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The use of yeast to biologically control the production of ochratoxin A, which is caused by filamentous fungal growth, in coffee farms is a promising alternative to conventional methods. However, yeast strains, environmental field conditions, and the chemical composition of grains / fruits can influence the effectiveness of biological control agents. We tested the efficiency of different yeast strains in controlling three species of ochratoxigenic fungi in a coffee-based medium. The reasons and mechanisms behind the varying sensitivities of different Aspergillus species to biological control remains unclear. Aspergillus carbonarius rapidly assimilated carbon sources, giving it an advantage over yeasts in substrate colonisation. Saccharomyces cerevisiae CCMA 0159 inhibited all three fungal species, achieving efficiencies of 74.4%, 100%, and 80.9% against A. carbonarius, A. westerdijkiae, and A. ochraceus, respectively. The strategies employed by S. cerevisiae CCMA 0159 to inhibit the growth of ochratoxigenic fungi included competition, production of fungicidal volatile compounds, and alteration of the substrate's physicochemical properties. Our results indicate that among the yeast isolates tested, S. cerevisiae CCMA 0159 is the most effective in inhibiting ochratoxigenic fungi in coffee, including the more resistant A. carbonarius., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Saccharomyces cerevisiae CCMA 0159 is reported as a promising biocontrol agent against ochratoxin A (OTA)-producing fungi in coffee. Coffea arabica and Coffea canephora (var. Conilon or Robusta) are the most widely consumed coffee species around the world, cultivated in tropical and subtropical regions, each exhibiting distinct physicochemical and sensory characteristics. The objective of this study was to compare the growth and OTA production by Aspergillus carbonarius, A. ochraceus, and A. westerdijkiae in C. arabica and C. canephora, along with assessing the efficiency of S. cerevisiae CCMA 0159 in biocontrolling ochratoxigenic fungi in both coffee varieties. A. carbonarius exhibited a higher growth rate and OTA production in both coffee varieties, with C. canephora showing particular susceptibility. Conversely, A. ochraceus and A. westerdijkiae demonstrated lower growth and OTA production. S. cerevisiae was effective in biocontrolling the fungal isolates, inhibiting over 80 % of A. carbonarius growth in both coffee varieties. Among the mechanisms of action of the biological control agent, the production of volatile organic compounds stands out. The results of this study confirm the significant potential of S. cerevisiae CCMA 0159 as a biocontrol agent against Aspergillus for application in coffee-producing areas., 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 © 2024 Elsevier B.V. All rights reserved.)

Reactive astrogliosis accompanies the two neuropathological hallmarks of Alzheimer's disease (AD)-Aβ plaques and neurofibrillary tangles-and parallels neurodegeneration in AD and AD-related dementias (ADRD). Thus, there is growing interest in developing imaging and fluid biomarkers of reactive astrogliosis for AD/ADRD diagnosis and prognostication. Monoamine oxidase-B (MAO-B) is emerging as a target for PET imaging radiotracers of reactive astrogliosis. However, a thorough characterization of MAO-B expression in postmortem control and AD/ADRD brains is lacking. We sought to: (1) identify the primary cell type(s) expressing MAO-B in control and AD brains; (2) quantify MAO-B immunoreactivity in multiple brain regions of control and AD donors as a proxy for PET radiotracer uptake; (3) correlate MAO-B level with local AD neuropathological changes, reactive glia, and cortical atrophy; (4) determine whether the MAOB rs1799836 SNP genotype impacts MAO-B expression level; (5) compare MAO-B immunoreactivity across AD/ADRD, including Lewy body diseases (LBD) and frontotemporal lobar degenerations with tau (FTLD-Tau) and TDP-43 (FTLD-TDP). We found that MAO-B is mainly expressed by subpial and perivascular cortical astrocytes as well as by fibrous white matter astrocytes in control brains, whereas in AD brains, MAO-B is significantly upregulated by both cortical reactive astrocytes and white matter astrocytes across temporal, frontal, and occipital lobes. By contrast, MAO-B expression level was unchanged and lowest in cerebellum. Cortical MAO-B expression was independently associated with cortical atrophy and local measures of reactive astrocytes and microglia, and significantly increased in reactive astrocytes surrounding Thioflavin-S+ dense-core Aβ plaques. MAO-B expression was not affected by the MAOB rs1799836 SNP genotype. MAO-B expression was also significantly increased in the frontal cortex and white matter of donors with corticobasal degeneration, Pick's disease, and FTLD-TDP, but not in LBD or progressive supranuclear palsy. These findings support ongoing efforts to develop MAO-B-based PET radiotracers to image reactive astrogliosis in AD/ADRD., (© 2024. The Author(s).)

Purpose of Review: All human beings undergo a lifelong cumulative exposure to potentially preventable adverse factors such as toxins, infections, traumatisms, and cardiovascular risk factors, collectively termed exposome. The interplay between the individual's genetics and exposome is thought to have a large impact in health outcomes such as cancer and cardiovascular disease. Likewise, a growing body of evidence is supporting the idea that preventable factors explain a sizable proportion of Alzheimer's disease and related dementia (ADRD) cases., Recent Findings: Here, we will review the most recent epidemiological, experimental preclinical, and interventional clinical studies examining some of these potentially modifiable risk factors for ADRD. We will focus on new evidence regarding cardiovascular risk factors, air pollution, viral and other infectious agents, traumatic brain injury, and hearing loss., Summary: While greater and higher quality epidemiological and experimental evidence is needed to unequivocally confirm their causal link with ADRD and/or unravel the underlying mechanisms, these modifiable risk factors may represent a window of opportunity to reduce ADRD incidence and prevalence at the population level via health screenings, and education and health policies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Construction and demolition waste, along with discarded PET plastic bottles, have evolved into a widespread global resource. However, their current disposal in landfills poses a significant environmental pollution challenge. This research is centered on evaluating the performance of cement mortar composed by larger PET particles in conjunction with sand, construction and demolition waste, and lightweight expanded polystyrene aggregates. The primary objective of this study is to formulate a blend suitable for non-structural elements that can be easily manufactured for social housing construction. This modified blend extends upon the original certified mixture employed at CEVE for brick production, which encompasses cement and 3 mm-long PET particles. The experimental analysis revealed that blend containing 8 mm-long PET particles, in combination with fine aggregates of construction and demolition waste, attained a required mechanical strength of 2 MPa, while preserving the bulk density and hydric properties of the initial PET bricks developed at CEVE in Argentina., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Clara Barrio García reports finaial support was provided by Universidad Politécnica de Madrid. Maria del Mar Barbero Barrera ncreports a relationship with Universidad Politécnica de Madrid that includes: employment., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment of metastatic urothelial carcinoma (mUC) upon platinum-based chemotherapy according to the positive results of large clinical trials. Nevertheless, results from unselected populations reflecting real-world data (RWD) are highly informative to the clinician. We reviewed daily clinical practice outcomes in patients with mUC who received atezolizumab in our institution., Methods: Here we evaluated the clinical activity and safety of atezolizumab in an unselected population of mUC patients who received atezolizumab between 2018 and 2022 reflecting RWD. Efficacy and safety information were retrospectively collected., Results: A total of 63 patients were included. The mean age was 68 years and the objective response rate was 14.3%. The median progression-free survival was 3 months and the median overall survival 6 months. At 1 year, 42% of the patients were alive. ECOG (0 vs 1) and neutrophil-lymphocytes ratio < 2 at the start of ICI were positive prognostic factors that discriminated between long vs short survivors. Overall tolerance was good with no new safety signals. Five patients (17%) had treatment-related adverse events grade ≥ 2 that required corticosteroids., Conclusion: In this retrospective study, atezolizumab was an effective and tolerable treatment option for patients with mUC after progression to platinum-based chemotherapy. Yet, patient selection remains critical to improve outcomes., (© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Besides its two defining misfolded proteinopathies-Aβ plaques and tau neurofibrillary tangles-Alzheimer's disease (AD) is an exemplar of a neurodegenerative disease with prominent reactive astrogliosis, defined as the set of morphological, molecular, and functional changes that astrocytes suffer as the result of a toxic exposure. Reactive astrocytes can be observed in the vicinity of plaques and tangles, and the relationship between astrocytes and these AD neuropathological lesions is bidirectional so that each AD neuropathological hallmark causes specific changes in astrocytes, and astrocytes modulate the severity of each neuropathological feature in a specific manner. Here, we will review both how astrocytes change as a result of their chronic exposure to AD neuropathology and how those astrocytic changes impact each AD neuropathological feature. We will emphasize the repercussions that AD-associated reactive astrogliosis has for the astrocyte-neuron interaction and highlight areas of uncertainty and priorities for future research., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPβ1, a surface receptor that triggers amyloid-β(Aβ) phagocytosis via TYROBP., Objective: To analyze the impact of this copy-number variant in SIRPβ1 expression and how it affects AD molecular etiology., Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPβ1 isoform-specific phagocytosis assays were performed in HEK393T cells., Results: The insertion alters the SIRPβ1 protein isoform landscape compromising its ability to bind oligomeric Aβ and its affinity for TYROBP. SIRPβ1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aβ ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPβ1 duplication allele correlates with higher TREM2 expression and an increased microglial activation., Conclusions: The SIRPβ1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aβ. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPβ1 structural variant might be considered as a potential modulator of this causative pathway.

