Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses.

Mucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. To be effective and stimulate an anti-MUC1 response, artificial antigens must mimic the conformational dynamics of natural antigens in solution and have an equivalent or higher binding affinity to anti-MUC1 antibodies than their natural counterparts. As a proof of concept, we have developed a glycopeptide that contains noncanonical amino acid (2S,3R)-3-hydroxynorvaline. The unnatural antigen fulfills these two properties and effectively mimics the threonine-derived antigen. On the one hand, conformational analysis in water shows that this surrogate explores a landscape similar to that of the natural variant. On the other hand, the presence of an additional methylene group in the side chain of this analog compared to the threonine residue enhances a CH/π interaction in the antigen/antibody complex. Despite an enthalpy-entropy balance, this synthetic glycopeptide has a binding affinity slightly higher than that of its natural counterpart. When conjugated with gold nanoparticles, the vaccine candidate stimulates the formation of specific anti-MUC1 IgG antibodies in mice and shows efficacy comparable to that of the natural derivative. The antibodies also exhibit cross-reactivity to selectively target, for example, human breast cancer cells. This investigation relied on numerous analytical (e.g., NMR spectroscopy and X-ray crystallography) and biophysical techniques and molecular dynamics simulations to characterize the antigen-antibody interactions. This workflow streamlines the synthetic process, saves time, and reduces the need for extensive, animal-intensive immunization procedures. These advances underscore the promise of structure-based rational design in the advance of cancer vaccine development.

Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) is a UDP-dependent galactosyltransferase.

Glycosyltransferases (GTs) are enzymes that catalyze the formation of glycosidic bonds and hundreds of GTs have been identified so far in humans. Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) has been associated with central nervous system diseases and cancer. However, evidence on its enzymatic properties, including its substrates, has been scarcely described. In this paper, we have produced and purified recombinant secretory GLT8D1. The enzyme was found to be N-glycosylated. Differential scanning fluorimetry was employed to analyze the stabilization of GLT8D1 by Mn2+ and nucleotides, revealing UDP as the most stabilizing nucleotide scaffold. GLT8D1 displayed glycosyltransferase activity from UDP-galactose onto N-acetylgalactosamine but with a low efficiency. Modeling of the structure revealed similarities with other GT-A fold enzymes in CAZy family GT8 and glycosyltransferases in other families with galactosyl-, glucosyl-, and xylosyltransferase activities, each with retaining catalytic mechanisms. Our study provides novel structural and functional insights into the properties of GLT8D1 with implications in pathological processes.

The links of stress, substance use and socio-demographic factors with domestic violence during the Covid-19 pandemic in Portugal.

BACKGROUND: Lockdown, as a measure implemented to combat the coronavirus disease 2019 (COVID-19) pandemic, left many domestic violence (DV) victims trapped with their abusers. This study intends to explore the links between perceived stress, substance use and socio-demographic factors with DV experiences during COVID-19 pandemic in Portugal. METHODS: A cross-sectional study was carried out on a sample of 1062 participants over 16 years old, residing in Portugal. Data were collected through an online survey conducted between April and October 2020. The associations between potential factors and DV were investigated using bivariable analysis and multivariable logistic regression. RESULTS: The prevalence of DV reported was 13.75% (n = 146), disaggregated into psychological violence (13%, n = 138), sexual violence (1.0%, n = 11) and physical violence (0.9%, n = 10). Multivariable analyses confirmed that perceived financial difficulties (OR = 1.608; P = 0.019), use of medications to sleep or calm down (OR = 1.851; P = 0.002) and perceived stress (OR = 2.443; P = 0.003) were responsible for DV exposure during COVID-19 pandemic. Younger age (<25 years old) and consumption of alcohol were associated with a higher risk of DV victimization. CONCLUSIONS: Interventions aimed at preventing and confronting DV are necessary within the strategies to combat COVID-19 in Portugal, especially aimed at groups in vulnerable situations, during and after the pandemic.

