad nature of the tourism market, it is necessary to identify smaller groups of individuals that have common traits. This study aims to explore if there are any segments of ecotourist based on attitude and behavior towards ecotourism, profiles the segments according to their sociodemographic characteristics, and analyzes the extent to which they differ by country of origin. The study used a sample of 809 ecotourists from Spain and Chile, while latent class cluster analysis was employed as the segmentation method. The ecotourists were divided into three segments (Basic ecotourists-ecotourists of thought-, Average ecotourists, and Conscientious and active ecotourists) and the bias-adjusted three-step methodology was used to examine the differences in the country of origin. In sum, the largest portion of tourists falls into the category of the average ecotourist segment, which lies between the two aforementioned segments and exhibits moderate attitudes and intentions to engage in ecotourism and pay a premium for it. This segment is more prevalent in Spain compared to Chile. This research adds to the body of knowledge on the marketing of ecotourism behavior by modeling the heterogeneity in the ecotourists' attitudes and behaviors. This study suggests that ecotourism organizations, whether they are accommodation providers, tourism operators, or companies that organize activities in nature, should be aware of the unique qualities of their customers, as well as their preferences, in order to create successful marketing strategies.

Invasive meningococcal disease epidemiology and vaccination strategies in four Southern European countries: a review of the available data.

INTRODUCTION: Invasive meningococcal disease (IMD) is a major health concern which can be prevented through vaccination. Conjugate vaccines against serogroups A, C, W, and Y and two protein-based vaccines against serogroup B are currently available in the European Union. AREAS COVERED: We present epidemiologic data for Italy, Portugal, Greece, and Spain using publicly available reports from national reference laboratories and national or regional immunization programs (1999-2019), aiming to confirm risk groups, and describe time trends in overall incidence and serogroup distribution, as well as impact of immunization. Analysis of circulating MenB isolates in terms of the surface factor H binding protein (fHbp) using PubMLST is discussed as fHbp represents an important MenB vaccine antigen. Predictions of potential reactivity of the two available MenB vaccines (MenB-fHbp and 4CMenB) with circulating MenB isolates are also provided as assessed using the recently developed MenDeVAR tool. EXPERT OPINION: Understanding dynamics of IMD and continued genomic surveillance are essential for evaluating vaccine effectiveness, but also prompting proactive immunization programs to prevent future outbreaks. Importantly, the successful design of further effective meningococcal vaccines to fight IMD relies on considering the unpredictable epidemiology of the disease and combining lessons learnt from capsule polysaccharide vaccines and protein-based vaccines.

Complete Circularized Genome Resources of Seven Strains of Xylella fastidiosa subsp. fastidiosa Using Hybrid Assembly Reveals Unknown Plasmids.

Xylella fastidiosa is a vascular plant pathogenic bacterium native to the Americas that is causing significant epidemics and economic losses in olive and almonds in Europe, where it is a quarantine pathogen. Since its first detection in 2013 in Italy, mandatory surveys across Europe revealed the presence of the bacterium also in France, Spain, and Portugal. Combining Oxford Nanopore Technologies and Illumina sequencing data, we assembled high-quality complete genomes of seven X. fastidiosa subsp. fastidiosa strains isolated from different plants in Spain, the United States, and Mexico. Comparative genomic analyses discovered differences in plasmid content among strains, including plasmids that had been overlooked previously when using the Illumina sequencing platform alone. Interestingly, in strain CFBP8073, intercepted in France from plants imported from Mexico, three plasmids were identified, including two (plasmids pXF-P1.CFBP8073 and pXF-P2.CFBP8073) not previously described in X. fastidiosa and one (pXF5823.CFBP8073) almost identical to a plasmid described in a X. fastidiosa strain from citrus. Plasmids found in the Spanish strains here were similar to those described previously in other strains from the same subspecies and ST1 isolated in the Balearic Islands and the United States. The genome resources from this work will assist in further studies on the role of plasmids in the epidemiology, ecology, and evolution of this plant pathogen.

Use of traC Gene to Type the Incidence and Distribution of pXFAS_5235 Plasmid-Bearing Strains of Xylella fastidiosa subsp. fastidiosa ST1 in Spain.