This study aimed to evaluate the concomitant use of the nematophagous fungus Duddingtonia flagrans (AC001) and its protease-rich crude extract for the in vitro control of Panagrellus sp., Haemonchus spp., and Trichostrongylus spp. The nematicidal tests were carried out on larvae of the free-living nematode Panagrellus sp. and infective larvae of the gastrointestinal parasitic nematodes of domestic ruminants (Haemonchus spp. and Trichostrongylus spp). Five experimental groups were set: (1) one control group (G1) and (4) four treated groups -G2 - active crude extract; G3 - denatured crude extract; G4 - fungus, and G5 - fungus + active extract. Plates were incubated at 28 ºC for 24 h followed by the recovery of the larvae using the Baermann technique. The results showed a lower recovery of Panagrellus sp. larvae in the experimental groups compared to the control group, as follows: 52 % (G2), 16 % (G3), 46 % (G4), and 77 % (G5). An even greater reduction (77 ± 5 %) occurred in the group (G5). In addition, the authors observed lower averages of L 3 of Haemonchus spp. and Trichostrongylus spp. in the experimental groups compared to the control group, as follows: 59 % (G2), 0 % (G3), 86 % (G4), and 76 % (G5). In turn, there was a difference (p < 0.01) between (G5) and (G2). The results this study indicate a positive effect from the compatible use of the D. flagrans fungus and its enzymatic crude extract (protease), which has been demonstrated here for the first time and with potential field applications for further designs., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively. Across both studies, the median age was 64.0 years, 80.9% were male, and 52.6% were former smokers. Clinical outcomes of interest included real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). The median rwOS was 9.2 months. Among patients with at least one assessment, 21.7% reported their best response as 'partial response', with 3.9% reporting 'complete response'. The median duration of response (DoR) and median rwPFS were 11.0 months and 3.9 months, respectively. At baseline, VOLUME-PRO patients reported difficulties relating to fatigue, physical and sexual functioning, dyspnea, nausea, sticky saliva, dry mouth, pain/discomfort, mobility, and financial difficulties. There were improvements in social functioning and financial difficulties throughout the study; however, no other clinically meaningful changes were noted. No new safety concerns were identified. This real-world, multinational, multicenter, retrospective and prospective study supports the effectiveness and safety of nivolumab for R/M SCCHN patients.

Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of the CNS and the pathogenesis of Alzheimer's disease (AD). However, the contribution of nonparenchymal or brain-infiltrated myeloid cells to disease progression remains to be demonstrated. Here, we show that monocyte-derived cells (MDC) invade brain parenchyma in advanced stages of AD continuum using transcriptional analysis and immunohistochemical characterization in post-mortem human hippocampus. Our findings demonstrated that a high proportion (60%) of demented Braak V-VI individuals was associated with up-regulation of genes rarely expressed by microglial cells and abundant in monocytes, among which stands the membrane-bound scavenger receptor for haptoglobin/hemoglobin complexes or Cd163. These Cd163-positive MDC invaded the hippocampal parenchyma, acquired a microglial-like morphology, and were located in close proximity to blood vessels. Moreover, and most interesting, these invading monocytes infiltrated the nearby amyloid plaques contributing to plaque-associated myeloid cell heterogeneity. However, in aged-matched control individuals with hippocampal amyloid pathology, no signs of MDC brain infiltration or plaque invasion were found. The previously reported microglial degeneration/dysfunction in AD hippocampus could be a key pathological factor inducing MDC recruitment. Our data suggest a clear association between MDC infiltration and endothelial activation which in turn may contribute to damage of the blood brain barrier integrity. The recruitment of monocytes could be a consequence rather than the cause of the severity of the disease. Whether monocyte infiltration is beneficial or detrimental to AD pathology remains to be fully elucidated. These findings open the opportunity to design targeted therapies, not only for microglia but also for the peripheral immune cell population to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying the progression of AD., (© 2023. The Author(s).)

There is a growing interest in expanding the multiplexing capability of immunohistochemistry to achieve a deeper phenotyping of various cell types in health and disease. Here, we describe a protocol of cyclic multiplex fluorescent immunohistochemistry that enables the labeling of up to 16 antigens on the same formalin-fixed paraffin-embedded section using "off-the-shelf," commercially available, primary antibodies as well as fluorescently conjugated secondary antibodies. Key steps include the denaturing/stripping of the antibodies by microwaving and the quenching of any remaining fluorescent signal between the cycles of otherwise traditional multiplexed fluorescent immunohistochemistry. We have successfully applied this protocol to characterize astrocytic and microglial responses to Aβ plaques and neurofibrillary tangles in Alzheimer's disease brains, but it could be easily adapted to other user's needs regarding cell types, disease, and organ., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Cylindrospermopsin (CYN) is a cyanotoxin whose incidence has been increasing in the last decades. Due to its capacity to exert damage at different levels of the organism, it is considered a cytotoxin. Although the main target organ is the liver, recent studies indicate that CYN has potential toxic effects on the nervous system, both in vitro and in vivo. Thus, the aim of the present work was to study the effects of this cyanotoxin on neuronal viability and synaptic integrity in murine primary cultures of neurons exposed to environmentally relevant concentrations (0-1 µg/mL CYN) for 12, 24, and 48 h. The results demonstrate a concentration- and time-dependent decrease in cell viability; no cytotoxicity was detected after exposure to the cyanotoxin for 12 h, while all of the concentrations assayed decreased this parameter after 48 h. Furthermore, CYN was also demonstrated to exert damage at the synaptic level in a murine primary neuronal culture in a concentration- and time-dependent manner. These data highlight the importance of studying the neurotoxic properties of this cyanotoxin in different experimental models.