O bem-estar da criança nos primeiros 3 anos de vida: suporte parental em situações não-urgentes / Child well-being in the first 3 years of life: parental support in non-urgent situations

Atualmente, o enfermeiro é um profissional clínico cuja complexidade e responsabilidade associada ao seu papel requer um desenvolvimento contínuo e a longo prazo (Benner, 2001). Para dar resposta à crescente responsabilidade e complexidade de intervenção que lhe é exigida, cabe-lhe trabalhar no sentido do seu desenvolvimento contínuo. Partindo da problemática da elevada afluência das crianças nos primeiros 3 anos de vida ao Serviço de Urgência Pediátrica, o tema central deste relatório define-se como o suporte parental em situações não-urgentes nos primeiros 3 anos de vida. Tendo na sua base a metodologia de projeto, este relatório descreve o percurso formativo de desenvolvimento das competências comuns e específicas de Enfermeiro Especialista em Enfermagem de Saúde Infantil e Pediátrica, com recurso a uma análise crítica e reflexiva das atividades desenvolvidas, assim como as consequentes aprendizagens e contributos para o alcance dos objetivos propostos. Sustentado num referencial teórico constituído pela Teoria de Sistemas de Betty Neuman, o Modelo Touchpoint de T. Berry Brazelton e o Modelo do Cuidado Centrado na Família, este relatório surge no culminar de um percurso de cinco estágios, no qual foi aplicado o projeto formativo previamente realizado, partindo da problemática identificada.

Currently, the nurse is a clinical professional whose complexity and responsibility associated with his role requires continuous and long-term development (Benner, 2001). In order to respond to the growing responsibility and complexity of the required intervention, it is up to him to work towards his continuous development. Starting from the problem of the high influx of children in the first 3 years of life to the Pediatric Emergency Service, the central theme of this report is defined as parental support in non-urgent situations in the first 3 years of life. Based on project methodology, this report describes the formative path for developing the common and specific skills of a Specialist Nurse in Child and Pediatric Health Nursing, using a critical and reflective analysis of the activities carried out, as well as the consequent learning and contributions to achieve the proposed objectives. Supported by a theoretical framework consisting of Betty Neuman's Theory of Systems, T. Berry Brazelton's Touchpoint Model and the Family-Centered Care Model, this report emerges at the end of a five-stage journey, in which the training project previously carried out, based on the identified problem.

Assessing Multi-Attribute Characterization of Enveloped and Non-Enveloped Viral Particles by Capillary Electrophoresis.

Virus-based biopharmaceutical products are used in clinical applications such as vaccines, gene therapy, and immunotherapy. However, their manufacturing remains a challenge, hampered by the lack of appropriate analytical tools for purification monitoring or characterization of the final product. This paper describes the implementation of a highly sensitive method, capillary electrophoresis (CE)-sodium dodecyl sulfate (SDS) combined with a laser-induced fluorescence (LIF) detector to monitor the impact of various bioprocess steps on the quality of different viral vectors. The fluorescence labelling procedure uses the (3-(2-furoyl) quinoline-2-carboxaldehyde dye, and the CE-SDS LIF method enables the evaluation of in-process besides final product samples. This method outperforms other analytical methods, such as SDS-polyacrylamide gel electrophoresis with Sypro Ruby staining, in terms of sensitivity, resolution, and high-throughput capability. Notably, this CE-SDS LIF method was also successfully implemented to characterize enveloped viruses such as Maraba virus and lentivirus, whose development as biopharmaceuticals is now restricted by the lack of suitable analytical tools. This method was also qualified for quantification of rAAV2 according to the International Council for Harmonisation guidelines. Overall, our work shows that CE-SDS LIF is a precise and sensitive analytical platform for in-process sample analysis and quantification of different virus-based targets, with a great potential for application in biomanufacturing.

Exploring Metabolic Signatures of Ex Vivo Tumor Tissue Cultures for Prediction of Chemosensitivity in Ovarian Cancer.

Predicting patient response to treatment and the onset of chemoresistance are still major challenges in oncology. Chemoresistance is deeply influenced by the complex cellular interactions occurring within the tumor microenvironment (TME), including metabolic crosstalk. We have previously shown that ex vivo tumor tissue cultures derived from ovarian carcinoma (OvC) resections retain the TME components for at least four weeks of culture and implemented assays for assessment of drug response. Here, we explored ex vivo patient-derived tumor tissue cultures to uncover metabolic signatures of chemosensitivity and/or resistance. Tissue cultures derived from nine OvC cases were challenged with carboplatin and paclitaxel, the standard-of-care chemotherapeutics, and the metabolic footprints were characterized by LC-MS. Partial least-squares discriminant analysis (PLS-DA) revealed metabolic signatures that discriminated high-responder from low-responder tissue cultures to ex vivo drug exposure. As a proof-of-concept, a set of potential metabolic biomarkers of drug response was identified based on the receiver operating characteristics (ROC) curve, comprising amino acids, fatty acids, pyrimidine, glutathione, and TCA cycle pathways. Overall, this work establishes an analytical and computational platform to explore metabolic features of the TME associated with response to treatment, which can leverage the discovery of biomarkers of drug response and resistance in OvC.

The Implication of the First Wave of COVID-19 on Mental Health: Results from a Portuguese Sample.

