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This article focuses on the analysis of plant remains (seeds/fruits, charcoal, pollen, spores, and non-pollen palynomorphs) from two archaeological sites (pre-Roman and Roman) located in Las Medulas, a cultural landscape, in the northwestern part of the Iberian Peninsula. The article explores the way the communities living in the area managed their environment and the impact of productive activities on the landscape. This research has shown the multiplicity of needs this landscape satisfied and the various ways these communities managed the surrounding environment through different productive activities (agriculture, animal husbandry, and mining amongst others). [ABSTRACT FROM AUTHOR]

Abstract: The palynological record of Puerto de Serranillos provides insights into the late Holocene vegetation history of Sierra de Gredos in the Central Mountain System of the Iberian Peninsula. Overgrazing around the timberline has occurred at least throughout the past two millennia, related to the human management of the landscape. Before the 12th century AD, Pinus sylvestris forests were dominant with a diversity of accompanying trees and understorey. The current landscape of the Gredos Range is clearly anthropogenic, and includes a combination of forest patches, pastures, dense shrubby formations and prostrate junipers, overall generated during the transition between the 17th and 18th centuries AD, when continued human activity in the mountain pine forests, using fire and intensifying grazing practices, caused a progressive deforestation, and the expansion of the current fire-prone scrub. [Copyright &y& Elsevier]

Abstract: In this paper we present a review of the available pollen analyses in the north-western Iberian Range with the aim of studying Fagus glacial refugia and Holocene expansion. The work collects the available pollen analyses in the area (24 sites and 58 14C dates). Based on the available palynological data, we try to reconstruct the changes that occurred in the distribution of Fagus sylvatica in the north-western Iberian Range during the late Pleistocene and the Holocene, its spread patterns and the possible causes for such changes. Results from pollen analyses allow establishing at the Middle Holocene the beginnings of Fagus expansion mostly in relation to anthropic activities. Also, the pollen data demonstrate the existence of Fagus glacial refuge during the Late Pleistocene and the Early Holocene. Therefore, we hypothesize that present-day beech forests, in the area under study, are the direct result of the relic populations that survived the last glaciations and that have been favoured by both environmental conditions and human activities. [Copyright &y& Elsevier]

Background: There is limited recent evidence about infective endocarditis (IE) in HIV-infected patients. Our aim was to compare IE according to HIV infection presence., Methods: Consecutive inclusion of IE patients at 46 Spanish hospitals between 2008 and 2021., Results: From 5667 patients, 99 were HIV-infected (1·7%; 50 intravenous drugs users). Compared to patients without HIV, HIV-infected patients were more frequently male (84% vs. 67%), had younger median age (46 vs. 69 years), and less comorbidities, except liver disease (52% vs. 9%) and intravenous drug use (51% vs. 1%). They had more common tricuspid location (36% vs. 5%) and community-acquired IE (82% vs. 63%), vascular (29% vs. 17%) and cutaneous (22% vs. 7%) foci of infection, and Staphylococcus aureus aetiology (46% vs. 22%). Vegetations (84% vs. 72%), vascular phenomena (17% vs. 9%), splenomegaly (30% vs. 11%), and embolisation (41% vs 21%) were also more common. Surgical indication and surgery were less frequent in HIV-infected patients (54% vs 67%, 28% vs 47%, respectively). Median CD4 count in HIV-infected patients was 318 cells/mm 3 . In-hospital mortality (23% vs. 26%) and one-year mortality (25% vs. 32%) were similar in both groups. HIV infection was not independently associated with in-hospital (odds ratio 1·1, 95% CI 0·6-1·9) nor one-year mortality (hazard ratio 0·8, 95% CI 0·4-1·3)., Conclusions: In the combined antiretroviral therapy era, less than 2% of IE patients have HIV infection. HIV-infected patients have a different clinical profile than those without HIV, but the presence of HIV does not seem to impact on IE prognosis.