Background: Astrocytes and microglia react to Aβ plaques, neurofibrillary tangles, and neurodegeneration in the Alzheimer's disease (AD) brain. Single-nuclei and single-cell RNA-seq have revealed multiple states or subpopulations of these glial cells but lack spatial information. We have developed a methodology of cyclic multiplex fluorescent immunohistochemistry on human postmortem brains and image analysis that enables a comprehensive morphological quantitative characterization of astrocytes and microglia in the context of their spatial relationships with plaques and tangles., Methods: Single FFPE sections from the temporal association cortex of control and AD subjects were subjected to 8 cycles of multiplex fluorescent immunohistochemistry, including 7 astroglial, 6 microglial, 1 neuronal, Aβ, and phospho-tau markers. Our analysis pipeline consisted of: (1) image alignment across cycles; (2) background subtraction; (3) manual annotation of 5172 ALDH1L1+ astrocytic and 6226 IBA1+ microglial profiles; (4) local thresholding and segmentation of profiles; (5) machine learning on marker intensity data; and (6) deep learning on image features., Results: Spectral clustering identified three phenotypes of astrocytes and microglia, which we termed "homeostatic," "intermediate," and "reactive." Reactive and, to a lesser extent, intermediate astrocytes and microglia were closely associated with AD pathology (≤ 50 µm). Compared to homeostatic, reactive astrocytes contained substantially higher GFAP and YKL-40, modestly elevated vimentin and TSPO as well as EAAT1, and reduced GS. Intermediate astrocytes had markedly increased EAAT2, moderately increased GS, and intermediate GFAP and YKL-40 levels. Relative to homeostatic, reactive microglia showed increased expression of all markers (CD68, ferritin, MHC2, TMEM119, TSPO), whereas intermediate microglia exhibited increased ferritin and TMEM119 as well as intermediate CD68 levels. Machine learning models applied on either high-plex signal intensity data (gradient boosting machines) or directly on image features (convolutional neural networks) accurately discriminated control vs. AD diagnoses at the single-cell level., Conclusions: Cyclic multiplex fluorescent immunohistochemistry combined with machine learning models holds promise to advance our understanding of the complexity and heterogeneity of glial responses as well as inform transcriptomics studies. Three distinct phenotypes emerged with our combination of markers, thus expanding the classic binary "homeostatic vs. reactive" classification to a third state, which could represent "transitional" or "resilient" glia., (© 2022. The Author(s).)

The puerperium is a complex period that begins with placental delivery and lasts for 6 weeks, during which readaptation of the female organism and redistribution of blood volume occur. This period is conducive to the occurrence of thromboembolic events. In the context of the SARS-CoV-2 pandemic, the virus responsible for COVID-19, the attention of the scientific community and health professionals has been focused on obtaining insights on different aspects of this disease, including etiology, transmission, diagnosis, and treatment. Regarding the pregnancy-postpartum cycle, it is opportune to review the clinical conditions that can occur during this period and to investigate dyspnea as a postpartum symptom in order to avoid its immediate association with COVID-19 without further investigation, which can lead to overlooking the diagnosis of other important and occasionally fatal conditions., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Microglia play a critical role in both homeostasis and disease, displaying a wide variety in terms of density, functional markers and transcriptomic profiles along the different brain regions as well as under injury or pathological conditions, such as Alzheimer's disease (AD). The generation of reliable models to study into a dysfunctional microglia context could provide new knowledge towards the contribution of these cells in AD. In this work, we included an overview of different microglial depletion approaches. We also reported unpublished data from our genetic microglial depletion model, Cx3cr1 CreER /Csf1r flx/flx , in which we temporally controlled microglia depletion by either intraperitoneal (acute model) or oral (chronic model) tamoxifen administration. Our results reported a clear microglial repopulation, then pointing out that our model would mimic a context of microglial replacement instead of microglial dysfunction. Next, we evaluated the origin and pattern of microglial repopulation. Additionally, we also reviewed previous works assessing the effects of microglial depletion in the progression of Aβ and Tau pathologies, where controversial data are found, probably due to the heterogeneous and time-varying microglial phenotypes observed in AD. Despite that, microglial depletion represents a promising tool to assess microglial role in AD and design therapeutic strategies.

Reactive astrocytes and dystrophic neurites, most aberrant presynaptic elements, are found surrounding amyloid-β plaques in Alzheimer's disease (AD). We have previously shown that reactive astrocytes enwrap, phagocytose, and degrade dystrophic synapses in the hippocampus of APP mice and AD patients, but affecting less than 7% of dystrophic neurites, suggesting reduced phagocytic capacity of astrocytes in AD. Here, we aimed to gain insight into the underlying mechanisms by analyzing the capacity of primary astrocyte cultures to phagocytose and degrade isolated synapses (synaptoneurosomes, SNs) from APP (containing dystrophic synapses and amyloid-β peptides), Tau (containing AT8- and AT100-positive phosphorylated Tau) and WT (controls) mice. We found highly reduced phagocytic and degradative capacity of SNs-APP, but not AT8/AT100-positive SNs-Tau, as compared with SNs-WT. The reduced astrocyte phagocytic capacity was verified in hippocampus from 12-month-old APP mice, since only 1.60 ± 3.81% of peri-plaque astrocytes presented phagocytic structures. This low phagocytic capacity did not depend on microglia-mediated astrocyte reactivity, because removal of microglia from the primary astrocyte cultures abrogated the expression of microglia-dependent genes in astrocytes, but did not affect the phagocytic impairment induced by oligomeric amyloid-β alone. Taken together, our data suggest that amyloid-β, but not hyperphosphorylated Tau, directly impairs the capacity of astrocytes to clear the pathological accumulation of oligomeric amyloid-β, as well as of peri-plaque dystrophic synapses containing amyloid-β, perhaps by reducing the expression of phagocytosis receptors such as Mertk and Megf10, thus increasing neuronal damage in AD. Therefore, the potentiation or recovery of astrocytic phagocytosis may be a novel therapeutic avenue in AD., (© 2020 The Authors. Glia published by Wiley Periodicals LLC.)

Objectives: This study aims to estimate the proportion of lung cancer cases and deaths attributable to tobacco smoking in Portugal in 2018, complemented by trends in incidence and mortality, by sex and region., Design: Cancer cases for 1998-2011 and cancer deaths for 1991-2018 were obtained from population-based registries and Statistics Portugal, respectively. We projected cases for 2018 and used reported deaths for the same year to estimate, using Peto's method, the number and proportion of lung cancer cases and deaths caused by tobacco smoking in 2018. We calculated the age-adjusted incidence and mortality rates in each year of diagnosis and death. We fitted a joinpoint regression to the observed data to estimate the annual percentage change (APC) in the rates., Setting: Portugal., Results: In 2018, an estimated 3859 cases and 3192 deaths from lung cancer were attributable to tobacco smoking in Portugal, with men presenting a population attributable fraction (PAF) of 82.6% (n=3064) for incidence and 84.1% (n=2749) for mortality, while in women those values were 51.0% (n=795) and 42.7% (n=443), respectively. In both sexes and metrics, the Azores were the region with the highest PAF and the Centre with the lowest. During 1998-2011, the APC for incidence ranged from 0.6% to 3.0% in men and 3.6% to 7.9% in women, depending on region, with mortality presenting a similar pattern between sexes., Conclusion: Exposure to tobacco smoking has accounted for most of the lung cancer cases and deaths estimated in Portugal in 2018. Differential patterns of tobacco consumption across the country, varying implementation of primary prevention programmes and differences in personal cancer awareness may have contributed to the disparities observed. Primary prevention of lung cancer remains a public health priority, particularly among women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In Alzheimer's disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has not been assessed so far. Here we have evaluated the impact of the brain-penetrant microtubule-stabilizing agent Epothilone D (EpoD) in an amyloidogenic model of AD. Three-month-old APP/PS1 mice, before the pathology onset, were weekly injected with EpoD for 3 months. Treated mice showed significant decrease in the phospho-tau levels and, more interesting, in the intracellular and extracellular hippocampal Aβ accumulation, including the soluble oligomeric forms. Moreover, a significant cognitive improvement and amelioration of the synaptic and neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Therefore, our results suggested that EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Aβ levels and promoting neuronal and cognitive protection. These results underline the existence of a crosstalk between cytoskeleton pathology and the two major AD protein lesions. Therefore, microtubule stabilizers could be considered therapeutic agents to slow the progression of both tau and Aβ pathology.