Xylella fastidiosa (Xf) is a phytopathogenic bacterium with a repertoire of self-replicating genetic elements, including plasmids, pathogenicity islands, and prophages. These elements provide potential avenues for horizontal gene transfer both within and between species and have the ability to confer new virulence traits, including the ability to colonize new host plants. However, they can also serve as a 'footprint' to type plasmid-bearing strains. Genome sequencing of several strains of Xf subsp. fastidiosa sequence type (ST) 1 from Mallorca Island, Spain, revealed the presence of a 38 kb plasmid (pXFAS_5235). In this study, we developed a PCR-based typing approach using primers targeting the traC gene to determine the presence of pXFAS_5235 plasmid or other plasmids carrying this gene in a world-wide collection of 65 strains X. fastidiosa from different subspecies and STs or in 226 plant samples naturally infected by the bacterium obtained from the different outbreaks of Xf in Spain. The traC gene was amplified only in the plant samples obtained from Mallorca Island infected by Xf subsp. fastidiosa ST1 and from all Spanish strains belonging to this ST. Maximum-likelihood phylogenetic tree of traC revealed a close relatedness among Spanish and Californian strains carrying similar plasmids. Our results confirm previous studies, which suggested that a single introduction event of Xf subsp. fastidiosa ST1 occurred in the Balearic Islands. Further studies on the presence and role of plasmids in Xf strains belonging to the same or different subspecies and STs can provide important information in studies of epidemiology, ecology, and evolution of this plant pathogen.

Modelo CBCRisk para determinar el riesgo de cáncer de mama contralateral en el cáncer de mama esporádico / CBCRisk model to determine the risk of contralateral breast cancer in sporadic breast cancer

Introducción: La mayoría de los cánceres de mama (CM) se diagnostican en mujeres sin antecedentes familiares y no portadoras de mutaciones de riesgo. En las últimas décadas se ha producido un aumento de mastectomías profilácticas contralaterales (MPC) en estas pacientes. El CBCRisk es un modelo que calcula el riesgo absoluto de cáncer de mama contralateral (CMC) y pretende servir para el asesoramiento de pacientes con CM esporádico sobre la MPC. Método: Análisis observacional retrospectivo de pacientes con un cáncer de mama esporádico sometidas a MPC durante 2017-2019. Análisis descriptivo, comparativo y de regresión logística univariante para identificar factores predictivos de LMAR y/o CMC oculto. Evaluación del modelo CBCRisk publicado en 2017 y distintos valores límite para la recomendación de MPC. Resultados: Se seleccionaron 42 pacientes. Incidencia de LMAR y cáncer oculto (CO) menor que la descrita en la literatura (9,52% LMAR, 2,38% CO). Ninguna de las variables evaluadas alcanzó significación estadística para la predicción de lesiones. El valor de CBCRisk a cinco años medio en pacientes con hallazgos patológicos fue de 2,08 (DE 0,97), superior al CBCRisk medio del conjunto (1,87 ± 0,91) y del subgrupo de MPC sin hallazgos patológicos (1,84 ± 0,91). Solo el CBCRisk ≥ 3 resultó significativo (p = 0,04) para la predicción de hallazgos patológicos. Conclusión: Las pacientes con CM esporádico deben ser adecuadamente informadas de los riesgos y beneficios estimados de la MPC. El CBCRisk puede ser útil para el asesoramiento de estas pacientes, pero precisa validación en cohortes más amplias y prospectivas. (AU)

Introduction: The great majority of breast cancer (BC) cases are diagnosed in women who have no known family history of the disease and are not carriers of any risk mutation. During the past few decades an increase in the number of contralateral prophylactic mastectomy (CPM) has been produced in these patients. The CBCRisk model calculates the absolute risk of suffering from contralateral breast cancer (CBC); thus, it can be used to counselling patients with sporadic breast cancer. Method: An observational, retrospective study including sporadic breast cancer patients treated with contralateral prophylactic mastectomy has been conducted between 2017 and 2019. A descriptive and comparative study with one variation of logistic regression has been carried out in order to identify predictive factors of occult tumors (OT) and medium/high risk damage (MHRD). Evaluation of the CBCRisk model published in 2017 and different limit values for the CPM recommendation. Results: 42 patients were selected. Incidence of MHRD and OT was lower than that described in the literatura (9.52% MHRD, 2.38% OT). None of the evaluated variables reached statistical significance for predicting injuries. The average value of CBCRisk 5 years ahead found in patients with pathological findings was 2.08 (SD 0.97), higher than the average value of the whole group (1.87 ± 0.91) and the subgroup without pathological findings (1.84 ± 0.91). Only values ≥ 3 for CBCRisk were considered statistically significant (p = 0.04) for the prediction of histological lesions. Conclusion: Patients with sporadic breast cancer should be adequately informed about the estimated risks and benefits of undergoing a contralateral prophylactic mastectomy. The CBCRisk may be useful for the counseling of these patients, but it requires validation in larger and prospective cohorts. (AU)

CBCRisk model to determine the risk of contralateral breast cancer in sporadic breast cancer.

