ULS_10.1-MED-Artigos
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- Detection of anti-infliximab antibodies is impacted by antibody titer, infliximab level and IgG4 antibodies: a systematic comparison of three different assaysPublication . Afonso, Joana; Lopes, Susana; Gonçalves, Raquel; Caldeira, Paulo; Lago, Paula; Sousa, Helena Tavares; Ramos, Jaime; Gonçalves, Ana Rita; Ministro, Paula; Rosa, Isadora; Vieira, Ana Isabel; Coelho, Rosa; Tavares, Patrícia; Soares, João; Sousa, Ana Lúcia; Carvalho, Diana; Sousa, Paula; Silva, João Pereira da; Meira, Tânia; Ferreira, Filipa Silva; Dias, Cláudia Camila; Chowers, Yehuda; Ben-Horin, Shomron; Magro, FernandoBackground: There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays.Methods: Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs.Results: The three assays showed 81-96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 mu g/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 mu g/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 mu g/ml. However, in samples with high levels of ADAs (> 25 mu g/ml) interference was only observed at IFX concentrations higher than 100 mu g/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA and IFX-/ADAs + were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination.Conclusions: All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs) or double-positive (IFX+/ADAs+) status, since agreement between assays is significantly lower in these circumstances.
- Proactive therapeutic drug monitoring of infliximab: a comparative study of a new point-of-care quantitative test with two established ELISA assaysPublication . Afonso, J.; Lopes, S.; Gonçalves, R.; Caldeira, Paulo; Lago, P.; Sousa, Helena Tavares; Ramos, J.; Gonçalves, A. R.; Ministro, P.; Rosa, I.; Vieira, A. I.; Dias, C. C.; Magro, F.BackgroundTherapeutic drug monitoring is a powerful strategy known to improve the clinical outcomes and to optimise the healthcare resources in the treatment of autoimmune diseases. Currently, most of the methods commercially available for the quantification of infliximab (IFX) are ELISA-based, with a turnaround time of approximately 8h, and delaying the target dosage adjustment to the following infusion.AimTo validate the first point-of-care IFX quantification device available in the market - the Quantum Blue Infliximab assay (Buhlmann, Schonenbuch, Switzerland) - by comparing it with two well-established methods.MethodsThe three methods were used to assay the IFX concentration of spiked samples and of the serum of 299 inflammatory bowel diseases (IBD) patients undergoing IFX therapy.ResultsThe point-of-care assay had an average IFX recovery of 92%, being the most precise among the tested methods. The Intraclass Correlation Coefficients of the point-of-care IFX assay vs. the two ELISA-based established methods were 0.889 and 0.939. Moreover, the accuracy of the point-of-care IFX compared with each of the two reference methods was 77% and 83%, and the kappa statistics revealed a substantial agreement (0.648 and 0.738).ConclusionsThe Quantum Blue IFX assay can successfully replace the commonly used ELISA-based IFX quantification kits. This point-of-care IFX assay is able to deliver the results within 15min makes it ideal for an immediate target concentration adjusted dosing. Moreover, it is a user-friendly desktop device that does not require specific laboratory facilities or highly specialised personnel.
- The who-when-why triangle of complementary and alternative medicine use among Portuguese IBD patientsPublication . Portela, Francisco; Dias, Camila C.; Caldeira, Paulo; Cravo, Marilia; Deus, João; Gonçalves, Raquel; Lago, Paula; Morna, Henrique; Peixe, Paula; Ramos, Jaime; Sousa, Helena Tavares; Tavares, Lurdes; Vasconcelos, Helena; Magro, Fernando; Ministro, PaulaBackground: The use of complementary and alternative medicines is increasing among chronic patients, particularly those afflicted with inflammatory bowel diseases. Aim: This study aimed to address the prevalence of complementary and alternative medicines use among Portuguese inflammatory bowel diseases' patients. Methods: Patients were invited to fill an anonymous questionnaire concerning the use of complementary and alternative medicines. Results: Thirty-one per cent of the patients reported having used complementary and alternative medicines in the past, whereas 12% were using them by the time the questionnaire was administered. Fifty-nine per cent of the users did not share this information with their physician, whereas 14% and 8% discontinued their medication and periodical examination, respectively. Steroids prescription (OR = 2.880) and a higher instruction level (OR = 3.669) were predictors of complementary and alternative medicines use in this cohort. Conclusions: Roughly a third of Portuguese IBD patients had used CAM. Steroid treatment and an academic degree are associated with CAM use. Given the potential side effects and interactions, patient information about the benefits and limitations of conventional and complementary treatments should be reinforced. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
- Delayed intramural duodenal hematoma after a simple diagnostic endoscopic ultrasonography fine-needle aspiration procedurePublication . Roseira, Joana; Cunha, Miguel; Sousa, Helena Tavares; Rachadell, J.; Brito, JorgeA 65-year-old man was evaluated for a difficult-to-characterize pancreatic head mass in the setting of idiopathic chronic pancreatitis. He had no other relevant medical history and was not taking any anticoagulant or antiplatelet treatment. Endoscopic ultrasonography fine-needle aspiration (EUS-FNA) failed to reveal neoplasm cells. A linear array echoendoscope (Olympus GF-UCT140, Center Valley, PA) was advanced up to the duodenal bulb, from which the head of the pancreas was visualized. After ensuring a vessel-free access to the pancreatic parenchyma, the FNA was performed using a 22G needle (Slimline 22G Handle Needle; Boston Scientific, Marlborough, MA) with a total of 3 passes (Figure 1). Three weeks after this procedure, the patient was admitted for hematemesis preceded by vomiting. On admission, his general physical examination was unremarkable except for jaundice. His blood tests showed no anemia; his platelet count, prothrombin time, amylase, and liver enzymes were within normal range, but his total bilirubin level was elevated (7.4 mg/dL). Upper gastrointestinal endoscopy showed Mallory-Weiss tears, an evident extrinsic compression of the knee, and the second portion of the duodenum, which could not be passed by the endoscope. The investigation by computed tomography and magnetic resonance cholangiopancreatography led to the diagnosis of an 11-cm intramural duodenal hematoma (IDH), leading to both gastric outlet and main biliary duct obstruction (Figure 2). The case was successfully managed with nasogastric decompression and exclusive parenteral feeding. Symptoms improved within 15 days, and cholestasis progressively disappeared.
