Percorrer por autor "Saraiva, J"
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- Fetal-maternal interface impedance parallels local NADPH oxidase related superoxide production.Publication . Guedes-Martins, L; Silva, E; Gaio, AR; Saraiva, J; Soares, AI; Afonso, J; Macedo, F; Almeida, HBlood flow assessment employing Doppler techniques is a useful procedure in pregnancy evaluation, as it may predict pregnancy disorders coursing with increased uterine vascular impedance, as pre-eclampsia. While the local causes are unknown, emphasis has been put on reactive oxygen species (ROS) excessive production. As NADPH oxidase (NOX) is a ROS generator, it is hypothesized that combining Doppler assessment with NOX activity might provide useful knowledge on placental bed disorders underlying mechanisms. A prospective longitudinal study was performed in 19 normal course, singleton pregnancies. Fetal aortic isthmus (AoI) and maternal uterine arteries (UtA) pulsatility index (PI) were recorded at two time points: 20-22 and 40-41 weeks, just before elective Cesarean section. In addition, placenta and placental bed biopsies were performed immediately after fetal extraction. NOX activity was evaluated using a dihydroethidium-based fluorescence method and associations to PI values were studied with Spearman correlations. A clustering of pregnancies coursing with higher and lower PI values was shown, which correlated strongly with placental bed NOX activity, but less consistently with placental tissue. The study provides evidence favoring that placental bed NOX activity parallels UtA PI enhancement and suggests that an excess in oxidation underlies the development of pregnancy disorders coursing with enhanced UtA impedance.
- Informed Treatment Consent and Refusal in Advanced Endonasal Surgery: The Ethical Dilemma of Olfaction Sacrifice in Surgery for Chronic Rhinosinusitis with PolyposisPublication . Subtil, J; Araújo, JP; Saraiva, J; Santos, A; Vera-Cruz, P; Paço, J; Pais, DINTRODUCTION: Olfaction is frequently affected in chronic rhino-sinusitis with polyposis and has been recognised to have important impact on quality of life. Surgical resolution on cases of maximal medical therapy failure is an option to relieve symptoms, with debates as to how extensive surgery should be. A more radical approach will achieve better disease control with less relapse, but can also compromise olfaction. This decision about a more radical surgical approach should be shared with the patient. Thorough informed consent regarding disease control and hyposmia should be taken. MATERIAL AND METHODS: Literature review and consultation with a board of experts. RESULTS AND DISCUSSION: We propose some elements to be included in the informed consent discussion, in order to broadly address the surgical limitations regarding anosmia as a frequent complaint, as well as the different options and their associated consequences. CONCLUSION: Radical surgery decision making should be shared with the patient and the informed consent should be as thorough as possible regarding disease control and hyposmia resolution.
- Internal iliac and uterine arteries Doppler ultrasound in the assessment of normotensive and chronic hypertensive pregnant womenPublication . Guedes-Martins, L; Cunha, A; Saraiva, J; Gaio, R; Macedo, F; Almeida, HThe objective of this work was to compare Doppler flows pulsatility index (PI) and resistance indexes (RI) of uterine and internal iliac arteries during pregnancy in low risk women and in those with stage-1 essential hypertension. From January 2010 and December 2012, a longitudinal and prospective study was carried out in 103 singleton uneventful pregnancies (72 low-risk pregnancies and 31 with stage 1 essential hypertension)at the 1(st), 2(nd) and 3(rd) trimesters. Multiple linear regression models, fitted using generalized least squares and whose errors were allowed to be correlated and/or have unequal variances, were employed; a model for the relative differences of both arteries impedance was utilized. In both groups, uterine artery PI and RI exhibited a gestational age related decreasing trend whereas internal iliac artery PI and RI increased. The model testing the hemodynamic adaptation in women with and without hypertension showed similar trend. Irrespective of blood pressure conditions, the internal iliac artery resistance pattern contrasts with the capacitance pattern of its immediate pelvic division, suggesting a pregnancy-related regulatory mechanism in the pelvic circulation.
- Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated Non Small Cell Lung Cancer (NSCLC)Publication . Figueiredo, A; Almeida, M A; Almodovar, M T; Alves, P; Araújo, A; Araújo, D; Barata, F; Barradas, L; Barroso, A; Brito, U; Camacho, E; Canário, D; Cardoso, T; Chaves, A; Costa, L; Cunha, J; Duarte, J; Estevinho, F; Felizardo, M; Fernandes, J P; Ferreira, L; Ferreira, L; Fidalgo, P; Freitas, C; Garrido, P; Gil, N; Hasmucrai, D; Jesus, E; Lopes, J A; de Macedo, J E; Meleiro, A; Neveda, R; Nogueira, F; Pantorotto, M; Parente, B; Pego, A; Rocha, M; Roque, J; Santos, C; Saraiva, J; Silva, E; Silva, S; Simões, S; Soares, M; Teixeira, E; Timóteo, T; Hespanhol, VOBJECTIVE: The main aim of the study was to evaluate the efficacy and safety profile of Nivolumab, an immune-checkpoint-inhibitor antibody, in advanced, previously treated, Non-Small Cell Lung Cancer (NSCLC) patients, in a real world setting. METHODS: We performed a retrospective, multicentre data analysis of patients who were included in the Portuguese Nivolumab Expanded Access Program (EAP). Eligibility criteria included histologically or citologically confirmed NSCLC, stage IIIB and IV, evaluable disease, sufficient organ function and at least one prior line of chemotherapy. The endpoints included Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Safety analysis was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and immune-related Adverse Events (irAEs) were treated according to protocol treatment guidelines. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Data was analysed using SPSS, version 21.0 (IBM Statistics). RESULTS: From June 2015 to December 2016, a total of 229 patients with advanced NSCLC were enrolled at 30 Portuguese centres. Clinical data were collected up to the end of July 2018. The baseline median age was 64 years (range 37-83) and the majority of patients were males (70.3%) and former/current smokers (69.4%). Patients with non-squamous histology predominated (88.1%), and 67.6% of the patients had received 2 or more prior lines of chemotherapy. Out of 229 patients, data was available for 219 patients (3 patients did not start treatment, while data was unavailable in 7 patients); of the 219 patients, 15.5% were not evaluated for radiological tumour assessment, 1.4% had complete response (CR), 21% partial response (PR), 31% stable disease (SD) and 31.1% progressive disease (PD). Thus, the ORR was 22.4% and DCR was 53.4% in this population. At the time of survival analysis the median PFS was 4.91 months (95% CI, 3.89-6.11) and median OS was 13.21 months (95% CI, 9.89-16.53). The safety profile was in line with clinical trial data. CONCLUSIONS: Efficacy and safety results observed in this retrospective analysis were consistent with observations reported in clinical trials and from other centres.
- Reference Ranges for Uterine Artery Pulsatility Index during the Menstrual Cycle: A Cross-Sectional Study.Publication . Guedes-Martins, L; Gaio, R; Saraiva, J; Cerdeira, S; Matos, L; Silva, E; Macedo, F; Almeida, HBACKGROUND: Cyclic endometrial neoangiogenesis contributes to changes in local vascular patterns and is amenable to non-invasive assessment with Doppler sonography. We hypothesize that the uterine artery (UtA) impedance, measured by its pulsatility index (PI), exhibits a regular pattern during the normal menstrual cycle. Therefore, the main study objective was to derive normative new day-cycle-based reference ranges for the UtA-PI during the entire cycle from days 1 to 34 according to the isolated time effect and potential confounders such as age and parity. METHODS: From January 2009 to December 2012, a cross-sectional study of 1,821 healthy women undergoing routine gynaecological ultrasound was performed. The Doppler flow of the right and left UtA-PI was studied transvaginally by colour and pulsed Doppler imaging. The mean right and left values and the presence or absence of a bilateral protodiastolic notch were recorded. Reference intervals for the PI according to the cycle day were generated by classical linear regression. RESULTS: The majority of patients (97.5%) presented unilateral or bilateral UtA notches. The crude 5th, 50th, and 95th reference percentile curves of the UtA-PI at 1-34 days of the normal menstrual cycle were derived. In all curves, a progressive significant decrease occurred during the first 13 days, followed by an increase and recovery in the UtA-PI. The adjusted 5th, 50th, and 95th reference percentile curves for the effects of age and parity were also obtained. These two conditions generated an approximately identical UtA-PI pattern during the cycle, except with small but significant reductions at the temporal extremes. CONCLUSIONS: The median, 5th, and the 95th percentiles of the UtA-PI decrease during the first third of the menstrual cycle and recover to their initial values during the last two thirds of the cycle. The rates of decrease and recovery depend significantly on age and parity.