INTRODUCTION: The great majority of breast cancer (BC) cases are diagnosed in women who have no known family history of the disease and are not carriers of any risk mutation. During the past few decades an increase in the number of contralateral prophylactic mastectomy (CPM) has been produced in these patients. The CBCRisk model calculates the absolute risk of suffering from contralateral breast cancer (CBC); thus, it can be used to counselling patients with sporadic breast cancer. METHOD: An observational, retrospective study including sporadic breast cancer patients treated with contralateral prophylactic mastectomy has been conducted between 2017 and 2019. A descriptive and comparative study with one variation of logistic regression has been carried out in order to identify predictive factors of occult tumors (OT) and medium/high risk damage (MHRD). Evaluation of the CBCRisk model published in 2017 and different limit values for the CPM recommendation. RESULTS: 42 patients were selected. Incidence of MHRD and OT was lower than that described in the literatura (9.52%MHRD, 2.38%OT). None of the evaluated variables reached statistical significance for predicting injuries. The average value of CBCRisk 5 years ahead found in patients with pathological findings was 2.08 (DE 0.97), higher than the average value of the whole group (1.87 ± 0.91) and the subgroup without pathological findings (1.84 ± 0.91). Only values >3 for CBCRisk were considered statistically significant (P = .04) for the prediction of histological lesions. CONCLUSION: Patients with sporadic breast cancer should be adequately informed about the estimated risks and benefits of undergoing a contralateral prophylactic mastectomy. The CBCRisk may be useful for the counseling of these patients, but it requires validation in larger and prospective cohorts.

Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals / Evaluación de la rigidez hepática y esplénica mediante Fibroscan® para la predicción de varices esofágicas en pacientes con cirrosis hepática por VHC tratados con antivirales orales

Introduction: The aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents. Patients and methods: This cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness–spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed. Results: Ninety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p=0.02), spleen stiffness measurement (39.4 vs 46.05; p=0.04), liver stiffness–spleen diameter to platelet ratio score (1.21 vs 2.02; p=0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p=0.04) and variceal risk index (−3.4 vs −1.02; p=0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3kPa for liver stiffness measurement and 27kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance. Discussion: Liver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.(AU)

Introducción: El objetivo de este estudio fue evaluar la rigidez hepática y esplénica medidas con Fibroscan® para la predicción de várices esofágicas (VE), en pacientes con cirrosis hepática por VHC tratados con antivirales orales. Pacientes y métodos: Estudio observacional y transversal que incluyó pacientes con cirrosis hepática por VHC compensada y respuesta virológica sostenida tras tratamiento. Se recogieron datos clínico-analíticos, ecográficos y endoscópicos y marcadores no invasivos como el Fibroscan® hepático y esplénico, el modelo predictivo «Liver stiffness-spleen diameter to platelet ratio score» (LSPS), el «Varices Risk Index» (VRI) y el índice n° plaquetas/diámetro mayor del bazo. Resultados: Se incluyeron 97 pacientes consecutivos. Los valores del Fibroscan® hepático (12,2 vs. 16; p = 0,02), esplénico (39,4 vs. 46,05; p = 0,04), LSPS (1,21 vs. 2,02; p = 0,008), índice n.° plaquetas/diámetro mayor del bazo (1.102,19 vs. 829,7; p = 0,04) y VRI (-3,4 vs. -1,02; p = 0,01) mostraron diferencias significativas entre pacientes sin/con VE. El mejor punto de corte del fibroscán hepático y esplénico para descartar la presencia de várices fue 12,3 y 27 kPas, respectivamente, con precisión diagnóstica moderada (AUROC: 0,671 y 0,624, respectivamente). La combinación de los parámetros no invasivos no mejoró el rendimiento global de estas pruebas. Discusión: Los valores del Fibroscan® hepático y esplénico mostraron resultados subóptimos para la evaluación no invasiva de VE en pacientes cirróticos por VHC tratados con antivirales orales. Nuestros resultados sugieren que estas pruebas no pueden sustituir a los procedimientos estándar para predecir la presencia de várices en esta subpoblación.(AU)

