Northern Portuguese Population Research Articles

Osteonecrosis of the Jaw Associated with Bisphosphonates Infusion for Treatment of Plasma Cell Myeloma-A Retrospective Observational Study of Northern Portuguese Population.

Objectives: To verify medication-related osteonecrosis of the jaw (MRONJ) frequency among patients with plasma cell myeloma (PCM) that had been treated with bisphosphonates, to identify predisposing factors that could influence the development of osteonecrosis. Methods: This observational retrospective study was performed at the Department of Hematology of Hospital Center of Porto (CHUP), Portugal. Results: The study population (n = 112) had a 15.2% (n = 17) prevalence of osteonecrosis. Clinically, bone exposure was the most frequently observed sign, present in 100% (n = 17) of the patients, followed by inflammation in 82.4% (n = 14), orofacial pain in 70.6% (n = 12), suppuration in 47.1% (n = 8), and intra or extra-oral fistula in 17.6% (n = 3) of the cases. The most frequent triggering local factor was dental extraction (82.4%). There was a dependence between the presence of extractions and the development of MRONJ (p < 0.001) but not with the time elapsed from the initiation of infusions with BPs and dental extractions (p = 0.499). In the sample of patients with multiple myeloma (MM), 13.8% were found to be more likely to develop MRONJ after an extraction. Conclusions: The most common local predisposing factor was dental extraction. No dependence was observed between the development of osteonecrosis and the time elapsed from the beginning of treatment with bisphosphonates infusions to surgical procedures.

Knowledge about COVID-19 Best Practices in the North of Portugal and the Importance of Health Education in the Prevention of Pandemic Events

Introduction: The rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made COVID-19 one of the biggest pandemics of all time, with several devastating public health challenges. In this study, we investigated the knowledge towards COVID-19 best practices in the north of Portugal. Methods: A descriptive cross-sectional study was performed with a convenience sample of the population of northern Portugal to assess their knowledge about COVID-19, SARS-CoV-2 and measures to prevent and mitigate pandemics. An online validated questionnaire was completed by 411 participants, from September to October 2020. Results: The overall correct knowledge was 81.3%, which indicates a good knowledge by the northern Portuguese respondents about COVID-19. The correct answer score differed considerably between men and women, being significantly higher among the latter (12.28 ± 1.22; p = 0.011). Moreover, the highest knowledge was observed in participants who attended high school or above (12.27 ± 1.21; p &lt; 0.000). Conclusion: This study contributes to the analysis of COVID-19 knowledge by the northern Portuguese population, emphasizes the crucial role of health education in the control and mitigation of the COVID-19 pandemic, and provides field-based evidence to prevent the next pandemic event.

Neuro-COVID frequency and short-term outcome in the Northern Portuguese population.

Background and purposeCOVID‐19‐related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population‐based perspective are lacking.MethodsWe conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020.ResultsAmong 1261 hospitalised COVID‐19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well‐defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID‐19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7–11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well‐defined CNS involvement.ConclusionsWe characterised the population of hospitalised COVID‐19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in‐hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID‐19 multidisciplinary patient care.

Epidemiology of Uveitis in a tertiary care centre in Portugal

ABSTRACT Purpose: Evaluate the prevalence and incidence, demographic characteristics, anatomical classification, concomitant complications and treatment of uveitis, as well as its association with systemic diseases in the northern Portuguese population referred to a tertiary care centre (São João Hospital, Porto). Methods: A retrospective observational study of 545 consecutive uveitis cases was performed between 12th April 2012 and the 26th October 2017. Uveitis was classified according to Standard Uveitis Nomenclature, while aetiology and complications were diagnosed by specific clinical and laboratory testing. Results: Prevalence was calculated to be 12,4 cases per 100,000 people while incidence was 3.9 cases per 100,000 people annual incidence. The ratio of females to males was 1.32:1 and the mean age at diagnosis was 47,86 years. Anterior uveitis was the most common classification making up 47.5%, followed by non-infectious posterior uveitis 18,0%, infectious posterior uveitis 8,4%, intermediate uveitis 5,5% and panuveitis 4,2%. Extra-uveal entities made up the rest of the causes (16.4%). In terms of aetiology, the majority of uveitis was idiopathic (32,1%) followed by axial spondylarthritis (12.1%), Behçet’s disease (8,8%), sarcoidosis (6,1%), tuberculosis (5,5%), herpes (5,1%), toxoplasmosis (3,1%) among other less frequent causes. Conclusion: In our referral region, 72% of uveitis cases were correctly identified surpassing other studies. There was a higher rate of intermediate uveitis and lower number of panuveitis cases when compared to a previous Portuguese study. Extensive monitoring of the development of uveitis by international multicentre prospective studies could be useful for increasing practitioner awareness and diagnostic approach.

