Publications by authors named "Luís Antunes"

200 Publications

Small cell lung cancer treatment and survival in Portugal: A retrospective analysis from the I-O Optimise initiative.

Eur J Cancer Care (Engl) 2021 Jul 20:e13496. Epub 2021 Jul 20.

MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal.

Objective: We aim to describe treatment patterns and overall survival (OS) among a Portuguese cohort of patients with small cell lung cancer (SCLC).

Methods: This study utilised a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with SCLC at IPO-Porto between January 2012 and June 2017, with follow-up to December 2017, were included. Patients were stratified into subgroups with limited disease (LD) or extensive disease (ED). Treatment analyses were performed from 2015 onwards.

Results: Overall, 227 patients diagnosed with SCLC (37 LD; 190 ED) were analysed. Median OS (interquartile range [IQR]) was 15.0 months (3.8-39.3) for LD-SCLC and 5.0 months (1.7-10.3) for ED-SCLC. Among 19 patients diagnosed with LD-SCLC from 2015 onwards, 12 (63.2%) received initial treatment with systemic anticancer therapy (SACT) ± radiotherapy; 6 (31.6%) received best supportive care (BSC). Among 89 patients with ED-SCLC, 57 (68.5%) received SACT ± palliative radiotherapy; 28 (31.5%) received BSC. For patients receiving platinum doublet chemotherapy (±radiotherapy), median OS (IQR) was not reached for LD-SCLC and 5.4 months (2.3-10.9) for ED-SCLC.

Conclusion: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for patients diagnosed with SCLC, particularly those with ED, and highlights a need for more effective therapies.
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http://dx.doi.org/10.1111/ecc.13496DOI Listing
July 2021

The impact of the coronavirus disease 2019 pandemic on the diagnosis and treatment of cancer in Northern Portugal.

Eur J Cancer Prev 2021 Jul 8. Epub 2021 Jul 8.

EPIUnit, Instituto de Saúde Pública, Universidade do Porto, Rua das Taipas nº135 Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina da Universidade do Porto, Alameda Professor Hernâni Monteiro Grupo de Epidemiologia do Cancro, Centro de Investigação do Instituto Português de Oncologia do Porto, Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino de Almeida Serviço de Imagem, Instituto Português de Oncologia do Porto, Rua Dr. António Bernardino de Almeida Departamento de Estudos de Populações, Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, Porto, Portugal.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has affected the availability of healthcare resources, and adjustments to cancer care have been necessary considering the risk of morbidity by COVID-19 and of cancer progression. This study aims to quantify the impact of the COVID-19 pandemic on the care of patients with cancer by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019.

Methods: Cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, prostate, non-Hodgkin lymphoma, and leukemia from the Portuguese Oncology Institute of Porto, and diagnosed between 2 March and 1 July 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Those with the first treatment outside the Portuguese Oncology Institute of Porto were excluded. Sociodemographic, clinical and treatment characteristics were obtained from the cancer registry database and clinical files.

Results: The absolute number of new cancer cases decreased nearly 40% after the COVID-19 pandemic (from 1430 to 866). The largest decreases were observed for cervical (-74.3%) and prostate (-71.7%) cancers. Cases were more often diagnosed at more advanced stages in 2020 (P = 0.001), and the proportion of patients not starting any treatment until 1 July was just under 20% in 2019 and nearly 40% in 2020. The median times from symptoms onset, first medical exam and first appointment to diagnosis, and from diagnosis to first appointment, multidisciplinary tumor board meeting and first treatment were shorter after COVID-19.

Conclusions: There was a notable overall decrease in cancer diagnoses after COVID-19, with changes in the characteristics of incident cases.
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http://dx.doi.org/10.1097/CEJ.0000000000000686DOI Listing
July 2021

Treatment and outcomes for early non-small-cell lung cancer: a retrospective analysis of a Portuguese hospital database.

Lung Cancer Manag 2021 Feb 19;10(2):LMT46. Epub 2021 Feb 19.

MEDCIDS, Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal.

Aim: This observational study evaluated treatment patterns and survival for patients with stage I-IIIA non-small-cell lung cancer (NSCLC).

Materials & Methods: Adults newly diagnosed with NSCLC in 2012-2016 at IPO-Porto hospital were included. Treatment data were available for patients diagnosed in 2015-2016.

Results: 495 patients were included (median age: 67 years). The most common treatments were surgery alone or with another therapy (stage I: 66%) and systemic anticancer therapy plus radiotherapy (stage II: 54%; stage IIIA: 59%). One-year OS (95% CI) for patients with stage I, II and IIIA NSCLC (diagnosed 2012-2016) were 92% (88-96), 71% (62-82) and 69% (63-75), respectively; one-year OS (95% CI) for treated patients with stage I-II or stage IIIA NSCLC (diagnosed 2015-2016) were 89% (81-97) and 86% (75-98) for non-squamous cell and 76% (60-95) and 49% (34-70) for squamous cell NSCLC.

Conclusion: Treatment advances are strongly needed for stage I-IIIA NSCLC, especially for patients with squamous cell histology.
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http://dx.doi.org/10.2217/lmt-2020-0028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162184PMC
February 2021

Fundamental privacy rights in a pandemic state.

PLoS One 2021 2;16(6):e0252169. Epub 2021 Jun 2.

Department of Computer Science, Faculty of Sciences, University of Porto, Porto, Portugal.

