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Introduction: This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Methods: Two consecutive retrospective cohorts (n = 94, 2012–2015 and 2015–2017) of adult women with HER2-positive breast cancer, receiving NeoT at the breast clinic in Portugal (IPO-Porto), were followed. All patients had surgery and received trastuzumab as adjuvant therapy. The 2012–2015 cohort received doxorubicin, cyclophosphamide, docetaxel plus trastuzumab, whereas the 2015–2017 cohort was treated with the same protocol plus pertuzumab. Results: The 2012–2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015–2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging (p = 0.001) and hormone receptor (p = 0.003) were significant predictors of pCR, but not treatment regimen (p = 0.304). Conclusion: Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.

BackgroundLow back pain (LBP) is a long-term health condition with distinct clinical courses. Its characterization together with the identification of prognostic factors for a persistent LBP course may trigger the development of personalized interventions. This study aimed to investigate the courses of chronic LBP (CLBP), its cumulative impact, and the indicators for the persistence of pain.Material and methodsPatients with active CLBP from the EpiDoC, a population-based cohort study of a randomly recruited sample of 10.661 adults with prolonged follow-up, were considered. Pain, disability, and health-related quality of life (HRQoL) were assessed at three time-points over five years. According to their pain symptoms over time, participants were classified as having a persistent (pain at the baseline and at all the subsequent time-points) or a relapsing pain course (pain at the baseline and no pain at least in one of the subsequent time-points). A mixed ANOVA was used to compare mean differences within and between patients of distinct courses. Prognostic indicators for the persistent LBP course were modulated through logistic regression.ResultsAmong the 1.201 adults with active CLBP at baseline, 634 (52.8%) completed the three time-points of data collection: 400 (63.1%) had a persistent and 234 (36.9%) a relapsing course. Statistically significant interactions were found between the group and time on disability (F (2,1258) = 23.779, pConclusionIn the long-term, patients with CLBP may follow a persistent or relapsing course of pain. Being female, presenting depressive symptoms, having a manual job and higher disability at baseline predicts a persistent course of LBP.

Chlorophylls play a crucial role in photosynthesis and are abundantly found in green fruits and vegetables that form an integral part of our diet. Although limited, existing studies suggest that these photosynthetic pigments and their derivatives possess therapeutic properties. These bioactive molecules exhibit a wide range of beneficial effects, including antioxidant, antimutagenic, antigenotoxic, anti-cancer, and anti-obesogenic activities. However, it is unfortunate that leafy materials and fruit peels often go to waste in the food supply chain, contributing to the prevailing issue of food waste in modern societies. Nevertheless, these overlooked materials contain valuable bioactive compounds, including chlorophylls, which offer significant health benefits. Consequently, exploring the potential of these discarded resources, such as utilizing them as functional food ingredients, aligns with the principles of a circular economy and presents exciting opportunities for exploitation.

Highlights i. The results obtained in the AC-DHP cohort, which included Pertuzumab as a NeoT, suggest better clinical outcomes compared to the AC-DH group, a confirmation based on real-world data. ii. Some patient profiles seem to be more promising concerning the overall costs for pathological complete response, but the present data does not include a long-term follow-up period, which suggests that interpretations should be performed with caution. iii. Pertuzumab cost estimated represented a great proportion of overall total costs per patient, but further research (including the costs of the whole episode of care) and continuously monitoring (additional RWE) is needed for a more robust cost-effectiveness analysis.

Objectives To estimate the prevalence of medical care-seeking among adults with low back pain (LBP) and to characterise and compare use of diagnostic procedures and medical management between primary and secondary care.Design Cross-sectional study.Setting Data from the EpiReumaPt, a nationwide population-based study conducted in Portugal including a representative sample of non-institutionalised adults (n=10 661) stratified by administrative territorial units was analysed.Participants Individuals who self-reported history of LBP within the previous 12 months (n=6434) and sought medical care for this problem in the same period (n=2618).Outcome measures Patients’ self-reported diagnostic workup and management procedures performed by medical care for LBP collected through a structured questionnaire. Medical care procedures were stratified by level of care.Results The prevalence of medical care-seeking for LBP was 38.0% (95% CI 35.9% to 40.1%). Primary care in isolation (45.3%) was the most sought level of care. Emergency departments (25.9%) and orthopaedics (19.4%) were the most sought secondary medical specialties. Several pathoanatomical diagnoses were used, supported by laboratory or imaging tests (91.1%). Disc herniation (20.4%) and osteoarthritis (19.7%) were the most frequent diagnoses, and X-ray (63.7%) was the most frequent diagnostic procedure self-reported by individuals. Most (75.1%) reported being treated for LBP: 80.4% with oral medication and 49.9% with injectables. The mean duration of pharmacological treatment was 104.24 (SD, 266.80) days. The use of pathoanatomical diagnoses, laboratory or imaging tests, and pharmacological treatments were generally more frequent for secondary care (p

Smart cities, leveraging IoT technologies, are revolutionizing the quality of life for citizens. However, the massive data generated in these cities also poses significant privacy risks, particularly in de-anonymization and re-identification. This survey focuses on the privacy concerns and commonly used techniques for data protection in smart cities, specifically addressing geolocation data and video surveillance. We categorize the attacks into linking, predictive and inference, and side-channel attacks. Furthermore, we examine the most widely employed de-identification and anonymization techniques, highlighting privacy-preserving techniques and anonymization tools; while these methods can reduce the privacy risks, they are not enough to address all the challenges. In addition, we argue that de-identification must involve properties such as unlikability, selective disclosure and self-sovereignty. This paper concludes by outlining future research challenges in achieving complete de-identification in smart cities.

Obesity, a rising concern in the Eastern world, encompasses several co-morbidities, namely non-alcoholic fatty liver disease (NAFLD). Potential natural-based interventions to decrease the burden of obesity complications are being investigated. Many of the edible parts of plants are not sold for consumption and end up as massive waste, losing nutritional potential. In fact, a sizeable amount of waste is generated within the different steps of the food supply chain, representing a massive loss of both plant material and natural resources. A good example is Brassica by-products (BBPs). The objective of this work was to investigate the effect of three different extracts from broccoli (Brassica oleracea var italica) by-products in an in vitro model of free fatty acid (FFA)-induced lipotoxicity using human hepatoma HepG2 cells. Broccoli leaf, stalk, and inflorescence extracts induced a dose-dependent decrease in the cell viability of HepG2 cells. However, the maximal non-lethal concentrations of leaves, stalks, and inflorescences (10 μg/mL) did not compromise mitochondrial function or neutral lipid accumulation in HepG2 cells. The extracts significantly decreased FFA-induced lipid accumulation in HepG2 cells either in a co-incubation or pre-incubation strategy. The broccoli extracts’ capacity to prevent the FFA-induced decrease in catalase activity in HepG2 may explain the observed effects.