Pulmonary Sarcoidosis: Prognostic Factors at Diagnosis in Patients from North of Portugal

BackgroundSarcoidosis is a multisystemic granulomatous disease that affects the lungs in more than 90% of the patients. It is associated with a variable clinical course and considering all the different forms of disease presentation, there are an absence of reliable clinical prognostic markers that can predict the outcome at diagnosis. ObjectiveThe aim of our study was to investigate prognostic factors at diagnosis in a population of sarcoidosis patients from Northern Portugal. MethodsA group of 110 patients with chronic evolution was compared with 129 patients with disease resolution regarding their clinical, radiologic and laboratorial features. ResultsWe found a positive association between the chronic forms and lung function impairment, radiologic stage II, lower lymphocyte CD4/CD8 and extrapulmonary disease. Löfgren syndrome and asthenia instead had a protective significant association to chronicity. Our final logistic regression model found a significant independent association between age (adjusted OR=1.06), extrapulmonary involvement (adjusted OR=2.68), Löfgren's syndrome (adjusted OR=0.15) with outcome toward chronicity. ConclusionsIn this first study searching for prognostic factors at diagnosis in a Northern Portuguese population, we found clinical prognosis factors that have been described in other populations that should be considered whenever sarcoidosis is identified.

Pulmonary Sarcoidosis: Prognostic Factors at Diagnosis in Patients from North of Portugal.

Sarcoidosis is a multisystemic granulomatous disease that affects the lungs in more than 90% of the patients. It is associated with a variable clinical course and considering all the different forms of disease presentation, there are an absence of reliable clinical prognostic markers that can predict the outcome at diagnosis. The aim of our study was to investigate prognostic factors at diagnosis in a population of sarcoidosis patients from Northern Portugal. A group of 110 patients with chronic evolution was compared with 129 patients with disease resolution regarding their clinical, radiologic and laboratorial features. We found a positive association between the chronic forms and lung function impairment, radiologic stage II, lower lymphocyte CD4/CD8 and extrapulmonary disease. Löfgren syndrome and asthenia instead had a protective significant association to chronicity. Our final logistic regression model found a significant independent association between age (adjusted OR=1.06), extrapulmonary involvement (adjusted OR=2.68), Löfgren's syndrome (adjusted OR=0.15) with outcome toward chronicity. In this first study searching for prognostic factors at diagnosis in a Northern Portuguese population, we found clinical prognosis factors that have been described in other populations that should be considered whenever sarcoidosis is identified.

The vitamin D receptor gene FokI polymorphism and Multiple Sclerosis in a Northern Portuguese population

