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Precise oral dosing in rodents is usually achieved by intragastric gavage. If performed incorrectly due to technical difficulties, inexperience, or animal resistance, oral gavage may have animal welfare implications such as esophageal and gastric rupture and aspiration. The stress that is induced by this procedure can also lead to confounding results. In several animal models, drug vehicles must be sugar-free, deliver drugs in a specific formulation, and sometimes supply water. Gelatin has all of these properties. The current study aimed to evaluate the use of gelatin vehicles with different sensory features as an alternative to oral gavage. We investigated the time taken by 2 different inbred mouse strains, FVB/N and C57BL/6J, to ingest sugar-free gelatin pellets of varying flavors. Results showed that FVB/N mice took more time to eat the unflavored, strawberry and diet-flavored gelatin pellets than did C57BL/6J mice. Both strains showed low preference for lemon flavor, with the same ingestion times after the second day. This study showed that the C57BL/6J mice are more likely to eat gelatin than are FVB/N mice, and that the 2 strains of mice show a lower preference for lemon flavoring as compared with other flavors. This method of voluntarily oral administration offers an alternative to gavage for studies that use oral dosing studies.

The aim of this work was to study the prevalence of hypocalcemia in cancer patients based on ionized calcium and, as a secondary aim, the influence that hypocalcemia may have on survival. For this retrospective study, a representative sample of all the records of low and normal ionized calcium measured in 2014 was studied. Patients under 18 years and patients from the bone marrow transplantation service were excluded. The number of patients included in this study was 471. The median patient age was 63 years (18 to 91), and 247 (52%) were female. The most represented cancers were thyroid, colorectal, and breast. Ionized calcium was in the normal range in 331 (70%) patients and low in 140 (30%). In a univariable analysis, there were no significant differences in survival at 4 years between normal (47%) and low-level (42%) ionized calcium (p = 0.192), but there were differences in gender, age, the primary site, the number of metastatic sites, and the level of albumin. In the multivariable analysis, only the primary cancer, the number of metastatic sites, and the albumin levels were associated with survival. In a multivariable analysis excluding thyroid cancer, hypocalcemia remained not associated with survival. Hypocalcemia occurs in a variety of cancer types, and it does not have an influence on survival.

Background Breast cancer (BC) is largely prevalent worldwide. HER2-positive BC account for roughly 20–25% of all BC cases and has an overall survival lower than other BC. Innovation on BC therapeutics is a constant, but novel therapies have higher costs. Therefore, cost-effectiveness research is essential to provide healthcare decision-makers with solid foundations for a resource allocation. This study aims to estimate the average direct medical costs/patient and cost-effectiveness of adding pertuzumab in neoadjuvant treatment (NeoT) for HER2-positive breast cancer (BC). Methods Two retrospective real-world consecutive cohorts of ≥18yo female patients diagnosed with HER2-positive BC treated with NeoT at the Breast Clinic of IPO-Porto were studied. The AC-DH regimen (2012–2015) comprised 8 cycles of neoadjuvant therapy (4 cycles of doxorubicin + cyclosphosphamide followed by 4 cycles ofdocetaxel + trastuzumab), while the AC-DHP regimen (2015–2017) included also pertuzumab as NeoT. NeoT was followed by surgery and adjuvant trastuzumab. Micro-costing technique and a bottom-up approach was used comprising all medical direct costs from the hospital perspective. Unit costs were obtained from government official prices or from IPO-Porto costing system. Costs were adjusted to 2017 and are expressed in euros. Multivariable logistic regression models were used for effectiveness assessment, while generalized linear models with gamma distribution were used for costs. ICER was calculated using the pathological complete response (pCR) as the preferential measure of effectiveness. Sensitivity analysis was also performed. Results AC-DHP (n = 40) and AC-DH (n = 54) cohorts had heterogenous patient profiles (median age 43y/53y; 67.5%/59.3% positive HR; 60.0%/27.8% operable; 25.0%/24.1% inflammatory, respectively). The AC-DHP average total cost/patient was 56,375€, with pertuzumab accounting for 13,978€ (24.79%) and increasing in 15,982€ the average cost/patient (p, 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. Supplementary Information The online version contains supplementary material available at 10.1186/s13561-021-00332-0.