For percutaneous endoscopic gastrostomy (PEG)-fed head and neck cancer (HNC) patients, risk markers of poor outcomes may identify those needing more intensive support. This retrospective study aimed to evaluate markers of poor outcomes using TNM-defined stages, initial anthropometry [body mass index (BMI), mid-upper arm circumference (MUAC), tricipital skinfold (TSF), mid-arm muscle circumference (MAMC)] and laboratory data (albumin, transferrin, cholesterol), with 138 patients, 42–94 years old, enrolled. The patients had cancer, most frequently in the larynx (n = 52), predominantly stage IV (n = 109). Stage IVc presented a four times greater death risk than stage I (OR 3.998). Most patients presented low parameters: low BMI (n = 76), MUAC (n = 114), TSF (n = 58), MAMC (n = 81), albumin (n = 47), transferrin (n = 93), and cholesterol (n = 53). In stages I, III, IVa, and IVb, MAMC and PEG-timing were major survival determinants. Each MAMC unit increase resulted in 16% death risk decrease. Additional 10 PEG-feeding days resulted in 1% mortality decrease. Comparing IVa/IVb vs. IVc, albumin and transferrin presented significant differences (p = 0.042; p = 0.008). All parameters decreased as severity of stages increased. HNC patients were malnourished before PEG, with advanced cancer stages, and poor outcomes. Initial MAMC, reflecting lean tissue, significantly increases survival time, highlighting the importance of preserving muscle mass. PEG duration correlated positively with increased survival, lowering death risk by 1% for every additional 10 PEG-feeding days, signaling the need for early gastrostomy.

Abstract 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.

Abstract 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 (MyIPOrisk-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 MyIPOrisk-score, 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 MyIPOrisk-score 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.

Objective: To compare the incidence rates of gastric cancer among cancer survivors with those in the general population, and estimate the probability of a gastric second primary cancer being diagnosed 10 years after any other first primary cancer. Method: A cohort of first primary cancers (other than gastric) diagnosed in Northern Portugal between 2000 and 2006 (n = 64,648) was followed until 31/12/2012 for gastric second primary cancers. Incidence rates, standardized incidence ratios and the cumulative incidence of gastric second primary cancers were calculated. Results: Overall, 330 patients developed gastric second primary cancers (21.2% within two months). The incidence rate of gastric second primary cancers was higher within two months of the first primary cancer (standardized incidence ratios: 5.20 in males and 7.89 in females), particularly among survivors of cancers of the oesophagus, colon and rectum, than in the remaining period (standardized incidence ratios: 0.64 in males and 0.74 in females). The 10-year risk of a gastric second primary cancer was 0.6% (males: 0.7%; females: 0.4%). Conclusion: The incidence rate of gastric second primary cancers among cancer survivors was higher than in the general population only soon after the first primary cancer, and lower thereafter. Despite the high mortality, the probability of a gastric second primary cancer within 10-years of the first primary cancer was 0.6%. Resumen: Objetivo: Comparar las tasas de incidencia de cáncer gástrico entre los sobrevivientes de cáncer con las de la población general y estimar la probabilidad de que se diagnostique un segundo cáncer primario gástrico 10 años después de cualquier otro primer cáncer primario. Método: Se siguió una cohorte de pacientes con un primer cáncer primario (excluyendo los gástricos) en el norte de Portugal entre 2000 y 2006 (n = 64.648) hasta el 31/12/2012 para identificar un segundo cáncer primario gástrico. Se calcularon las tasas de incidencia, las razones de incidencia estandarizadas (RIE) y la incidencia acumulada de segundos cánceres primarios gástricos. Resultados: En total, 330 pacientes desarrollaron un segundo cáncer primario gástrico (21,2% en 2 meses). La tasa de incidencia de los segundos cánceres primarios gástricos fue mayor dentro de los 2 meses posteriores al primero (RIE: 5,20 en hombres y 7,89 en mujeres), en particular entre los sobrevivientes de cáncer de esófago, colon y recto, que en el período restante (RIE: 0,64 en hombres y 0,74 en mujeres). El riesgo a 10 años de un segundo cáncer primario gástrico fue del 0,6% (hombres: 0,7%; mujeres: 0,4%). Conclusiones: La tasa de incidencia de segundos cánceres primarios gástricos entre los sobrevivientes de cáncer fue más alta que en la población general solo poco después del primer cáncer, y más baja a partir de entonces. A pesar de la alta mortalidad, la probabilidad de un segundo cáncer primario gástrico a 10 años del primero fue del 0,6%.

Abstract 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.

Abstract 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.

Abstract Background Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Methods Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. Results MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. Conclusions MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients’ monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.

Abstract Hip arthroplasty is a common and safe intervention in orthopedic surgery. However, the proximity of this joint to large vessels makes the occurrence of vascular injury a rare but serious and possibly lethal complication of this surgical technique. Acute vascular injuries in the context of a hip arthroplasty have variable etiologies and clinical presentations, and are more common in revision surgeries and in situations of medial intrapelvic migration and of chronic infection of the hip prosthesis. In the present article, the authors present a case of acute and late major vascular complication in the context of hip arthroplasty revision. The patient developed an acute laceration of the external iliac artery caused by chronic and progressive medial intrapelvic acetabular migration of the hip prosthesis associated with chronic infection.

