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- Author response to: Comment on: Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery.Publication . Chapman, S; Blanco-Colino, R; Clerc, D; Otto, A; Nepogodiev, D; Pagano, G; Schaeff, V; Soares, A, et al.
- Design and validation of a patient-reported outcome measure scale in acute pancreatitis: the PAN-PROMISE studyPublication . de-Madaria, E; Sánchez-Marin, C; Carrillo, I; Vege, SS; Chooklin, S; Bilyak, A; Mejuto, R; Mauriz, V; Hegyi, P; Márta, K; Kamal, A; Lauret-Braña, E; Barbu, ST; Nunes, V, et al.Objective: This study aimed to develop and validate a patient-reported outcome measure (PROM) in acute pancreatitis (AP) as an endpoint centred on the patient. DESIGN: A PROM instrument (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, PAN-PROMISE scale) was designed based on the opinion of patients, professionals and an expert panel. The scale was validated in an international multicentre prospective cohort study, describing the severity of AP and quality of life at 15 days after discharge as the main variables for validation. The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) methodology was applied. Both the design and validation stages considered the content and face validity of this new instrument; the metric properties of the different items, reliability (reproducibility and internal consistence), the construct, structural and criterion validity, responsiveness and interpretability of this scale. RESULTS: PAN-PROMISE consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. The validation cohort involved 15 countries, 524 patients. The intensity of symptoms changed from higher values during the first 24 hours to lower values at discharge and 15 days thereafter. Items converged into a unidimensional ordinal scale with good fit indices. Internal consistency and split-half reliability at discharge were adequate. Reproducibility was confirmed using test-retest reliability and comparing the PAN-PROMISE score at discharge and 15 days after discharge. Evidence is also provided for the convergent-discriminant and empirical validity of the scale. CONCLUSION: The PAN-PROMISE scale is a useful tool to be used as an endpoint in clinical trials, and to quantify patient well-being during the hospital admission and follow-up.
- Surgical Training During and After COVID-19: A Joint Trainee and Trainers ManifestoPublication . Blanco-Colino, R; Soares, AS; Kuiper, SZ; Zaffaroni, G; Pata, F; Pellino, G
- Time to invest on research during medical training.Publication . Peyroteo, M; Almeida, MM; Cunha, M; Simões, J; João, A, et al.
- Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations.Publication . Párniczky, A; Lantos, T; Tóth, EM; Gomes, AAlthough evidence indicates that use of procalcitonin to guide antibiotic decisions for the treatment of acute respiratory infections (ARI) decreases antibiotic consumption and improves clinical outcomes, algorithms used within studies had differences in PCT cut-off points and frequency of testing. We therefore analyzed studies evaluating procalcitonin-guided antibiotic therapy and propose consensus algorithms for different respiratory infection types. Areas covered: We systematically searched randomized-controlled trials (search strategy updated on February 2018) on procalcitonin-guided antibiotic therapy of ARI in adults using a pre-specified Cochrane protocol and analyzed algorithms from 32 trials that included 10,285 patients treated in primary care settings, emergency departments (ED), and intensive care units (ICU). We derived consensus algorithms for use of procalcitonin by the type of ARI including community-acquired pneumonia, bronchitis, chronic obstructive pulmonary disease or asthma exacerbation, sepsis, and post-operative sepsis due to respiratory infection. Consensus algorithm recommendations differ with regard to timing of treatment (i.e. timing of initiation in low-risk patients or discontinuation in high-risk patients) and procalcitonin cut-off points for the recommendation/strong recommendation to discontinue antibiotics (≤ 0.25/≤ 0.1 µg/L in ED and inpatients, ≤ 0.5/≤ 0.25 µg/L in ICU patients, and reduction by ≥ 80% from peak levels in sepsis patients). Expert commentary: Our proposed algorithms may facilitate safe and efficient implementation of procalcitonin-guided antibiotic protocols in diverse healthcare settings. Still, the decision about initiation and cessation of antibiotic treatment remains a clinical decision based on the patient assessment and the severity of illness and use of procalcitonin should not delay empirical treatment in high risk situations.