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.

Abdominal aortic aneurysms (AAAs) secondary to Coxiella burnetii infections are rare but carry important implications. The diagnosis is difficult due to unspecific symptoms. To the authors' knowledge, this is the first AAA caused by chronic Q fever treated with an endoprosthesis.

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. Electronic supplementary material The online version of this article (10.1007/s00405-020-06133-1) contains supplementary material, which is available to authorized users.

PurposeThe aim of this paper is to evaluate the use of blockchain for identity management (IdM) in the context of the Internet of things (IoT) while focusing on privacy-preserving approaches and its applications to healthcare scenarios.Design/methodology/approachThe paper describes the most relevant IdM systems focusing on privacy preserving with or without blockchain and evaluates them against ten selected features grouped into three categories: privacy, usability and IoT. Then, it is important to analyze whether blockchain should be used in all scenarios, according to the importance of each feature for different use cases.FindingsBased on analysis of existing systems, Sovrin is the IdM system that covers more features and is based on blockchain. For each of the evaluated use cases, Sovrin and UniquID were the chosen systems.Research limitations/implicationsThis paper opens new lines of research for IdM systems in IoT, including challenges related to device identity definition, privacy preserving and new security mechanisms.Originality/valueThis paper contributes to the ongoing research in IdM systems for IoT. The adequacy of blockchain is not only analyzed considering the technology; instead the authors analyze its application to real environments considering the required features for each use case.

Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern-Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0-14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (n = 6,014) were retrieved from 16 population-based SEE registries (1983-2015). Poisson regression and meta-analyses on birth season were performed in nine countries with available live birth data (n = 4,987). Subanalyses by birth month, age, gender and principal histology were also conducted. Children born during winter were at a slightly increased risk of developing a CNS tumor overall [incidence rate ratio (IRR): 1.06, 95% confidence intervals (CI): 0.99-1.14], and of embryonal histology specifically (IRR: 1.13, 95% CI: 1.01-1.27). The winter peak of embryonal tumors was higher among boys (IRR: 1.24, 95% CI: 1.05-1.46), especially during the first 4 years of life (IRR: 1.33, 95% CI: 1.03-1.71). In contrast, boys

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.

The ever-increasing demand for higher quality live streams is driving the need for better networking infrastructures, specially when disseminating content over highly congested areas, such as stadiums, concerts and museums. Traditional approaches to handle this type of scenario relies on a combination of cellular data, through 4G distributed antenna arrays (DAS), with a high count of WiFi (802.11) access points. This obvious requires a substantial upfront cost for equipment, planning and deployment. Recently, new efforts have been introduced to securely leverage the capabilities of wireless multipath, including WiFi multicast, 4G, and device-to-device communications. In order to solve these issues, we propose an approach that lessens the requirements imposed on the wireless infrastructures while potentially expanding wireless coverage through the crowd-sourcing of mobile devices. In order to achieve this, we propose a novel pervasive approach that combines secure distributed systems, WiFi multicast, erasure coding, source coding and opportunistic offloading that makes use of hyperlocal mobile edge clouds. We empirically show that our solution is able to offer a 11 fold reduction on the infrastructural WiFi bandwidth usage without having to modify any existing software or firmware stacks while ensuring stream integrity, authorization and authentication.

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.

Background Food 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. Objective This 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. Methods A 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). Results A 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. Conclusions The 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

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.