The analysis of fetal heart rate variability has served as a scientific and diagnostic tool to quantify cardiac activity fluctuations, being good indicators of fetal well-being. Many mathematical analyses were proposed to evaluate fetal heart rate variability. We focused on non-linear analysis based on concepts of chaos, fractality, and complexity: entropies, compression, fractal analysis, and wavelets. These methods have been successfully applied in the signal processing phase and increase knowledge about cardiovascular dynamics in healthy and pathological fetuses. This review summarizes those methods and investigates how non-linear measures are related to each paper's research objectives. Of the 388 articles obtained in the PubMed/Medline database and of the 421 articles in the Web of Science database, 270 articles were included in the review after all exclusion criteria were applied. While approximate entropy is the most used method in classification papers, in signal processing, the most used non-linear method was Daubechies wavelets. The top five primary research objectives covered by the selected papers were detection of signal processing, hypoxia, maturation or gestational age, intrauterine growth restriction, and fetal distress. This review shows that non-linear indices can be used to assess numerous prenatal conditions. However, they are not yet applied in clinical practice due to some critical concerns. Some studies show that the combination of several linear and non-linear indices would be ideal for improving the analysis of the fetus's well-being. Future studies should narrow the research question so a meta-analysis could be performed, probing the indices' performance.

BackgroundFood insecurity is a global public health challenge, affecting predominately the most vulnerable people in society, including older adults. For this population, eHealth interventions represent an opportunity for promoting healthy lifestyle habits, thus mitigating the consequences of food insecurity. However, before their widespread dissemination, it is essential to evaluate the feasibility and acceptability of these interventions among end users. ObjectiveThis study aims to explore the feasibility and acceptability of a home-based eHealth intervention focused on improving dietary and physical activity through an interactive television (TV) app among older adults with food insecurity. MethodsA pilot noncontrolled quasi-experimental study was designed with baseline and 3-month follow-up assessments. Older adult participants with food insecurity were recruited from 17 primary health care centers in Portugal. A home-based intervention program using an interactive TV app aimed at promoting healthy lifestyle behaviors was implemented over 12 weeks. Primary outcomes were feasibility (self-reported use and interest in eHealth) and acceptability (affective attitude, burden, ethicality, perceived effectiveness, and self-efficacy), which were evaluated using a structured questionnaire with a 7-point Likert scale. Secondary outcomes were changes in food insecurity (Household Food Insecurity Scale), quality of life (European Quality of Life Questionnaire with five dimensions and three levels and Functional Assessment of Chronic Illness Therapy-Fatigue), physical function (Health Assessment Questionnaire, Elderly Mobility Scale, grip strength, and regularity of exercise), and nutritional status (adherence to the Mediterranean diet). ResultsA sample of 31 older adult individuals with food insecurity was enrolled in the 12-week intervention program with no dropouts. A total of 10 participants self-reported low use of the TV app. After the intervention, participants were significantly more interested in using eHealth to improve food insecurity (baseline median 1.0, IQR 3.0; 3-month median 5.0, IQR 5.0; P=.01) and for other purposes (baseline median 1.0, IQR 2.0; 3-month median 6.0, IQR 2.0; P=.03). High levels of acceptability were found both before and after (median range 7.0-7.0, IQR 2.0-0.0 and 5.0-7.0, IQR 2.0-2.0, respectively) the intervention, with no significant changes for most constructs. Clinically, there was a reduction of 40% in food insecurity (P=.001), decreased fatigue (mean −3.82, SD 8.27; P=.02), and improved physical function (Health Assessment Questionnaire: mean −0.22, SD 0.38; P=.01; Elderly Mobility Scale: mean −1.50, SD 1.08; P=.01; regularity of exercise: baseline 10/31, 32%; 3 months 18/31, 58%; P=.02). No differences were found for the European Quality of Life Questionnaire with five dimensions and three levels, grip strength, or adherence to the Mediterranean diet. ConclusionsThe home-based eHealth intervention was feasible and highly acceptable by participants, thus supporting a future full-scale trial. The intervention program not only reduced the proportion of older adults with food insecurity but also improved participants’ fatigue and physical function. International Registered Report Identifier (IRRID)RR2-10.2196/resprot.6626

Abstract Background Covalent RNA modifications, such as N-6-methyladenosine (m6A), have been associated with various biological processes, but their role in cancer remains largely unexplored. m6A dynamics depends on specific enzymes whose deregulation may also impact in tumorigenesis. Herein, we assessed the differential abundance of m6A, its writer VIRMA and its reader YTHDF3, in testicular germ cell tumors (TGCTs), looking for clinicopathological correlates. Methods In silico analysis of TCGA data disclosed altered expression of VIRMA (52%) and YTHDF3 (48%), prompting subsequent validation. Formalin-fixed paraffin-embedded tissues from 122 TGCTs (2005–2016) were selected. RNA extraction, cDNA synthesis and real-time qPCR (Taqman assays) for VIRMA and YTHDF3 were performed, as well as immunohistochemistry for VIRMA, YTHDF3 and m6A, for staining intensity assessment. Associations between categorical variables were assessed using Chi square and Fisher’s exact test. Distribution of continuous variables between groups was compared using the nonparametric Mann–Whitney and Kruskal–Wallis tests. Biomarker performance was assessed through receiver operating characteristics (ROC) curve construction and a cut-off was established by Youden’s index method. Statistical significance was set at p

Abstract Background Completing mortality data by information on possible socioeconomic inequalities in mortality is crucial for policy planning. The aim of this study was to build deprivation-specific life tables using the Portuguese version of the European Deprivation Index (EDI) as a measure of area-level socioeconomic deprivation, and to evaluate mortality trends between the periods 2000–2002 and 2010–2012. Methods Statistics Portugal provided the counts of deaths and population by sex, age group, calendar year and area of residence (parish). A socioeconomic deprivation level was assigned to each parish according to the quintile of their national EDI distribution. Death counts were modelled within the generalised linear model framework as a function of age, deprivation level and calendar period. Mortality Rate Ratios (MRR) were estimated to evaluate variations in mortality between deprivation groups and periods. Results Life expectancy at birth increased from 74.0 and 80.9 years in 2000–2002, for men and women, respectively, and to 77.6 and 83.8 years in 2010–2012. Yet, life expectancy at birth differed by deprivation, with, compared to least deprived population, a deficit of about 2 (men) and 1 (women) years among most deprived in the whole study period. The higher mortality experienced by most deprived groups at birth (in 2010–2012, mortality rate ratios of 1.74 and 1.29 in men and women, respectively) progressively disappeared with increasing age. Conclusions Persistent differences in mortality and life expectancy were observed according to ecological socioeconomic deprivation. These differences were larger among men and mostly marked at birth for both sexes.