- Relationship between body mass index and mean arterial pressure in normotensive and chronic hypertensive pregnant women: a prospective, longitudinal study.Publication . Guedes-Martins, L; Carvalho, M; Silva, C; Cunha, A; Saraiva, J; Macedo, F; Almeida, H; Gaio, ARBACKGROUND: Being overweight is associated with both higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) during pregnancy and increased risk of gestational hypertensive disorders. The objective of this study was to determine and quantify the effect of body mass index (BMI) on mean arterial pressure (MAP) at several time points throughout pregnancy in normotensive (NT) and chronic hypertensive pregnant (HT) women. METHODS: A prospective longitudinal study was carried out in 461 singleton pregnancies (429 low-risk and 32 with chronic arterial hypertension), with measurements taken at the 1(st), 2(nd), and 3(rd) trimesters and at delivery. Linear mixed-effects regression models were used to evaluate the time-progression of BMI, SBP, DBP and MAP during pregnancy (NT vs. HT). The longitudinal effect of BMI on MAP, adjusted for the hypertensive status, was investigated by the same methodology. RESULTS: BMI consistently increased with time in both NT and HT women. In contrast, MAP decreased during the first half of pregnancy, after which it increased until the moment of delivery in both groups. A 5-unit increase in BMI was predicted to produce an increase of approximately 1 mmHg in population MAP values. This effect is independent from the time period and from hypertensive status. CONCLUSIONS: In both NT and HT pregnant women, MAP is strongly (and significantly) influenced by increases in BMI.
- Uterine artery impedance during the first eight postpartum weeks.Publication . Guedes-Martins, L; Gaio, AR; Saraiva, J; Cunha, A; Macedo, F; Almeida, HThe aim of this study was to construct reference ranges for the uterine artery (UtA) mean pulsatility (PI) and resistance (RI) indices from 1-8 weeks postpartum. A prospective, cross-sectional, and observational study was performed with 320 healthy women from week 1 through week 8 postpartum. UtAs were examined transvaginally using colour and pulsed Doppler imaging, and the means of the right and left values of the PI and RI, as well as the presence or absence of a bilateral protodiastolic notch, were recorded. The 5(th), 50(th) and 95(th) reference percentile curves for the UtA-PI and UtA-RI were derived using regression models. The adjusted reference intervals uncovered a convergence trend at the week 8 time-point, although impedance was lower at the week 1 time-point in multiparous women compared with primiparous women. The notching prevalence was 22.5% (9/40) at week 1 and 95.0% (38/40) at week 8. The study revealed consistent evidence of a progressive increase of postpartum uterine impedance and provided new average UtA-PI and UtA-RI reference charts for weeks 1 through 8. Multiparity does not change the trend but does impart a lower rate of increase, likely as a consequence of previous vascular structural and functional differences.
- Water protection after tympanostomy (Shepard) tubes does not decrease otorrhea incidence - retrospective cohort studyPublication . Subtil, J; Jardim, A; Peralta Santos, A; Araújo, J; Saraiva, J; Paço, JINTRODUCTION: Myringotomy for tube insertion is the most common otologic surgery. Otorrhea is a frequent complication of this procedure and, to prevent it, most surgeons strongly recommend avoiding contact with water as this is thought to adversely impact on post-operative quality of life. OBJECTIVE: To understand the benefit of this recommendation. METHODS: Observational study - retrospective cohort study comparing the incidence of post-operative otorrhea and its impact on patients' quality of life, in two groups of patients comprising children under 10 years of age who underwent bilateral myringotomy and tube placement for chronic otitis media with effusion between May 2011 and May 2012. One group received water protection care after surgery, the other did not. Data was collected through telephonic interview, after one year of follow up (one year after the procedure). Water exposure without protection was considered the exposure event. Incidence of otorrhea and perceived impact on quality of life were the outcome measures. Results were compared after logistic regression. RESULTS: We included 143 children: 116 were not exposed to water without protection and 27 were exposed. In the not exposed group 36.2% had at least one episode of otorrhea, compared to 40.0% of the exposed group. Odds ratio for otorrhea on exposed was 1.21 (95% CI 0.51-2.85, p=0.6). Negative impact on quality of life was reported by parents of 48.2% on the not exposed children, compared to 40.7% on the exposed group. This difference was not significant (p=0.5). CONCLUSION: We found that recommending water protection did not have beneficial effect on the incidence of otorrhea after myringotomy with tubes on chronic otitis media with effusion. However, such measures did not appear to have a negative impact on quality of life. This is a populational observational study with few cases (143 cases); these final statements would be better stated by a very large populational study with another large control group.