Mastectomía preservadora de piel con colgajo dermograso desepitelizado (técnica de Spira modificada) y reconstrucción mediante implante directo / Nipple sparing mastectomy with a de-epithelialized derma-fat flap (modified Spira technique) and direct-to implant reconstruction

Introducción: La técnica de Spira es un tipo de mastectomía preservadora de piel que permite la reconstrucción inmediata (RMI), ideal en mamas ptósicas. Si bien, persiste controversia sobre resultados oncológicos en el cáncer de mama. El objetivo es analizar complicaciones, secuelas cosméticas, causas de reintervención y resultados oncológicos. Métodos: Estudio observacional retrospectivo de pacientes intervenidas durante 2003-2018 en nuestro centro. La población de estudio la constituyen pacientes con carcinoma de mama o sometidas a mastectomía profiláctica por alto riesgo, en las que se realizó una mastectomía preservadora de piel con colgajo dermograso desepitelizado (técnica de Spira modificada) y reconstrucción mediante implante directo. Se analiza la presencia de complicaciones precoces y tardías, secuelas, recidiva tumoral y supervivencia. Resultados: Se realizaron 247 mastectomías con reconstrucción en 139 pacientes, 216 bilaterales (87,4%) y 31 unilaterales (12,5%); 121 terapéuticas (49%) y 126 profilácticas (51%). La mediana de seguimiento fue de 81 meses. Se observaron complicaciones en un 16,2%; necrosis cutánea en 5,3% y cinco casos de necrosis del CAP (2%). La tasa de reintervención por secuelas cosméticas fue del 17,4% (la más frecuente fue contractura capsular 11,3%) y, de ellas, el 39,3% recibieron RT. La tasa de recidiva fue del 14% (0,8% cutánea, 3,3% locorregional y 9,9% a distancia). Ocho pacientes fallecieron (6,6%). La SLE y SG fue del 92,6% y 93,3% a cinco años. Conclusión: La técnica de Spira constituye una opción segura y ofrece buenos resultados cosméticos y oncológicos como tratamiento y profilaxis de cáncer de mama en mamas ptósicas de moderado a gran tamaño. (AU)

Introduction: Spira technique is a type of nipple-sparing mastectomy that allows immediate reconstruction (IBR), ideal for ptosic breasts. Although, controversy persists regarding oncological results in breast cancer. The aim is to analyze complications, cosmetic outcomes, causes of reoperation and oncological results. Methods: Retrospective observational analysis of patients undergone surgery during 2003-2018 in our center. Study population is based on patients with breast carcinoma or undergoing prophylactic mastectomy due to high-risk, in which a skin-sparing mastectomy with a de-epithelialized derma-fat flap (modified Spira technique) and direct to implant reconstruction was performed. Short and long-term complications, sequelae, tumor recurrence and survival rates are analyzed. Results: A total of 247 mastectomies with immediate reconstruction in 139 patients, 216 bilateral (87.4%) and 31 unilateral (12.5%) were performed. 121 therapeutic (49%) and 126 prophylactic (51%). Median follow-up 81 months. Complications were observed in 16.2%; skin necrosis 5.3% and 5 cases of NAC necrosis (2%). Reoperation rate due to cosmetic sequelae was 17.4% (capsular contracture was the most frequent,11.3%) and a 39.3% of these patients have received RT. Recurrence of 14% (0.8% skin, 3.3% locoregional and 9.9% metastatic), 8 patients died (6.6%). Rates of FSD and OS were 92.6% and 93.3% respectively. Conclusion: Spira mastectomy is a safe option and provides good cosmetic and oncologic results as breast cancer treatment and prophylaxis in moderate-large ptosic breasts. (AU)

Nipple sparing mastectomy with a de-epithelialized derma-fat flap (modified Spira technique) and direct-to implant reconstruction. / Mastectomía preservadora de piel con colgajo dermograso desepitelizado (técnica de Spira modificada) y reconstrucción mediante implante directo.