The social conditions created by the COVID-19 pandemic had a great potential to affect the mental health of individuals. Meta-analyses indicate a rise in these problems in these periods among general populations, patients and health professionals, even with substantial heterogeneous results. This paper examines mental health impacts specifically during the first wave of COVID-19. An online survey was conducted with a Portuguese convenience sample (N = 1.062) comprising questions about substance use, perceived stress, post-traumatic stress disorder and self-damage behaviors. The results concerning substance use show an extensive use of medication to sleep or calm down, especially among women and older respondents, a small percentage of alcohol consumers with a high pattern of use and less frequent cannabis consumption, even with a quarter of users who began only in the COVID-19 period. The rates of perceived stress and PTSD were higher compared with international prevalence estimations during the pandemic conditions. Both correlated measures were worse for women and young people. Another problematic issue was the rate of suicidal ideation, with a relevant proportion of starters during this period. These data reinforce the need to promote access to mental health services.

Controlled masking and targeted release of redox-cycling ortho-quinones via a C-C bond-cleaving 1,6-elimination.

Natural products that contain ortho-quinones show great potential as anticancer agents but have been largely discarded from clinical development because their redox-cycling behaviour results in general systemic toxicity. Here we report conjugation of ortho-quinones to a carrier, which simultaneously masks their underlying redox activity. C-benzylation at a quinone carbonyl forms a redox-inactive benzyl ketol. Upon a specific enzymatic trigger, an acid-promoted, self-immolative C-C bond-cleaving 1,6-elimination mechanism releases the redox-active hydroquinone inside cells. By using a 5-lipoxygenase modulator, ß-lapachone, we created cathepsin-B-cleavable quinone prodrugs. We applied the strategy for intracellular release of ß-lapachone upon antibody-mediated delivery. Conjugation of protected ß-lapachone to Gem-IgG1 antibodies, which contain the variable region of gemtuzumab, results in homogeneous, systemically non-toxic and conditionally stable CD33+-specific antibody-drug conjugates with in vivo efficacy against a xenograft murine model of acute myeloid leukaemia. This protection strategy could allow the use of previously overlooked natural products as anticancer agents, thus extending the range of drugs available for next-generation targeted therapeutics.

Republication: Targeting PI3KC2ß Impairs Proliferation and Survival in Acute Leukemia, Brain Tumours and Neuroendocrine Tumours.

BACKGROUND: Eight human catalytic phosphoinositide 3-kinase (PI3K) isoforms exist which are subdivided into three classes. While class I isoforms have been well-studied in cancer, little is known about the functions of class II PI3Ks. MATERIALS AND METHODS: The expression pattern and functions of the class II PI3KC2ß isoform were investigated in a panel of tumour samples and cell lines. RESULTS: Overexpression of PI3KC2ß was found in subsets of tumours and cell lines from acute myeloid leukemia (AML), glioblastoma multiforme (GBM), medulloblastoma (MB), neuroblastoma (NB), and small cell lung cancer (SCLC). Specific pharmacological inhibitors of PI3KC2ß or RNA interference impaired proliferation of a panel of human cancer cell lines and primary cultures. Inhibition of PI3KC2ß also induced apoptosis and sensitised the cancer cells to chemotherapeutic agents. CONCLUSION: Together, these data show that PI3KC2ß contributes to proliferation and survival in AML, brain tumours and neuroendocrine tumours, and may represent a novel target in these malignancies.

Metabolomics profile responses to changing environments in a common bean (Phaseolus vulgaris L.) germplasm collection.

Metabolomics is one of the most powerful -omics to assist plant breeding. Despite the recognized genetic diversity in Portuguese common bean germplasm, details on its metabolomics profiles are still missing. Aiming to promote their use and to understand the environment's effect in bean metabolomics profiles, 107 Portuguese common bean accessions, cropped under contrasting environments, were analyzed using spectrophotometric, untargeted and targeted mass spectrometry approaches. Although genotype was the most relevant factor on bean metabolomics profile, a clear genotype × environment interaction was also detected. Multivariate analysis highlighted, on the heat-stress environment, the existence of higher levels of salicylic acid, and lower levels of triterpene saponins. Three clusters were defined within each environment. White accessions presented the lowest content and the colored ones the highest levels of prenol lipids and flavonoids. Sources of interesting metabolomics profiles are now identified for bean breeding, focusing either on local or on broad adaptation.

Bioorthogonal Self-Immolative Linker Based on Grob Fragmentation.

