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- Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumabPublication . Magro, Fernando; Lopes, Susana; Silva, Marco; Coelho, Rosa; Portela, Francisco; Branquinho, Diogo; Correia, Luís; Fernandes, Samuel; Cravo, Marília; Caldeira, Paulo; Tavares de Sousa, Helena; Patita, Marta; Lago, Paula; Ramos, Jaime; Afonso, Joana; Redondo, Isabel; Machado, Patrícia; Philip, George; Lopes, Joanne; Carneiro, FátimaBackground: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab. Methods: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated. Results: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 (n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus -2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity (rs = 0.45, p = 0.007) but not with histological activity (rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 μg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 (n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6. Conclusions: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels.
- Lipid Antigen Presentation by CD1b and CD1d in Lysosomal Storage Disease PatientsPublication . Pereira, C.; Pérez-Cabezas, B.; Ribeiro, H.; Maia, M.; Cardoso, M.; Dias, A.; Azevedo, O.; Ferreira, M.; Garcia, P.; Rodrigues, E.; Castro-Chaves, P.; Martins, Esmeralda; Aguiar, P.; Pineda, M.; Amraoui, Y.; Fecarotta, S.; Leão-Teles, E.; Deng, S.; Savage, P.; Macedo, M.The lysosome has a key role in the presentation of lipid antigens by CD1 molecules. While defects in lipid antigen presentation and in invariant Natural Killer T (iNKT) cell response were detected in several mouse models of lysosomal storage diseases (LSD), the impact of lysosomal engorgement in human lipid antigen presentation is poorly characterized. Here, we analyzed the capacity of monocyte-derived dendritic cells (Mo-DCs) from Fabry, Gaucher, Niemann Pick type C and Mucopolysaccharidosis type VI disease patients to present exogenous antigens to lipid-specific T cells. The CD1b- and CD1d-restricted presentation of lipid antigens by Mo-DCs revealed an ability of LSD patients to induce CD1-restricted T cell responses within the control range. Similarly, freshly isolated monocytes from Fabry and Gaucher disease patients had a normal ability to present α-Galactosylceramide (α-GalCer) antigen by CD1d. Gaucher disease patients' monocytes had an increased capacity to present α-Gal-(1-2)-αGalCer, an antigen that needs internalization and processing to become antigenic. In summary, our results show that Fabry, Gaucher, Niemann Pick type C, and Mucopolysaccharidosis type VI disease patients do not present a decreased capacity to present CD1d-restricted lipid antigens. These observations are in contrast to what was observed in mouse models of LSD. The percentage of total iNKT cells in the peripheral blood of these patients is also similar to control individuals. In addition, we show that the presentation of exogenous lipids that directly bind CD1b, the human CD1 isoform with an intracellular trafficking to the lysosome, is normal in these patients.
- Effects of a nursing care program on functional outcomes in older acute medical in-patients: protocol for a randomized controlled trialPublication . Rodrigues, Cecília; Mendonça, Denisa; Martins, Maria ManuelaBackground: Hospitalization often leads to long periods of bed rest and inactivity which is associated with an increase in length of hospital stay, loss of capacity for basic self-care and discharge into a nursing home. Objective: This trial aims to verify if a nursing care program centered on basic self-care and predefined physical activity, improves functional outcomes in older hospitalized patients. Methods: This is a 2-group randomized controlled trial with repeated measures: 182 older acute medical patients will be blindly randomly allocated to the control group (n = 91) or intervention group (n = 91). The intervention will consist of nursing care intervention centered on basic self-care that includes a twice daily walking training, plus privileging pre-established trips to the toilet by walking and all daytime meals seated, off the bed. The main outcome was changes in the number of independent activities of daily living from 2 weeks before admission (baseline) to discharge. Trial registration: ClinicalTrials.gov (Identifier NCT03106064). Results: This intervention has the potential to change the outcomes of the older patient in the acute setting. Conclusion: The loss of independence in self-care is determinant in future health care needs. If our hypothesis is correct and demonstrate that this nursing care program centered on basic self-care for older acute medical patients improves functional outcomes, a change in the paradigmatic organization of hospital care may be justifiable.
