Primary Antiphospholipid Syndrome: Pregnancy Outcome in a Portuguese Population

Introduction:Women with antiphospholipid syndrome(APS) may suffer from recurrent miscarriage, fetal death, fetal growth restriction (FGR), pre-eclampsia, placental abruption, premature delivery and thrombosis. Treatment with aspirin and low molecular weight heparin (LMWH) combined with close maternal-fetal surveillance can change these outcomes. Objective: To assess maternal and perinatal outcome in a cohort of Portuguese women with primary APS. Patients and Methods: A retrospective analysis of 51 women with primary APS followed in our institution (January 1994 to December 2007). Forty one(80.4%) had past pregnancy morbidity and 35.3%(n=18) suffered previous thrombotic events. In their past they had a total of 116 pregnancies of which only 13.79 % resulted in live births. Forty four patients had positive anticardiolipin antibodies and 33 lupus anticoagulant. All women received treatment with low dose aspirin and LMWH. Results: There were a total of 67 gestations (66 single and one multiple). The live birth rate was 85.1%(57/67) with 10 pregnancy failures: seven in the first and second trimesters, one late fetal death and two medical terminations of pregnancy (one APS related). Mean (± SD) birth weight was 2837 ± 812 g and mean gestational age 37 ± 3.3 weeks. There were nine cases of FGR and 13 hypertensive complications(4 HELLP syndromes). 54.4% of the patients delivered by caesarean section. Conclusions: In our cohort, early treatment with aspirin and LMWH combined with close maternal-fetal surveillance was associated with a very high chance of a live newborn.

Factor V Leiden and Prothrombin G20210A in Portuguese Women with Recurrent Miscarriage: Is it Worthwhile to Investigate?

OBJECTIVE: To compare the prevalence of factor V Leiden (FVL) and prothrombin (PT) G20210A mutations in Portuguese women with unexplained recurrent miscarriage (RM) and a control group of parous women. MATERIALS AND METHODS: FVL and PT G20210A analysis were carried out in 100 women with three or more consecutive miscarriages and 100 controls with no history of pregnancy losses. Secondary analysis was made regarding gestational age at miscarriage (embryonic and fetal losses). RESULTS: Overall, the prevalence of FVL and PT G20210A was similar in women with RM (5 and 3%) compared with controls (5 and 1%) OR 1.36 (CI 95% 0.45-4.08). In RM embryonic subgroup, PT G20210A was observed in 1.3% of women and FVL prevalence (2.6%) was inclusively lesser than that of controls. Both polymorphisms were more prevalent in women with fetal losses than in controls, although statistical significance was not reached due to the small size of the >10 weeks' subgroup. CONCLUSION: These data indicate that neither FVL nor PT G20210A is associated with RM prior to 10 weeks of gestation. Therefore, its screening is not indicated as an initial approach in Portuguese women with embryonic RM and negative personal thromboembolic history.

Validation of Two US Risk Scores for Percutaneous Coronary Intervention in a Single-Center Portuguese Population of Patients with Acute Coronary Syndrome

INTRODUCTION: New scores have been developed and validated in the US for in-hospital mortality risk stratification in patients undergoing coronary angioplasty: the National Cardiovascular Data Registry (NCDR) risk score and the Mayo Clinic Risk Score (MCRS). We sought to validate these scores in a European population with acute coronary syndrome (ACS) and to compare their predictive accuracy with that of the GRACE risk score. METHODS: In a single-center ACS registry of patients undergoing coronary angioplasty, we used the area under the receiver operating characteristic curve (AUC), a graphical representation of observed vs. expected mortality, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analysis to compare the scores. RESULTS: A total of 2148 consecutive patients were included, mean age 63 years (SD 13), 74% male and 71% with ST-segment elevation ACS. In-hospital mortality was 4.5%. The GRACE score showed the best AUC (0.94, 95% CI 0.91-0.96) compared with NCDR (0.87, 95% CI 0.83-0.91, p=0.0003) and MCRS (0.85, 95% CI 0.81-0.90, p=0.0003). In model calibration analysis, GRACE showed the best predictive power. With GRACE, patients were more often correctly classified than with MCRS (NRI 78.7, 95% CI 59.6-97.7; IDI 0.136, 95% CI 0.073-0.199) or NCDR (NRI 79.2, 95% CI 60.2-98.2; IDI 0.148, 95% CI 0.087-0.209). CONCLUSION: The NCDR and Mayo Clinic risk scores are useful for risk stratification of in-hospital mortality in a European population of patients with ACS undergoing coronary angioplasty. However, the GRACE score is still to be preferred.