A self-immolative bioorthogonal conditionally cleavable linker based on Grob fragmentation is described. It is derived from 1,3-aminocyclohexanols and allows the release of sulfonate-containing compounds in aqueous media. Modulation of the amine pKa promotes fragmentation even at slightly acidic pH, a common feature of several tumor environments. The Grob fragmentation can also occur under physiological conditions in living cells, highlighting the potential bioorthogonal applicability of this reaction.

Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2-5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression.

The use of computational tools to identify biological targets of natural products with anticancer properties and unknown modes of action is gaining momentum. We employed self-organizing maps to deconvolute the phenotypic effects of piperlongumine (PL) and establish a link to modulation of the human transient receptor potential vanilloid 2 (hTRPV2) channel. The structure of the PL-bound full-length rat TRPV2 channel was determined by cryo-EM. PL binds to a transient allosteric pocket responsible for a new mode of anticancer activity against glioblastoma (GBM) in which hTRPV2 is overexpressed. Calcium imaging experiments revealed the importance of Arg539 and Thr522 residues on the antagonistic effect of PL and calcium influx modulation of the TRPV2 channel. Downregulation of hTRPV2 reduces sensitivity to PL and decreases ROS production. Analysis of GBM patient samples associates hTRPV2 overexpression with tumor grade, disease progression, and poor prognosis. Extensive tumor abrogation and long term survival was achieved in two murine models of orthotopic GBM by formulating PL in an implantable scaffold/hydrogel for sustained local therapy. Furthermore, in primary tumor samples derived from GBM patients, we observed a selective reduction of malignant cells in response to PL ex vivo. Our results establish a broadly applicable strategy, leveraging data-motivated research hypotheses for the discovery of novel means tackling cancer.

Adolescent and young adult patients as co-researchers: A scoping review.

BACKGROUND: As part of a research project aimed at evaluating a hospital-based adolescent transition programme, we asked ourselves what is known about the ethical and methodological challenges of research involving adolescent patients as co-researchers. The aim of our review was to summarize empirical evidence and identify knowledge gaps about the involvement of young patients as co-researchers. METHODS: We conducted a scoping review through searches in MEDLINE, EMBASE, PsychINFO, AMED. RESULTS: We found reports of young patients being actively engaged as co-researchers in any stage of a research project, although commonly they were not involved in every stage. Including young patients as co-researchers is resource demanding and time-consuming. Involving young patients as co-researchers contributes to the fulfilment of their right to participation and may improve the relevance of research. Benefits for the young co-researcher include empowerment, skills building and raised self-esteem. Few authors go into detail about ethical considerations when involving young co-researchers. None of the included articles discuss legal considerations. DISCUSSION AND CONCLUSION: No lists of recommendations are given, but recommendations can be deduced from the articles. There is need for time, funding and flexibility when including young patients as co-researchers. Knowledge gaps concern legal and ethical dilemmas of including a vulnerable group as co-researchers. More reflection is needed about what meaningful participation is and what it entails in this context. PATIENT OR PUBLIC CONTRIBUTION: This review is part of a research project where the hospital youth council has been involved in discussions of focus area and methods.

Sequential dual site-selective protein labelling enabled by lysine modification.

Methods that allow for chemical site-selective dual protein modification are scarce. Here, we provide proof-of-concept for the orthogonality and compatibility of a method for regioselective lysine modification with strategies for protein modification at cysteine and genetically encoded ketone-tagged amino acids. This sequential, orthogonal approach was applied to albumin and a therapeutic antibody to create functional dual site-selectively labelled proteins.

Mining for Peaks in LC-HRMS Datasets Using Finnee - A Case Study with Exhaled Breath Condensates from Healthy, Asthmatic, and COPD Patients.

Separation techniques hyphenated to high-resolution mass spectrometry are essential in untargeted metabolomic analyses. Due to the complexity and size of the resulting data, analysts rely on computer-assisted tools to mine for features that may represent a chromatographic signal. However, this step remains problematic, and a high number of false positives are often obtained. This work reports a novel approach where each step is carefully controlled to decrease the likelihood of errors. Datasets are first corrected for baseline drift and background noise before the MS scans are converted from profile to centroid. A new alignment strategy that includes purity control is introduced, and features are quantified using the original data with scans recorded as profile, not the extracted features. All the algorithms used in this work are part of the Finnee Matlab toolbox that is freely available. The approach was validated using metabolites in exhaled breath condensates to differentiate individuals diagnosed with asthma from patients with chronic obstructive pulmonary disease. With this new pipeline, twice as many markers were found with Finnee in comparison to XCMS-online, and nearly 50% more than with MS-Dial, two of the most popular freeware for untargeted metabolomics analysis.