Breast cancer is a heterogeneous disease and additional biomarkers for individually predicting patient outcomes are needed. Aberrant membrane E-cadherin immunoexpression has been demonstrated in lobular breast cancer. Also, E-cadherin nuclear staining has been reported, associating with prognosis in various tumors. Here, we explore whether membrane or nuclear staining of E-cadherin has the potential to dictate prognosis of patients with lobular breast cancer. We selected a cohort of 285 consecutively diagnosed lobular breast cancer patients and performed immunohistochemistry for E-cadherin (clones 36, EP700Y, and NCH38) and P-cadherin (clone 56C1) in representative formalin-fixed paraffin-embedded blocks. All patients were female, HER2-negative and surgically treated in a single institution. Survival curves were computed by Kaplan-Meier analysis. Hazard ratios and respective 95% confidence intervals were estimated using Cox regression models. Statistical significance was set at p

Background Evaluation of nociceptive-antinociceptive balance during general anesthesia is still challenging and routinely based on clinical criteria. Analgesic drug delivered may be optimized with parasympathetic tone activity (PTA) monitor. This study compares ketorolac and ketorolac/tramadol balance analgesia using a PTA monitor. Methods Pain intensity response was assessed using a 0-100 numerical state scale (PTA) after nociceptive stimuli in pigs under stable sevoflurane anesthesia. Bispectral index, heart rate, noninvasive blood pressure, and respiratory parameters were also measured. Animals were divided into 3 groups: without analgesia, ketorolac, and ketorolac/tramadol. Mean values or mean areas under the curve (AUC) in selected time periods were compared over time and between groups through a mixed-model repeated measures analysis of variance and nonparametric Kruskal-Wallis tests, followed by Bonferroni or Dunn's multiple comparisons. Results It was observed a significant decrease in the PTA AUC mean value after application of the stimulus in animals treated without analgesia and only with ketorolac. The PTA AUC mean value in the control group was significantly lower than the corresponding mean in ketorolac group. The ketorolac/tramadol group showed the highest PTA AUC mean values, significantly different from those obtained for the other 2 groups, with no significant differences detected over time. Bispectral index means showed no statistically significant differences either over time periods or between different treatment groups. Heart rate showed only a statistically significant increase in AUC mean between without analgesia and ketorolac/tramadol group, in the time period after the stimulus application. Noninvasive blood pressure means showed no statistically significant differences over time and between treatment groups. Conclusions This study shows that a low dose combination of ketorolac and tramadol is sufficient to block the pain responses induced with a needle holder in pigs 20 minutes after its administration. The PTA monitor was able to clearly recognize the analgesic level between treatments and may be used to optimize analgesic drug delivered.

ResumoA artroplastia da anca é uma intervenção frequente e segura na cirurgia ortopédica. No entanto, a proximidade dessa articulação com vasos de grande calibre faz com que a ocorrência de lesão vascular maior seja uma complicação rara, mas grave e possivelmente letal, dessa técnica cirúrgica. As lesões vasculares agudas no contexto de uma artroplastia da anca têm etiologia e apresentação clínica variáveis e são mais frequentes em cirurgias de revisão e situações de migração medial intrapélvica e de infecção crônica de próteses da anca. No presente artigo, os autores apresentam um caso com complicação vascular maior aguda e tardia em contexto de revisão de prótese da anca. Trata-se de um paciente que desenvolveu uma laceração aguda da artéria ilíaca externa em contexto de migração acetabular intrapélvica crônica progressiva da prótese da anca associada a infecção crônica.

Despite all the potential of augmented reality to improve the human-computer interface (HCI) and the user experience, it's still below the expected usage. The reason may be related to the fact that until recently the AR implementation was mostly marker-based or GPS-based to trigger additional content (video, 3D, or other) to the reality identified with the camera. The research in this paper is focused on AR marker-less solutions that allows sharing AR content between users across the Cloud, based on the anchor identification. With this technological paradigm shift, the potential for use of new functional environments and an unprecedented status of HCI enrichment is achieved. In addition to the operations related to the applications functionality, the door opens for media-art artists to create AR models that can be shared in a multiple user environment across the Cloud.