Spectrum and Frequency of GJB2 Mutations in a Cohort of 264 Portuguese Nonsyndromic Sensorineural Hearing Loss Patients

OBJECTIVE: To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese nonsyndromic sensorineural hearing loss (NSSHL) patients. DESIGN: Sequencing of the coding region, basal promoter, exon 1, and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions. STUDY SAMPLE: A cohort of 264 Portuguese NSSHL patients. RESULTS: At least one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only one mutant allele. Subsequent analysis revealed that the GJB6 deletion del(GJB6-D13S1854) was present in at least 7.4% (2/27) of the patients carrying only one mutant GJB2 allele. Overall, one in five (55/264) of the patients were diagnosed as having DFNB1-related NSSHL, of which the vast majority (53/55) harboured only GJB2 mutations. CONCLUSIONS: This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families.

Rhinoscleroma in a 5-year-old Portuguese Child

Rhinoscleroma is a chronic granulomatous infectious disease that is rare in Western Europe. We report the case of a 5-year-old Portuguese boy diagnosed with rhinoscleroma in the context of recurrent epistaxis. He had a 6-month course of antibiotic (amoxicillin plus clavulanate) therapy with full recovery.

Trends in Primary Angioplasty in Portugal From 2002 to 2013 According to the Portuguese National Registry of Interventional Cardiology

INTRODUCTION AND OBJECTIVES: The aim of the present paper was to report trends in coronary angioplasty for the treatment of ST-elevation myocardial infarction (STEMI) in Portugal. METHODS: Prospective multicenter data from the Portuguese National Registry of Interventional Cardiology (RNCI) and official data from the Directorate-General for Health (DGS) were studied to analyze percutaneous coronary intervention (PCI) procedures for STEMI from 2002 to 2013. RESULTS: In 2013, 3524 primary percutaneous coronary intervention (p-PCI) procedures were performed (25% of all procedures), an increase of 315% in comparison to 2002 (16% of all interventions). Between 2002 and 2013 the rate increased from 106 to 338 p-PCIs per million population per year. Rescue angioplasty decreased from 70.7% in 2002 to 2% in 2013. During this period, the use of drug-eluting stents grew from 9.9% to 69.5%. After 2008, the use of aspiration thrombectomy increased, reaching 46.7% in 2013. Glycoprotein IIb-IIIa inhibitor use decreased from 73.2% in 2002 to 23.6% in the last year of the study. Use of a radial approach increased steadily from 8.3% in 2008 to 54.6% in 2013. CONCLUSION: During the reporting period there was a three-fold increase in primary angioplasty rates per million population. Rescue angioplasty has been overtaken by p-PCI as the predominant procedure since 2006. New trends in the treatment of STEMI were observed, notably the use of drug-eluting stents and radial access as the predominant approach.

Next-Generation Sequencing of Hereditary Hemochromatosis-Related Genes: Novel Likely Pathogenic Variants Found in the Portuguese Population

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1G>C)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5'-UTR of HAMP gene (c.-25G>A). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders.

Symptom Clusters and Survival in Portuguese Patients with Advanced Cancer

This study aimed to identify clusters of symptoms, to determine the patient characteristics associated with identified, and determine their strength of association with survival in patients with advanced cancer (ACPs). Consecutively eligible ACPs not receiving cancer-specific treatment, and referred to a Tertiary Palliative Care Clinic, were enrolled in a prospective cohort study. At first consultation, patients rated 9 symptoms through the Edmonton Symptom Assessment System (0-10 scale) and 10 others using a Likert scale (1-5). Principal component analysis was used in an exploratory factor analysis to identify. Of 318 ACPs, 301 met eligibility criteria with a median (range) age of 69 (37-94) years. Three SCs were identified: neuro-psycho-metabolic (NPM) (tiredness, lack of appetite, lack of well-being, dyspnea, depression, and anxiety); gastrointestinal (nausea, vomiting, constipation, hiccups, and dry mouth) and sleep impairment (insomnia and sleep disturbance). Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter survival was observed for patients with the NPM cluster (58 vs. 23, P < 0.001), as well as for patients with two or more SCs (45 vs. 21, P = 0.005). In a multivariable model for survival at 30-days, age (HR: 0.98; 95% CI: 0.97-0.99; P = 0.008), hospitalization at inclusion (HR: 2.27; 95% CI: 1.47-3.51; P < 0.001), poorer performance status (HR: 1.90, 95% CI: 1.24-2.89; P = 0.003), and NPM (HR: 1.64; 95% CI: 1.17-2.31; P = 0.005), were associated with worse survival. Three clinically meaningful SC in patients with advanced cancer were identifiable. The NPM cluster and the presence of two or more SCs, had prognostic value in relation to survival.