Tetrazine Carbon Nanotubes for Pretargeted In†Vivo "Click-to-Release" Bioorthogonal Tumour Imaging.

The bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) cleavage reaction between tetrazine and trans-cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single-walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO-caged molecule was used to deliver active effector molecules. To optimize a turn-on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near-infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real-time, non-invasive tumour visualization with a high target-to-background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine-functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off-site activation of fluorophore/drug.

Usability of an Intelligent Virtual Assistant for Promoting Behavior Change and Self-Care in Older People with Type 2 Diabetes.

In the context of the VASelfCare project, we developed an application prototype of an intelligent anthropomorphic virtual assistant. Designed as a relational agent, the virtual assistant has the role of supporting older people with Type 2 Diabetes Mellitus (T2D) in medication adherence and lifestyle changes. Our paper has two goals: describing the essentials of this prototype, and reporting on usability evaluation. We describe the general architecture of the prototype, including the graphical component, and focus on its main feature: the incorporation, in the way the dialogue flows, of Behavior Change Techniques, identified through a theoretical framework, the Behaviour Change Wheel. Usability was experimentally evaluated in field tests in a purposive sample of 20 participants (11 older adults with T2D and 9 experts). The Portuguese version of the System Usability Scale was employed, supplemented with qualitative data from open questions, diaries, digital notes and telephone follow-ups. The aggregated mean SUS score was 73,75 (SD 13,31), which corresponds to a borderline rating of excellent. Textual data were content analyzed and will be prioritized to further improve usability.

Thirtieth anniversary of the UN Convention on the Rights of the Child: advancing a child rights-based approach to child health and well-being.

Global challenges to children's health are rooted in social and environmental determinants. The UN Convention on the Rights of the Child (CRC) articulates the rights required to address these civil-political, social, economic and cultural determinants of child well-being. The principles of child rights-universality, interdependence and accountability-define the tenets of social justice and health equity required to ensure all rights accrue to all children, and the accountability of individuals and organisations (duty-bearers) to ensure these rights are fulfilled. Together, the CRC and child rights principles establish the structure and function of a child rights-based approach (CRBA) to child health and well-being-that provides the strategies and tools to transform child health practice into a rights, justice and equity-based paradigm. The 30th anniversary of the CRC is an opportune time to translate a CRBA to health and well-being into a global practice of paediatrics and child health.

EPIDEMIOLOGICAL STUDY OF TRAUMATIC BRACHIAL PLEXUS INJURIES.

OBJECTIVE: To conduct an epidemiological study on brachial plexus injuries, through data collection of patients treated in the Hospital São Paulo, which is the referral center for high complexity in this region. METHODS: We conducted a retrospective study with a review of the electronic medical records of the Hospital, from August 2008 to June 2013. RESULTS: We estimated an 1.88/100,000 annual incidence, considering that the Hospital is the only referral center for brachial plexus injuries. The mean time between injury and the first visit to the reference hospital was 8.25 months. The mean time interval between injury and surgery was 11.25 months. The percentage of total injuries was 33%, while the upper and middle trunk injuries were 33% and 28%, respectively. CONCLUSION: We observed many aspects in common with those reported by other centers of excellence in Brazil such as: sex, age and mechanism of injury. However, some findings were different from most other epidemiological studies, namely: level of injury, time between the accident and the first appointment and the time between injury and surgery. Level of evidence IV, case series.

OBJETIVO: Realizar um estudo epidemiológico das lesões do plexo braquial através do levantamento de dados dos pacientes atendidos no Hospital de referência para alta complexidade da região metropolitana de São Paulo. MÉTODOS: Estudo retrospectivo com avaliação dos prontuários eletrônicos do HMC-SA, de agosto de 2008 até junho de 2013. RESULTADOS: Levando-se em consideração que o Hospital é o único centro de referência para lesões do plexo braquial, chegamos a uma incidência anual estimada em 1,88/100.000 habitantes. A média de tempo entre a lesão e a primeira consulta no hospital foi de 8,25 meses. O intervalo de tempo entre a lesão e a cirurgia foi em média de 11,25 meses. A porcentagem de lesões totais foi de 33%, enquanto as lesões de tronco superior e tronco superior e médio foram de 33% e 28%, respectivamente. CONCLUSÃO: Observamos muitos aspectos em comum com os relatados por outros centros de referência no Brasil, tais como: gênero, idade e mecanismo de trauma. No entanto, alguns achados foram diferentes da maioria dos outros estudos epidemiológicos: nível de lesão, tempo decorrido entre o acidente e o primeiro atendimento e o intervalo de tempo entre a lesão e o tratamento cirúrgico. Nível de evidência IV, série de casos.