Over the years, the potential toxicity of anesthetics has raised serious concerns about its safe use during pregnancy. As evidence emerged from research in animal models, showing that some anesthetic drugs are potential teratogenic, the determination of the risk of exposures to anesthetic drugs at early life stages became mandatory. However, due to inaccessibility and ethical constrains related to experimental conditions, the use of early life stages in mammalian models is limited. In this regard, some animal and nonanimal models have been suggested to surpass mammalian use in experimentation. Among them, the zebrafish embryo test has been recognized as a promising alternative in toxicology research, as well as an inexpensive and practical test. Substantial information collected from developmental research following compounds exposure, has contributed to the application of zebrafish assays in research, although only a few studies have focused on the use of early life stages of zebrafish to evaluate the developmental effects of anesthetics. Based on the recent advances of science and technology, there is a clear potential for zebrafish early life stages to provide new insights into anesthetics teratogenicity. This review provides an overview of recent anesthesia research using zebrafish embryos, demonstrating its usefulness to the anesthesia field, discussing the recent findings on various aspects related to the effects of anesthetics during early life development and the strengths and limitations of this model system. This work was supported by European Investment Funds by FEDER/ COMPETE/POCI– Operational Competitiveness and Internationalization Program, under Project POCI-01–0145-FEDER-006958, POCI-01–0145- FEDER-029542 and FCOMP-01–0124-FEDER-028683 and National Funds by FCT – Portuguese Foundation for Science and Technology, under the projects PTDC/CVT-WEL/4672/2012, PTDC/CVT-CVT/29542/2017 and UID/ AGR/04033/2019. This work was also supported by Fundação para a Ciência e a Tecnologia.

Objectives Gastric first primary cancers (FPCs) have an increased risk of developing second primary cancers (SPCs). However, their effect on mortality remains poorly understood. Thus, we aimed to estimate the contribution of SPCs to the mortality of gastric FPCs. Patients and methods A population-based cohort of gastric FPCs diagnosed in 2000-2006 was followed for SPCs (31 December 2012) and vital status (31 December 2017). SPCs (138 synchronous and 205 metachronous, ≤1 and >1 year after the FPC, respectively) were matched (1 : 3, by sex, 5-year age group, and year of FPC diagnosis) with those without an SPC and alive when the corresponding SPC was diagnosed. Results In synchronous SPCs, the hazard ratio (95% confidence interval) for death was 1.07 (0.81-1.40) in males and 0.86 (0.58-1.28) in females; the corresponding estimates for metachronous SPCs were 1.89 (1.49-2.41) and 2.08 (1.42-3.05). In synchronous SPCs, the 10-year cumulative mortality was similar to that of FPCs only; the estimates were higher in lung SPCs. The 10-year cumulative mortality was 75.5% in males and 65.5% in females with metachronous SPCs, which is more than 20% higher than for FPCs only. Conclusion Among patients with gastric FPCs who survive long enough for metachronous SPCs, the latter substantially increases mortality over 10 years, whereas the effect of synchronous SPCs is generally smaller.

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. Electronic supplementary material The online version of this article (10.1186/s12889-019-6579-6) contains supplementary material, which is available to authorized users.

There are many cryptographic protocols in the literature that are scientifically and mathematically sound. By extension, cryptography today seeks to respond to numerous properties of the communication process beyond confidentiality (secrecy), such as integrity, authenticity, and anonymity. In addition to the theoretical evidence, implementations must be equally secure. Due to the ever-increasing intrusion from governments and other groups, citizens are now seeking alternatives ways of communication that do not leak information. In this paper, we analyze multiparty computation (MPC), which is a sub-field of cryptography with the goal of creating methods for parties to jointly compute a function over their inputs while keeping those inputs private. This is a very useful method that can be used, for example, to carry out computations on anonymous data without having to leak that data. Thus, due to the importance of confidentiality in this type of technique, we analyze active and passive attacks using complexity measures (compression and entropy). We start by obtaining network traces and syscalls, then we analyze them using compression and entropy techniques. Finally, we cluster the traces and syscalls using standard clustering techniques. This approach does not need any deep specific knowledge of the implementations being analyzed. This paper presents a security analysis for four MPC frameworks, where three were identified as insecure. These insecure libraries leak information about the inputs provided by each party of the communication. Additionally, we have detected, through a careful analysis of its source code, that SPDZ-2’s secret sharing schema always produces the same results.