Cutaneous melanoma incidence is rising. Early diagnosis and treatment administration are key for increasing the chances of survival. For patients with locoregional advanced melanoma that can be treated with complete resection, adjuvant-and more recently neoadjuvant-with targeted therapy-BRAF and MEK inhibitors-and immunotherapy-anti-PD-1-based therapies-offer opportunities to reduce the risk of relapse and distant metastases. For patients with advanced disease not amenable to radical treatment, these treatments offer an unprecedented increase in overall survival. A group of medical oncologists from the Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines, based on a thorough review of the best evidence available. The following guidelines try to cover all the aspects from the diagnosis-clinical, pathological, and molecular-staging, risk stratification, adjuvant therapy, advanced disease therapy, and survivor follow-up, including special situations, such as brain metastases, refractory disease, and treatment sequencing. We aim help clinicians in the decision-making process., (© 2024. The Author(s).)

Background: Topical imiquimod has been shown to be an effective treatment for extramammary Paget disease (EMPD), although available evidence supporting its use is based on case reports and small series of patients., Objectives: To investigate the therapeutic outcomes and analyse potential clinicopathological factors associated with the imiquimod response in a large cohort of patients with EMPD., Methods: Retrospective chart review of 125 patients with EMPD treated with imiquimod at 20 Spanish tertiary-care hospitals., Results: During the study period, patients received 134 treatment regimens with imiquimod, with 70 (52.2%) treatments achieving a complete response (CR), 41 (30.6%) a partial response and 23 (17.2%) no response. The cumulative CR rates at 24 and 48 weeks of treatment were 46.3% and 71.8%, respectively, without significant differences between first-time and previously treated EMPD. Larger lesions (≥ 6 cm; P = 0.04) and EMPD affecting > 1 anatomical site (P = 0.002) were significantly associated with a worse treatment response. However, the CR rate did not differ significantly by the number of treatment applications (≤ 4 vs. > 4 times per week; P = 0.112). Among patients who achieved CR, 30 of 69 (43%) treatments resulted in local recurrences during a mean follow-up period of 36 months, with an estimated 3- and 5-year recurrence-free survival of 55.7% and 36.4%, respectively., Conclusions: Imiquimod appears as an effective therapeutic alternative for both first-line and previously treated EMPD lesions. However, a less favourable therapeutic response could be expected in larger lesions and those affecting > 1 anatomical site. Based on our results, a three to four times weekly regimen of imiquimod with a treatment duration of at least 6 months could be considered an appropriate therapeutic strategy for patients with EMPD., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I-III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available.

Breast cancer (BC) is the most common cancer in women in Spain. During the COVID-19 pandemic caused by the SARS-CoV-2 virus, patients with BC still require timely treatment and follow-up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in-hospital visit to minimize pandemic-associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the lack of evidence about COVID-19 infection, these recommendations are mainly based on expert opinion, medical organizations' and societies' recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing. IMPLICATIONS FOR PRACTICE: This work presents a set of guidelines regarding available options for breast cancer (BC) patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the suddenness of this health crisis, specialists have to make decisions with little evidence at hand. Thus, these expert guidelines may be a useful tool to facilitate medical decision making in the context of a worldwide pandemic with no resources to spare., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Posidonia oceanica (L.) Delile meadows are highly productive coastal marine ecosystems that provide multiple ecosystem services. The seagrass is not always the major contributor to total primary production, however, little is known about long-term changes in the composition of primary producers within seagrass meadows. Understanding compositional shifts within the community of primary producers is crucial to evaluate how climate and anthropogenic change affect the functioning of seagrass ecosystems. Here we analysed marker pigment composition in seagrass cores from two bays of the Cabrera Island (Balearic Islands, Spain) to asses long-term changes in phototrophic community composition and production in seagrass meadows, and identify the environmental factors triggering those changes. The proxy dataset was explored using principal component analyses (PCA): one including the pigment dataset to look for associations between producers' groups, and another one combining the pigment dataset with plausible local and global regulatory factors to assess the environmental drivers of change. Analyses of characteristic pigments and morphological fossils (cysts) showed that the abundance of dinoflagellates increased over the last 150-300 years, coeval with a rise in solar irradiance and air temperature. When compared among embayments, pigments from cyanobacteria predominated in seagrass meadows located at Es Port, a sheltered bay receiving higher terrestrial runoff; whereas pigments from diatoms, seagrasses and rodophytes were more common at Santa Maria, an exposed bay with clearer waters. Water depth also played a role in controlling the phototrophic community composition, with greater abundance of diatoms in the shallowest waters (<5 m). Overall, our results suggested that historical and spatial variation in seagrass meadows' phototrophic community composition was influenced by the interaction between local factors (catchment-bay characteristics) and global climate processes (energy influx). Together these patterns forecast how marine primary producers and seagrass ecosystem structure may respond to future global warming., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background/objective: There is evidence supporting that there are no relevant clinical differences between dosing rituximab 1000 mg or 2000 mg per cycle in rheumatoid arthritis (RA) patients in clinical trials, and low-dose cycles seem to have a better safety profile. Our objective was to describe the pattern of use of rituximab in real-life practice conditions., Methods: Rituximab for RA in clinical practice (RITAR) study is a retrospective cohort study from 2005 to 2015. Eligibility criteria were RA adults treated with rituximab for active articular disease. Response duration was the main outcome defined as months elapsed from the date of rituximab first infusion to the date of flare. A multivariable analysis was performed to determine the variables associated with response duration., Results: A total of 114 patients and 409 cycles were described, 93.0% seropositive and 80.7% women. Rituximab was mainly used as second-line biological therapy. On demand retreatment was used in 94.6% of cases versus fixed 6 months retreatment in 5.4%. Median response duration to on demand rituximab cycles was 10 months (interquartile range, 7-13). Multivariable analysis showed that age older than 65 years, number of rituximab cycles, seropositivity, and first- or second-line therapy were associated with longer response duration. The dose administered at each cycle was not significantly associated with response duration., Conclusions: Our experience suggests that 1000 mg rituximab single infusion on demand is a reasonable schedule for long-term treatment of those patients with good response after the first cycles, especially in seropositive patients and when it is applied as a first- or second-line biological therapy.

