Biomarkers in breast cancer 2024: an updated consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

This revised consensus statement of the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathological Anatomy (SEAP) updates the recommendations for biomarkers use in the diagnosis and treatment of breast cancer that we first published in 2018. The expert group recommends determining in early breast cancer the estrogen receptor (ER), progesterone receptor (PR), Ki-67, and Human Epidermal growth factor Receptor 2 (HER2), as well as BReast CAncer (BRCA) genes in high-risk HER2-negative breast cancer, to assist prognosis and help in indicating the therapeutic options, including hormone therapy, chemotherapy, anti-HER2 therapy, and other targeted therapies. One of the four available genetic prognostic platforms (Oncotype DX®, MammaPrint®, Prosigna®, or EndoPredict®) may be used in ER-positive patients with early breast cancer to establish a prognostic category and help decide with the patient whether adjuvant treatment may be limited to hormonal therapy. In second-line advanced breast cancer, in addition, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and estrogen receptor 1 (ESR1) should be tested in hormone-sensitive cases, BRCA gene mutations in HER2-negative cancers, and in triple-negative breast cancer (TNBC), programmed cell death-1 ligand (PD-L1). Newer biomarkers and technologies, including tumor-infiltrating lymphocytes (TILs), homologous recombination deficiency (HRD) testing, serine/threonine kinase (AKT) pathway activation, and next-generation sequencing (NGS), are at this point investigational.

Pain in Long-Term Cancer Survivors: Prevalence and Impact in a Cohort Composed Mostly of Breast Cancer Survivors.

Cancer survival is becoming more common which means that there is now a growing population of cancer survivors, in whom pain may be common. However, its prevalence has hardly been addressed systematically. We aimed to assess the prevalence and explore the pathophysiology and impact of pain on health outcomes in cancer survivors. We conducted a retrospective-prospective cohort study in cancer-free patients diagnosed with cancer at least five years before the study start date. We used multivariable regression to establish the association of patients' cancer characteristics with pain, and then the association of patients' pain features with health outcomes and related symptoms. Between March and July 2021, 278 long-term cancer survivors were evaluated. Almost half of them (130/278, 46.8%) had pain, of whom 58.9% had a probable neuropathic component, but only 18 (13.8%) were taking specific drugs for neuropathic pain. A history of surgery-related pain syndrome in breast cancer patients was more than twice as frequent in the pain cohort. Post-chemotherapy and post-radiotherapy pain syndromes were uncommon. Pain was associated with lower QoL, emotional functioning, professional performance, and disability scores. Pain is a frequent health determinant in cancer survivors. Referral to specialised pain services may be a reasonable move in some cases.

Lateral-flow assays for bovine paratuberculosis diagnosis.

Mycobacterium avium subsp. paratuberculosis (MAP) causes bovine paratuberculosis (PTB). PTB is responsible for significant economic losses in dairy herds around the word. PTB control programs that rely on testing and culling of test-positive cows have been developed. Current diagnostics, such as ELISA for detecting MAP antibodies in serum samples and PCR detecting MAP DNA in feces, have inadequate sensitivity for detecting subclinical animals. Innovative "omics" technologies such as next-generation sequencing (NGS) technology-based RNA-sequencing (RNA-Seq), proteomics and metabolomics can be used to find host biomarkers. The discovered biomarkers (RNA, microRNAs, proteins, metabolites) can then be used to develop new and more sensitive approaches for PTB diagnosis. Traditional approaches for measuring host antibodies and biomarkers, such as ELISAs, northern blotting, quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR), cDNA microarrays, and mass spectrometry are time-consuming, expensive, and sometimes exhibit poor sensitivity. With the rapid development of nanotechnology, low-cost monitoring devices for measuring antibodies against MAP proteins in point-of-care (POC) settings have been developed. Lateral flow assays (LFAs), in particular, are thought to be appropriate for the on-site detection of antibodies to MAP antigens and/or host biomarkers. This review aims to summarize LFAs that have recently been developed to accurately detect antibodies against MAP antigens, as well as the benefits that host biomarkers linked with MAP infection give to PTB diagnosis. The identification of these novel biomarkers could be the basis for the development of new LFAs. The dairy industry and producers are likely to benefit from reliable and rapid technologies capable of detecting MAP infection in situ to establish a quick and sensitive PTB diagnosis.