Faced with the emergence of the Covid-19 pandemic, and to better understand and contain the disease's spread, health organisations increased the collaboration with other organisations sharing health data with data scientists and researchers. Data analysis assists such organisations in providing information that could help in decision-making processes. For this purpose, both national and regional health authorities provided health data for further processing and analysis. Shared data must comply with existing data protection and privacy regulations. Therefore, a robust de-identification procedure must be used, and a re-identification risk analysis should also be performed. De-identified data embodies state-of-the-art approaches in Data Protection by Design and Default because it requires the protection of direct and indirect identifiers (not just direct). This article highlights the importance of assessing re-identification risk before data disclosure by analysing a data set of individuals infected by Covid-19 that was made available for research purposes. We stress that it is highly important to make this data available for research purposes and that this process should be based on the state of the art methods in Data Protection by Design and by Default. Our main goal is to consider different re-identification risk analysis scenarios since the information on the intruder side is unknown. Our conclusions show that there is a risk of identity disclosure for all of the studied scenarios. For one, in particular, we proceed to an example of a re-identification attack. The outcome of such an attack reveals that it is possible to identify individuals with no much effort.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252169PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171945PMC
June 2021

Innominate artery post-traumatic pseudoaneurysm presenting with Horner's syndrome.

Interact Cardiovasc Thorac Surg 2021 May 24. Epub 2021 May 24.

Department of Angiology and Vascular Surgery, Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal.

Isolated innominate artery trauma after blunt thoracic contusion is rare and occurs mostly at its origin. We report a case of a post-traumatic distal innominate artery pseudoaneurysm presenting with Horner's syndrome treated by conventional surgical approach.
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http://dx.doi.org/10.1093/icvts/ivab156DOI Listing
May 2021

Bioactive small molecules produced by the human gut microbiome modulate sessile and planktonic lifestyles.

Gut Microbes 2021 Jan-Dec;13(1):1-19

Instituto Nacional de Ciência e Tecnologia de Inovação Em Doenças De Populações Negligenciadas, Centro De Desenvolvimento Tecnológico em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Humans live in symbiosis with a diverse community of microorganisms, which has evolved to carry out many specific tasks that benefit the host, including protection against invading pathogens. Within the chemical diversity of the gastrointestinal tract, small molecules likely constitute chemical cues for the communication between the microbiota and pathogens. Therefore, we sought to investigate if molecules produced by the human gut microbiota show biological activity against the human pathogen . To probe the effects of the gut metabolome on , we investigated its response to small-molecule extracts from human feces, from a complex bacterial community cultivated , and from culture supernatants of , and . Using RNA sequencing, we determined the impact of the human gut metabolome on global gene expression. Among the genes downregulated in the presence of the fecal extract, the most overrepresented functional category was cell motility, which accounted for 39% of repressed genes. Repression of motility by the fecal extract was confirmed phenotypically, and extracts reproduced this phenotype. A complex microbial community led to increased motility, as did extracts from , a species present in this community. Accordingly, mucin penetration was also repressed by fecal and extracts, suggesting that the phenotypes observed may have implications for host colonization. Together with previous studies, this work shows that small molecules from the gut metabolome may have a widespread, significant impact on microbe-microbe interactions established in the gut environment.
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http://dx.doi.org/10.1080/19490976.2021.1918993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143261PMC
May 2021

Refinement of Animal Model of Colorectal Carcinogenesis through the Definition of Novel Humane Endpoints.

Animals (Basel) 2021 Apr 1;11(4). Epub 2021 Apr 1.

Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal.

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid (EDTA)-saline solutions and two induced groups (CRC1 and CRC2) injected with 1,2-dimethylhydrazine (DMH) for seven weeks. A score sheet with 14 biological parameters was used to assess animal welfare. Groups CRC1 and CTRL1 and groups CRC2 and CTRL2 were euthanized 11 and 17 weeks after the first DMH administration, respectively. Five animals from the induced groups died unexpectedly during the protocol (survival rates of 75.0% and 66.7% for groups CRC1 and CRC2, respectively). The final mean body weight (BW) was smaller in the CRC groups when compared with that in the CTRL groups. A uniformity of characteristics preceding the premature animals' death was observed, namely an increase of 10% in mean BW, swollen abdomen, diarrhea, and priapism. The surface abdominal temperature of group CRC2 was significantly higher, when compared with that of group CTRL2. The parameters already described in other cancer models proved to be insufficient. For the CRC model, we considered assessing the abdominal temperature, priapism, and sudden increase in the BW.
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http://dx.doi.org/10.3390/ani11040985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066901PMC
April 2021

Phenological and productive characteristics of blackberry genotypes grown in an organic production system.

An Acad Bras Cienc 2021 16;93(1):e20181265. Epub 2021 Apr 16.

Programa de Pós-Graduação em Agronomia na Área de Fruticultura de Clima Temperado, Universidade Federal de Pelotas/UFPel, Faculdade de Agronomia Eliseu Maciel, Campus-UFPEL, Departamento de Fitotecnia, Av. Eliseu Maciel, s/n, Caixa Postal 354, 96010-900 Capão do Leão, RS, Brazil.

Blackberry is a species which has high potential to grow in an organic production system. However, there is scarce information on the behavior of cultivars and selections of this species conducted in an ecologically based system, a fact that makes it difficult to recommend cultivars for this production system. This study aimed to evaluate and characterize the phenology and productive aspects of six blackberry genotypes grown in an organic system, in Pelotas, Rio Grande do Sul (RS) state, Brazil. Evaluation of the following variables was carried out in the three first production cycles (2015-2016, 2016-2017 and 2017-2018): phenology, number of fruits.pl-¹, mean fruit yield.pl-¹, yield (kg.ha-¹), mean fruit mass (g) and soluble solid content (° Brix). Regarding phenology, genotype Black 112 was later than the others whereas Black 178 was the most precocious one. In the last year under evaluation, genotypes yielded around 10 ton.ha-¹, except Black 128 selection, which yielded approximately 6,767 ton.ha-¹. Genotypes Black 178, Black 112 and Black 145 and both cultivars BRS Xingu and Tupy exhibited potential to grow in an organic production system.
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http://dx.doi.org/10.1590/0001-3765202120181265DOI Listing
April 2021

The Entropy Universe.

Entropy (Basel) 2021 Feb 11;23(2). Epub 2021 Feb 11.

Centre for Health Technology and Services Research (CINTESIS), Faculty of Medicine University of Porto, 4200-450 Porto, Portugal.

