Browsing by Author "Fonseca, C"
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- A 2018 Overview of Diuretic Resistance in Heart FailurePublication . Jardim, SI; Ramos dos Santos, L; Araújo, I; Marques, F; Branco, P; Gaspar, A; Fonseca, CHeart failure is a disease with high direct and indirect costs. Current treatment includes drugs that alter disease progression and drugs that to improve symptoms. Loop diuretics are the cornerstone of congestion relief for acute management, as well as for chronic stabilization. In heart failure patients, maximal diuretic response is reduced by many individual factors. Diuretic resistance is defined as failure to achieve effective congestion relief despite appropriate or escalating diuretic doses. Its causes include impaired delivery of the diuretic to its luminal site of action, neurohormonal activation, tubular compensatory adaptation and drug interactions. Several strategies can be employed to aid decongestion of patients with impaired diuretic response. These include salt restriction, a higher effective single dose or higher dose frequency of loop diuretics, continuous infusion of diuretics and/or sequential nephron blockade through a synergistic combination of two or more diuretics from different classes. Ultrafiltration has also been found to be another effective and safe therapeutic option and should be considered in patients with refractory diuretic resistance. Overall, there is a lack of high-quality clinical data to guide the choice of treatment strategy and therapy should be tailored on a case-by-case basis.
- Circulating Tumor DNA Tracking Through Driver Mutations as a Liquid Biopsy-Based Biomarker for Uveal MelanomaPublication . Bustamante, P; Tsering, T; Coblentz, J; Mastromonaco, C; Abdouh, M; Fonseca, C; Proença, RP; Blanchard, N; Dugé, CL; Andujar, RAS; Youhnovska, E; Burnier, MN; Callejo, SA; Burnier, JVBackground: Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite good primary tumor control, up to 50% of patients develop metastasis, which is lethal. UM often presents asymptomatically and is usually diagnosed by clinical examination and imaging, making it one of the few cancer types diagnosed without a biopsy. Hence, alternative diagnostic tools are needed. Circulating tumor DNA (ctDNA) has shown potential as a liquid biopsy target for cancer screening and monitoring. The aim of this study was to evaluate the feasibility and clinical utility of ctDNA detection in UM using specific UM gene mutations. Methods: We used the highly sensitive digital droplet PCR (ddPCR) assay to quantify UM driver mutations (GNAQ, GNA11, PLCβ4 and CYSTLR2) in cell-free DNA (cfDNA). cfDNA was analyzed in six well established human UM cell lines with known mutational status. cfDNA was analyzed in the blood and aqueous humor of an UM rabbit model and in the blood of patients. Rabbits were inoculated with human UM cells into the suprachoroidal space, and mutated ctDNA was quantified from longitudinal peripheral blood and aqueous humor draws. Blood clinical specimens were obtained from primary UM patients (n = 14), patients presenting with choroidal nevi (n = 16) and healthy individuals (n = 15). Results: The in vitro model validated the specificity and accuracy of ddPCR to detect mutated cfDNA from UM cell supernatant. In the rabbit model, plasma and aqueous humor levels of ctDNA correlated with tumor growth. Notably, the detection of ctDNA preceded clinical detection of the intraocular tumor. In human specimens, while we did not detect any trace of ctDNA in healthy controls, we detected ctDNA in all UM patients. We observed that UM patients had significantly higher levels of ctDNA than patients with nevi, with a strong correlation between ctDNA levels and malignancy. Noteworthy, in patients with nevi, the levels of ctDNA highly correlated with the presence of clinical risk factors. Conclusions: We report, for the first time, compelling evidence from in vitro assays, and in vivo animal model and clinical specimens for the potential of mutated ctDNA as a biomarker of UM progression. These findings pave the way towards the implementation of a liquid biopsy to detect and monitor UM tumors.
- Conjunctival Melanoma: Association of Cyclooxygenase-2 Tumor Expression to PrognosisPublication . Proença, R; Santos, M; Fonseca, C; Fernandes, J; Gaspar, MF; Proença, RPURPOSE: Conjunctival melanoma is a rare but potentially lethal tumor. Its biologic profile is still largely unknown, with recent studies aiming at establishing histopathological and genetic tumor profiles. The aim of this study was to analyze the association between clinicopathological characteristics and tumor expression of cyclooxygenase-2 (COX-2) to prognosis, assessing its usefulness as a possible prognostic marker. METHODS: Case series of 50 patients from 1991 to 2008 with pathologically proven conjunctival melanoma. Demographic, clinical, and pathological characteristics were evaluated by reviewing clinical files and pathology. Expression of COX-2 was studied by immunohistochemistry of formalin-fixed paraffin-embedded tissue samples of 20 melanomas. Samples were classified in a score which included intensity of staining and percentage of cells with positive reactivity. RESULTS: Clinicopathological features significantly associated (p < .05) with a poor prognosis (death) included involvement of fornix and tarsal conjunctiva, tumor thickness exceeding 2 mm, local tumor recurrence, lymph node, and systemic metastasis. In the immunohistochemistry study (n = 20), 18 cases expressed COX-2 although with different scores. However, only cases with a high score were associated with a poor outcome. Multivariate association analysis revealed that recurrence rate, metastasis, corneal invasion, and tumor thickness were associated with high score cases and, therefore, with a clinical profile with a higher risk of death. CONCLUSIONS: Results suggest that higher COX-2 expression may be a negative prognostic factor in conjunctival melanoma. Further studies can address the potential use of anti-COX-2 drugs as adjuvant therapy of this disease.