Summary Testicular germ cell tumors (TGCTs) are strikingly heterogeneous, reflecting a complex tumor model, posing serious challenges for pathologists. Accurate classification and staging, according to most recent systems, is fundamental. We aimed to revise a series of consecutively diagnosed TGCTs (2005–2016) in light of the new World Health Organization (WHO) classification and American Joint Committee on Cancer (AJCC) staging systems, discussing dilemmas imposed to pathologists. All 164 patients' clinical files/histological slides were reviewed. Follow-up was last updated on November 2017. Statistical analysis was performed with SPSS (v24). P 50%EC component, but not rete testis invasion, were associated with higher stage (P

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.

After the transition from fetal to neonatal life, the cardio-respiratory system needs to adapt to the extrauterine condition. Both the cardiac and respiratory systems display complex dynamics. This study aimed to investigate the relationship between cardiorespiratory coupling, heart rate variability (HRV), and respiration of neonatal with gestational age (GA). Several complexity measures have been developed to quantify the complexity of physiological signals. In this study, we applied sample entropy (SampEn) and the bzip2 compressor to the time series. The mutual information (MI) and the normalized compression distance (NCD) were used to quantify the complexity of the cardiorespiratory coupling. We analyzed a dataset composed of 30-minutes traces of RR intervals and respiration signals, acquired in the first two days of life, for 33 neonates with GA between 27 and 41 weeks. Of these 33 neonates, 22 babies were premature (

Kolmogorov complexity, or algorithmic information theory, measures information in an individual object as its smallest possible representation. These metrics have been applied in Computer Science and in several other scientific disciplines. It is known that this measure is not computable, however, we can approach it from above using standard compressors. In the scope of statistical or clustering methods, it is important to measure the absolute information distance between individual objects. The Normalized Information Distance (NID) measures the minimal amount of information needed to translate between two objects, however, it is uncomputable. There is a set of metrics used to approximate the NID, such as Normalized Compression Distance (NCD), Compression-Based Dissimilarity Measure (CDM) and Lempel–Ziv Jaccard Distance (LZJD). These methods, unlike other approaches, do not require any specific background knowledge of the dataset, that is, the user of this method only needs to have some knowledge about data mining techniques or data visualization. It is utmost important to improve current implementations in order to create a central, simply usable repository that supports multiple metrics, ensuring that a researcher can use some of the most important past work techniques to extract the most accurate information with the approach of NID. Current implementations are poorly document and lake the support to some enhancements already presented in past work literature. An example is the need to replace the compressed size with the percentage of compression in each of the files to achieve comparison with different file sizes.

Simple Summary Ensuring animal welfare is essential in protocols using laboratory animals. Applying a score sheet with 14 biological parameters, we assessed the welfare of 29 male Wistar rats used as models of colorectal carcinogenesis (CRC). We found a uniformity of characteristics preceding the premature animals’ death, including an increase of 10% in body weight, swollen abdomen, diarrhea, and priapism. In addition, we observed that surface abdominal temperature was higher in animals with CRC. We considered that the parameters already described in other cancer models are insufficient and considered assessing the abdominal temperature, priapism, and sudden increase in the body weight in the model of CRC. Abstract 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.