Abstract Background Prostate cancer (PCa) is one of the most common cancers among men worldwide. Current screening methods for PCa display limited sensitivity and specificity, not stratifying for disease aggressiveness. Hence, development and validation of new molecular markers is needed. Aberrant gene promoter methylation is common in PCa and has shown promise as clinical biomarker. Herein, we assessed and compared the diagnostic and prognostic performance of two-gene panel promoter methylation in the same sample sets. Methods Promoter methylation of panel #1 (singleplex-miR-34b/c and miR-193b) and panel #2 (multiplex-APC, GSTP1, and RARβ2) was evaluated using MethyLight methodology in two different cohorts [prostate biopsy (#1) and urine sediment (#2)]. Biomarkers’ diagnostic (validity estimates) and prognostic (disease-specific survival, disease-free survival, and progression-free survival) performance was assessed. Results Promoter methylation levels of both panels showed the highest levels in PCa samples in both cohorts. In tissue samples, methylation panel #1 and panel #2 detected PCa with AUC of 0.9775 and 1.0, respectively, whereas in urine samples, panel #2 demonstrated superior performance although a combination of miR-34b/c, miR-193b, APC, and RARβ2 disclosed the best results (AUC = 0.9817). Furthermore, higher mir-34b/c and panel #2 methylation independently predicted for shorter DSS. Furthermore, time-dependent ROC curves showed that both miR-34b/c and GSTP1 methylation levels identify with impressive performance patients that relapse up to 15 years after diagnosis (AUC = 0.751 and AUC = 0.765, respectively). Conclusions We concluded that quantitative gene panel promoter methylation might be a clinically useful tool for PCa non-invasive detection and risk stratification for disease aggressiveness in both tissue biopsies and urines.

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.

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.

Introduction: We present the case of a superficial femoral artery ruptured aneurysm treated with an endoprothesis outside the “Instructions for Use”. Case report: 83 years old patient with sequential rupture of both superficial femoral arteries aneurysms. In the right limb the patient was submitted to conventional bypass surgery that resulted in an extended recovery period. An endovascular approach was the choice to treat the left ruptured superficial femoral artery aneurysm. The patient was submitted to aneurysm exclusion with two Endurant™II Medtronic® endoprothesis. At two-year follow-up the patient is asymptomatic and the aneurysm remains excluded with no endoleaks. Conclusions: Despite outside “Instructions for Use”, the use of an endoprothesis to treat SFA ruptured aneurysm presented as limb salvage procedure with excellent technical success and medium-term results.

Spontaneous and isolated dissection of external iliac artery is very rare. The natural course of this condition is not well established. The authors report a case of a 54 year old male, military, with ankylosing spondylitis presenting with limb claudication secondary to isolated dissection of external iliac artery. Dissection was successfully managed by percutaneous stent placement.

Introdução: A evolução na técnica de assepsia e antibioterapia profilática tem mantido a incidência de infeção de próteses vasculares (IPV) baixa. No entanto, uma proporção de doentes ainda se encontra suscetível a uma patologia que coloca em risco a função do enxerto e do órgão-alvo perfundido, enquanto ameaça com complicações sépticas a vida de cada um dos afetados. A abordagem das IPV depende da manifestação da infeção e do microrganismo em questão, da topografia da prótese infetada e do estado geral do doente. Desde explantação total da prótese até antibioterapia prolongada são várias as estratégias terapêuticas, cabendo ao cirurgião avaliar qual contribuirá para uma evolução natural mais favorável para o doente. Com este trabalho, os autores propõem-se a caracterizar clinicamente a população de doentes com IPV, no seu centro hospitalar. Métodos: Usando o sistema informático hospitalar, foram colhidas as cartas de alta relativas ao Serviço de Cirurgia Vascular, entre os anos 2000–2018, com as palavras-chave “infeção” e “prótese”. Foram excluídos todas as infeções não relacionadas, infeções de próteses para acessos de diálise e os doentes cujos processos não tinham informação relativamente ao procedimento de implantação do enxerto. Resultados: Foram incluídos 47 processos de doentes entre os 46 e 84 anos (média 69 anos), 89% do sexo masculino. Apenas 15% eram diabéticos e apenas 2 doentes se encontravam sob imunossupressão. Cerca de 51% das próteses infetadas foram de enxertos aorto-bifemorais e os restantes relativos a procedimentos periféricos. Na casuística verificada, 13 das próteses infetadas foram colocadas em regime de urgência. As infeções tardias (>4 meses) assumem a maioria dos casos (70%). Os agentes gram-positivos foram os agentes mais frequentemente observados (50% dos quais o MRSA). A apresentação mais comum foi o aparecimento de falsos aneurismas anastomóticos e apenas 25% das próteses infetadas se encontravam ocluídas. A antibioterapia mais usada foram combinações incluindo Vancomicina, com duração entre as 1 e as 12 semanas. Em 85% dos doentes foi removido o enxerto. Destes, 57% foram revascularizados. O follow up foi heterogéneo com uma média de 26,5 meses. Como outcome, de referir 20% dos doentes submetidos a amputação major, 18% com mortalidade atribuída a IPV e 29% com mortalidade global não relacionada. Discussão: As IPV continuam a ser uma patologia desafiante, não só pelas consequências sépticas ou da isquemia de órgão-alvo, mas também pelo enquadramento dos doentes que são afetados. A crescente prevalência de agentes multirresistentes numa população cada vez mais envelhecida gera a necessidade de abordar esta patologia de uma forma multidisciplinar. A incidência IPV envolvendo a Aorta, e a exigência técnica de uma cirurgia major com impacto hemodinâmico, particularmente em infeções por agentes de reduzida virulência, pode obrigar a adequar as estratégias terapêuticas em doentes que não sejam aptos para cirurgia. No entanto, um tratamento conservador geralmente está associado a recorrência da infeção ou a possíveis complicações de uma infeção latente. Conclusão: É necessária uma abordagem multidisciplinar, com diagnóstico sensível e precoce, e um equilíbrio entre o local e agressividade da infeção ao contexto clínico de cada doente de forma a otimizar os resultados.