- Epilepsia Partialis Continua After an Anterior Circulation Ischaemic StrokePublication . Bentes, C; Franco, AC; Peralta, A; Viana, P; Martins, H; Morgado, C; Casimiro, C; Fonseca, C; Geraldes, R; Canhão, P; Pinho e Melo, T; Paiva, T; Ferro, JMBackground and purpose: Although cerebrovascular disorders are the main cause of epilepsia partialis continua (EPC) in adulthood, the frequency of EPC after stroke is unknown. The aim was to prospectively ascertain its frequency 1 year after an ischaemic stroke. Methods: This was a prospective study of consecutive acute anterior circulation ischaemic stroke patients, previously independent, with an admission National Institutes of Health Stroke Scale score ≥4, an acute ischaemic lesion on imaging and no previous epileptic seizures. During admission patients received standardized diagnostic and medical care and were submitted to a neurophysiological evaluation protocol. One year after stroke, patients were re-evaluated by an epilepsy expert neurologist and performed a video-electroencephalogram with electromyography co-registration whenever myoclonus was observed during neurological examination for jerk-locked back averaging analysis (JLBA). EPC was defined as continuously repeated fragments of epileptic seizures, with preserved consciousness, lasting at least 1 h, and representing locally restricted epileptic activity. Results: In all, 151 acute anterior circulation stroke patients were consecutively included and prospectively evaluated, but 23 died in the first year. One year after stroke, from 127 patients alive, 117 (92.1%) underwent clinical and neurophysiological evaluation. In two (1.7%) patients, EPC diagnosis was made both by clinical and electroencephalographic criteria, namely JLBA. Both patients had a history of remote symptomatic seizures and one of them acute symptomatic seizures and non-convulsive status epilepticus criteria during the first 7 days after stroke. Conclusions: Despite its low frequency, the high stroke incidence makes post-stroke EPC relevant. This study draws attention to this recognizable condition with therapeutic and eventually prognostic implications.
- Increased Risk for Metachronous Gastric Adenocarcinoma Following Gastric MALT Lymphoma-A US Population-Based StudyPublication . Palmela, C; Fonseca, C; Faria, R; Baptista, RB; Ribeiro, S; Ferreira, AOGastric mucosa-associated lymphoid tissue lymphoma (gMALT) and gastric adenocarcinoma (GC) are long-term complications of chronic Helicobacter pylori (HP) gastritis. Treatment of HP infection induces remission in most patients with gMALT. Endoscopic follow-up is not currently endorsed after complete remission. However, the risk of GC in these patients is unclear. OBJECTIVE: The objective of this study is to estimate GC risk in gMALT patients. METHODS: The National Cancer Institute Surveillance, Epidemiology and End Results 13 (SEER) database-Nov 2014 Sub (1992-2012) was used to identify adult patients diagnosed with gMALT between 1992 and 2012. The standardized incidence ratio of second primary GC after a latency period of 12 months was calculated and compared to a reference SEER cohort of identical age, sex and time period. The risk of GC in these patients was also stratified by latency period (five years) and age. RESULTS: We identified 2195 cases of gMALT lymphoma, and 20 (0.91%) of them subsequently developed GC with a relative risk (RR) of 4.32 (95% CI 2.64-6.67) compared to the American population. The median latency time was five years and the risk was maintained afterward (RR 4.92, 95% CI 2.45-8.79). When stratified by age group the risk was highest for the 45-64 group (RR 14.04, 95% CI 5.64-28.93). CONCLUSION: gMALT lymphoma is associated with an increased risk of metachronous gastric adenocarcinoma. The risk is still present after more than five years of follow-up. Further studies may clarify the most adequate follow-up strategy.
- The 2021 Portuguese Society of Ophthalmology Joint Guidelines with Paediatric Rheumatology on the Screening, Monitoring and Medical Treatment of Juvenile Idiopathic Arthritis-Associated UveitisPublication . Leal, I; Miranda, V; Fonseca, C; Barbosa-Breda, J; Cordeiro Sousa, D; Mesquita-Marques, P; Araújo, J; Silva, MI; Pedrosa, AC; Palmares, J; Furtado, MJ; Macedo, M; Lages, V; Fonseca, S; Gonçalves, R; Ruão, M; Gomes Rodrigues, F; Ribeiro, M; Proença, R; Almeida, M; Liverani, M; Morais Pina, S; Bernardo, M; Nogueira, V; Guerra Pinto, R; Pinto Ferreira, F; Pinto Proença, R; Domingues, I; Guedes, M; Cordeiro, M; Fragata, F; Berens, O; Gregório, T; Brito, I; Oliveira-Ramos, F; Fonseca, JE; Figueira, LAim: To develop the first Ophthalmology joint guidelines with Paediatric Rheumatology with recommendations on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis (JIA-U), endorsed by the Portuguese Society of Ophthalmology (SPO). Methods: A systematic literature review was conducted to include publications up to July 14th 2020, with no language restrictions, in order to include all the international position papers/guidelines concerning the medical management of JIA-U and randomised clinical trials assessing the efficacy and safety of medical treatment in this field. We searched through MEDLINE (PubMed), Scopus, Web of Science and Cochrane Library. The Delphi modified technique to generate consensus was used. Preliminary evidence statements were subject to an anonymous agreement assessment and discussion process using an online survey, followed by further discussion and update at a national meeting. A draft of the manuscript with all recommendations was then circulated among all participants and suggestions were incorporated. The final version was again circulated before publication. Results: Twenty-six recommendations were developed focusing on the following topics: general management (3), screening and follow-up of uveitis (4), treatment (17) and health education in JIA-U among patients and families (2). Conclusion: These guidelines were designed to support the shared medical management of patients with JIA-U and emphasize the need for a multidisciplinary approach between Ophthalmology and Paediatric Rheumatology regarding the comprehensive care of JIA-U. We acknowledge that updating these recommendations will be warranted in the future, as more evidence becomes available.