About 160 years ago, the concept of entropy was introduced in thermodynamics by Rudolf Clausius. Since then, it has been continually extended, interpreted, and applied by researchers in many scientific fields, such as general physics, information theory, chaos theory, data mining, and mathematical linguistics. This paper presents , which aims to review the many variants of entropies applied to time-series. The purpose is to answer research questions such as: How did each entropy emerge? What is the mathematical definition of each variant of entropy? How are entropies related to each other? What are the most applied scientific fields for each entropy? We describe in-depth the relationship between the most applied entropies in time-series for different scientific fields, establishing bases for researchers to properly choose the variant of entropy most suitable for their data. The number of citations over the past sixteen years of each paper proposing a new entropy was also accessed. The Shannon/differential, the Tsallis, the sample, the permutation, and the approximate entropies were the most cited ones. Based on the ten research areas with the most significant number of records obtained in the Web of Science and Scopus, the areas in which the entropies are more applied are computer science, physics, mathematics, and engineering. The universe of entropies is growing each day, either due to the introducing new variants either due to novel applications. Knowing each entropy's strengths and of limitations is essential to ensure the proper improvement of this research field.
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http://dx.doi.org/10.3390/e23020222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916845PMC
February 2021

The impact of the COVID-19 pandemic on the short-term survival of patients with cancer in Northern Portugal.

Int J Cancer 2021 07 13;149(2):287-296. Epub 2021 Mar 13.

EPIUnit - Instituto de Saúde Pública, Universidade do Porto, Porto, Portugal.

The COVID-19 pandemic led to potential delays in diagnosis and treatment of cancer patients, which may negatively affect the prognosis of these patients. Our study aimed to quantify the impact of COVID-19 on the short-term survival of cancer patients by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. All cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, and prostate, from the Portuguese Oncology Institute of Porto (IPO-Porto) and diagnosed between 2 March and 1 July of 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Information regarding sociodemographic, clinical and treatment characteristics were collected from the cancer registry database and clinical files. Vital status was assessed to 31 October of the respective years. Cox proportional hazards regression was used to estimate crude and propensity score-adjusted hazards ratio (HR) and 95% confidence intervals (95% CIs) of death. During follow-up to 31 October, there were 154 (11.8%) deaths observed before COVID-19 and 131 (17.2%) after COVID-19, corresponding to crude and adjusted HRs (95% CI) of 1.51 (1.20-1.91) and 1.10 (0.86-1.40), respectively. Significantly higher adjusted hazards of death were observed for patients with Stage III cancer (HR = 2.37; 95% CI: 1.14-4.94) and those undergoing surgical treatment (HR = 3.97; 95% CI: 1.14-13.77) or receiving radiotherapy (HR = 1.96; 95% CI: 1.96-3.74), while patients who did not receive any treatment had a lower mortality hazards (HR = 0.62; 95% CI: 0.46-0.83). The higher overall short-term mortality observed during the COVID-19 pandemic largely reflects the effects of the epidemic on the case-mix of patients being diagnosed with cancer.
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http://dx.doi.org/10.1002/ijc.33532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014057PMC
July 2021

Malformations and mortality in zebrafish early stages associated with elevated caspase activity after 24 h exposure to MS-222.

Toxicol Appl Pharmacol 2021 02 25;412:115385. Epub 2020 Dec 25.

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Laboratory Animal Science, IBMC - Instituto de Biologia Molecular Celular, Universidade do Porto, Porto, Portugal; Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.

Tricaine methanesulfonate (MS-222) is a commonly used anaesthetic agent for immobilization of aquatic species. However, delayed development and malformations have been observed in 24 hpf (hours post-fertilization) zebrafish embryos after long-term immobilization. Still, no comprehensive study has been described regarding zebrafish exposure to MS-222 during the first hours of development, which are one of the most sensitive life stages to toxicants. Therefore, this research aimed to assess the toxicity of a 24 h exposure to MS-222 on zebrafish embryonic development. Based on the MS-222 LC, early blastula stage embryos (~2 hpf) were exposed to 0, 12.5, 25 and 50 mg L for 24 h and then allowed to develop up to 144 hpf. The chromatographic analysis showed that this anaesthetic agent bioaccumulates in 26 hpf zebrafish larvae in a concentration-dependent manner. In addition, increased mortalities and skeletal abnormalities were observed at 144 hpf, namely in the highest tested concentration. Yet, no craniofacial anomalies were observed either by alcian blue or calcein staining methods. Independently of the tested concentration, decreased speed and distance travelled were perceived in 144 hpf larvae. At the biochemical level, decreased in vivo reactive oxygen species (ROS) generation and apoptosis was observed. Additionally, catalase activity was increased at 26 hpf while results of mRNA expression showed a decreased gclc transcript content at the same time-point. Overall, data obtained highlight the toxicological risk of MS-222 and support ROS-mediated cell death signalling changes through the elevation of catalase activity as an adaptative or protective response.
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http://dx.doi.org/10.1016/j.taap.2020.115385DOI Listing
February 2021

Nonlinear Methods Most Applied to Heart-Rate Time Series: A Review.

Entropy (Basel) 2020 Mar 9;22(3). Epub 2020 Mar 9.

Centre for Health Technology and Services Research (CINTESIS), Faculty of Medicine University of Porto, 4200-450 Porto, Portugal.

The heart-rate dynamics are one of the most analyzed physiological interactions. Many mathematical methods were proposed to evaluate heart-rate variability. These methods have been successfully applied in research to expand knowledge concerning the cardiovascular dynamics in healthy as well as in pathological conditions. Notwithstanding, they are still far from clinical practice. In this paper, we aim to review the nonlinear methods most used to assess heart-rate dynamics. We focused on methods based on concepts of chaos, fractality, and complexity: Poincaré plot, recurrence plot analysis, fractal dimension (and the correlation dimension), detrended fluctuation analysis, Hurst exponent, Lyapunov exponent entropies (Shannon, conditional, approximate, sample entropy, and multiscale entropy), and symbolic dynamics. We present the description of the methods along with their most notable applications.
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http://dx.doi.org/10.3390/e22030309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516766PMC
March 2020

Clinical Significance of ARID1A and ANXA1 in HER-2 Positive Breast Cancer.