Introdução e métodos: A abordagem das fístulas com origem na artéria aorta permanece um desafio em Cirurgia Vascular. O objetivo deste trabalho é rever os outcomes da intervenção cirúrgica em doentes com fístulas com origem na aorta torácica descendente e abdominal através da consulta dos processos clínicos durante um período de 16 anos num Departamento de Cirurgia Vascular. Resultados: Obtiveram-se um total de vinte e dois casos que correspondem a vinte doentes (dois doentes com fístulas primária e secundária consecutivas), com uma média de idades de 66,6 anos. Dezoito doentes eram do sexo masculino e 50% dos casos correspondem a fístulas primárias. A localização da fístula foi aorto-cava em cinco, aorto-duodenal em catorze, aorto-esofágica em três e aorto-jejunal em dois casos. As fístulas primárias abdominais estavam na sua maioria associadas a aneurisma da aorta abdominal. Relativamente às fístulas secundárias, a intervenção cirúrgica prévia foi bypass aorto-bi-femoral em quatro casos e enxertos aórticos em sete. O tempo entre a intervenção até ao diagnóstico de fístula variou entre 2 meses a 19 anos. A apresentação clínica mais comum foi hematemeses em 59% e melenas ou hematoquézias em 32%, com choque hipovolémico em 41% dos casos. Todos os casos foram submetidos a cirurgia convencional, com exceção dos três casos de fístula aorta-esofágica que foram corrigidos por cirurgia endovascular. A 3ª porção do duodeno foi o local mais comum da fístula aorto-entérica e foi necessária cirurgia intestinal em 72,7% dos casos. Nos doentes com fístulas secundárias, foi realizada exérese de prótese em oito casos e, posteriormente, cirurgia de revascularização dos membros inferiores em cinco. A complicação mais frequente no pós-operatório foi isquemia irreversível do membro inferior, com uma taxa de amputação major de 25%. Oito doentes necessitaram de intervenção cirúrgica posterior, nomeadamente trombectomia ou amputação major, exclusão com endoprótese de fístula persistente e cirurgia de Hartmann. A mortalidade foi de 50%, correspondente a quatro casos de fístulas primárias e a sete de secundárias. O tempo médio de internamento foi de 22,4 dias. A sobrevida dos doentes variou entre dois meses a dezasseis anos e entre as causas de mortalidade conhecidas estão fístula secundária após fístula primária da aorta, isquemia intestinal, persistência da fístula apesar de intervenção, pneumonia ou infeção protésica. Conclusão: As fístulas com origem na aorta são uma entidade com uma mortalidade cirúrgica elevada. Os resultados apresentados vão de encontro ao previamente publicado na literatura.

Pseudoaneurysms of the superficial temporal artery are uncommon but mainly result secondary to blunt or penetrating trauma of the frontotemporal region of the head. The authors report a clinical case of a young male with a false aneurysm of superficial temporal artery. Five weeks before he had a blunt trauma of the head. The authors did surgical resection via proximal and distal artery ligatio

Visceral artery aneurysms are rare, with an estimated incidence of less than 2% in the general population. Left gastric artery aneurysm are particularly uncommon, accounting for 4% of all visceral aneurysms. Usually an incidental finding, they can manifest with rupture and be life threatening. The authors present a case of an 83 year-old male with haemorrhagic shock caused by a ruptured left gastric artery aneurysm. Coil embolization of afferent and efferent arteries was performed with good morphologic results. Management of a ruptured visceral aneurysm is aimed at controlling life-threatening bleeding usually by embolisation in the emergency setting.

Introduction: Stroke is a major health problem. Overall, 10–15% of all strokes are related to a previous asymptomatic carotid stenosis >50%. Carotid endarterectomy (CEA) is e!ective in stroke prevention; risk/benefit assessment is less apparent for elderly. The authors evaluate department CEA outcomes in elderly population aged 75 years and older, focusing in perioperative outcomes and long term survival. Material and methods: Retrospective unicentric analysis was performed, encompassing 156 surgeries in 149 patients aged 75 years and older, between January 2010 and December 2017. Results: Perioperative stroke/mortality was 2.6% (4.0% for symptomatic, 0% for asymptomatic); perioperative morbidity was 6.4%; estimated "ve-year survival was 71.9%. Conclusion: CEA continues to be a low-risk approach to treat carotid bifurcation atherosclerosis, even in elderly population, with perioperative morbidity and mortality resembling international standards for general population. Long term survival is quite good and age alone should not be a reason to refrain from offering carotid endarterectomy to this patients.

Abstract Background Colorectal cancer (CRC) is one of the most incident cancers, associated with significant morbidity and mortality, and usually classified into three main molecular pathways: chromosomal instability, microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Currently, available screening methods are either costly or of limited specificity, impairing global implementation. More cost-effective strategies, including DNA methylation-based tests, might prove advantageous. Although some are already available, its performance is suboptimal, entailing the need for better candidate biomarkers. Herein, we tested whether combined use of APC, IGF2, MGMT, RASSF1A, and SEPT9 promoter methylation might accurately detect CRC irrespective of molecular subtype. Methods Selected genes were validated using formalin-fixed paraffin-embedded tissues from 214 CRC and 50 non-malignant colorectal mucosae (CRN). Promoter methylation levels were assessed using real-time quantitative methylation-specific PCR. MSI and CIMP status were determined. Molecular data were correlated with standard clinicopathological features. Diagnostic and prognostic performances were evaluated by receiver operator characteristics curve and survival analyses, respectively. Results Except for IGF2, promoter methylation levels were significantly higher in CRC compared to CRN. A three-gene panel (MGMT, RASSF1A, SEPT9) identified malignancy with 96.6% sensitivity, 74.0% specificity and 91.5 positive predictive value (area under the curve: 0.97), independently of tumor location, stage, and molecular pathway. Conclusions Combined promoter methylation analysis of MGMT/RASSF1A/SEPT9 displays a better performance than currently available epigenetic-based biomarkers for CRC, providing the basis for the development of a non-invasive assay to detect CRC irrespective of the molecular pathway.