Objective: To determine the required learning time for high-resolution anoscopy (HRA)-guided biopsy to detect histological high-risk squamous intraepithelial lesions (hHSIL) and to identify factors that impact on the training process., Methods: All HIV-infected, screening-naïve men-who-have-sex-with-men who underwent HRA conducted by one single observer from 2010 to 2017 in a Spanish HIV-outpatient clinic were analysed., Results: Eighty-five (14.7%) of the 581 patients included presented hHSIL. The factors associated with the capacity to detect hHSIL [adjusted odds ratio (aOR), 95% confidence interval (95%CI)] were the presence of cytological HSIL (3.04, 1.78-5.21; p < 0.001), infection with high-risk human papilloma virus (HR-HPV) (2.89, 1.38-6.05; p = 0.005), the number of biopsies taken/HRA (aOR: 1.28, 1.07-1.52; p = 0.006) and tobacco smoking (1.75; 1.12-2.73; p = 0.014). Two events independently augmented the detection rate of hHSIL: one single experienced pathologist interpreted biopsies after 409 HRA (2.80, 1.74-4.48; p = 0.035) and the anoscopist underwent an additional training after 536 HRA (2.57, 1.07-6.16; p = 0.035). A learning process could be observed throughout the whole study with stable HR-HPV prevalence., Conclusion: The data support the growing evidence that the proposed training volume of 50-200 performances is underestimated. Extensive training of both anoscopist and pathologist is warranted and the development of tools to support the diagnostic performance may be considered., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype. The histological transformation (HT) of FL is an event considered frequent in the natural history of this tumor. We studied the transformation rates, predictive factors, and treatment characteristics that may impact in the survival of patients with FL and HT. A total of 1074 patients diagnosed with FL were prospectively enrolled from 1990 to 2016 in a Spanish registry. Sixty-four HTs were recorded based on clinical criteria (55%) or histological confirmation (45%). The cumulative incidence rate of transformation at 5 years is 7.3%. The 5-year overall survival (OS) without HT was 85% (95% confidence interval [CI], 70%-90%) vs 66% (95% CI, 51%-76%; P = 0.0012) with HT. Factors associated with HT were elevated lactate dehydrogenase (LDH) (odds ratio [OR] 1.83), intermediate-high Follicular lymphoma international prognostic index (FLIPI) (OR 2.16-OR 3.21), B symptoms (OR 2.46), or Eastern Cooperative Oncology Group (ECOG) 1 (OR 2.35). Treatment options related to HT were "watch and wait" or no rituximab or anthracyclines initially. A 5-year OS for patients treated with chemotherapy before HT was 55% (95% CI, 38%-69%) versus 81% (95% CI, 53%-93%; P = 0.009) for those who had not received it. The HT rate has decreased after the introduction of rituximab, as has been previously described. The timing of this treatment had an impact on the survival of these patients., (© 2019 John Wiley & Sons, Ltd.)