Topography modulates climate sensitivity of multidecadal trends of holm oak decline.

Forest decline events have increased worldwide over the last decades being holm oak (Quercus ilex L.) one of the tree species with the most worrying trends across Europe. Since this is one of the tree species with the southernmost distribution within the European continent, its vulnerability to climate change is a phenomenon of enormous ecological importance. Previous research identified drought and soil pathogens as the main causes behind holm oak decline. However, despite tree health loss is a multifactorial phenomenon where abiotic and biotic factors interact in time and space, there are some abiotic factors whose influence has been commonly overlooked. Here, we evaluate how land use (forests versus savannas), topography, and climate extremes jointly determine the spatiotemporal patterns of holm oak defoliation trends over almost three decades (1987-2014) in Spain, where holm oak represents the 25% of the national forested area. We found an increasing defoliation trend in 119 out of the total 134 holm oak plots evaluated, being this defoliation trend significantly higher in forests compared with savannas. Moreover, we have detected that the interaction between topography (which covariates with the land use) and summer precipitation anomalies explains trends of holm oak decline across the Mediterranean region. While a higher occurrence of dry summers increases defoliation trends in steeper terrains where forests dominate, an inverse relationship was found in flatter terrains where savannas are mainly located. These opposite relationships suggest different causal mechanisms behind decline. Whereas hydric stress is likely to occur in steeper terrains where soil water holding capacity is limited, soil waterlogging usually occurs in flatter terrains what increases tree vulnerability to soil pathogens. Our results contribute to the growing evidence of the influence of local topography on forest resilience and could assist in the identification of potential tree decline hotspots and its main causes over the Mediterranean region.

Osificación heterotópica tras artroplastia de cadera: papel de la gammagrafía SPECT/TC ósea / Heterotopic ossification after hip arthroplasty: role of bone SPECT/CT scintigraphy

La osificación heterotópica es una condición limitante, que afecta predominantemente a la cadera. Dada su relación con patología postraumática/posquirúrgica, la gammagrafía ósea SPECT/TC resulta de especial utilidad en el diagnóstico diferencial con movilización protésica, aun cuando no hay alteraciones radiológicas. Además, resulta ser una herramienta eficaz para planificación quirúrgica atendiendo al grado de maduración ósea y la posibilidad de fabricar biomodelos mediante impresión 3D.(AU)

Heterotopic ossification is a limiting condition that predominantly affects the hip. Because of its association with post-trau-matic/postoperative pathology, bone SPECT/CT scintigraphy has proven to be especially useful regarding differential diag-nosis involving prosthetic mobilization, even in the absence of radiological abnormalities. Additionally, it is an effective toolfor surgical planning, considering the degree of bone maturation and the possibility of creating biomodels using 3Dprinting.(AU)

Monitoring of Circulating Tumor DNA Predicts Response to Treatment and Early Progression in Follicular Lymphoma: Results of a Prospective Pilot Study.