INTRODUCTION: Spira technique is a type of nipple-sparing mastectomy that allows immediate reconstruction (IBR), ideal for ptosic breasts. Although, controversy persists regarding oncological results in breast cancer. The aim is to analyze complications, cosmetic outcomes, causes of reoperation and oncological results. METHODS: Retrospective observational analysis of patients undergone surgery during 2003-2018 in our center. Study population is based on patients with breast carcinoma or undergoing prophylactic mastectomy due to high-risk, in which a skin-sparing mastectomy with a de-epithelialized derma-fat flap (modified Spira technique) and direct to implant reconstruction was performed. Short and long-term complications, sequelae, tumor recurrence and survival rates are analyzed. RESULTS: A total of 247 mastectomies with immediate reconstruction in 139 patients, 216 bilateral (87.4%) and 31 unilateral (12.5%) were performed. 121 therapeutic (49%) and 126 prophylactic (51%). Median follow-up 81 months. Complications were observed in 16.2%; skin necrosis 5.3% and 5 cases of NAC necrosis (2%). Reoperation rate due to cosmetic sequelae was 17.4% (capsular contracture was the most frequent,11.3%) and a 39.3% of these patients have received RT. Recurrence of 14% (0.8% skin, 3.3% locoregional and 9.9% metastatic), 8 patients died (6.6%). Rates of FSD and OS were 92.6% and 93.3% respectively. CONCLUSION: Spira mastectomy is a safe option and provides good cosmetic and oncologic results as breast cancer treatment and prophylaxis in moderate-large ptosic breasts.

Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals.

INTRODUCTION: The aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents. PATIENTS AND METHODS: This cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness-spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed. RESULTS: Ninety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p=0.02), spleen stiffness measurement (39.4 vs 46.05; p=0.04), liver stiffness-spleen diameter to platelet ratio score (1.21 vs 2.02; p=0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p=0.04) and variceal risk index (-3.4 vs -1.02; p=0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3kPa for liver stiffness measurement and 27kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance. DISCUSSION: Liver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.

CBCRisk model to determine the risk of contralateral breast cancer in sporadic breast cancer. / Modelo CBCRisk para determinar el riesgo de cáncer de mama contralateral en el cáncer de mama esporádico.

INTRODUCTION: The great majority of breast cancer (BC) cases are diagnosed in women who have no known family history of the disease and are not carriers of any risk mutation. During the past few decades an increase in the number of contralateral prophylactic mastectomy (CPM) has been produced in these patients. The CBCRisk model calculates the absolute risk of suffering from contralateral breast cancer (CBC); thus, it can be used to counselling patients with sporadic breast cancer. METHOD: An observational, retrospective study including sporadic breast cancer patients treated with contralateral prophylactic mastectomy has been conducted between 2017 and 2019. A descriptive and comparative study with one variation of logistic regression has been carried out in order to identify predictive factors of occult tumors (OT) and medium/high risk damage (MHRD). Evaluation of the CBCRisk model published in 2017 and different limit values for the CPM recommendation. RESULTS: 42 patients were selected. Incidence of MHRD and OT was lower than that described in the literatura (9.52% MHRD, 2.38% OT). None of the evaluated variables reached statistical significance for predicting injuries. The average value of CBCRisk 5 years ahead found in patients with pathological findings was 2.08 (SD 0.97), higher than the average value of the whole group (1.87 ± 0.91) and the subgroup without pathological findings (1.84 ± 0.91). Only values ≥ 3 for CBCRisk were considered statistically significant (p = 0.04) for the prediction of histological lesions. CONCLUSION: Patients with sporadic breast cancer should be adequately informed about the estimated risks and benefits of undergoing a contralateral prophylactic mastectomy. The CBCRisk may be useful for the counseling of these patients, but it requires validation in larger and prospective cohorts.