- 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; Sousa, Helena Tavares; Patita, Marta; Lago, Paula; Ramos, Jaime; Afonso, Joana; Redondo, Isabel; Machado, Patrícia; Philip, George; Lopes, Joanne; Carneiro, FátimaSuppressor 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.
- Use of alfentanil in palliative carePublication . Ferraz, José António; Sousa, Filipa; Alves, Lucy; Liu, Patricia; Coelho, SaraAlfentanil is used for chronic pain relief in palliative care. However, there is a dearth of data on its use. For this reason, a decision was made to review the use of alfentanil in palliative care. Retrospective study was carried out in a palliative care service. The files of patients who received alfentanil as an intravenous or subcutaneous continuous infusion for pain relief, between January 2018 and April 2019. In total, 111 patients received alfentanil out of 113 admissions. Of them, 56 were male, and the median age was 70 years. The median number of days on alfentanil was 6 (range 1 to 129). The most frequent primary reasons for switching to alfentanil was uncontrolled pain in 52 (46%) patients and renal impairment in 24 (21%) patients. The median 24-h initial dose of alfentanil was 4 mg (1–20), and the median final 24-h dose of alfentanil was 5 mg (1–60), (p < 0.001). The initial 24-h median number of rescue doses was 2 (0–8), and the final median number of rescue doses was 1 (0 to 8), (p = 0.025). In 56 patients who were on alfentanil for at least 7 days, the dose decreased in 3 (5%), remained stable in 10 (18%) and increased in 43 (77%). The patient on alfentanil for 129 days maintained the same dose throughout that period. Alfentanil can be a useful second-line opioid. The induction of tolerance does not seem to be particularly rapid with alfentanil.
- Functional analysis of two novel TBX5 variants present in individuals with Holt-Oram syndrome with different clinical manifestationsPublication . Varela, Debora; Varela, Tatiana; Conceição, Natércia; Ferreira, Angela; Marques, Nuno; Silva, Ana Paula; Azevedo, Pedro; Pereira, Salome; Camacho, Ana; de Jesus, Ilidio; Cancela, M. LeonorHolt-Oram syndrome (HOS) is a rare disorder characterized by cardiac and upper-limb defects. Pathogenic variants in TBX5-a gene encoding a transcription factor important for heart and skeletal development-are the only known cause of HOS. Here, we present the identification and functional analysis of two novel TBX5 pathogenic variants found in two individuals with HOS presenting distinct phenotypes. The individual with the c.905delA variant has a severe cardiac phenotype but mild skeletal defects, unlike the individual with the c.246_249delGATG variant who has no cardiac problems but severe upper limbs malformations, including phocomelia. Both frameshift variants, c.246_249delGATG and c.905delA, generate mRNAs harbouring premature stop codons which, if not degraded by nonsense mediated decay, will lead to the production of shorter TBX5 proteins, p.Gln302Argfs*92 and p.Met83Phefs*6, respectively. Immunocytochemistry results suggest that both mutated proteins are produced and furthermore, like the wild-type protein, p.Gln302Argfs*92 mutant appears to be mainly localized in the nucleus, in contrast with p.Met83Phefs*6 mutant that displays a higher level of cytoplasmic localization. In addition, luciferase activity analysis revealed that none of the TBX5 mutants are capable of transactivating the NPPA promoter. In conclusion, our results provide evidence that both pathogenic variants cause a severe TBX5 loss-of-function, dramatically reducing its biological activity. The absence of cardiac problems in the individual with the p.Met83Phefs*6 variant supports the existence of other mechanisms/genes underlying the pathogenesis of HOS and/or the existence of an age-related delay in the development of a more serious cardiac phenotype. Further studies are required to understand the differential effects observed in the phenotypes of both individuals.