PURPOSE: Follicular lymphoma (FL) is the most frequent indolent non-Hodgkin lymphoma. Around 20% of patients suffer early disease progression within 24 months (POD24) of diagnosis. This study examined the significance of circulating tumor DNA (ctDNA) in predicting response to therapy and POD24 in patients with FL. EXPERIMENTAL DESIGN: We collected 100 plasma samples, before and during the treatment, from 36 patients with FL prospectively enrolled in 8 Spanish hospitals. They were treated with a chemotherapy-rituximab regimen and followed up for a median of 3.43 years. We performed targeted deep sequencing in cell-free DNA (cfDNA) and tumor genomic DNA from 31 diagnostic biopsy samples. RESULTS: Of the alterations detected in the diagnostic tissue samples, 73% (300/411) were also identified in basal cfDNA. The mean numbers of alterations per basal cfDNA sample in patients who suffered progression of disease within 24 months (POD24-pos) or did not achieve complete response (non-CR) were significantly higher than in POD24-neg or CR patients (unpaired samples t test, P = 0.0001 and 0.001, respectively). Pretreatment ctDNA levels, as haploid genome equivalents per milliliter of plasma, were higher in patients without CR (P = 0.02) and in POD24-pos patients compared with POD24-neg patients (P < 0.001). Dynamic analysis showed that ctDNA levels decreased dramatically after treatment, although the reduction was more significant in patients with CR and POD24-neg patients. CONCLUSIONS: Basal ctDNA levels are associated with the risk of early progression and response to treatment in FL. cfDNA monitoring and genotyping during treatment and follow-up predict response to treatment and early progression.

[Assessment of pulmonary embolism related to active SARS-CoV-2 infection in pregnant women.] / Valoración del tromboembolismo pulmonar relacionado con infección SARS-CoV-2 activa en pacientes embarazadas.

AIM: To analyze the sample of pregnant patients who underwent pulmonary perfusion scintigraphy to rule out the pulmonary embolism (PE) suspicion during the acute COVID-19 infection hospitalization period in our hospital. MATERIAL AND METHODS: SPECT scintigraphy with a reduced dose (111 MBq) of 99mTc-macroaggregated albumin was performed in all of the patients (n=5). The obtained images were interpreted by comparing the findings with the radiological images according to the PISAPED criteria. RESULTS: Only one of the 5 patients was diagnosed with PE. Two patients obtained pathological findings of the scintigraphy attributable to radiological alterations due to COVID-19 pneumonia, and the other two had normal pulmonary perfussion. CONCLUSION: Given the non-specific features of the clinical manifestations and D-dimer values in COVID-19, as well as their similarity to those of PE, the pulmonary perfusion scintigraphy plays a crucial role in the screening of PE in these patients due to its high sensitivity and lower irradiation compared to CT. Despite the limited number of patients, the results obtained have special relevance related to the absence of scientific publications on this group of patients within the context of COVID-19 pandemic exceptional situation.

Executive summary of the consensus statement of: Clinical recommendations for sport practice in people with diabetes (RECORD Guide). Update 2021. Diabetes Mellitus Area of the Spanish Society of Endocrinology and Nutrition (SEEN).

OBJECTIVE: To guide professionals involved in the care of people with diabetes mellitus who practice sport. PARTICIPANTS: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition. METHODS: A group of experts in each area covered by the statement carried out a bibliographic review of the available evidence for each topic, based on which recommendations were subsequently agreed upon within the Diabetes Mellitus Working Group. CONCLUSIONS: The statement provides practical recommendations for the management of diabetes mellitus during sports practice.

Assessing availability of European plant protection product data: an example evaluating basic area treated.

Besides the benefits of plant protection products (PPPs) for agricultural production, there is an increasing acknowledgement of the associated potential environmental risks. Here, we examine the feasibility of summarizing the extent of PPP usage at the country level, using Ireland as a case study, as well as at the European level. We used the area over which PPPs are applied (basic area) as an example variable that is relevant to initially assess the geographic extent of environmental risk. In Irish agricultural systems, which are primarily grass-based, herbicides fluroxypyr and glyphosate are the most widely applied active substances (ASs) in terms of basic area, followed by the fungicides chlorothalonil and prothioconazole that are closely associated with arable crops. Although all EU countries are subject to Regulation (EC) No 1185/2009, which sets the obligation of PPP usage data reporting at the national level, we only found usable data that met our criteria for Estonia, Germany, Finland, and Spain (4 of 30 countries reviewed). Overall, the most widely applied fungicide and herbicide in terms of basic area were prothioconazole (20%, 7% and 5% of national cultivated areas of Germany, Estonia and Ireland) and glyphosate (11%, 8% and 5% of national cultivated areas of Spain, Estonia and Ireland) respectively, although evaluations using application frequency may result in the observation of different trends. Several recommendations are proposed to tackle current data gaps and deficiencies in accessibility and usability of pesticide usage data across the EU in order to better inform environmental risk assessment and promote evidence-based policymaking.