Background/Objective Temporary intravascular shunts are widely used in military surgery, representing a bridging until definitive vascular reconstruction. In civilian practice, shunts are mainly used as damage control and as a temporary measure until orthopaedic fixation. The objective of this report is to illustrate a new approach to the temporary restoration of perfusion during open management of extremity arterial injury. Methods The authors present a technique that uses sheaths introducers, instead of commercial or purpose-built shunts, which can be used through surgical or percutaneous approaches. Three clinical cases are presented where this technique was performed. Results/Conclusion: In the presented cases, this technique reduced time of shunt construction by avoiding artery surgical approach. This technique can facilitate the creation of an intravascular shunt among other than vascular surgeons.

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.

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.

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., What's new The coronavirus disease 2019 (COVID‐19) pandemic, owing to efforts to limit the spread of disease, greatly restricted routine healthcare services, including those relevant to cancer diagnosis and treatment. The present study investigated the impact of these restrictions on the care of patients at the Portuguese Oncology Institute of Porto, one of the largest cancer‐care hospitals in Portugal. Cancer registry data reveal increased overall short‐term mortality during the pandemic. After COVID‐19, cancers were more often diagnosed at more advanced stages and were more often symptomatic. The differing case‐mix of patients during the COVID‐19 pandemic, however, warrants cautious interpretation of results.

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.

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 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.

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., Lay abstract Hematopoietic stem cell transplant is a lifesaving treatment, involving collecting blood-forming cells from a healthy donor and infusing them into a patient. Donor immune cells may attack patient tissues causing severe complications, including death (graft-versus-host disease [GvHD]). Primary treatment for GvHD are steroids. Extracorporeal photopheresis (ECP) is an alternative treatment that induces immunological tolerance, in part, due to Treg. We studied both clinical response and circulating Treg in six patients treated with ECP for up to 8 years. ECP responding patients had less GvHD, reduced the dose of steroids and increased the number of Treg.

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.

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.

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(5), 65.2/10(5) in males, and 15.7/10(5) 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.

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&rsquo, 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&ndash, 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, 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 proliferation of electronic health (e-Health) initiatives in Brazil over the last 2 decades has resulted in a considerable fragmentation within health information technology (IT), with a strong political interference. The problem regarding this issue became twofold: 1) there are considerable flaws regarding interoperability and security involving patient data; and 2) it is difficult even for an experienced company to enter the Brazilian health IT market. In this article, the authors aim to assess the current state of IT interoperability and security in hospitals in Brazil and evaluate the best business strategy for an IT company to enter this difficult but very promising health IT market. A face-to-face questionnaire was conducted among 11 hospital units to assess their current status regarding IT interoperability and security aspects. Global Brazilian socio-economic data was also collected, and helped to not only identify areas of investment regarding health IT security and interoperability, but also to derive a business strategy, composed out of recommendations listed in the paper.

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%.

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.

Security and privacy concerns are challenging the way users interact with devices. The number of devices connected to a home or enterprise network increases every day. Nowadays, the security of information systems is relevant as user information is constantly being shared and moving in the cloud, however, there are still many problems such as, unsecured web interfaces, weak authentication, insecure networks, lack of encryption, among others, that make services insecure. The software implementations that are currently deployed in companies should have updates and control, as cybersecurity threats increasingly appearing over time. There is already some research towards solutions and methods to predict new attacks or classify variants of previous known attacks, such as (algorithmic) information theory. This survey combines all relevant applications of this topic (also known as Kolmogorov Complexity) in the security and privacy domains. The use of Kolmogorov-based approaches is resource-focused without the need for specific knowledge of the topic under analysis. We have defined a taxonomy with already existing work to classify their different application areas and open up new research questions.

BackgroundPostoperative 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.MethodsFrom 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.ResultsSixty 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.ConclusionPPCs 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.