J Clin Med 2020 Dec 2;9(12). Epub 2020 Dec 2.

Cancer Biology & Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.

Background: trastuzumab is considered the standard of care for human epidermal growth factor receptor-2 (HER-2+) breast cancer patients. Regardless of the benefits of its use, many early-stage patients eventually recur, and usually, the disease progresses within a year. Since about half of the HER-2+ patients do not respond to trastuzumab, new biomarkers of prognosis and prediction are warranted to allow a better patient stratification. Annexin A1 (ANXA1) was previously reported to contribute to trastuzumab resistance through AKT activation. An association between adenine thymine-rich interactive domain 1A (ARID1A) loss and ANXA1 upregulation was also previously suggested by others.

Methods: in this study, we examined tissue samples from 215 HER-2+ breast cancer patients to investigate the value of ARID1A and ANXA1 protein levels in trastuzumab response prediction and patient outcome. Expression of ARID1A and ANXA1 were assessed by immunohistochemistry.

Results: contrary to what was expected, no inverse association was found between ARID1A and ANXA1 expression. HER-2+ (non-luminal) tumours displayed higher ANXA1 expression than luminal B-like (HER-2+) tumours. Concerning trastuzumab resistance, ARID1A and ANXA1 proteins did not demonstrate predictive value as biomarkers. Nevertheless, an association was depicted between ANXA1 expression and breast cancer mortality and relapse.

Conclusions: overall, our results suggest that ANXA1 may be a useful prognostic marker in HER-2+ patients. Additionally, its ability to discriminate between HER-2+ (non-luminal) and luminal B-like (HER-2+) patients might assist in patient stratification regarding treatment strategy.
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http://dx.doi.org/10.3390/jcm9123911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761245PMC
December 2020

Should we use extracorporeal photopheresis more often? Evidence from graft-versus-host disease patients monitored with Treg as a biomarker.

Future Sci OA 2020 Aug 10;6(8):FSO623. Epub 2020 Aug 10.

Center for Health Technology & Services Research (CINTESIS), Department of Community Medicine, Information & Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, 4200-319, Porto, Portugal.

Background: Chronic graft-versus-host disease (cGvHD) is a major complication after allogeneic hematopoietic cell transplantation. Extracorporeal photopheresis (ECP) is an immunotherapy treatment for cGvHD, although suitable response biomarkers are lacking.

Materials & Methods: We analyzed data from six cGvHD patients undergoing ECP at a reference center from 826 to 2866 days. Circulating Tregs were enumerated, patient's clinical evolution, immunosuppression dose and adverse events (AEs) registered.

Results: We observed an increase in Tregs, a decrease in immunosuppression dosage and symptoms improvement. Mild AEs occurred at a very low rate.

Conclusion: In these patients, the improvement of cGvHD, with low AEs, confirms a place for ECP as treatment. Improvements were accompanied by an increase in circulating Tregs, suggesting their role as a biomarker.
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http://dx.doi.org/10.2144/fsoa-2020-0107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491011PMC
August 2020

Differential expression of DNA methyltransferases and demethylases among the various testicular germ cell tumor subtypes.

Epigenomics 2020 09 22;12(18):1579-1592. Epub 2020 Sep 22.

Cancer Biology & Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

Characterize DNA methyltransferases/demethylases expression in testicular germ cell tumors (TGCTs). analysis of TCGA database, assessment of transcript levels of most relevant enzymes in four TGCT cell lines and validation in patient cohort (real-time quantitative polymerase chain reaction; immunohistochemistry). , and were the most differentially expressed between seminomas (SEs) and nonseminomas (NSs). was significantly overexpressed in NS-related cell lines, and the opposite was found for . Significantly higher mRNA expression was observed in NS, indicating a role for methylation in reprogramming. Significantly higher TET2 protein expression was observed in SEs, suggesting active demethylation contributes for SE hypomethylated state. More differentiated histologies disclosed distinct expression patterns. DNA-modifying enzymes are differentially expressed between TGCT subtypes, influencing reprogramming and differentiation.
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http://dx.doi.org/10.2217/epi-2020-0066DOI Listing
September 2020

Real-world treatment patterns and survival outcomes for advanced non-small cell lung cancer in the pre-immunotherapy era in Portugal: a retrospective analysis from the I-O Optimise initiative.

BMC Pulm Med 2020 Sep 10;20(1):240. Epub 2020 Sep 10.

MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal.

Background: As part of the multinational I-O Optimise research initiative, this retrospective cohort study of patients with advanced non-small cell lung cancer (NSCLC) evaluated real-world treatment patterns and survival prior to immunotherapy reimbursement in Portugal.

Methods: This study utilized a database held by IPO-Porto, Portugal's largest oncology hospital. Adult patients diagnosed with stage IIIB or IV NSCLC from January 2012 to December 2016 at IPO-Porto, with follow-up to June 2017, were included. Treatment analyses were performed from 2015 onwards. Kaplan-Meier methods were used for overall survival (OS). Factors associated with OS and systemic anti-cancer therapy (SACT) treatment were assessed using multivariate statistical models.

Results: Of 1524 patients diagnosed with NSCLC at IPO-Porto, 1008 patients had advanced disease (stage IIIB: 10.1%, 154/1524, stage IV: 56.0%, 854/1524). For those with advanced disease, median age was 65 years (range: 21-92) and 75.6% (762/1008) were male. Median OS (interquartile range [IQR]) was 11.4 (5.2-26.9) months for stage IIIB and 6.3 (2.4-15.0) months for stage IV. Factors associated with decreased risk of death included female sex and epidermal growth factor receptor gene (EGFR)/anaplastic lymphoma kinase gene (ALK) mutations/rearrangements; factors associated with increased risk of death included older age and stage IV disease. Among patients diagnosed in 2015 or 2016, 75.8% (297/392) received ≥1 line of SACT. Platinum-based chemotherapy was the most common first-line therapy (non-squamous cell carcinoma [NSQ]: 72.9%; squamous cell carcinoma [SQ] 87.3%, 55/63; patients with EGFR/ALK mutations/rearrangements primarily received tyrosine kinase inhibitors). The likelihood of receiving SACT was lower in older patients and those diagnosed with stage IV disease. Patients not receiving SACT had poor survival outcomes (median OS [IQR]: NSQ, 1.8 [1.1-3.1] months; SQ, 2.3 (1.3-3.4) months), while median OS (IQR) in SACT-treated patients was 12.6 (6.1-24.5) months for NSQ and 10.3 (5.7-15.9) months for SQ.