Introduction: For stage III colon cancer (CC), surgery followed by chemotherapy is the main curative approach, although optimum times between diagnosis and surgery, and surgery and chemotherapy, have not been established., Materials and Methods: We analysed a population-based sample of 1912 stage III CC cases diagnosed in eight European countries in 2009-2013 aiming to estimate: (i) odds of receiving postoperative chemotherapy, overall and within eight weeks of surgery; (ii) risks of death/relapse, according to treatment, Charlson Comorbidity Index, time from diagnosis to surgery for emergency and elective cases, and time from surgery to chemotherapy; and (iii) time-trends in chemotherapy use., Results: Overall, 97% of cases received surgery and 65% postoperative chemotherapy, with 71% of these receiving chemotherapy within eight weeks of surgery. Risks of death and relapse were higher for cases starting chemotherapy with delay, but better than for cases not given chemotherapy. Fewer patients with high comorbidities received chemotherapy than those with low (P < 0.001). Chemotherapy timing did not vary (P = 0.250) between high and low comorbidity cases. Electively-operated cases with low comorbidities received surgery more promptly than high comorbidity cases. Risks of death and relapse were lower for elective cases given surgery after four weeks than cases given surgery within a week. High comorbidities were always independently associated with poorer outcomes. Chemotherapy use increased over time., Conclusions: Our data indicate that promptly-administered postoperative chemotherapy maximizes its benefit, and that careful assessment of comorbidities is important before treatment. The survival benefit associated with slightly delayed elective surgery deserves further investigation., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

This report describes the cancer cases that occurred between 2017 and 2018 in Santiago Island, Cape Verde, according to the Hospital Agostinho Neto Cancer Registry. The five most common cancers were prostate, breast, stomach, cervix and oesophageal in order of frequency. There are no national data. Therefore, it is essential to create the conditions for the establishment of Cape Verde's population-based cancer registry as quickly as possible., Competing Interests: There is no conflict of interest., (© the authors; licensee ecancermedicalscience.)

Background: Postoperative pulmonary complications (PPCs) contribute significantly to overall postoperative morbidity and mortality. In abdominal surgery, PPCs remain frequent. The study aimed to analyze the profile and outcomes of PPCs in patients submitted to abdominal surgery and admitted in a Portuguese polyvalent intensive care unit., Methods: From January to December 2017 in the polyvalent intensive care unit of Hospital Garcia de Orta, Almada, Portugal, we conducted a retrospective, observational study of inpatients submitted to urgent or elective abdominal surgery who had severe PPCs. We evaluated the perioperative risk factors and associated mortality. Logistic regression was performed to find which perioperative risk factors were most important in the occurrence of PPCs., Results: Sixty patients (75% male) with a median age of 64.5 [47-81] years who were submitted to urgent or elective abdominal surgery were included in the analysis. Thirty-six patients (60%) developed PPCs within 48 h and twenty-four developed PPCs after 48 h. Pneumonia was the most frequent PPC in this sample. In this cohort, 48 patients developed acute respiratory failure and needed mechanical ventilation. In the emergency setting, peritonitis had the highest rate of PPCs. Electively operated patients who developed PPCs were mostly carriers of digestive malignancies. Thirty-day mortality was 21.7%. The risk of PPCs development in the first 48 h was related to the need for neuromuscular blocking drugs several times during surgery and preoperative abnormal arterial blood gases. Median abdominal surgical incision, long surgery duration, and high body mass index were associated with PPCs that occurred more than 48 h after surgery. The American Society of Anesthesiologists physical status score 4 and COPD/Asthma determined less mechanical ventilation needs since they were preoperatively optimized. Malnutrition (low albumin) before surgery was associated with 30-day mortality., Conclusion: PPCs after abdominal surgery are still a major problem since they have profound effects on outcomes. Our results suggest that programs before surgery, involve preoperative lifestyle changes, such as nutritional supplementation, exercise, stress reduction, and smoking cessation, were an effective strategy in mitigating postoperative complications by decreasing mortality., Competing Interests: Competing interestsThere is no competing interests or financial interest amongst authors to disclose., (© The Author(s). 2019.)

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data., Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning., Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence., Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs)., Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

Background: Visceral pain conducted by sympathetic fibers with pelvic and perineal origin can be treated using ganglion impar (GIB) or Walters' block in a simple and effective manner. This article aims to evaluate the effectiveness, security, and performance difficulty of GIB in patients with pelvic and perineal oncological pain., Methods: A retrospective study between January 2016 and August 2017. Patients with poorly controlled pelvic oncological pain and patients experimenting opioid side effects in which GIB was performed ambulatory were included. Prognostic GIB was performed, under echographic and fluoroscopic control, with local anesthetic and corticoid. The neurolytic block was performed under fluoroscopic guidance. The technique was performed by the same anesthetist with pain management competence. For statistical analysis, Microsoft Excel 2013® and IBM SPSS Statistics version 22.0 were used., Results: Fifteen patients were included. One patient was excluded. A statistical significant basal pain score reduction was observed ((median of the verbal numerical scale (VNS) 7 (p25 = 7; p75 = 8)) compared with 72 h median VNS 4 ((p25 = 3; p75 = 5.3) p = 0.001, and 3 months (median VNS 4 (p25 = 3, p75 = 7)) p = 0.003 after the procedure. Regarding morphine consumption, a statistically significant reduction was observed 3 months after GIB performance (p = 0.012)., Discussion/conclusion: GIB is a safe and easy-to-perform technique achieving satisfactory and statistically significant results, regarding pain control improvement and opioid consumption reduction in patients which meet selection criteria. Prospective, randomized studies with more patients are needed for further conclusions.

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs ( n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30-14.53) and disseminated disease (OR 4.52 95%CI 1.44-14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions., Competing Interests: The authors declare no potential conflicts of interest.

To quantify the association between prediagnosis lifestyles with the risk of second primary cancers (SPCs) and survival of patients with gastric first primary cancer (FPC). We recruited 574 gastric patients from two major public hospitals in North Portugal (2001-2006). Smoking, alcohol and dietary habits in the year before FPC diagnosis were evaluated. Patients were followed up to 31 December 2011 for an SPC and to 31 May 2017 for vital status. Cox proportional hazards regression was used to estimate adjusted hazard ratios for incidence of an SPC or death. During follow-up, SPCs were diagnosed in five women and 23 men, and 409 patients died, corresponding to an estimated 10-year cumulative incidence of 5.2% for SPC and an estimated 15-year cumulative mortality of 72.1%. A significantly higher hazard ratio (95% confidence interval) for SPCs was observed in patients reporting a higher consumption of red and processed meat versus the lowest third (4.49: 1.31-15.37), and for mortality in those with heavy alcohol intake versus never drinkers (1.73: 1.00-2.99) and excess weight versus normal weight (1.31: 1.04-1.65); no other significant associations were observed according to prediagnosis lifestyle. Prediagnosis lifestyles may affect the occurrence of an SPC and survival among gastric FPC survivors in the long term.

Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7581 stage I/IIA cases diagnosed in 9 European countries in 2009-2013, and 4 STs: surgery; breast-conserving surgery plus radiotherapy (BCS + RT); reconstruction after mastectomy; and prompt treatment (≤6 weeks after diagnosis). Covariate-adjusted models estimated odds of receiving STs and risks of death/relapse, according to comorbidities. Pearson's R assessed correlations between odds and risks. The z-test assessed the significance of time-trends. Most women received surgery: 72% BCS; 24% mastectomy. Mastectomied patients were older with more comorbidities than BCS patients (p < 0.001). Women given breast reconstruction (25% of mastectomies) were younger with fewer comorbidities than those without reconstruction (p < 0.001). Women treated promptly (45%) were younger than those treated later (p = 0.001), and more often without comorbidities (p < 0.001). Receiving surgery/BCS + RT correlated strongly (R = -0.9), but prompt treatment weakly (R = -0.01/-0.02), with reduced death/relapse risks. The proportion receiving BCS + RT increased significantly (p < 0.001) with time in most countries. This appears to be the first analysis of the influence of comorbidities on receiving STs, and of consequences for outcomes. Increase in BCS + RT with time is encouraging. Although women without comorbidities usually received STs, elderly patients often received non-standard less prompt treatments, irrespective of comorbidities, with increased risk of mortality/relapse. All women, particularly the elderly, should receive ST wherever possible to maximise the benefits of modern evidence-based treatments., (© 2018 UICC.)