BackgroundThe cause of Multiple Sclerosis (MS) remains poorly understood, but it is widely believed to be an autoimmune disease occurring in genetically susceptible individuals after exposure to as-yet undefined environmental factors. One of these environmental factors is vitamin D, a well-known immune modulator. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3, has been shown to exert its immune modulatory properties through its nuclear receptor (VDR) namely by inhibiting the proliferation of Th cells. The purpose of this study was to evaluate the influence of FokI VDR polymorphism in MS development and progression. MethodsA group of 533 unrelated Portuguese patients with a definitive diagnosis of MS and 446 ethnically matched healthy controls were included in the study. FokI was genotyped using a PCR-based TaqMan Genotyping Assay and serum 25-hydroxyvitamin D [25(OH)D] was also assessed. ResultsA statistically significant higher frequency of the ff genotype was observed in MS patients (15.6% vs. 10.1%, p=0.012, OR (95% CI)=1.687(1.120–2.541)). No differences were observed in the frequencies of the FokI polymorphism according to disease course or with progression of disability. None of the genotypes was significantly associated with 25(OH)D serum levels. ConclusionsAn association between FokI ff genotype and MS susceptibility was found, but not with disease form or progression. Additional clinical and experimental studies should take the FokI VDR polymorphism into account, and further clarify the role of vitamin D, its metabolites and its receptor in MS.

Síndrome de apnea obstructiva del sueño y HLA en el norte de Portugal

The obstructive sleep apnoea syndrome (OSAS) is a common, complex and polygenic disease with diverse aetiologies interacting to produce a single phenotype. OSAS occurs throughout the entire lifespan and familial aggregation has been suggested. Several predisposing factors, as age, gender and obesity have been described. Associations between HLA polymorphisms and sleep disorders are confirmed, in European and Non-European descendent populations. However the associations found between HLA alleles and OSAS have not been consistent and have no informative value for sleep disorder classification. To explore the genetic association of HLA with OSAS in a northern Portuguese population and to evaluate the role of obesity in the context of HLA in OSAS. A cohort of 131 patients with OSAS was studied. Patients followed up in an Outpatient Sleep Clinic were assessed by clinical history, night sleep polygraphic recording, multiple sleep latency test (when necessary for differential diagnosis), laboratorial and demographic studies. A control population (CP) of 223 healthy individuals was used for comparison. HLA-DRB1 genotyping was performed using a polymerase chain reaction with sequence specific primers methodology. In this cohort, the HLA-DRB1*03 allele was identified as a susceptibility factor for OSAS (24% OSAS vs. 15% CP; p = 0.025; odds ratio = 1.861; 95% CI = 1.081-3.205). No significant differences were found for other HLA-DBR1* alleles. HLA-DRB1*03 is a susceptibility factor for OSAS in Portuguese population.

110 Gastric adenocarcinoma development in patients with atrophy or/and intestinal metaplasia: the role of COX-2 polymorphisms in a Northern Portuguese population

The present study showed that atherosclerotic lesions may be readily visualized in the thoracic aorta using transesophageal echocardiography. The absence of aortic plaque in the thoracic aorta rules out significant coronary artery obstruction, while the existence of the former appears to be a sensitive and specific predictor of the latter. The negative predictive value is the most interesting clinical finding of our study.

Linkage of TP53 codon 72 pro/pro genotype as predictive factor for nasopharyngeal carcinoma development

Genetic predisposition has been suggested as a cofactor for cancer aetiology and a polymorphism in TP53 codon 72 has been associated as a susceptibility factor for several cancers. Nasopharyngeal carcinoma is a rare neoplasia in western civilizations and genetic predisposition might play an important role in its development. We evaluated the linkage of the polymorphic variants (Arg/Pro) on TP53 codon 72 with nasopharyngeal cancer development in a case-control study with 392 individuals from a northern Portuguese population, including 107 patients with nasopharyngeal carcinoma and 285 healthy controls. This study revealed a three-fold risk for carriers of Pro/Pro genotype either against carriers of Arg/Arg (OR=2.62; 95% CI=1.10-6.30; P=0.016) or total Arg carriers (OR=2.67; 95% CI=1.21-5.90; P=0.012). Moreover, step-wise logistic regression analysis identified Pro/Pro genotype (OR=3.1; 95% CI=1.3-7.3; P=0.009), age >49 at diagnosis (OR=2.5; 95% CI=1.6-4.0; P<0.001) and male gender (OR=2.7; 95% CI=1.6-4.4; P<0.001) as predictive factors for the development of nasopharyngeal carcinoma. These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.