Conclusions: This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for advanced NSCLC in the pre-immunotherapy era, with nearly one-quarter of patients not receiving SACT. Even in patients receiving SACT, median survival was only about 1 year.
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http://dx.doi.org/10.1186/s12890-020-01270-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488009PMC
September 2020

Lung Cancer: A Nationwide Study to Characterize Sex Differences, Incidence, and Spatial Patterns in Portugal.

In Vivo 2020 Sep-Oct;34(5):2711-2719

NOVA National School of Public Health, Universidade NOVA de Lisboa, Lisbon, Portugal.

Background/aim: This study characterized lung cancer (LC) in Portugal, to capture sex differences, regional variation, and spatial distribution.

Patients And Methods: Variables: age, sex, vital status, region of residence, degree of urbanization, histologic types and stage at diagnosis. Spatial analyses conducted to identify high (HIC) and low incidence (LIC) clusters.

Results: In total, 11,642 cases were diagnosed (76.6% male, 23.4% female), with a similar mean age at diagnosis. There were 23,6% locally advanced and 58.4% metastatic disease cases, with 13.4% alive five years after diagnosis. Non-small-cell LC accounted for 77.3% of which 40.8% was adenocarcinoma and 22.7% was squamous cell carcinoma. Standardized incident rate (IR) was 37.5/10, 65.2/10 in males, and 15.7/10 in females, with four HIC (urban) clusters and four LIC (non-urban).

Conclusion: This study highlighted the sex differences in incidence, mortality, histology, and geographic distribution of LC in Portugal. Considering the advanced stages and the poor overall survival, understanding sex and geographic differences is important for public health interventions.
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http://dx.doi.org/10.21873/invivo.12092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652535PMC
May 2021

Is There an Impact of COVID-19 on Admission of Patients to the Emergency Department for Vascular Surgery?

Ann Vasc Surg 2020 Nov 11;69:100-104. Epub 2020 Aug 11.

Cirurgia Vascular, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Background: On March 2020, the World Health Organization declared the coronavirus disease 2019 outbreak a pandemic. During this period, surgical activity and admission to the Emergency Department (ED) decreased globally. The aim of this article is to understand how the admission of a patient to the ED for vascular surgery changed in our center in Portugal and if this situation prevented urgent surgical procedures.

Methods: Through a retrospective study, we compared the volume of patients admitted to the ED during the emergency state (ES) in Portugal with the same period in 2019. In addition, we analyzed the urgent surgical activity during the ES and in the correspondent period of the previous 10 years, regarding limb acute ischemia, acute aortic pathology, and vascular trauma. Two groups of patients were formed-patients operated during the ES and during the non-ES, for control. Statistical analysis was performed using IBM SPSS® Statistics, version 25.

Results: In the ES, 115 patients were observed at the ED and 179 in the 2019 corresponding period. During the ES, patients significantly recurred less to the ED directly from home (P < 0.001) and were less referred to the ED by primary care doctors (P < 0.001). Patients observed at the ED were significantly more urgent-required urgent surgery or were admitted to the department-than those in 2019 (40% vs. 24%). However, there were no differences when only considering urgent surgery (14% in ES vs. 10% in 2019). In the ES, 38% of patients observed at the ED were discharged with no follow-up related to vascular surgery against 60% in 2019, although this difference was not significant. Compared with the preceding 10 years, there are not significant differences in the number of patients who underwent urgent surgery in both ES and non-ES periods. In patients with acute limb ischemia, we did not find an increase in the time between onset of symptoms and ED admission, during the ES.

Conclusions: Fewer patients were admitted at the ED during the ES, and those admitted were significantly more urgent. We did not find a decrease in the number of urgent surgeries when compared with the preceding 10 years. Therefore, we cannot assume that coronavirus pandemic precluded urgent surgical procedures.
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http://dx.doi.org/10.1016/j.avsg.2020.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417287PMC
November 2020

Development of a preoperative risk score on admission in surgical intermediate care unit in gastrointestinal cancer surgery.

Perioper Med (Lond) 2020 6;9:23. Epub 2020 Aug 6.

Experimental Pathology and Therapeutics Group, Portuguese Oncology Institute of Porto FG, EPE (IPO-Porto), Porto, Portugal.

Background: Gastrointestinal cancer surgery continues to be a significant cause of postoperative complications and mortality in high-risk patients. It is crucial to identify these patients. Our study aimed to evaluate the accuracy of specific perioperative risk assessment tools to predict postoperative complications, identifying the most informative variables and combining them to test their prediction ability as a new score.

Methods: A prospective cohort study of digestive cancer surgical patients admitted to the surgical intermediate care unit of the Portuguese Oncology Institute of Porto, Portugal was conducted during the period January 2016 to April 2018. Demographic and medical information including sex, age, date from hospital admission, diagnosis, emergency or elective admission, and type of surgery, were collected. We analyzed and compared a set of measurements of surgical risk using the risk assessment instruments P-POSSUM Scoring, ACS NSQIP Surgical Risk Calculator, and ARISCAT Risk Score according to the outcomes classified by the Clavien-Dindo score. According to each risk score system, we studied the expected and observed post-operative complications. We performed a multivariable regression model retaining only the significant variables of these tools (age, gender, physiological P-Possum, and ACS NSQIP serious complication rate) and created a new score (). The predictive ability of each continuous score and the final panel obtained was evaluated using ROC curves and estimating the area under the curve (AUC).