Evolución y resultados del tratamiento neoadyuvante en cáncer de mama durante un periodo de 10 años / Progress and oncological outcome of neoadjuvant therapy in breast cancer patients during a 10-year period

Introducción: el cáncer de mama es la neoplasia más frecuente en mujeres españolas. Los continuos avances en su tratamiento han contribuido a mejorar de forma progresiva la supervivencia en estadios precoces. Entre los avances durante los últimos años, hay que destacar el tratamiento neoadyuvante.Material y métodoshemos valorado la evolución temporal de las indicaciones y los resultados del tratamiento neoadyuvante del cáncer de mama durante un periodo de 10 años. Para ello, se han analizado las características clínicas, la respuesta completa patológica (RCp), la supervivencia global (SG) y libre de progresión (SLP) de todos los pacientes con cáncer de mama tratados con neoadyuvancia entre el 1 de enero de 2007 y el 31 de diciembre de 2016.Resultadosse han tratado 212 pacientes con cáncer de mama. A lo largo de los 10 años hemos observado un progresivo aumento en el número de pacientes tratadas con neoadyuvancia, en la edad de los pacientes incluidos (p < 0,001), en los casos de menopausia (p = 0,029), de casos triple negativo y HER2 positivo. También, hemos observado un aumento en el número de casos en los que se ha realizado cirugía conservadora y biopsia selectiva del ganglio centinela.Conclusionesel tratamiento neoadyuvante se utiliza cada vez más en las pacientes con cáncer de mama, sobre todo en los subtipos de mal pronóstico (triple negativo y HER2). La incorporación de nuevos fármacos y el tratamiento de estadios más precoces está contribuyendo a la mejora de las tasas de RCp y las cirugías conservadoras. (AU)

Introduction: Breast cancer is the most frequent tumor in Spanish women. Continuous advances in the treatment of this neoplasm, have contributed to progressively improve survival in early stages. In the last years, neoadjuvant treatment has evolved and changes have occurred in the treatment indication and in the results.Material and methodsWe have assessed the temporal evolution of indications and results of neoadjuvant therapy in breast cancer over a 10-year period. We have analyzed the clinical characteristics, the complete pathological response (CRp), overall survival (OS) and progression-free survival (PFS) of all patients with breast cancer treated with neoadjuvant therapy between January 1st 2007 and December 31st 2016.ResultsDuring the study period, 212 patients were treated.  Throughout the 10-year period, we observed that increasingly older patients had been treated (p < 0.001), a greater number of menopausal patients (p = 0.029), a greater number of triple negative and HER2 positive cases. In addition, a larger number of conservative surgeries and sentinel lymph node biopsies had been performed.ConclusionsNeoadjuvant therapy is increasing in patients with breast cancer, especially in subtypes with poor prognosis (triple negative and HER2). The emerging new drugs and treatment in earlier stages has increased the rate of pCR and breast conserving surgery. (AU)

Ecosystem CO2 release driven by wind occurs in drylands at global scale.