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. 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., Research Center of Portuguese Oncology Institute of Porto (PI 74-CI-IPOP-19-2016). JL and CSG are supported by a PhD fellowship from FCT - Fundação para a Ciência e Tecnologia (SFRH/ BD/132751/2017 and SFRH/BD/92786/2013, respectively). SS is supported by a PhD fellowship IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027. BMC is funded by FCT-Fundação para a Ciência e a Tecnologia (IF/00601/2012)

Background Despite advances in the management of nephroblastoma (Wilms’ tumor, WT), the etiology of the tumor remains obscure. We aimed to compare nephroblastoma incidence rates and time trends among children (0–14 years) in 12 Southern and Eastern European (SEE) countries and the Surveillance, Epidemiology, and End Results Program (SEER), USA, in relation to the human development index (HDI). Methods In total 1776 WT cases were recorded in 13 SEE collaborating registries (circa 1990–2016), whereas data on 2260 cases (1990–2012) were extracted from the SEER database. Age-standardized incidence rates (AIRs) were calculated and correlated with HDI, whereas temporal trends were evaluated using Poisson regression and Joinpoint analyses. Results The overall SEE AIR (9.2/106) was marginally higher than that of the SEER (8.3/106), whereas significant differences were noted among the 13 SEE registries which comprised mainly Caucasian populations. A statistically significant temporal increase in incidence was noted only in Belarus. Most cases (∼75%) were diagnosed before the fifth year of life, with rates steadily declining thereafter; median age at diagnosis was similar in SEE countries and SEER. A slight male preponderance in the first year of life (male:female = 1.1) was followed by a female preponderance in the older age groups (male:female = 0.7). Lastly, a statistically significant positive association between higher HDI and increasing nephroblastoma incidence was noted (regression coefficient: +3.25, 95%CI: +1.35, +5.15). Conclusions Variations in incidence and time trends across the examined registries, changing male-to-female patterns with advancement in age, and positive associations with the HDI imply a plausible role for environmental and genetic factors in disease etiology, and these need to be explored further.

Tibiofemoral unilateral knee dislocations are uncommon, making bilateral dislocations even rarer injuries. Knee dislocation is considered one of the most serious injuries that can affect this joint. Associated complications such as popliteal artery injury are responsible for the important morbidity in these patients. The authors report the case of a 52-year-old man with a traumatic bilateral knee dislocation with associated bilateral popliteal arterial injury. His clinical presentation along with radiographic and angiographic findings are described. Surgical and non-surgical treatment and functional outcomes are also reported. info:eu-repo/semantics/publishedVersion

Aim To present incidence of central nervous system (CNS) tumours among adolescents and young adults (AYAs; 15–39 years) derived from registries of Southern and Eastern Europe (SEE) in comparison to the Surveillance, Epidemiology and End Results (SEER), US and explore changes due to etiological parameters or registration improvement via evaluating time trends. Methods Diagnoses of 11,438 incident malignant CNS tumours in AYAs (1990–2014) were retrieved from 14 collaborating SEE cancer registries and 13,573 from the publicly available SEER database (1990–2012). Age-adjusted incidence rates (AIRs) were calculated; Poisson and joinpoint regression analyses were performed for temporal trends. Results The overall AIR of malignant CNS tumours among AYAs was higher in SEE (28.1/million) compared to SEER (24.7/million). Astrocytomas comprised almost half of the cases in both regions, albeit the higher proportion of unspecified cases in SEE registries (30% versus 2.5% in SEER). Similar were the age and gender distributions across SEE and SEER with a male-to-female ratio of 1.3 and an overall increase of incidence by age. Increasing temporal trends in incidence were documented in four SEE registries (Greater Poland, Portugal North, Turkey-Izmir and Ukraine) versus an annual decrease in Croatia (−2.5%) and a rather stable rate in SEER (−0.3%). Conclusion This first report on descriptive epidemiology of AYAs malignant CNS tumours in the SEE area shows higher incidence rates as compared to the United States of America and variable temporal trends that may be linked to registration improvements. Hence, it emphasises the need for optimisation of cancer registration processes, as to enable the in-depth evaluation of the observed patterns by disease subtype.