Results: We studied 341 patients. Our results showed that the predictive accuracy and agreement of P-POSSUM Scoring, ACS NSQIP Surgical Risk Calculator, and ARISCAT Risk Score were limited. The , shows to have greater discrimination ability than the one obtained with the other risk tools when evaluated individually (AUC = 0.808; 95% CI: 0.755-0.862). The expected and observed complication rates were similar to the new risk tool as opposed to the other risk calculators.

Conclusions: The feasibility and usefulness of the have been demonstrated for the evaluation of patients undergoing digestive oncologic surgery. However, it requires further testing through a multicenter prospective study to validate the predictive accuracy of the proposed risk score.
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http://dx.doi.org/10.1186/s13741-020-00151-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409477PMC
August 2020

Characterization of a SPM-1 metallo-beta-lactamase-producing Pseudomonas aeruginosa by comparative genomics and phenotypic analysis.

Sci Rep 2020 08 6;10(1):13192. Epub 2020 Aug 6.

Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, 21040-360, Brazil.

Pseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of the bla[Formula: see text] gene, encoding a metallo-beta-lactamase, in combination with other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify key features of their physiology that may lead to the identification of new targets for therapy. Using both Illumina and PacBio sequencing data, we obtained a single contig representing the CCBH4851 genome with annotated features that were consistent with data reported for the species. However, comparative analysis with other Pseudomonas aeruginosa strains revealed genomic differences regarding virulence factors and regulatory proteins. In addition, we performed phenotypic assays that revealed CCBH4851 is impaired in bacterial motilities and biofilm formation. On the other hand, CCBH4851 genome contained acquired genomic islands that carry transcriptional factors, virulence and antimicrobial resistance-related genes. Presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations may also influence the multidrug-resistant behavior of CCBH4851. Overall, characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed the presence of features that strongly relates to the virulence and antibiotic resistance profile of this important infectious agent.
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http://dx.doi.org/10.1038/s41598-020-69944-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413544PMC
August 2020

Aortic Anastomotic Aneurysm After Infra Renal Grafting.

Rev Port Cir Cardiotorac Vasc 2020 Apr-Jun;27(2):145

Angiology and Vascular Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

An 87 year-old male presented with a 71mm proximal anastomotic aneurysm causing left renal artery displacement (Figures 1 and 2), 19 years after infra-renal aorto-aortic grafting for an infra-renal abdominal aortic aneurysm. Dilatation of visceral aorta was also observed. Management would be challenging but patient denied further intervention.
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October 2020

Designing a National Curriculum to Advance Surgical Oncology in Mozambique: A Delphi Consensus Study.

J Surg Educ 2021 Jan-Feb;78(1):140-147. Epub 2020 Jul 6.

Surgical Oncology Department, Portuguese Institute of Oncology, Porto, Portugal; Experimental Pathology and Therapeutics Research Group, Surgical Oncology Department, Portuguese Institute of Oncology, Porto, Portugal; ONCOCIR-Education and Care in Oncology-Lusophone Africa, Moreira da Maia, Portugal. Electronic address:

Objective: Mozambique is currently experiencing an increase in chronic diseases including cancer. There is a large unmet need for cancer surgery in Mozambique. The aim of this study was to define the content and the design of a training program for practicing surgeons in surgical oncology that would be consensually regarded as adequate to care for oncological patients requiring surgical interventions.

Design & Setting: A 3-round modified-Delphi approach was implemented to obtain consensus on surgical oncology training curriculum. The participants were purposefully selected experts in surgical oncology working in Mozambique. In round 1, participants answered a questionnaire with open-ended questions regarding the content of the curriculum and the timing and venue of training. In round 2, answers from the first round were presented to a purposeful selected sample of nationally recognized experts in oncology and surgical oncology, including members of the Mozambican College of Surgeons and leadership of the Ministry of Health. A final round was carried out to discuss the draft version of the training program aiming to achieve a predetermined consensus level of 80%.

Participants: Fifteen of 23 experts (65.2%) responded to round one.The response rate for round 1 and 3 was 80% (12 of the 15 participants in round one).

Results: The responses collected in the first round were analyzed and revealed that basic principles of oncology and basic principles of surgical oncology should be included in the curriculum of surgical residency in Mozambique (80% of the experts agree; Cronbach α = 0.93); a 24-months fellowship in surgical oncology should take place after residency in the surgical field (86.6% of experts agree; Cronbach α = 0.97); and should occur at Maputo Central Hospital and at comprehensive cancer centers abroad (100% agree). In round 2 the proposal for the program of surgical oncology fellowship obtained a strong agreement amongst the experts (97.3%). The final proposal for the program was divided into the following structure: (1) theoretical components; (2) duration; (3) location; (4) methodology; (5) technical skills in oncology; and (6) competency and paid particular attention to the oncological diseases prevalent in Mozambique. The agreement amongst the experts was 97.3%.

Conclusions: The experts reached a consensus regarding the general structure for a cancer surgery postgraduate training program in Mozambique, which should be a 24-months fellowship after residency in surgical disciplines. This fellowship should mostly take place in Mozambique, but it should also include dedicated internships in recognized cancer hospitals abroad. Such curricula embrace the Global Curriculum in Surgical Oncology including in particular the oncological nosology of Mozambique and should advance the quality of oncology surgical care provided in the country.
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http://dx.doi.org/10.1016/j.jsurg.2020.06.030DOI Listing
June 2021

MS-222 induces biochemical and transcriptional changes related to oxidative stress, cell proliferation and apoptosis in zebrafish embryos.

Comp Biochem Physiol C Toxicol Pharmacol 2020 Nov 23;237:108834. Epub 2020 Jun 23.

Instituto de Investigação e Inovação em Saúde (i3S), Laboratory Animal Science (LAS), Instituto de Biologia Molecular Celular (IBMC), Universidade of Porto (UP), Porto, Portugal.