Microglial cells are crucial players in the pathological process of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglial response in AD has been principally studied in relation to amyloid-beta pathology but, comparatively, little is known about inflammatory processes associated to tau pathology. In the hippocampus of AD patients, where tau pathology is more prominent than amyloid-beta pathology, a microglial degenerative process has been reported. In this work, we have directly compared the microglial response in two different transgenic tau mouse models: ThyTau22 and P301S. Surprisingly, these two models showed important differences in the microglial profile and tau pathology. Where ThyTau22 hippocampus manifested mild microglial activation, P301S mice exhibited a strong microglial response in parallel with high phospho-tau accumulation. This differential phospho-tau expression could account for the different microglial response in these two tau strains. However, soluble (S1) fractions from ThyTau22 hippocampus presented relatively high content of soluble phospho-tau (AT8-positive) and were highly toxic for microglial cells in vitro , whereas the correspondent S1 fractions from P301S mice displayed low soluble phospho-tau levels and were not toxic for microglial cells. Therefore, not only the expression levels but the aggregation of phospho-tau should differ between both models. In fact, most of tau forms in the P301S mice were aggregated and, in consequence, forming insoluble tau species. We conclude that different factors as tau mutations, accumulation, phosphorylation, and/or aggregation could account for the distinct microglial responses observed in these two tau models. For this reason, deciphering the molecular nature of toxic tau species for microglial cells might be a promising therapeutic approach in order to restore the deficient immunological protection observed in AD hippocampus.

Purpose: Eastern Africa was recently described as a high-incidence geographic area for esophageal cancer. Mozambique is included in this region. This study aimed to characterize this malignant disease at Maputo Central Hospital (MCH) to develop a global program for esophageal cancer management in Mozambique., Methods: MCH records from between 2012 and 2016 were used to assess the clinical, pathologic, and outcome profiles of esophageal tumors. A descriptive analysis of data collected was performed. Overall survival was evaluated using Kaplan-Meier curves., Results: In the study, 522 consecutive patient cases of esophageal cancer were recorded. The median patient age was 56.1 years (range, 27 to 97 years); 291 (55.7%) patients were women, and 230 (44.1%) were men. Regarding tumor site, 113 patients (21.6%) had a tumor in the lower third, 154 (29.5%) in the middle, and 50 (9.6%) in the upper third of the esophagus; in the remaining 196 (37.5%), tumor site was unknown. Squamous cell carcinoma comprised 94.4% of cases with documented histopathology (74.9% of the sample). Surgical treatment was possible in 32 patients (6.1%). Disease stage was documented only in these 32 surgical patients; 28.1%, 53.1%, and 18.8% had stage I, II, and III disease, respectively. The remaining patient cases seemed to involve clinically advanced tumors. The median follow-up time was of 1.6 months. The median survival time was of 3.5 months for all patients; for patients treated with curative intent, it was of 8.7 months., Conclusion: Esophageal carcinoma is a common malignant tumor at MCH and is diagnosed in the advanced stages resulting in poor prognosis. Therefore, implementation of an Esophageal Cancer Program in Mozambique is essential.

The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs ( n = 96) were cross-matched for age, gender, and district of residence with a control group ( n = 96) derived from the general population in a case-control study. Patients presented gastro-intestinal (75.0%) or pancreatic (22.9%) tumors, grade G1 (66.7%) or G2 (27.1%) with localized disease (31.3%), regional metastasis (16.7%) or distant metastasis (43.8%) at diagnosis, and 45.8% had clinical hormonal syndromes. MetS was defined according to Joint Interim Statement (JIS) criteria. Well-differentiated GEP-NETs were associated with MetS criteria as well as the individual components' waist circumference, fasting triglycerides, and fasting plasma glucose ( p = 0.003, p = 0.002, p = 0.011 and p < 0.001, respectively). The likelihood of the association was higher when the number of individual MetS components was greater than four. MetS and some individual MetS components including visceral obesity, dyslipidemia, and increased fasting glucose are associated with well-differentiated GEP-NET. This data provides a novel insight in unraveling the mechanisms leading to GEP-NET disease.

Background: Female breast cancer incidence rates have been increasing in Portugal for years. We, therefore, conducted the first nationwide breast cancer study to assess regional differences., Methods: Cases were obtained from population-based cancer registries covering the country's Mainland (South, North, Centre), as well as the two Autonomous Regions (Azores and Madeira), for the time-period 1998 through 2011. Analyses were restricted to ages 30-84 years and stratified by region. We used the age-period-cohort (APC) framework to complement standard descriptive techniques and to forecast future trends. Estimable APC parameters included net drift, longitudinal age-specific incidence rate curves, and fitted age-specific incidence rate ratios., Results: There were 71 545 breast cancer cases diagnosed in Portugal at ages 30-84 years from 1998 to 2011. The South presented the highest age-standardized rate (155.8/100 000), while the North presented the fastest rate of increase (3.6%/year). Age-specific statistical interactions were observed between regions. Younger women in the North revealed a decreased risk of developing breast cancer compared to women from the same age group in the South and Centre, while that risk was reversed in older women (p < 0.05). We estimate that from 2014 onwards, the North might rank first among all regions., Conclusion: The variant patterns observed could be due to a combination of different screening practices and/or exposure to risk factors across regions. Disease heterogeneity among younger and older women may also explain part of the differences in age-specific rates. These results justify continued monitoring of breast cancer incidence by region., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) play a central role. In other degenerative processes, such as Alzheimer's disease (AD), the role of microglia is far to be elucidated. In this "mini-review" article, we briefly highlight our recent data comparing the microglial response between amyloidogenic transgenic models, such as APP/PS1 and AD patients. Since the AD pathology could display regional heterogeneity, we focus our work at the hippocampal formation. In APP based models a prominent microglial response is triggered around amyloid-beta (Aβ) plaques. These strongly activated microglial cells could drive the AD pathology and, in consequence, could be implicated in the neurodegenerative process observed in models. On the contrary, the microglial response in human samples is, at least, partial or attenuated. This patent difference could simply reflect the lower and probably slower Aβ production observed in human hippocampal samples, in comparison with models, or could reflect the consequence of a chronic long-standing microglial activation. Beside this differential response, we also observed microglial degeneration in Braak V-VI individuals that, indeed, could compromise their normal role of surveying the brain environment and respond to the damage. This microglial degeneration, particularly relevant at the dentate gyrus, might be mediated by the accumulation of toxic soluble phospho-tau species. The consequences of this probably deficient immunological protection, observed in AD patients, are unknown.

Objectives: Although second generation long-acting injectable antipsychotics (SG-LAIAs) have been approved and are widely used in adults, there is limited evidence for the use of long-acting formulations in children and adolescents. Thus, we systematically describe the off-label use of SG-LAIAs in clinical practice in adolescent inpatients., Methods: All individuals admitted to our Children and Adolescent Inpatient Psychiatry Unit receiving treatment with SG-LAIAs between January 2013 and June 2016 were reviewed. A retrospective analysis of medical records was conducted. Clinical diagnoses were established using DSM-5 criteria., Results: Thirty individuals (53.3% female) out of a total of 1,148 admitted patients (2.6%) were identified. The mean age was 16.3 (SD = 1.3; range: 12.5-17.9).The main diagnoses were psychosis (70%) and disruptive behavior disorders (DBDs) (30%), although comorbidity was frequent (96.6%), especially drug use (55.2%, mostly cannabis). SG-LAIAs used were aripiprazole (40%), risperidone (36.7%), and paliperidone palmitate (23.3%), and the main reasons were a history of low compliance (90%) and/or poor insight (73.3%). A mean improvement of 31.7 (SD = 8.7) between admission and discharge was registered in the Children's Global Assessment Scale (CGAS); no differences were observed between different SG-LAIAs. Although they were generally well tolerated, 23.3% of patients reported mild short-term side effects, which were more frequent with risperidone than with aripiprazole (p = .014)., Conclusions: Our clinical experience suggests that SG-LAIAs may be a safe treatment option during adolescence in inpatients with psychotic disorders, as well as with DBD. No differences were found in CGAS improvement scores between the three SGA-LAIAs used, although patients on risperidone reported more side effects than those on aripiprazole. Further research is needed so as to evaluate safety and effectiveness of SG-LAIAs in this population.