- The role of prediagnostic data in injury epidemiology in preprofessional dancersPublication . Moita, JP; Gomes, A; Xarez, L; Coelho, CINTRODUCTION: preprofessional dance training starts at very early ages, on a highly demanding environment placing students at significant risk for injury. Injury management and prevention are a matter of concern. Given the constant interchangeability of risk factors, identifying injury patterns may prove to be equally as important. Data looking back from the time of injury through context-specific approaches are missing. OBJECTIVES: To identify activity-related injury patterns based on prediagnostic data. METHODS: Prospective, non-randomized, observational study, over a 3 years period on a full-time preprofessional dance school featuring both gender students aged 9-21 years old. Non-parametric statistics were used. RESULTS: A total of 625 dance injury records from 209 students, n = 68 males and n = 141 females, were analyzed. Season injury risk probability was identified, proving different for each skill level (SkL). Multiple individual injuries revealed a trend toward prevalence rates in advanced level, while index injuries incidence becomes more noticeable in entry level students. Overall incidence rates had no significant differences within SkL. Anatomical location was in line with previous research, although differences were found between gender and SkL. Most injuries occurred in classes, with jumps standing out as the main motor action associated with injury symptoms of gradual onset mechanism. CONCLUSION: Dance injuries happen because of dance practice. Knowing the context of injury history from the injured dancer perspective is determinant for management and prevention. prediagnostic data are an umbrella term encompassing several aspects of injury background and represents fertile ground for research. Context-specific methodological approaches are recommended.
- On the utility of 3D hand cursors to explore medical volume datasets with a touchless interface.Publication . Lopes, S; Parreira, F; Paulo, F; Nunes, V; Rego, A; Neves, C; Rodrigues, S; Jorge, AAnalyzing medical volume datasets requires interactive visualization so that users can extract anatomo-physiological information in real-time. Conventional volume rendering systems rely on 2D input devices, such as mice and keyboards, which are known to hamper 3D analysis as users often struggle to obtain the desired orientation that is only achieved after several attempts. In this paper, we address which 3D analysis tools are better performed with 3D hand cursors operating on a touchless interface comparatively to a 2D input devices running on a conventional WIMP interface. The main goals of this paper are to explore the capabilities of (simple) hand gestures to facilitate sterile manipulation of 3D medical data on a touchless interface, without resorting on wearables, and to evaluate the surgical feasibility of the proposed interface next to senior surgeons (N=5) and interns (N=2). To this end, we developed a touchless interface controlled via hand gestures and body postures to rapidly rotate and position medical volume images in three-dimensions, where each hand acts as an interactive 3D cursor. User studies were conducted with laypeople, while informal evaluation sessions were carried with senior surgeons, radiologists and professional biomedical engineers. Results demonstrate its usability as the proposed touchless interface improves spatial awareness and a more fluent interaction with the 3D volume than with traditional 2D input devices, as it requires lesser number of attempts to achieve the desired orientation by avoiding the composition of several cumulative rotations, which is typically necessary in WIMP interfaces. However, tasks requiring precision such as clipping plane visualization and tagging are best performed with mouse-based systems due to noise, incorrect gestures detection and problems in skeleton tracking that need to be addressed before tests in real medical environments might be performed.
- Single-cell functional and chemosensitive profiling of combinatorial colorectal therapy in zebrafish xenografts.Publication . Fior, R; Póvoa, V; Mendes, V; Carvalho, T; Gomes, A; Figueiredo, N; Ferreira, GCancer is as unique as the person fighting it. With the exception of a few biomarker-driven therapies, patients go through rounds of trial-and-error approaches to find the best treatment. Using patient-derived cell lines, we show that zebrafish larvae xenotransplants constitute a fast and highly sensitive in vivo model for differential therapy response, with resolution to reveal intratumor functional cancer heterogeneity. We screened international colorectal cancer therapeutic guidelines and determined distinct functional tumor behaviors (proliferation, metastasis, and angiogenesis) and differential sensitivities to standard therapy. We observed a general higher sensitivity to FOLFIRI [5-fluorouracil(FU)+irinotecan+folinic acid] than to FOLFOX (5-FU+oxaliplatin+folinic acid), not only between isogenic tumors but also within the same tumor. We directly compared zebrafish xenografts with mouse xenografts and show that relative sensitivities obtained in zebrafish are maintained in the rodent model. Our data also illustrate how KRAS mutations can provide proliferation advantages in relation to KRASWT and how chemotherapy can unbalance this advantage, selecting for a minor clone resistant to chemotherapy. Zebrafish xenografts provide remarkable resolution to measure Cetuximab sensitivity. Finally, we demonstrate the feasibility of using primary patient samples to generate zebrafish patient-derived xenografts (zPDX) and provide proof-of-concept experiments that compare response to chemotherapy and biological therapies between patients and zPDX. Altogether, our results suggest that zebrafish larvae xenografts constitute a promising fast assay for precision medicine, bridging the gap between genotype and phenotype in an in vivo setting.