MS-222, the most widely used anaesthetic in fish, has been shown to induce embryotoxic effects in zebrafish. However, the underlying molecular effects are still elusive. This study aimed to investigate the effects of MS-222 exposure during early developmental stages by evaluating biochemical and molecular changes. Embryos were exposed to 50, 100 or 150 mg L MS-222 for 20 min at one of three developmental stages (256-cell, 50% epiboly, or 1-4 somite stage) and oxidative-stress, cell proliferation and apoptosis-related parameters were determined at two time-points (8 and 26 hpf). Following exposure during the 256-cell stage, the biochemical redox balance was not affected. The genes associated with glutathione homeostasis (gstpi and gclc) were affected at 8 hpf, while genes associated with apoptosis (casp3a and casp6) and cellular proliferation (pcna) were found affected at 26 hpf. An inverted U-shaped response was observed at 8 hpf for catalase activity. After exposure at the 50% epiboly stage, the gclc gene associated with oxidative stress was found upregulated at 8 hpf, while gstpi was downregulated and casp6 was upregulated later on, coinciding with a decrease in glutathione peroxidase (GPx) activity and a non-monotonic elevation of protein carbonyls and casp3a. Additionally, MS-222 treated embryos showed a decrease in DCF-staining at 26 hpf. When exposure was performed at the 1-4 somite stage, a similar DCF-staining pattern was observed. The activity of GPx was also affected whereas RT-qPCR showed that caspase transcripts were dose-dependently increased (casp3a, casp6 and casp9). The pcna mRNA levels were also found to be upregulated while gclc was changed by MS-222. These results highlight the impact of MS-222 on zebrafish embryo development and its interference with the antioxidant, cell proliferation and cellular death systems by mechanisms still to be explained; however, the outcomes point to the Erk/Nrf2 signalling pathway as a target candidate.
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http://dx.doi.org/10.1016/j.cbpc.2020.108834DOI Listing
November 2020

Optimizing classical risk scores to predict complications in head and neck surgery: a new approach.

Eur Arch Otorhinolaryngol 2021 Jan 18;278(1):191-202. Epub 2020 Jun 18.

Surgical Intermediate Care Unit, Portuguese Institute of Oncology of Porto FG (IPO-Porto), Porto, Portugal.

Purpose: To validate tools to identify patients at risk for perioperative complications to implement prehabilitation programmes in head and neck surgery (H&N).

Methods: Retrospective cohort including 128 patients submitted to H&N, with postoperative Intermediate Care Unit admittance. The accuracy of the risk calculators ASA, P-POSSUM, ACS-NSQIP and ARISCAT to predict postoperative complications and mortality was assessed. A multivariable analysis was subsequently performed to create a new risk prediction model for serious postoperative complications in our institution.

Results: Our 30-day morbidity and mortality were 45.3% and 0.8%, respectively. The ACS-NSQIP failed to predict complications and had an acceptable discrimination ability for predicting death. The discrimination ability of ARISCAT for predicting respiratory complications was acceptable. ASA and P-POSSUM were poor predictors for mortality and morbidity. Our new prediction model included ACS-NSQIP and ARISCAT (area under the curve 0.750, 95% confidence intervals: 0.63-0.87).

Conclusion: Despite the insufficient value of these risk calculators when analysed individually, we designed a risk tool combining them which better predicts the risk of serious complications.
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http://dx.doi.org/10.1007/s00405-020-06133-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302498PMC
January 2021

Global priority pathogens: virulence, antimicrobial resistance and prospective treatment options.

Future Microbiol 2020 05 4;15:649-677. Epub 2020 Jun 4.

Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

, , , , , spp. and spp. are part of a group of pathogens that pose a major threat to human health due to the emergence of multidrug-resistant strains. Moreover, these bacteria have several virulence factors that allow them to successfully colonize their hosts, such as toxins and the ability to produce biofilms, resulting in an urgent need to develop new strategies to fight these pathogens. In this review, we compile the most up-to-date information on the epidemiology, virulence and resistance of these clinically important microorganisms. Additionally, we address new therapeutic alternatives, with a focus on molecules with antivirulence activity, which are considered promising to combat multidrug-resistant bacteria.
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http://dx.doi.org/10.2217/fmb-2019-0333DOI Listing
May 2020

Levels as a Potential Predictive Biomarker for PD-1 Blockade Response in Non-Small Cell Lung Cancer.

J Clin Med 2020 Apr 2;9(4). Epub 2020 Apr 2.

Cancer Biology and Epigenetics Group, IPO Porto Research Center (GEBC CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.

Lung cancer (LC) cells frequently express high levels of programmed death-ligand 1 (PD-L1). Although these levels grossly correlate with the likelihood of response to specific checkpoint inhibitors, the response prediction is rather imperfect, and more accurate predictive biomarkers are mandatory. We examined the methylation profile of () as a candidate predictive biomarker for anti-PD-1 therapy efficacy in non-small cell lung cancer (NSCLC), correlating with patients' outcome. PD-L1 immunoexpression and levels were analysed in NSCLC samples obtained from patients not treated with anti-PD-1 (Untreated Cohort (#1)) and patients treated with PD-1 blockade (Treated Cohort (#2)). Of a total of 127 patients assessed, 58.3% depicted PD-L1 positivity (PD-L1). levels were significantly associated with PD-L1 immunoexpression. Patients with PD-1 blockade clinical benefit disclosed higher levels ( = 0.0390) and significantly lower risk of disease progression (HR 0.37; 95% CI: 0.15-0.88; = 0.025). Combining with PD-L1 improved the sensitivity of the test to predict immunotherapy response. PD-L1 was also associated with lower risk of death (HR 0.35; 95% CI: 0.15-0.81; = 0.014). Thus, levels might be combined with validated predictive biomarker PD-L1 immunostaining to select patients who will most likely experience clinical benefit from PD-1 blockade. The predictive value of should be confirmed in prospective studies.
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http://dx.doi.org/10.3390/jcm9041000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230458PMC
April 2020

New Oral Anticoagulants (NOACs) are The Gold Standard Invenous Thromboembolism.