Variations in the exposure to risk factors may be used to explain past cancer trends and to predict its future burden. This study aimed to develop a model to describe and predict the variation of esophageal cancer incidence in 1995-2005, taking into account changes in exposures to risk factors. We adapted an existing model to calculate the expected variation in the number of esophageal cancer cases, between 1995 and 2005, in Australia, Japan, Italy, Portugal, the UK, and the USA, because of changes in exposures to risk factors, taking into account the corresponding lag times. Analyses were based on country-specific data of cancer incidence and exposures to risk factors. We computed 95% credibility intervals through Monte Carlo simulation methods. Absolute deviations between the number of cases predicted and those observed in 2005 ranged between 1.8% in Japan and 23.6% in the UK among men and 0.0% in Japan and 18.0% in Australia among women. In Italy and Japan, deviations did not exceed 3%. The UK registered the worst model performance. The variation in esophageal cancer incidence was mainly influenced by changes in fruit and red meat intake, and BMI. For nearly half of the sex-specific and histological type-specific predictions performed, credibility intervals included the observed number of cases. This study proposes a framework for the analysis of the contribution of changes in exposure to different factors to esophageal cancer incidence trends and for long-term predictions at a population level.

Background: Even though mass gastric cancer screening is controversial in Western countries, diverse strategies have been proposed in intermediate-risk to high-risk areas., Aim: The aim of this study was to determine the long-term accuracy of the pepsinogen test (PG) for early diagnosis of gastric cancer., Participants and Methods: A cohort of inhabitants from the Northern part of Portugal, aged between 40 and 74 years (n=5913), subjected to the PG test (PGI≤70 ng/ml and PGI/PGII≤3), were followed up between November 2006 and December 2015. The diagnosis of gastric cancer was determined through linkage to the population-based registry of cancer [North Region Cancer Registry of Portugal (RORENO)]., Results: Twenty-six gastric cancers were diagnosed (0.4%): nine (4%) among individuals 'positive' for the PG test (n=225) and 15 (0.3%) among those who were 'negative' (n=5688) [hazard ratio=12.7; 95% confidence interval (CI): 5.6-28.6]. Individuals with a 'negative PG test' had a 3-year risk of gastric cancer of 0.1%, representing a sensitivity of 35% (95% CI: 17-56%), globally, and of 58% (95% CI: 28-85%) at 3 years follow-up. The median survival rate in both groups was over 24 months., Conclusion: The PG test was found to be suboptimal as a screening test and, if used (before upper gastrointestinal endoscopy), it is mandatory to repeat it after 3 years.

There are marked differences in the etiology of the major histological types of esophageal cancer (EC)-squamous cell carcinomas (ESCC) and adenocarcinomas (EAC). This study aimed to summarize the current scientific knowledge on modifiable risk factors for EC, by histological type, through a systematic review of meta-analyses referenced in PubMed and ISI Web of Knowledge. We identified 100 meta-analyses on risk factors for ESCC (n = 54), EAC (n = 43), or EC (n = 51). ESCC risk significantly increased with alcohol and maté drinking, smoking, red and processed meat consumption and human papillomavirus infection, while it was negatively associated with body mass index and consumption of fruit, vegetables, white meat, folate, and some carotenoids. Cessation of drinking and smoking significantly reduced ESCC risk. For EAC, an increased risk was reported for smoking, body mass index, and red and processed meat consumption, while risk decreased with Helicobacter pylori infection, low/moderate alcohol drinking, physical activity, and consumption of fruit, vegetables, folate, fiber, beta-carotene, and vitamin C. Differences in results between meta-analyses and mechanisms underlying some of the associations found are discussed. This work reinforces the importance of a separate assessment of EC subtypes to allow for a proper evaluation of incidence trends and planning of prevention/control interventions.

There is a large geographical variability in prostate cancer incidence and mortality trends, mostly because of heterogeneity in control efforts across regions. We aimed to describe the time trends in prostate cancer incidence and mortality in Portugal, overall and by region, and to estimate the number of incident cases and deaths in 2020. The number of cases and incidence rates in 1998-2009 were collected from the Regional Cancer Registries. The number of deaths and mortality rates were obtained from the WHO mortality database (1988-2003 and 2007-2013) and Statistics Portugal (2004-2006; 1991-2013 by region). JoinPoint analyses were used to identify significant changes in trends in age-standardized incidence and mortality rates. Incidence and mortality predictions for 2020 were performed using Poisson regression models and population projections provided by Statistics Portugal. In Portugal, prostate cancer incidence has been increasing since 1998 (1.8%/year), with the exception of the North Region, with a decrease since 2006 (-3.2%/year). An overall mortality decline has been observed since 1997 (-2.2%/year), although there were two patterns of mortality variation at the regional level: one with an inflection point or significant variation in the rates and the other without significant variation. If these trends are maintained, ∼8600 incident cases and 1700 deaths may be expected to occur in Portugal in 2020. Despite the overall increasing incidence and decreasing mortality, there is a large heterogeneity across regions. Future studies should address regional differences in the trends of prostate specific antigen screening and in the effective management of prostate cancer.

Introduction: Gastric cancer (GC) and esophageal cancer (EC) share risk factors, and the incidence trends reflect differences in etiology according to their subtypes. We aimed to describe the incidence trends of GC (by topography) and EC (by histological type) in northern Portugal for 1994-2009 and to estimate the incidence for 2015. We further analyzed exposure to the main risk factors for these cancers in the region over the last decades., Methods: GC and EC data were obtained from the North Region Cancer Registry of Portugal (RORENO). Joinpoint regression was used to compute annual percent changes (APC) in incidence trends. Poisson regression yielded estimates for 2015. A literature review up to 2014 provided data on exposure to risk factors., Results: GC rates decreased in 1994-2009 (men, APC = -1.3; women, APC = -1.6); GC, unspecified subtype, had the steepest decline since the early 2000s (men, APC = -4.9; women, APC = -6.3). The incidence for 2015 will increase for EC in men (up to ≈190 cases) and stabilize in women (≈30) and for GC (≈730 men, ≈500 women). Increasing prevalence of tobacco smoking among women and overweight/obesity, fairly stable prevalence of alcohol, fruit and vegetable consumption, and no trend for Helicobacter pylori infection were observed., Conclusions: The declining incidence of GC unspecified subtype indicated an improvement in cancer registration accuracy, but precluded a sound assessment of trends by subtype. Variations in the prevalence of exposure to some risk factors were consistent with observed incidence trends, and future studies should aim to quantify their contribution to the GC and EC burden in the region.

Esophageal cancer represents a major clinical challenge because of its poor prognosis. The aim of the SUDCAN collaborative study was to compare the net survival from esophageal cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland) and report the trends in net survival and the dynamics of excess mortality rates (EMRs) up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the period 2000-2004 using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results were reported from 1992 to 2004 in France, Italy, Spain, and Switzerland and from 2000 to 2004 in Belgium and Portugal. These trend analyses were carried out using a flexible excess rate modeling strategy. There were some differences between countries in age-standardized net survival (2000-2004). The 5-year net survival ranged between 9 (Spain) and 21% (Belgium). The small increase in net survival from 1992 and 2004 was mostly observed at ages 55 and 65, but was less marked at age 75. There was a slight decrease in EMR between 1992 and 2004 until ∼24 months after diagnosis. Beyond this period, the decrease in the EMR was moderate and the same in all countries irrespective of the year of diagnosis. Some improvement in the 5-year net survival was observed in all countries limited to the 24 months after diagnosis. However, survival differences between countries persisted. Further improvement is expected from innovative treatments.

Objective: Many assessment tools have been developed for palliative care and there are a number of differences between them. Therefore, we felt that there was room for improvement., Methods: In a previous study, the relevant items were selected by a Delphi process with international experts in palliative care. A 5-point verbal scale was added to the items selected and adapted to the different kind of items., Results: The study included 123 patients, 63 (51%) were female and the median age was 64 (37 to 88). A four-factor structure was found through the principal components analysis, explaining 60.1% of the total variance. The scale presented good reliability, with a Cronbach's alpha of 0.72. It was hypothesized as a validity of construct that as the total symptom burden increased, survival time would decrease. This hypothesis was confirmed by the statistical analysis performed. A hazard ratio of 1.016 (P=0.019) was obtained in the Cox regression model including the final score as an explanatory variable of survival time, which means that for each increment of 1% in the total score, there was an increased risk of death of 1.6%., Conclusions: This tool is in accordance with the recommended characteristics that an assessment tool should have. It is simple to administer and easy to explain, complete and analyze. It is also a valid tool.