Subterranean ventilation is a non-diffusive transport process that provokes the abrupt transfer of CO2 -rich air (previously stored) through water-free soil pores and cracks from the vadose zone to the atmosphere, under high-turbulence conditions. In dryland ecosystems, whose biological carbon exchanges are poorly characterized, it can strongly determine eddy-covariance CO2 fluxes that are used to validate remote sensing products and constrain models of gross primary productivity. Although subterranean ventilation episodes (VE) may occur in arid and semi-arid regions, which are unsung players in the global carbon cycle, little research has focused on the role of VE CO2 emissions in land-atmosphere CO2 exchange. This study shows clear empirical evidence of globally occurring VE. To identify VE, we used in situ quality-controlled eddy-covariance open data of carbon fluxes and ancillary variables from 145 sites in different open land covers (grassland, cropland, shrubland, savanna, and barren) across the globe. We selected the analyzed database from the FLUXNET2015, AmeriFlux, OzFlux, and AsiaFlux networks. To standardize the analysis, we designed an algorithm to detect CO2 emissions produced by VE at all sites considered in this study. Its main requirement is the presence of considerable and non-spurious correlation between the friction velocity (i.e., turbulence) and CO2 emissions. Of the sites analyzed, 34% exhibited the occurrence of VE. This vented CO2 emerged mainly from arid ecosystems (84%) and sites with hot and dry periods. Despite some limitations in data availability, this research demonstrates that VE-driven CO2 emissions occur globally. Future research should seek a better understanding of its drivers and the improvement of partitioning models, to reduce uncertainties in estimated biological CO2 exchanges and infer their contribution to the global net ecosystem carbon balance.

The Homologous Recombination Deficiency Scar in Advanced Cancer: Agnostic Targeting of Damaged DNA Repair.

BRCA1 and BRCA2 are the most recognized tumor-suppressor genes involved in double-strand DNA break repair through the homologous recombination (HR) system. Widely known for its role in hereditary cancer, HR deficiency (HRD) has turned out to be critical beyond breast and ovarian cancer: for prostate and pancreatic cancer also. The relevance for the identification of these patients exceeds diagnostic purposes, since results published from clinical trials with poly-ADP ribose polymerase (PARP) inhibitors (PARPi) have shown how this type of targeted therapy can modify the long-term evolution of patients with HRD. Somatic aberrations in other HRD pathway genes, but also indirect genomic instability as a sign of this DNA repair impairment (known as HRD scar), have been reported to be relevant events that lead to more frequently than expected HR loss of function in several tumor types, and should therefore be included in the current diagnostic and therapeutic algorithm. However, the optimal strategy to identify HRD and potential PARPi responders in cancer remains undefined. In this review, we summarize the role and prevalence of HRD across tumor types and the current treatment landscape to guide the agnostic targeting of damaged DNA repair. We also discuss the challenge of testing patients and provide a special insight for new strategies to select patients who benefit from PARPi due to HRD scarring.

Epigenome-Wide Analysis Reveals DNA Methylation Alteration in ZFP57 and Its Target RASGFR2 in a Mexican Population Cohort with Autism.

Autism Spectrum Disorders (ASD) comprise a group of heterogeneous and complex neurodevelopmental disorders. Genetic and environmental factors contribute to ASD etiology. DNA methylation is particularly relevant for ASD due to its mediating role in the complex interaction between genotype and environment and has been implicated in ASD pathophysiology. The lack of diversity in DNA methylation studies in ASD individuals is remarkable. Since genetic and environmental factors are likely to vary across populations, the study of underrepresented populations is necessary to understand the molecular alterations involved in ASD and the risk factors underlying these changes. This study explored genome-wide differences in DNA methylation patterns in buccal epithelium cells between Mexican ASD patients (n = 27) and age-matched typically developing (TD: n = 15) children. DNA methylation profiles were evaluated with the Illumina 450k array. We evaluated the interaction between sex and ASD and found a differentially methylated region (DMR) over the 5'UTR region of ZFP57 and one of its targets, RASGRF2. These results match previous findings in brain tissue, which may indicate that ZFP57 could be used as a proxy for DNA methylation in different tissues. This is the first study performed in a Mexican, and subsequently, Latin American, population that evaluates DNA methylation in ASD patients.