Authors:
Luís F Antunes

Rev Port Cir Cardiotorac Vasc 2020 Jan-Mar;27(1):33-37

Serviço de Angiologia e Cirurgia Vascular, Centro Hospitalar e Universitário de Coimbra Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.

Introduction: Venous Thromboembolism (VTE) is an important cause of morbidity and mortality. The risk of recur- rence could be very high without thromboprophylaxis. New oral anticoagulants (NOACs or DOACs) represent a new step in anticoagulation.

Material And Methods: We searched for papers with trials, systematic reviews and meta-analysis involving NOACs in the treatment and secondary prevention of VTE. We also searched for guidelines of two medical societies (American College of Chest Physicians and International Society of Thrombosis and Haemostasis - ISTH).

Results: Six RCT (randomized controlled trial) comparing NOACs with Warfarin shew a non-inferiority in relation with recurrent VTE and major bleeding. Two RCT (SELECT-D and Hokusay cancer) and one meta-analysis shew low recurrence rate of VTE in cancer patients and higher rate of bleeding, mainly in gastrointestinal and genitourinary cancers. There are two RCTs involving NOACs in treatment of patients with Antiphospholipid Syndrome (APS).

Discussion: NOACs shew non-inferiority over AVK. Guidelines of CHEST 2016 recommend NOACs for VTE treatment in no cancer patients, and Low Molecular Weight Heparin (LMWH) for cancer patients. ISTH suggest NOACs as the first option in VTE cancer patients with low risk of bleeding. A recent RCT shews no benefit and increased risk of vascular events in APS patients treated with NOACs. NOACs are the gold standard for VTE treatment and secondary prevention in no cancer patients. They could be the first option in cancer patients with low risk of bleeding.
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October 2020

A Multiplex Test Assessing and in Urine Accurately Discriminates Bladder Cancer from Inflammatory Conditions.

J Clin Med 2020 Feb 24;9(2). Epub 2020 Feb 24.

Cancer Biology and Epigenetics Group-Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), and Porto Comprehensive Cancer Center (P.CCC), Maimonides Biomedical Research Institute of Cordoba, 14004 Cordoba, Spain.

Bladder cancer (BlCa) is a common malignancy with significant morbidity and mortality. Current diagnostic methods are invasive and costly, showing the need for newer biomarkers. Although several epigenetic-based biomarkers have been proposed, their ability to discriminate BlCa from common benign conditions of the urinary tract, especially inflammatory diseases, has not been adequately explored. Herein, we sought to determine whether VIM and miR663a might accurately discriminate those two conditions, using a multiplex test. Performance of VIM and miR663a in tissue samples and urines in testing set confirmed previous results (96.3% sensitivity, 88.2% specificity, area under de curve (AUC) 0.98 and 92.6% sensitivity, 75% specificity, AUC 0.83, respectively). In the validation sets, VIM-miR663a multiplex test in urine discriminated BlCa patients from healthy donors or patients with inflammatory conditions, with 87% sensitivity, 86% specificity and 80% sensitivity, 75% specificity, respectively. Furthermore, positive likelihood ratio (LR) of 2.41 and negative LR of 0.21 were also disclosed. Compared to urinary cytology, VIM-miR663a multiplex panel correctly detected 87% of the analysed cases, whereas cytology only forecasted 41%. Furthermore, high miR663a independently predicted worse clinical outcome, especially in patients with invasive BlCa. We concluded that the implementation of this panel might better stratify patients for confirmatory, invasive examinations, ultimately improving the cost-effectiveness of BlCa diagnosis and management. Moreover, miR663a analysis might provide relevant information for patient monitoring, identifying patients at higher risk for cancer progression.
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http://dx.doi.org/10.3390/jcm9020605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073678PMC
February 2020

Digital imaging-assisted quantification of H3K27me3 immunoexpression in luminal A/B-like, HER2-negative, invasive breast cancer predicts patient survival and risk of recurrence.

Mol Med 2020 02 12;26(1):22. Epub 2020 Feb 12.

Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Institute of Oncology of Porto (IPO Porto), Research Center-LAB 3, F Bdg., 1st floor, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

Background: Breast cancer (BC) is a major health concern and better understanding of its biology might improve treatment decisions and patient outcomes. Histone3 Lysine27 tri-methylation (H3K27me3) is a post-translational histone modification frequently associated with altered gene expression. In BC patients, lower H3K27me3 expression has been associated with worse prognosis. We assessed H3K27me3 immunoexpression with digital imaging software assistance, in a cohort of luminal-like BC patients with long-term follow-up time and evaluated its association with clinically relevant endpoints and its clinical usefulness.

Methods: H3K27me3 immunoexpression was assessed, by means of digital-imaging system, in archival tissue samples of 160 luminal A/B-like HER2-negative invasive BC, stages I-III. Survival analysis was performed using Kaplan-Meier and Cox regression. Cases were categorized as 'low' or 'high' expression based on cut-off defined by receiver operating characteristic (ROC) curve analysis.

Results: The patient cohort showed a median age of 61-years, with a median follow-up time of 11.7 years. Low H3K27me3 expression (below 85% cut-off) was significantly associated with recurrence, both in univariable (HR = 1.99, 95%CI 1.066-3.724) and multivariable analysis when adjusting for grade and age (HR = 1.89, 95%CI 1.004-3.559). A trend for higher risk of death in low H3K27me3 expression BC was observed (p = 0.069), reaching statistical significance in younger patients (p = 0.021).

Conclusions: H3K27me3 immunoexpression assessed by digital imaging scoring software is an independent prognosis biomarker in luminal-like BC patients and may assist in more individualized adjuvant treatment decisions, thus potentially reducing recurrences after curative-intent treatment, while sparing unnecessary toxicity.
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http://dx.doi.org/10.1186/s10020-020-0147-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017542PMC
February 2020