- Short Inflammatory Bowel Disease Questionnaire: translation and validation to the Portuguese languagePublication . Roseira, Joana; Sousa, Helena Tavares; Marreiros, Ana; Contente, Luís F.; Magro, FernandoBackground The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a widely used instrument to assess Health-related Quality of Life (HRQoL) among inflammatory bowel disease (IBD) patients. Our aim was to translate and adapt the SIBDQ so that it could be adequately used in Portugal. Methods This is a prospective design cohort study undertaken at a tertiary hospital. This study took place simultaneously with the first part of the SexIDI study, a study aiming to assess the impact of IBD on patients’ sexual QoL. The original SIBDQ was translated by two independent translators and adapted by an IBD expert panel following the opinions of a convenient sample of 5 IBD patients. Afterwards, IBD patients from the outpatient clinic were consecutively invited to fill the Portuguese version of the questionnaire (SIBDQ-PT) at three different timepoints (0, 2, 4 weeks). Ninety-two patients completed the SIBDQ-PT at baseline, whereas 33 did so after 2 and 4 weeks (approximately). Statistical analysis was performed using SPSS version 25, and the following aspects were analysed: reliability (through internal consistency, test–retest and intraclass correlation), validity (through exploratory factor analysis [EFA], and Pearson correlation coefficient for linear correlations), score distribution, and responsiveness analysis (through t-student tests). Results Overall, SIBDQ-PT was shown to have a high internal consistency (Cronbach's α = 0.80) and a high test–retest reliability (0.80 [CI 0.74–0.86] and 0.69 [CI 0.50–0.82]). EFA detected four dimensions—bowel, social, emotional and systemic. As expected, an overall SIBDQ-PT score was positively correlated with sexual satisfaction (r = 0.27; p < 0.05) and negatively correlated with depression (r = − 0.63; p < 0.01). Moreover, SIBDQ-PT was found to have an adequate score distribution, and to be responsive, as there was a significant subscore change for patients who reported an “overall worsening in general well-being” (0.93 ± 0.13 decrease; p < 0.01). Conclusions The Portuguese version of the SIBDQ hereby presented is a reliable, valid and responsive instrument that can be used to measure HRQoL among Portuguese IBD patients.
- O suporte é básico e salva vidas uma história de sucesso da cadeia de sobrevivência:caso clinicoPublication . Costa, Hugo; Jacob, Miguel; Pereira, Rafaela; Ribeiro, SofiaReportamos um caso clínico de um jovem de 38 anos, vítima de paragem cardiorrespiratória em fibrilhação ventricular. O doente foi recuperado após 7 minutos de suporte básico de vida mais 26 minutos de suporte avançado de vida com 5 choques pelo monitor- desfibrilhador e LUCAS adaptado até à recuperação da circulação espontânea. Após estabilização o doente foi internado na Unidade de Cuidados Intensivos Polivalentes e posteriormente transferido para o serviço de Cardiologia, onde efetuou avaliação da anatomia coronária com coronárias sem lesões. Após descartadas as principais causas para o sucedido e passiveis de tratamento, o doente teve indicação para a colocação de um cardioversor - desfibrilhador- implantável. O caso clínico enaltece a rápida atuação e o elo de ligação da cadeia de sobrevivência, com suporte básico de vida e o contacto precoce com o centro de orientação de doentes urgentes, essenciais para a chegada em tempo útil da equipa de emergência médica e posterior ressuscitação cardiopulmonar avançada.
- Bradiarritmias: abordagem em contexto pré e intra-hospitalarPublication . Costa, Hugo; Azevedo, Pedro; Carvalho, Daniela; Candeias, Rui; Jesus, IlidioAs bradiarritmias são eventos arrítmicos frequentes em contexto urgente e emergente. A sua frequência aumenta com a idade devido à evolução degenerativa do sistema de condução cardíaco, embora também possam ser encontradas em idades jovens e atletas treinados. A doença sinoauricular e os bloqueios auriculoventriculares são os mecanismos fisiopatológicos mais comuns no que diz respeito aos distúrbios da condução. Uma correta investigação é essencial na identificação etiológica (intrínseca ou extrínseca ao tecido cardíaco) bem como na forma de instalação e no caráter de reversibilidade. As causas reversíveis devem ser prontamente corrigidas e são essenciais na estabilização do doente. Na presença de bradicardia, a apresentação clínica deve guiar a abordagem inicial, assim como a existência de sinais de gravidade no electrocardiograma. A terapêutica farmacológica e o pacing transcutâneo são medidas/atitudes intermédias de suporte hemodinâmico como ponte para intervenções especializadas. Assim, uma correta avaliação e rápida abordagem em ambiente pré-hospitalar ou hospitalar possibilita a estabilização do doente e posterior encaminhamento para estudo dirigido.