The use of anesthetics has been suggested as a strategy to hamper live fish transport-induced stress. Still, there is insufficient data available on the use of alternative anesthetics to MS-222. This study investigated the use of propofol to mitigate stress in Nile tilapia (Oreochromis niloticus, 143.8 ± 20.9 g and 20.4 ± 0.9 cm) during a 6 h simulated transport. Individuals (n = 7) were divided into three groups: control, 40 mg L−1 MS-222, and 0.8 mg L−1 propofol. A naïve group non-transported was also considered. During the 6 h transport and 24 h after, the response to external stimuli, opercular movements, water quality parameters, behavior, blood hematology and other physiological values, the histopathology of the gills, the quality of the fillet, and oxidative-stress changes in gills, muscle, brain, and liver were evaluated. Propofol increased swimming activity of fish but decreased opercular movements and responses to external stimuli, indicating oscillations of the sedation depth. Water pH and glucose levels increased, while hematocrit (HCT) and lactate decreased in propofol groups at 6 h. At this time-point, MS-222 also induced a decrease in the HCT and lactate levels while increasing cortisol levels. Despite these effects, the stress-related behaviors lessened with anesthetics compared to the control group. After the recovery period, physiological responses normalized in animals from both anesthetic groups, but the control still had high cortisol levels. Overall, propofol is a good alternative for the transportation of this species, showing efficient sedation without compromising health or fillet quality. However, further pharmacodynamics and pharmacokinetics knowledge is required to support its use in aquaculture settings.

There is no generally accepted definition for conditional Tsallis entropy. The standard definition of (unconditional) Tsallis entropy depends on a parameter α that converges to the Shannon entropy as α approaches 1. In this paper, we describe three proposed definitions of conditional Tsallis entropy suggested in the literature—their properties are studied and their values, as a function of α, are compared. We also consider another natural proposal for conditional Tsallis entropy and compare it with the existing ones. Lastly, we present an online tool to compute the four conditional Tsallis entropies, given the probability distributions and the value of the parameter α.

Increasing detection of small renal masses by imaging techniques entails the need for accurate discrimination between benign and malignant renal cell tumors (RCTs) as well as among malignant RCTs, owing to differential risk of progression through metastization. Although histone methylation has been implicated in renal tumorigenesis, its potential as biomarker for renal cell carcinoma (RCC) progression remains largely unexplored. Thus, we aimed to characterize the differential expression of histone methyltransferases (HMTs) and histone demethylases (HDMs) in RCTs to assess their potential as metastasis biomarkers. We found that SETDB2 and RIOX2 (encoding for an HMT and an HDM, respectively) expression levels was significantly altered in RCTs; these genes were further selected for validation by quantitative RT-PCR in 160 RCTs. Moreover, SETDB2, RIOX2, and three genes encoding for enzymes involved in histone methylation (NO66, SETD3, and SMYD2), previously reported by our group, were quantified (RT-PCR) in an independent series of 62 clear cell renal cell carcinoma (ccRCC) to assess its potential role in ccRCC metastasis development. Additional validation was performed using TCGA dataset. SETDB2 and RIOX2 transcripts were overexpressed in RCTs compared to renal normal tissues (RNTs) and in oncocytomas vs. RCCs, with ccRCC and papillary renal cell carcinoma (pRCC) displaying the lowest levels. Low SETDB2 expression levels and higher stage independently predicted shorter disease-free survival. In our 62 ccRCC cohort, significantly higher RIOX2, but not SETDB2, expression levels were depicted in cases that developed metastasis during follow-up. These findings were not apparent in TCGA dataset. We concluded that SETDB2 and RIOX2 might be involved in renal tumorigenesis and RCC progression, especially in metastatic spread. Moreover, SETDB2 expression levels might independently discriminate among RCC subgroups with distinct outcome, whereas higher RIOX2 transcript levels might identify ccRCC cases with more propensity to endure metastatic dissemination.

The increasing pervasiveness of the Internet of Things is resulting in a steady increase of cyberattacks in all of its facets. One of the most predominant attack vectors is related to its identity management, as it grants the ability to impersonate and circumvent current trust mechanisms. Given that identity is paramount to every security mechanism, such as authentication and access control, any vulnerable identity management mechanism undermines any attempt to build secure systems. While digital certificates are one of the most prevalent ways to establish identity and perform authentication, their provision at scale remains open. This provisioning process is usually an arduous task that encompasses device configuration, including identity and key provisioning. Human configuration errors are often the source of many security and privacy issues, so this task should be semi-autonomous to minimize erroneous configurations during this process. In this paper, we propose an identity management (IdM) and authentication method called YubiAuthIoT. The overall provisioning has an average runtime of 1137.8 ms ±65.11+δ. We integrate this method with the FIWARE platform, as a way to provision and authenticate IoT devices.

The growing demand for everyday data insights drives the pursuit of more sophisticated infrastructures and artificial intelligence algorithms. When combined with the growing number of interconnected devices, this originates concerns about scalability and privacy. The main problem is that devices can detect the environment and generate large volumes of possibly identifiable data. Public cloud-based technologies have been proposed as a solution, due to their high availability and low entry costs. However, there are growing concerns regarding data privacy, especially with the introduction of the new General Data Protection Regulation, due to the inherent lack of control caused by using off-premise computational resources on which public cloud belongs. Users have no control over the data uploaded to such services as the cloud, which increases the uncontrolled distribution of information to third parties. This work aims to provide a modular approach that uses cloud-of-clouds to store persistent data and reduce upfront costs while allowing information to remain private and under users’ control. In addition to storage, this work also extends focus on usability modules that enable data sharing. Any user can securely share and analyze/compute the uploaded data using private computing without revealing private data. This private computation can be training machine learning (ML) models. To achieve this, we use a combination of state-of-the-art technologies, such as MultiParty Computation (MPC) and K-anonymization to produce a complete system with intrinsic privacy properties.

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.