Background: Several locoregional techniques have been described for the management of acute and chronic pain after breast surgery. The optimal technique should be easy to perform, reproducible, with little discomfort to the patient, little complications, allowing good control of acute pain and a decreased incidence of chronic pain, namely intercostobrachial neuralgia for being the most frequent entity., Objectives: The aim of this study was to evaluate the paravertebral block with preoperative single needle prick for major breast surgery and assess initially the control of postoperative nausea and vomiting (PONV) and acute pain in the first 24h and secondly the incidence of neuropathic pain in the intercostobrachial nerve region six months after surgery., Methods: The study included 80 female patients, ASA I-II, aged 18-70 years, undergoing major breast surgery, under general anesthesia, stratified into 2 groups: general anesthesia (inhalation anesthesia with opioids, according to hemodynamic response) and paravertebral (paravertebral block with single needle prick in T4 with 0.5% ropivacaine+adrenaline 3μgmL(-1) with a volume of 0.3mLkg(-1) preoperatively and subsequent induction and maintenance with general inhalational anesthesia). In the early postoperative period, patient-controlled analgesia (PCA) was placed with morphine set for bolus on demand for 24h. Intraoperative fentanyl, postoperative morphine consumption, technique-related complications, pain at rest and during movement were recorded at 0h, 1h, 6h and 24h, as well as episodes of PONV. All variables identified as factors contributing to pain chronicity age, type of surgery, anxiety according to the Hospital Anxiety and Depression Scale (HADS), preoperative pain, monitoring at home; body mass index (BMI) and adjuvant chemotherapy/radiation therapy were analyzed, checking the homogeneity of the samples. Six months after surgery, the incidence of neuropathic pain in the intercostobrachial nerve was assessed using the DN4 scale., Results: The Visual Analog Scale (VAS) values of paravertebral group at rest were lower throughout the 24h of study 0h 1.90 (±2.59) versus 0.88 (±1.5) 1h 2.23 (±2.2) versus 1.53 (±1.8) 6h 1.15 (±1.3) versus 0.35 (±0.8); 24h 0.55 (±0.9) versus 0.25 (±0.8) with statistical significance at 0h and 6h. Regarding movement, paravertebral group had VAS values lower and statistically significant in all four time points: 0h 2.95 (±3.1) versus 1.55 (±2.1); 1h 3.90 (±2.7) versus 2.43 (±1.9) 6h 2.75 (±2.2) versus 1.68 (±1.5); 24h 2.43 (±2.4) versus 1.00 (±1.4). The paravertebral group consumed less postoperative fentanyl (2.38±0.81μgkg(-1) versus 3.51±0.81μgkg(-1)) and morphine (3.5mg±3.4 versus 7mg±6.4) with statistically significant difference. Chronic pain evaluation of at 6 months of paravertebral group found fewer cases of neuropathic pain in the intercostobrachial nerve region (3 cases versus 7 cases), although not statistically significant., Conclusions: Single-injection paravertebral block allows proper control of acute pain with less intraoperative and postoperative consumption of opioids but apparently it cannot prevent pain chronicity. Further studies are needed to clarify the role of paravertebral block in pain chronicity in major breast surgery., (Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Decision making towards cancer prevention and control requires monitoring of trends in cancer incidence and accurate estimation of its burden in different settings. We aimed to estimate the number of incident cases in northern Portugal for 2015 and 2020 (all cancers except nonmelanoma skin and for the 15 most frequent tumours). Cancer cases diagnosed in 1994-2009 were collected by the North Region Cancer Registry of Portugal (RORENO) and corresponding population figures were obtained from Statistics Portugal. JoinPoint regression was used to analyse incidence trends. Population projections until 2020 were derived by RORENO. Predictions were performed using the Poisson regression models proposed by Dyba and Hakulinen. The number of incident cases is expected to increase by 18.7% in 2015 and by 37.6% in 2020, with lower increments among men than among women. For most cancers considered, the number of cases will keep rising up to 2020, although decreasing trends of age-standardized rates are expected for some tumours. Cervix was the only cancer with a decreasing number of incident cases in the entire period. Thyroid and lung cancers were among those with the steepest increases in the number of incident cases expected for 2020, especially among women. In 2020, the top five cancers are expected to account for 82 and 62% of all cases diagnosed in men and women, respectively. This study contributes to a broader understanding of cancer burden in the north of Portugal and provides the basis for keeping population-based incidence estimates up to date.

Background: Several locoregional techniques have been described for the management of acute and chronic pain after breast surgery. The optimal technique should be easy to perform, reproducible, with little discomfort to the patient, little complications, allowing good control of acute pain and a decreased incidence of chronic pain, namely intercostobrachial neuralgia for being the most frequent entity., Objectives: The aim of this study was to evaluate the paravertebral block with preoperative single needle prick for major breast surgery and assess initially the control of postoperative nausea and vomiting (PONV) and acute pain in the first 24hours and secondly the incidence of neuropathic pain in the intercostobrachial nerve region six months after surgery., Methods: The study included 80 female patients, ASA I-II, aged 18-70 years, undergoing major breast surgery, under general anesthesia, stratified into 2 groups: general anesthesia (inhalation anesthesia with opioids, according to hemodynamic response) and paravertebral (paravertebral block with single needle prick in T4 with 0.5% ropivacaine + adrenaline 3μg/mL with a volume of 0.3mL/kg preoperatively and subsequent induction and maintenance with general inhalational anesthesia). In the early postoperative period, patient-controlled analgesia (PCA) was placed with morphine set for bolus on demand for 24hours. Intraoperative fentanyl, postoperative morphine consumption, technique-related complications, pain at rest and during movement were recorded at 0h, 1h, 6h and 24h, as well as episodes of PONV. All variables identified as factors contributing to pain chronicity age, type of surgery, anxiety according to the Hospital Anxiety and Depression Scale (HADS), preoperative pain, monitoring at home; body mass index (BMI) and adjuvant chemotherapy/radiation therapy were analyzed, checking the homogeneity of the samples. Six months after surgery, the incidence of neuropathic pain in the intercostobrachial nerve was assessed using the DN4 scale., Results: The Visual Analogue Scale (VAS) values of paravertebral group at rest were lower throughout the 24hours of study 0h 1.90 (± 2.59) versus 0.88 (± 1.5) 1h 2.23 (± 2.2) versus 1.53 (± 1.8) 6h 1.15 (± 1.3) versus 0.35 (± 0.8); 24h 0.55 (± 0.9) versus 0.25 (± 0.8) with statistical significance at 0h and 6h. Regarding movement, paravertebral group had VAS values lower and statistically significant in all four time points: 0h 2.95 (± 3.1) versus 1.55 (± 2.1); 1h 3.90 (± 2.7) versus 2.43 (± 1.9) 6h 2.75 (± 2.2) versus 1.68 (± 1.5); 24h 2.43 (± 2.4) versus 1.00 (± 1.4). The paravertebral group consumed less postoperative fentanyl (2.38±0.81μg/kg versus 3.51±0.81μg/kg) and morphine (3.5mg±3.4 versus 7mg±6.4) with statistically significant difference. Chronic pain evaluation of at 6 months of paravertebral group found fewer cases of neuropathic pain in the intercostobrachial nerve region (3 cases versus 7 cases), although not statistically significant., Conclusions: Single-injection paravertebral block allows proper control of acute pain with less intraoperative and postoperative consumption of opioids but apparently it cannot prevent pain chronicity. Further studies are needed to clarify the role of paravertebral block in pain chronicity in major breast surgery., (Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Assessing the impact that patterns of Na intake may have on gastric cancer will provide a more comprehensive estimation of Na reduction as a primary prevention approach. We aimed to estimate the proportion of gastric cancer cases that are attributable to Na intake above the recommendation by the WHO (≤2 g/d) throughout the world in 2010, as well as expected values for 2030. Population attributable fractions (PAF) were computed for 187 countries, using Na intakes in 1990 and 2010 and estimates of the association between Na intake and gastric cancer, assuming a time lag of 20 years. Median PAF ranged from 10·1% in low to 22·5 % in very high Human Development Index (HDI) countries in men (P<0·001) and from 7·2 to 16·6 %, respectively, among women (P<0·001). An increase in median PAF until 2030 is expected in most settings, except for countries classified as low HDI, in both sexes. High Na intakes account for a large proportion of gastric cancer cases, and proportions are expected to increase in almost all of the countries. Intensified efforts to diminish Na intake in virtually all populations are needed to further reduce gastric cancer burden.