Objective: To determine the usefulness of ultrasound examination in Primary Care (PC) for the detection of abdominal aortic aneurysm (AAA) in male patients from 65-75 years old, as well as the consistency between observers on the diagnosis between general practitioners and the reference specialty in this area, Vascular Surgery. To estimate the prevalence of AAA in that population and its association with risk factors., Design: Cross-sectional descriptive study., Location: Healthcare Centres of Coto and Calzada II (Gijón, Spain)., Participants: Males born between 1 January 1939 and 31 December 1950., Interventions: From the 2,511 males found, 407 were selected using stratified random sampling. Aortic diameter was measured, with those ≥3cm and 20% from the <3cm being referred for a second measurement by a vascular surgeon., Variables: Dependent: presence/absence of aneurism. Independent: age, abdominal perimeter, smoking, arterial hypertension, diabetes, dyslipidaemia, familial cases of AAA, cerebrovascular accident, and coronary disease. The analysis was performed using Bayesian inference with models for proportions and a multivariate logistic regression., Results: From 304 ultrasound scans performed, 13 were referred with suspicion of AAA, and 63 with were within normal. The sensitivity was 93.3% and specificity 98.5% with a 95% credibility interval (CredI) of 75.4-99.9%, and 94.3-100%, respectively. The prevalence was 4.6% (95% CredI: 2.5-7.2%, and the intraclass correlation coefficient between PC and Vascular Surgery was 0.88 (95% CredI: 0.79-0.94). Age, smoking, dyslipidaemia, and diabetes tended to increase the odds of prevalence of AAA., Conclusion: The ultrasound performed by GPs for the detection of AAA had high diagnostic validity. Further studies on the effectiveness should be conducted in order to assess the appropriateness of introducing a system of early detection of AAA in the risk population., (Copyright © 2017 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.

Aim: The risk of presenting synchronous or metachronous neoplasm, either adenoma or carcinoma, increases after an initial colonic lesion develops. It is known as tumor multicentricity and constitutes the rationale for surveillance programs. This study was designed to identify the clinical, pathologic, and molecular features related to previous or synchronous colorectal cancer (CRC) in patients with advanced adenomas (AA) or serrated polyps (SP)., Patients and Methods: We carried out a prospective analysis of 4143 colonoscopies performed at our medical department between 1 September 2014 and 30 September 2015. Patients with AA/SP associated with previous or synchronous CRC are compared with patients with solitary AA/SP. We also performed immunohistochemical for the mismatch repair proteins in 120 AA or SP, 60 of them related to CRC., Results: Three-hundred and seventy-nine AA or SP were removed. Among these, 66 (17.3%) were associated with a previous (n=31) or synchronous CRC (n=35). Age older than or equal to 65 years (odds ratio: 1.15, 95% confidence interval: 1.05-1.26, P=0.002) and male sex (odds ratio: 2.13, 95% confidence interval: 1.3-3.49, P=0.003) were found to be independent predictive factors for CRC in patients with AA/SP by multivariate analysis. Only one of the 120 AA/SP available for immunohistochemical testing showed loss of staining and it was not related to CRC., Conclusion: In patients with AA or SP, it is possible to identify a subgroup that is more likely to be associated with CRC and then prone to tumor multicentricity. These results have potential implications for establishing criteria for a more targeted surveillance.

Introduction: Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain., Patients and Methods: An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments., Results: In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups., Conclusions: Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

HLA-B45, in contrast to B44, does not show molecular polymorphism. We have found a group of Caucasian Spanish individuals, serologically typed as B45, showing an unexpected HLA-B12 PCR-SSO subtyping pattern. Complete coding region sequencing and B45 subtyping by PCR-SSO demonstrated that the B45 serologic specificity is constituted by two molecular alleles: B*4501 and B*5002. B*5002 is recognized by polyclonal and monoclonal allosera against B12 and B45, whereas it is not detected by B21, B49, or B50 reagents, providing a new example of poor correlation between serology and structure. B*5002 explains an important subset (18%) of the B45-positive individuals of the Spanish population studied, and almost half are included in a very infrequent haplotypic association, Cw6-B*5002-DRB1*0406-DQA1*03-DQB1*0402.