- Hemangioma of the Internal Auditory Canal and PHACES Syndrome: A Rare Finding in a Rare SyndromePublication . Santos, Mariline; Mendes, Gonçalo J.; Pinto, Ana N.; Coutinho, Miguel B.; Sousa, Cecília A.
- Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and MetabolismPublication . Santos, A.; Vinagre, J.; Soares, P.; Claro, I.; Sanches, A.; Gomes, L.; Fernandes, I.; Catarino, A.; Preto, J.; Pereira, B.; Marques, A.; Rodrigues, F.; Amaral, C.; Rocha, G.; Mellidez, J.; Simões, H.; Lopes, J.; Bugalho, M.Background: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has been increasing in the last five decades, but there is no large-scale data regarding these tumours in Portugal. We conducted a cross-sectional, multicentric study in main Portuguese centers to evaluate the clinical, pathological, and therapeutic profile of GEP-NENs. Methods: From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. Results: Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p = 0.017), were larger (p < 0.001), and presented more vascular (p = 0.004) and lymphatic (p = 0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. Conclusion: In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal. Methods: From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. Results: Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p = 0.017), were larger (p < 0.001), and presented more vascular (p = 0.004) and lymphatic (p = 0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. Conclusion: In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal.
- Frailty in cardiovascular disease: Screening toolsPublication . Zão, Ana; Magalhães, Sandra; Santos, MarioCardiovascular disease (CVD) is the leading cause of death in developed countries and disproportionately affects older adults. Frailty is a complex clinical syndrome with multiple causes and contributing factors in which there is increased vulnerability when exposed to a minor stressor and increased risk for adverse outcomes, such as disability, hospitalization and mortality. Frailty is an important prognostic factor in patients with CVD, and so identifying this feature when assessing these patients may help to individually tailor cardiovascular treatment. The first step is to identify frailty. Several tools have been validated as screening methods for frailty. However, they diverge with regard to complexity, nature, feasibility and the outcome they can predict. The aim of this review is to describe the available screening tools for frailty and to examine their usefulness in patients with CVD.
- Phakic Intraocular Lens Implantation After Deep Anterior Lamellar Keratoplasty: Retrospective Case Series Analysis With Long-Term Follow-UpPublication . Malheiro, Luisa; Coelho, João; Neves, Miguel Mesquita; Gomes, Miguel; OLIVEIRA, LUISPurpose: To report outcomes of phakic intraocular lens (IOL) implantation after deep anterior lamellar keratoplasty (DALK) to correct high ametropia. Setting: Centro Hospitalar Universitário do Porto, Portugal. Methods: Retrospective case series with 11 eyes submitted to phakic IOL implantation after DALK. Main outcomes measured were uncorrected and corrected distance visual acuity (UDVA and CDVA), refractive error components, tomographic parameters and endothelial cell density (ECD). The minimum follow-up was 3 years for all cases. Results: Mean ECD loss was 8.7±6.7% at 1 year, 13.1±8.6% at 3 years (n=11; p=0.016, p=0.007, respectively) and 14.0±20.4% at 5 years (n=5, p=0.212). Mean logMAR UDVA increased from 1.27±0.90logMAR preoperatively to 0.16±0.15logMAR postoperatively (p≤0.001) and no statistically significant differences were registered during follow-up. All patients gained at least 5 lines of UDVA. 54.5% of the eyes gained 1 line in CDVA postoperative and only one eye lost one CDVA line through follow-up. Efficacy and safety indexes at 1 and 3 years were 1.01-0.97 and 1.24-1.21, respectively. Mean spherical equivalent was reduced from -7.84±4.63 D preoperatively to -1.05±1.07 D postoperatively (p=0.001). Mean percentage of reduction in refractive cylinder and spherical error was 83.8±15.8% and 73.1±31.5%, respectively, p≤0.001 for both. In one eye there was a significantly gradual ECD loss over 5 years follow-up and the patient will be submitted to IOL explant. Conclusion: Phakic IOLs were effective for correction high ametropia after DALK, showing high efficacy and safety indexes with stability over time. However, it was registered a continuing endothelial cell loss postoperatively, which assumed to be higher than those reported in eyes without DALK.
- Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019Publication . Pimentel-Nunes, P.; Libânio, D.; Marcos-Pinto, Ricardo; Areia, M.; Leja, M.; Garrido, Mónica; Esposito, j.; Kikuste, .; Megraud, F.; Matysiak-Budnik, T.; Annibale, B.; Dumonceau, J.; Barros, R.; Fléjou, J.; Carneiro, F.; van Hooft, J.; Kuipers, E.; Dinis-Ribeiro, M.Patients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk stratification for these patients. High definition endoscopy with chromoendoscopy (CE) is better than high definition white-light endoscopy alone for this purpose. Virtual CE can guide biopsies for staging atrophic and metaplastic changes and can target neoplastic lesions. Biopsies should be taken from at least two topographic sites (antrum and corpus) and labelled in two separate vials. For patients with mild to moderate atrophy restricted to the antrum there is no evidence to recommend surveillance. In patients with IM at a single location but with a family history of gastric cancer, incomplete IM, or persistent Helicobacter pylori gastritis, endoscopic surveillance with CE and guided biopsies may be considered in 3 years. Patients with advanced stages of atrophic gastritis should be followed up with a high quality endoscopy every 3 years. In patients with dysplasia, in the absence of an endoscopically defined lesion, immediate high quality endoscopic reassessment with CE is recommended. Patients with an endoscopically visible lesion harboring low or high grade dysplasia or carcinoma should undergo staging and treatment. H. pylori eradication heals nonatrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions, and it is recommended. H. pylori eradication is also recommended for patients with neoplasia after endoscopic therapy. In intermediate to high risk regions, identification and surveillance of patients with precancerous gastric conditions is cost-effective.
- A pair of peptides inhibits seeding of the hormone transporter transthyretin into amyloid fibrilsPublication . Saelices, L.; Nguyen, B.; Chung, K.; Wang, Y.; Ortega, A.; Lee, J.; Coelho, T.; Bijzet, J.; Benson, M.; Eisenberg, D.The tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However, this procedure, which replaces the patient's variant transthyretin with the WT protein, can fail to stop subsequent cardiac deposition, ultimately requiring heart transplantation. We recently showed that preformed amyloid fibrils present in the heart at the time of surgery can template or seed further amyloid aggregation of native transthyretin. Here we assess possible interventions to halt this seeding, using biochemical and EM assays. We found that chemical or mutational stabilization of the transthyretin tetramer does not hinder amyloid seeding. In contrast, binding of the peptide inhibitor TabFH2 to ex vivo fibrils efficiently inhibits amyloid seeding by impeding self-association of the amyloid-driving strands F and H in a tissue-independent manner. Our findings point to inhibition of amyloid seeding by peptide inhibitors as a potential therapeutic approach.
- Abdominal Actinomycosis misdiagnosed as liposarcomaPublication . Vieira E Monteiro, Eunice; Gaspar, Joana; Paiva, Cláudia; Correia, Raquel; Valente, Vítor; Coelho, André; Lamas, Nuno JorgeActinomycosis is an uncommon, endogenous, and chronic infection with varied and nonspecific clinical features such as abdominal, pelvic or cervical masses, ulcerative lesions, abscesses, draining fistula, fibrosis, and constitutional symptoms. The disease ensues when the bacteria disrupt the mucosal barrier, invade, and spread throughout interfascial planes. Currently, the diagnosis of actinomycosis is challenging because of its very low frequency and depending on the clinical presentation it may masquerade malignancies. Therapy consists initially in intravenous penicillin, followed by an oral regimen that may be extended until a year of treatment. A timely diagnosis is crucial to avoid extensive therapeutic attempt as surgery. However, a biopsy or drainage of abscesses and fistula's tract may be required not only as a diagnostic procedure as part of the therapy. We report the case of a 72-year-old woman with an abdominal mass initially misdiagnosed as a liposarcoma. A second biopsy of a skin lesion of the abdominal wall made the diagnosis of actinomycosis, avoiding a major surgical procedure. The patient was treated with a long-term course of antibiotics with favorable outcome. Liposarcoma was ruled out after the patient's full recovery with antibiotics and the misdiagnosis was credit to the overconfidence on the immunohistochemical positivity to MDM2.