Cáncer de mama contralateral y recurrencia en portadoras BRCA1/2 y no portadoras con alto riesgo de cáncer de mama hereditario tras mastectomía bilateral / Contralateral breast cancer and tumor recurrence in BRCA1/2 carriers and non-carriers at a high risk of hereditary breast cancer after bilateral mastectomy

INTRODUCCIÓN: La mastectomía contralateral profiláctica (MCP) reduce el riesgo de cáncer contralateral en al menos un 90%. Además, las portadoras de mutación BRCA tienen mayor riesgo de recurrencia ipsilateral y de un segundo tumor primario. El objetivo es evaluar el riesgo de cáncer contralateral y la recurrencia, y analizar factores predictivos en pacientes con cáncer de mama y mutaciones BRCA1/2 y no portadoras con alto riesgo de cáncer hereditario. MÉTODOS: Análisis observacional retrospectivo de 46 pacientes sometidas a mastectomía bilateral durante 2004-2018. Nueve pacientes BRCA1, 12 BRCA2 y 25 con alto riesgo sin mutación. RESULTADOS: Dieciséis pacientes con diagnóstico de novo y 30 tratadas previamente por cáncer de mama a las que realizamos MCP de manera diferida (en 10 de ellas por detección de mutación en BRCA a posteriori); mediana de seguimiento 79 meses. La técnica quirúrgica más usada fue la incisión lateral externa. En todas las pacientes se realizó reconstrucción inmediata. En las piezas de MCP se encontraron 4 tumores in situ, 3 invasivos y una hiperplasia atípica. La incidencia de cáncer contralateral oculto fue del 15,2%. Cinco pacientes presentaron recidiva 21,2 meses de media tras la intervención; SLE 83,74 meses y SG 84,33 meses. Los modelos de regresión identificaron mutación BRCA1/2 y alto riesgo sin mutación como factores predictivos significativos para tumor oculto, mientras que el tamaño tumoral ≥ 2 cm fue predictivo de recidiva. CONCLUSIONES: En nuestra serie 7 pacientes (15,2%) habrían desarrollado un tumor contralateral en los años posteriores, y un 10,8% presentaron recurrencia a pesar de MCP

INTRODUCTION: Contralateral prophylactic mastectomy (CPM) has been reported to reduce risk of contralateral breast cancer (CBC) by at least 90%.In addition, BRCA carriers presents higher risk of ipsilateral recurrence and a second primary tumor. The aim is to evaluate risk of CBC and recurrence and to analyze predictive factors in BRCA1/2 mutation carriers and non-carriers at high-risk of hereditary breast cancer patients. METHODS: Retrospective observational study. 46 patients underwent bilateral mastectomy during 2004-2018. RESULTS: Cohort comprised 9 patients BRCA1,12 BRCA2 and 25 at high-risk without mutation. Median follow-up 79 months. 16 patients recently diagnosed and 30 previously treated by breast cancer whom underwent CPM at second time (because of later detection of BRCA mutation in 10 cases). The external lateral incision was most frequent surgical technique. In all patients immediate reconstruction was performed. In CPM pieces, 4 in situ carcinoma, 3 invasive and 1 atypical hyperplasia were found. The incidence of occult contralateral cancer was 15.2%. Recurrence was observed in 5 patients a media of 21.2 months after surgery. FSD was 83.74 months and OS 84.33 months. Regression models identified BRCA1/2 mutation and high risk without mutation as significant occult tumor predictive factors while tumor size ≥ 2 cm was predictive of recurrence. CONCLUSIONS: In our series we found a10.8% recurrence despite CPM and 7 patients (15.2%) would have developed a CBC in subsequent years

Phylogenetic inference enables reconstruction of a long-overlooked outbreak of almond leaf scorch disease (Xylella fastidiosa) in Europe.

The recent introductions of the bacterium Xylella fastidiosa (Xf) into Europe are linked to the international plant trade. However, both how and when these entries occurred remains poorly understood. Here, we show how almond scorch leaf disease, which affects ~79% of almond trees in Majorca (Spain) and was previously attributed to fungal pathogens, was in fact triggered by the introduction of Xf around 1993 and subsequently spread to grapevines (Pierce's disease). We reconstructed the progression of almond leaf scorch disease by using broad phylogenetic evidence supported by epidemiological data. Bayesian phylogenetic inference predicted that both Xf subspecies found in Majorca, fastidiosa ST1 (95% highest posterior density, HPD: 1990-1997) and multiplex ST81 (95% HPD: 1991-1998), shared their most recent common ancestors with Californian Xf populations associated with almonds and grapevines. Consistent with this chronology, Xf-DNA infections were identified in tree rings dating to 1998. Our findings uncover a previously unknown scenario in Europe and reveal how Pierce's disease reached the continent.