- Impact of bowel resection margins in node negative colon cancer.Publication . Rocha, R; Marinho, R; Aparício, D; Fragoso, M; Sousa, M; Gomes, A; Leichsenring, C; Carneiro, C; Geraldes, V; Nunes, VSurgical intestinal resection margins in colon cancer are a longstanding debate in terms the optimal distance between the tumor and the colonic section line. The aim of this study is to define the oncological outcomes in relation to surgical margins, measured in terms or recurrence rate, time-to-recurrence, disease-free survival and overall survival in a population of node negative colon cancer patients. METHODS: We conducted a retrospective observational longitudinal single institution study. All patients submitted to colon cancer surgery between January 2006 and December 2010 were analyzed. Only node negative patients were included in the study, with analysis of 215 patient charts, divided in two groups (Intestinal margin lower than 5 cm-group 1; and 5 cm or higher-group 2). RESULTS: Mean age of patients was 70.4 years (±11.7), with a male predominance (57.7%). Group 2 more frequently corresponded to Stage II (83 vs 71%; p = 0.05). Global mean total lymph nodes harvested were 12, and were higher in group II than in group I (13.8 ± 8.2 vs 10.4 ± 5.7; p = 0.001). In terms of time-to-recurrence patients of group 2 had longer time than patients of group 1 (32.3 ± 12.1 vs 21.8 ± 13.8 months; p = 0.03), as well as a lower recurrence rate in group I (13.7 vs 17.2%), despite not statistically significant. CONCLUSIONS: This study has showed that patients with 5 cm or higher bowel resection margins had longer time-to-recurrence that was statistically significant. Recurrence rates were lower in the group of patients with longer surgical margins, however not statistically significant.
- High-risk features in potentially resectable colon cancer: a prospective MDCT-pathology agreement studyPublication . Santiago, I; Rodrigues, E; Germano, A; Costa, A; Manso, RT; Gomes, A; Leichsenring, C; Geraldes, VNeoadjuvant chemotherapy in potentially resectable high-risk Stage II and Stage III colon cancer has demonstrated promising results in the PRODIGE 22-ECKINOXE Phase II trial. Identification of adverse morphologic features, namely T3 with >5 mm extramural extension/T4 stages and/or N2, is fundamental and requires accurate noninvasive imaging. Our aim was to assess the value of optimized preoperative MDCT to stratify potentially resectable colon cancer patients for neoadjuvant therapy. METHODS: this is an observational prospective cross-sectional radiologic-pathologic agreement study. All patients with colon cancer referred to our Institution's Radiology department for preoperative MDCT staging between 01-10-2013 and 11-02-2015 underwent independent reading based on axial and multiplanar reconstruction images by 3 radiologists with 3, 6, and 20 years of experience in gastrointestinal radiology. T stage, extramural extension if T3 (≤5 mm or >5 mm), and N stage were recorded. Surgical specimens subsequently obtained underwent micro-pathologic analysis by a gastrointestinal pathologist with 9 years of experience in gastrointestinal pathology. Main outcome measures were sensitivity, specificity, PPV, NPV, AUROC, diagnostic accuracy, and interobserver agreement of optimized MDCT, and pathologic analysis of the surgical specimen considered the reference standard. RESULTS: 74 patients [43 males; median age 73 (45-89)] were eligible. MDCT sensitivity, specificity, PPV, NPV, AUROC, and diagnostic accuracy ranged between 42.9-76.2, 75.5-90.6, 55.2-76.2, 80.0-90.6, 0.67-0.83 and 0.76-0.86%, respectively, for the identification of T3 > 5 mm/T4 disease, with moderate interobserver agreement (0.49); and 8.3-33.3, 93.5-98.4, 20-66.7, 84.1-88.2, 0.51-0.65 and 0.80-0.86%, respectively, for the identification of N2 disease, with absent interobserver agreement (0.10). CONCLUSIONS: Specificity of MDCT in the stratification of patients for neoadjuvant therapy may be high enough to prevent overtreatment. However, it may lead to undertreatment in a meaningful proportion of patients. Observer performance may benefit from targeted training programs, given the variability and observer dependence of the results. Limitations include 4-slice MDCT equipment, time to surgery and lack of long-term outcome information based on imaging parameters per se.