Abstract Background Promoter methylation has emerged as a promising class of epigenetic biomarkers for diagnosis and prognosis of renal cell tumors (RCTs). Although differential gene promoter methylation patterns have been reported for the major subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma), validation of diagnostic performance in independent series have been seldom performed. Herein, we aimed at assessing the diagnostic performance of genes previously shown to be hypermethylated in RCTs in different clinical settings. Methods Promoter methylation levels of HOXA9 and OXR1 were assessed by quantitative methylation specific PCR. ROC curves were generated for OXR1, OXR1 combined with MST1R and HOXA9. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were computed, maximizing specificity. Methylation levels were also correlated with clinical and pathological relevant parameters. Results HOXA9 and OXR1 promoter methylation was disclosed in 73 and 87% of RCTs, respectively. A two-gene methylation panel comprising OXR1 and MST1R identified malignancy with 98% sensitivity and 100% specificity, and clear cell renal cell carcinoma with 90% sensitivity and 98% specificity. HOXA9 promoter methylation allowed for discrimination between oncocytoma and both papillary and chromophobe renal cell carcinoma but only with 77% sensitivity and 73% specificity. Significantly higher OXR1 promoter methylation levels (p = 0.005) were associated with high nuclear grade in ccRCC. Conclusions A panel including OXR1 and MST1R promoter methylation allows specific and sensitive identification of renal cell tumors, and, especially, of clear cell renal cell carcinoma. Moreover, higher OXR1 promoter methylation levels associate with clear cell renal cell carcinoma nuclear grade, a surrogate for tumor aggressiveness. Thus, gene promoter methylation analysis might a useful ancillary tool in diagnostic management of renal masses.

Prostate Cancer (PCa) overdiagnosis and overtreatment, as a consequence of the limited specificity of current detection and prognostication methods, remains a major challenge in clinical practice. Therefore, development and validation of new molecular biomarkers amenable of detecting clinically significant disease is crucial. MicroRNAs (miRNA) deregulation is common in cancer, constituting potential non-invasive biomarkers for PCa detection and prognostication. Herein, we evaluated the screening and prognostic biomarker potential of two onco-microRNAs (miR-182-5p and miR-375-3p) in liquid biopsies (plasma) of PCa patients with clinically localized disease undergoing curative-intent treatment. A first cohort of 98 PCa and 15 normal prostates were used to assess PCa-specificity of miR-182-5p in tissues. A cohort composed of PCa 252 patients and 52 asymptomatic controls allowed for assessment of diagnostic and prognostic value in plasmas. After RNA extraction from tissue and plasma samples, cDNA synthesis specific for miRNAs was performed followed by measurement of miR-182-5p and miR-375-3p relative expression by RT-qPCR, using U6 snRNA gene as reference. MiR-182-5p was significantly overexpressed in PCa tissues (p < 0.0001) and in plasma of PCa patients (p = 0.0020), compared to respective controls. Moreover, miR-182-5p expression identified PCa with AUC = 0.81 (95% CI: 0.725–0.892, p = 0.0001) in tissue and with 77% specificity and 99% NPV (AUC = 0.64, 95% CI: 0.561–0.709, p = 0.0021) in plasma. Both circulating miR-182-5p and miR-375-3p levels associated with more advanced pathologic stage and the former was significantly higher in patients that developed metastasis (p = 0.0145). Indeed, at the time of diagnosis, circulating miR-375-3p levels predicted which patients would develop metastasis, with almost 50% sensitivity, 76% specificity, and a NPV of 89% (AUC = 0.62, 95% CI: 0.529–0.713, p = 0.0149). We conclude that these two circulating miRNAs might be clinical useful as non-invasive biomarkers for detection and prediction of metastasis development at the diagnosis together with clinical variables used in routine practice.

Breast cancer (BrC) is the most frequent malignancy and the leading cause of cancer death among women worldwide. Approximately 70% of BrC are classified as luminal-like subtype, expressing the estrogen receptor. One of the most common and effective adjuvant therapies for this BrC subtype is endocrine therapy. However, its effectiveness is limited, with relapse occurring in up to 40% of patients. Because microRNAs have been associated with several mechanisms underlying endocrine resistance and sensitivity, they may serve as predictive and/or prognostic biomarkers in this setting. Hence, the main goal of this study was to investigate whether miRNAs deregulated in endocrine-resistant BrC may be clinically relevant as prognostic and predictive biomarkers in patients treated with adjuvant endocrine therapy. A global expression assay allowed for the identification of microRNAs differentially expressed between luminal BrC patients with or without recurrence after endocrine adjuvant therapy. Then, six microRNAs were chosen for validation using quantitative reverse transcription polymerase chain reaction in a larger set of tissue samples. Thus, miR-30c-5p, miR-30b-5p, miR-182-5p, and miR-200b-3p were found to be independent predictors of clinical benefit from endocrine therapy. Moreover, miR-182-5p and miR-200b-3p displayed independent prognostic value for disease recurrence in luminal BrC patients after endocrine therapy. Our results indicate that selected miRNAs’ panels may constitute clinically useful ancillary tools for management of luminal BrC patients. Nevertheless, additional validation, ideally in a multicentric setting, is required to confirm our findings.

INTRODUCTION: cancer is a growing concern in Mozambique. However, the country has limited facilities and few oncologists. Surgical oncologists are an unmet need. The aim of this study was to assess residents' knowledge in prevalent cancer domains and to identify and characterize prevalent cancers treated by surgery at Maputo Central Hospital, the largest hospital in Mozambique. The expectations were that the findings shall inform the development of a comprehensive curriculum in surgical oncology fellowship fit for the Hospital. METHODS: to identify and characterize prevalent cancers, we performed a retrospective analysis of individual cancer patient registries of Maputo Central Hospital (MCH), Mozambique. Information was recorded into data collection sheets and analyzed with SPSS 21. To assess MCH residents oncologic knowledge, we invited Twenty-six junior residents (49% of all residents) of different specialties to take a 30 item multiple choice written test used elsewhere in previous studies. The test focused on the domains of Basis of oncology, Radiotherapy, Pathology, Chemotherapy, Pain management, Surgical oncology and Clinical Pathway. The test was administered anonymously and without prior notice. We analyzed the overall test and topic performance of residents. RESULTS: the study covered a period of 3 years and 203 patients. The most prevalent malignant tumors treated by general and thoracic surgery in MCH cancer registry were esophageal (7%), female breast (6.5%) and colorectal cancer (2.8%). Globally these malignancies were diagnosed at an advanced stage of the disease and required a multimodal treatment. The mean percent correct score of residents was 37.3%. The dimension with the highest percent correct score were clinical management (46%) and surgical oncology (28%) showed the lowest correct score. CONCLUSION: in Maputo, Mozambique esophageal, breast and colorectal cancer were the most prevalent malignancies treated, with surgery, by thoracic or general surgery in MCH. The test scores suggest that, among residents, the knowledge in oncology needs to be improved, rendering support to the need of a surgical oncology training tailored to suit the local needs. Specific training should take into account local cancer prevalence, resources, their quality and the support of surgical oncology services with volume and experience.