Reflexiones y evidencias sobre la mastectomía reductora de riesgo. Respuesta de los autores / Risk reducing mastectomy: reflections and evidences. Author's reply

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Contralateral breast cancer and tumor recurrence in BRCA1/2 carriers and non-carriers at a high risk of hereditary breast cancer after bilateral mastectomy. / Cáncer de mama contralateral y recurrencia en portadoras BRCA1/2 y no portadoras con alto riesgo de cáncer de mama hereditario tras mastectomía bilateral.

INTRODUCTION: Contralateral prophylactic mastectomy (CPM) has been reported to reduce risk of contralateral breast cancer (CBC) by at least 90%.In addition, BRCA carriers presents higher risk of ipsilateral recurrence and a second primary tumor. The aim is to evaluate risk of CBC and recurrence and to analyze predictive factors in BRCA1/2 mutation carriers and non-carriers at high-risk of hereditary breast cancer patients. METHODS: Retrospective observational study. 46 patients underwent bilateral mastectomy during 2004-2018. RESULTS: Cohort comprised 9 patients BRCA1,12 BRCA2 and 25 at high-risk without mutation. Median follow-up 79 months. 16 patients recently diagnosed and 30 previously treated by breast cancer whom underwent CPM at second time (because of later detection of BRCA mutation in 10 cases). The external lateral incision was most frequent surgical technique. In all patients immediate reconstruction was performed. In CPM pieces, 4 in situ carcinoma, 3 invasive and 1 atypical hyperplasia were found. The incidence of occult contralateral cancer was 15.2%. Recurrence was observed in 5 patients a media of 21.2 months after surgery. FSD was 83.74 months and OS 84.33 months. Regression models identified BRCA1/2 mutation and high risk without mutation as significant occult tumor predictive factors while tumor size≥2cm was predictive of recurrence. CONCLUSIONS: In our series we found a10.8% recurrence despite CPM and 7 patients (15.2%) would have developed a CBC in subsequent years.

Mastectomía ahorradora de piel y pezón en carcinoma ductal in situ. Seguridad oncológica a 10 años / Nipple-sparing mastectomy in ductal carcinoma in situ. Oncological results over a 10-year period

OBJETIVO: El objetivo es evaluar la seguridad oncológica a 10 años de la mastectomía ahorradora de piel y pezón (MAP) en pacientes con carcinoma ductal in situ (CDIS). MÉTODO: Análisis observacional retrospectivo. Se realizaron 35 MAP en pacientes con CDIS durante 2005-2018. Evaluamos resultados histológicos, oncológicos y de morbilidad. RESULTADOS: Las indicaciones más frecuentes fueron márgenes afectos tras tumorectomía (31,5%), multifocalidad/multicéntricidad (22,8%), tumor >3 cm (8,6%) correlación desfavorable tamaño tumoral/mama (8,6%) y decisión de la paciente (8,6%). La técnica más usada fue incisión lateral externa en 11 pacientes, seguida de técnica de Spira en nueve casos. La presencia de CDIS se confirmó en 22 pacientes y en 11 no se encontró tumor en la pieza de mastectomía. La tasa de complicaciones fue 22,8%. Tras una mediana de seguimiento de 104 meses (DE 69,9) no se observó necrosis del pezón. Un 20% de pacientes precisó reintervención a largo plazo. Once pacientes (31,4%) recibieron tratamiento adyuvante (QT y/o RT). Solamente una paciente presentó recurrencia local (2,8%) 28 meses tras la intervención. Una paciente presentó metástasis tras 78 meses de SLE. Las tasas de SLE y SG fueron 94,3% y 97,22%. El análisis univariante mostró dos factores de riesgo de recurrencia: edad <40 [OR (IC95) 2,529 (1,230 - 5,199)] y márgenes afectos [OR (IC95) 5,242 (2,041 - 13,464)]. CONCLUSIÓN: La MAP es factible y segura en pacientes con CDIS no candidatas a cirugía conservadora