Portugal has the highest gastric cancer mortality rates in Western Europe, along with high prevalences of Helicobacter pylori infection. Monitoring their trends is essential to predict the burden of this cancer. We aimed to quantify time trends in gastric cancer mortality in Portugal and in each administrative region, and to compute short-term predictions, as well as to describe the prevalence of H. pylori infection, through a systematic review. Joinpoint analyses were used to identify significant changes in sex-specific trends in gastric cancer age-standardized mortality rates (ASMR) and to estimate annual percent changes (APC). The most recent trends were considered to compute estimates up to 2020 by adjusting Poisson regression models. We searched PubMed and IndexRMP to identify studies carried out in Portugal reporting the prevalence of H. pylori. Gastric cancer mortality has been decreasing in Portugal since 1971 in men (from ASMR=55.3/100 000; APC=-2.4, 95% confidence interval: -2.5 to -2.3) and since 1970 in women (from ASMR=28.0/100 000; APC=-2.8, 95% confidence interval: -2.9 to -2.7), although large regional differences were observed. Predicted ASMR for 2015 and 2020 were 18.8/100 000 and 16.7/100 000 for men and 8.5/100 000 and 7.4/100 000 for women, respectively. The prevalence of H. pylori varied from almost 5% at 0.5-2 years to just over 90% at 70 years or more. No consistent variation was observed since the 1990s. The downward trends in mortality rates are expected to remain in the next decades. The high prevalence of H. pylori infection across age groups and studies from different periods shows a large potential for decrease in the burden of gastric cancer in Portugal.

The regional and temporal variation in patterns of fruit and vegetable intake contributes to differences in the impact on gastric cancer burden across regions and over the years. We aimed to estimate the proportion and absolute number of gastric cancer cases that could have been prevented in 2012 with an increase in fruit and vegetable intake up to the levels defined by the Global Burden of Disease as the theoretical minimum-risk exposure distribution (300 and 400 g/d, respectively), as well as the corresponding figures expected for 2025. Preventable fractions (PF) were computed for 161 countries, using data on fruit and vegetable availability in 1997 and 2010 and published estimates of the magnitude of the association between fruit and vegetable intake and gastric cancer, assuming a time lag of approximately 15 years. Countries classified as very high Human Development Index (HDI) presented median PF in 2012 much lower than low-HDI countries for both fruits (3·0 v. 10·2%, P<0·001) and vegetables (6·0 v. 11·9%, P<0·001). For vegetables only, PF significantly decreased until 2025 in most settings; however, this corresponded to a reduction in the absolute number of preventable gastric cancer cases in less than half of the countries. Increasing fruit and vegetable intake would allow preventing a relatively high proportion of gastric cancer cases, mostly in developing countries. Although declines in PF are predicted in the near future, changes in order to achieve healthier lifestyles may be insufficient to overcome the load of demographic variation to further reduce the gastric cancer burden.

Background: It is expected that, by 2020, 15 million new cases of cancer will occur every year in the world, one million of them in Africa. Knowledge of cancer trends in African countries is far from adequate, and improvements in cancer prevention efforts are urgently needed. The aim of this study was to characterize breast cancer clinically and pathologically at presentation in Luanda, Angola; we additionally provide quality information that will be useful for breast cancer care planning in the country., Methods: Data on breast cancer cases were retrieved from the Angolan Institute of Cancer Control, from 2006 to 2014. For women diagnosed in 2009 (5-years of follow-up), demographic, clinical and pathological information, at presentation, was collected, namely age at diagnosis, parity, methods used for pathological diagnoses, tumor pathological characteristics, stage of disease and treatment. Descriptive statistics were performed., Results: The median age of women diagnosed with breast cancer in 2009 was 47 years old (range 25-89). The most frequent clinical presentation was breast swelling with axillary lymph nodes metastasis (44.9 %), followed by a mass larger than 5 cm (14.2 %) and lump (12.9 %). Invasive ductal carcinoma was the main histologic type (81.8 %). Only 10.1 % of cancer cases had a well differentiated histological grade. Cancers were diagnosed mostly at advanced stages (66.7 % in stage III and 11.1 % in stage IV)., Discussion: In this study, breast cancer was diagnosed at a very advanced stage. Although it reports data from a single cancer center in Luanda, Angola it reinforces the need for early diagnosis and increasing awareness. According to the main challenges related to breast cancer diagnosis and treatment herein presented, we propose a realistic framework that would allow for the implementation of a breast cancer care program, built under a strong network based on cooperation, teaching, audit, good practices and the organization of health services., Conclusion: Angola needs urgently a program for early diagnosis of breast cancer.

Objective: To evaluate the first 10 years of operation of the population-based breast cancer screening programme implemented in the Northern Region of Portugal, using selected recommended standard performance indicators., Methods: Data from women aged 50-69 screened with two-view mammography, biennially, in the period 2000-2009, were included. Main performance indicators were compared with the recommended levels of the European Guidelines., Results: A total of 202,039 screening examinations were performed, 71,731 (35.5%) in the initial screening and 130,308 (64.5%) in the subsequent screening. Coverage rate by examination reached 74.3% of the target population, in the last period evaluated. Recall rates were 8.1% and 2.4% and cancer detection rates were 4.4/1000 and 2.9/1000 respectively, for initial and subsequent screenings. The breast cancer detection rate, expressed as a multiple of the background expected incidence was 3.1 in initial screen and 2.2 in subsequent screen. The incidence of invasive interval cancers met the desirable recommended levels both the first and second years since last screening examination, in the initial and subsequent screenings. Invasive tumours <15mm were 50.4% and 53.8% of the invasive cancers detected in initial and subsequent screenings. Less favourable size, grading and biomarkers expression were found in interval cancers compared to screen-detected cancers., Conclusions: Breast cancer screening programme in the Northern Region of Portugal was well accepted by the population. Most of the performance indicators were consistent with the desirable levels of the European Guidelines, which indicate an effective screening programme. Future research should verify the consistency of some of these results by using updated information from a larger population., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The heterogeneous patterns and trends in tobacco consumption contribute to regional and gender differences in the burden of gastric cancer attributable to smoking., Aims: To estimate the proportion and absolute number of gastric cancer cases that can be attributed to smoking in different countries, in 2012 and 2020., Methods: Population attributable fractions (PAFs) were computed for 118 countries, using data of smoking prevalence in 2002 and 2011 and published estimates of the magnitude of the association between smoking and gastric cancer, assuming a time lag of ≈10 years., Results: For men, the highest PAF estimates in 2012 were observed in Eastern Asia and the lowest in North America, whereas for women the highest were in Western Europe and the lowest in Africa. Very high Human Development Index (HDI) countries presented the lowest median PAF in men (very high vs. high, medium, and low HDI: 17.2 vs. 20.8 %, p = 0.014) and the highest median PAF in women (very high vs. high, medium, and low HDI: 4.3 vs. 1.8 %, p < 0.001). Estimates for 2020 show a decrease in median PAFs, but the estimated absolute number of cases attributable to smoking in the countries analyzed increased for men (≈154,000 vs. ≈160,000) and decreased for women (≈6200 vs. ≈5600)., Conclusions: Smoking accounts for a larger number of gastric cancer cases among men, and gender differences are expected to increase in the next decade, despite the decrease in PAFs. Intensified efforts to control smoking are needed to further reduce the burden of gastric cancer.