Os aneurismas micóticos periféricos são complicações raras de endocardite infecciosa. Relata-se o caso de um homem de 49 anos com um aneurisma da artéria radial num contexto de endocardite infecciosa por Streptococcos bovis em período pós-operatório de substituição valvular aórtica mecânica por homoenxerto. Após confirmação diagnóstica por eco-Doppler, optou-se por ressecção do saco aneurismático com anastomose termino-terminal. Aos 2 anos de follow-up presenta-se assintomático, com pulso radial palpável e fluxo trifásico na arcada palmar e artéria cubital.

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 The Entropy Universe, 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.

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.

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 RAD51B (RAD51Bme) 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 RAD51Bme 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+). RAD51Bme levels were significantly associated with PD-L1 immunoexpression. Patients with PD-1 blockade clinical benefit disclosed higher RAD51Bme levels (p = 0.0390) and significantly lower risk of disease progression (HR 0.37; 95% CI: 0.15–0.88; p = 0.025). Combining RAD51Bme+ 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; p = 0.014). Thus, RAD51Bme 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 RAD51Bme should be confirmed in prospective studies.

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.

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 VIMme and miR663ame might accurately discriminate those two conditions, using a multiplex test. Performance of VIMme and miR663ame 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, VIMme-miR663ame 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, VIMme-miR663ame multiplex panel correctly detected 87% of the analysed cases, whereas cytology only forecasted 41%. Furthermore, high miR663ame 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, miR663ame analysis might provide relevant information for patient monitoring, identifying patients at higher risk for cancer progression.

In the last decades, the use of zebrafish (Danio rerio) in biomedical research has increased. Anaesthesia is daily used in fish during experimental procedures to avoid discomfort, stress or pain. Also, fish welfare and the reliability of results can be compromised if an unsuitable anaesthetic protocol is used. Therefore, we aimed to refine anaesthetic protocols to be used in adult zebrafish by evaluating the efficacy of different anaesthetics, used alone or in combination. For that, zebrafish were randomly assigned to 8 different groups: 100 μg/mLMS-222 (MS); 0.2 μg/mL etomidate (E); 0.2 μg/mL etomidate + 100 μg/mL lidocaine (E+L); 1.25 μg/mL propofol (P); 1.25 μg/mL propofol + 100 μg/mL lidocaine (P+L); 100 μg/mL ketamine (K); 100 μg/mL ketamine + 1.25 μg/mL medetomidine (K+M); and 100 μg/mL ketamine + 1.25 μg/mL medetomidine/3.125 μg/mL atipamezole (K+M/A). The animals were placed in an anaesthetic water bath, then, the following parameters were registered: time for equilibrium loss and anaesthesia induction, loss of sensitivity to soft and painful stimuli, respiratory rate, recovery time, and activity after recovery. The combined forms of E+L, P+L and K+M were the fastest to induce a surgical anaesthetic stage. Nevertheless, E+L induced respiratory depression, while K+M was shown to have the longer recovery time compared to MS-222, even when atipamezole was added. In conclusion, the P+L combination was shown to provide good anaesthesia with analgesia, without causing a major respiratory depression, providing as well a quick recovery, similar to MS-222.

Objective: Type 2 endoleak occurs in up to 30% of endovascular aneurysm repair (EVAR), but its long-term significance continues to be one of the most controversial topics. We reviewed our experience to evaluate late outcomes associated with type 2 endoleak. Methods: Between January 2008 to December 2014, 57 patients undergoing EVAR were enrolled in the presenting study. Computed tomography (angioCT) scan assessment was performed to evaluate aneurysm sac evolution. Primary end points included type 2 endoleak incidence, aneurysm sac growth, abdominal aortic aneurysm (AAA) related rupture and death. Secondary endpoints included conversion to open repair, reintervention rate, type 2 endoleak persistence and failure to shrinkage > 5mm and abdominal aortic aneurysm (AAA) rupture. Results: We identified 10 (17.5%) patients with type 2 endoleaks (6 early at the first follow-up CT scan). Median followup was 39.0 ± 31,6 months. Endoleaks persisted in 7 patients (12,2% of total patients; 70,0% of type 2 endoleaks) for >6 months. Overall survival rate was 100%, 98% and 80% at 1, 2 and 5 years. Spontaneous sealing occurred in 6/10 (60%): 3/3 (100.0%) transient type 2 endoleaks and 3/7 (43%) persistent type 2 endoleak. Transient type 2 endoleak (those that resolved

Introduction: Mortality rates after lower limb amputation are notoriously high and age is associated with increased mortality. The aim of this retrospective study was to determine mortality rates after a first major lower limb amputation in a cohort of patients older 80 years old. Methods: We performed an analysis of factors affecting early and late outcome after major lower limb amputation for peripheral vascular disease or diabetic complications at a tertiary referral vascular center between 2008 and 2015 in patients older than 80 years old. Results: 557 patients underwent a major amputation (54% female), of median age 86.3 ± 4.4 years and 20% had bilateral amputations during the study period. Median follow-up was 4.8 [0.8; 16.4] months. 30-day and 2-year mortality rates were 27% and 77%. Age adjusted 1-year mortality rate after trans-femoral amputation (TFA) was 68%, almost double that of trans-tibial amputation (TTA) (36%, p= .04). The rate of re-operation was substantially greater after TTA (36% vs 17%, p< .01). Survival and Cox regression analysis demonstrated that long-term mortality was associated with hospital re-admission (HR: 2.00, p

Os pseudoaneurismas da artéria temporal superficial são raros, sendo responsáveis por cerca de 1% de todos os pseudo aneurismas. Estão maioritariamente associados a traumatismos contusos ou penetrantes da região frontotemporal da cabeça. Relata-se o caso de um jovem de 18 anos com aparecimento de massa pulsátil na região frontotemporal após traumatismo contuso cinco semanas antes. Submetido a tratamento cirúrgico com laqueação dos topos arteriais e exérese do falso aneurisma.