OBJECTIVE: The aim of this study was to assess the oncological safety of nipple-sparing mastectomy (NSM) in patients with ductal in situ carcinoma (DCIS) over a 10-year period. METHOD: Retrospective observational analysis. A total of 35 NSM were performed in patients with DCIS from 2005 - 2018. We assessed the histological, oncological and morbidity results. RESULTS: The most frequent indications were margin involvement after lumpectomy (31.5%), multifocality / multicentricity (22.8%), tumour size >3 cm (8.6%) unfavourable tumour / breast size correlation (8.6%) and patient choice (8.6%). The most commonly used technique was external lateral incision in 11 patients, followed by the Spira technique in 9 patients. DCIS was confirmed in 22 patients and no tumour was found in mastectomy specimen in 11 patients. The complication rate was 22.8%. After a median follow-up of 104 months (SD 69.9) there was no nipple necrosis. In all, 20% of the patients required long-term reintervention. Eleven patients (31.4%) underwent adjuvant treatment (chemotherapy and / or radiotherapy). Only one patient showed local recurrence (2.8%) 28 months after the intervention. One patient developed metastases after 78 months of disease-free survival (DFS). DFS and overall survival rates were 94.3% and 97.22%. Univariate analysis showed two risk factors for recurrence: age <40 years [OR (95% CI) 2.529 (1.230-5.199)] and margin involvement [OR (95% CI) 5.242 (2.041 - 13.464)]. CONCLUSION: NSM is safe and feasible in patients with DCIS who are not candidates for conservative surgery

Factores relacionados con la obtención de respuesta patológica completa tras quimioterapia neoadyuvante en cáncer de mama y su efecto sobre la reconstrucción tras mastectomía ahorradora de piel / Effect of complete pathological response related factors after neoadjuvant chemotherapy on skin-sparing mastectomy and breast reconstruction

INTRODUCCIÓN: La reconstrucción mamaria inmediata tras mastectomías ahorradoras de piel en pacientes sometidas a quimioterapia neoadyuvante todavía resulta controvertida. El objetivo es determinar factores relacionados con downstaging axilar y respuesta patológica completa (RPC), y como esta, condiciona la decisión de someterse a mastectomía bilateral con reconstrucción inmediata. MÉTODOS: Se realizó un análisis retrospectivo de pacientes con cáncer de mama sometidas a quimioterapia neoadyuvante y mastectomía bilateral con reconstrucción inmediata entre 2000-2018. Se compararon dos grupos: 1) RPC y 2) no RPC. Se analizaron datos demográficos, anatomopatológicos y el estadio clínico inicial y final. Análisis estadístico descriptivo y comparativo. RESULTADOS: Sesenta y nueve pacientes; Grupo1: 26 (37,68%) alcanzaron RPC y 43(62,32%) no RPC. Mediana de seguimiento 45,3meses (RIQ: 23,0-94,0). En análisis bivariante, edad menor a 35 (p < 0,001), menor T al diagnóstico (p = 0,006) y subtipo HER2 (p < 0,001) se asociaron significativamente con mayores tasas de RPC. La indicación más frecuente fue la elección de la paciente (31,8%). La tasa de negativización axilar fue del 80% en el grupo 1 y 59,3% en grupo 2 y las tasas de linfadenectomía axilar fueron similares (73,1% y 83,72%). CONCLUSIONES: La RPC tras la quimioterapia neoadyuvante no parece ser un factor de peso en la decisión de realizar la mastectomía bilateral con reconstrucción inmediata

INTRODUCTION: Immediate breast reconstruction after skin-sparing mastectomy in patients undergoing neoadjuvant chemotherapy is still controversial. The objective of this study is to determine factors related with axillary downstaging and complete pathological response (CPR), and how CPR influences the decision to perform bilateral mastectomy with immediate reduction. METHODS: A retrospective analysis of breast cancer patients who had undergone neoadjuvant chemotherapy and bilateral mastectomy with immediate reduction between 2000-2018 was performed. Two groups were compared:1) CPR and 2) non-CPR. Descriptive and comparative statistical analyses are provided. RESULTS: 69 patients; 26 (37.68%) reached CPR and 43 (62.32%) non-CPR. Median follow-up of 45.3 months (IQR: 23.0-94.0). Age under 35 (p < .001), small size tumor at diagnosis (p = .006) and subtype HER2 (p < .001) were associated with higher rates of CPR in bivariate analysis. Axillary negativization rate was 80% in group 1 and 59.3% in group 2, and lymphadenectomy rates were similar (73.1% and 83.72%). CONCLUSIONS: CPR after neoadjuvant chemotherapy did not influence the decision to perform bilateral mastectomy with immediate reduction