Lobar Brain Hemorrhages and White Matter Changes: Clinical, Radiological and Laboratorial Profiles

Background: White matter changes have several histopathologic correlates including cerebral amyloid angiopathy (CAA). The aim of this study was to characterize the clinical, laboratorial and neuroradiological profile of a CAA-related lobar hemorrhages case series. Methods: A cohort of 50 consecutive patients with cerebral lobar hemorrhages was studied and clinical, radiological data and ApoE polymorphisms were analyzed. White matter changes were graded and microbleeds were characterized according to number and location using T₂* MRI. Results: A statistically significant association was found between the prestroke cognitive performance and poststroke dementia and between hemorrhage volume and mortality. More severe white matter changes were found in probable CAA when comparing to possible CAA. The most prominent white matter lesions are associated with the presence and the number of microbleeds. The frequency of APOE υ2 and υ4 alleles was higher in this cohort when compared to a Northern Portuguese population. Conclusion: White matter changes are frequent in lobar hemorrhage patients and are associated with cortical microbleeds, the radiological hallmark of CAA. Therefore, white matter changes may be the sole phenotype of CAA and, potentially, involved in the pre-stroke cognitive impairment presented by the patients, which are genetically distinct from the population in general.

Allele frequencies and population data for 17 Y-STR loci (AmpFℓSTR ® Y-filer™) in a Northern Portuguese population sample

Allele frequencies and population data for 17 Y-STR loci included in a new commercial kit that has recently been available, the AmpFℓSTR ® Y-filer™ PCR amplification kit (Applied Biosystems), that permits the simultaneous amplification of all the markers included in the actually used European “extended haplotype”, DYS19, DYS189I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385I/II, DYS438, DYS439 and also DYS437, DYS448, DYS456, DYS458, DYS635 and Y GATA H4, were obtained from a sample of 175 healthy unrelated males and 45 father–son pairs from the North of Portugal. A total of 171 haplotypes were identified, of which 167 were unique and 4 were found in 2 individuals. The haplotype diversity (99.97%) and discrimination capacity (95.43%) were calculated. We report some non-standard situations, such as allele duplications and mutations. We also report a case of disputed paternity in which duplicated alleles plus an inconsistency of the transmitted alleles appeared.

Extended Northern Portuguese database on 21 autosomal STRs used in genetic identification

21 autosomal STRs are used in our laboratory in routine casework by using two commercially available STR kits (Applied Biosystems' Identifiler and Promega's Powerplex 16) and also an in-house multiplex system, used especially in deficient paternity cases, which amplifies four more loci (CD4, F13A01, FES and MBPB). Northern Portuguese population data are presented here extensively, including D2S1338 and D19S433 for the first time. Deviations from Hardy–Weinberg equilibrium were detected in D8S1179 and Penta D loci, but applying the Bonferroni correction for the number of loci analysed, the departure in both loci was not significant (0.05/21=0.0024).Both commercial STR kits share 13 loci but use different primer pairs, and so genotype inconsistencies may occur. For individuals genotyped as homozygotes with one kit and as heterozygotes with the other, the latter genotype was the one considered.The overall matching probability for the 21 STRs in our population sample is of 1 in 1.56×1024 individuals and combined power of exclusion of 0.9999999914.

Complex paternity investigations: The need for more genetic information

The use of extra mono- or multiplex fluorescent amplification STR systems has become an important way of supplementing occasional insufficient genetic information, provided by routinely employed similar systems, namely in cases of complex parentage testing. In this work we discussed the supplementary use of the commercial amplification kit FFFL (Promega) in the solution of a complex parentage investigation. We also reported allelic frequencies and some statistical parameters with forensic interest, relative to FFFL's loci, for the Northern Portuguese population.

TP53 codon 72 polymorphism and risk for cervical cancer in Portugal

High-risk human papillomavirus are essential for the development of cervical cancer; however, TP53 is the most frequently altered tumor suppressor gene among tumors and is described as a cofactor for cervical carcinogenesis. TP53 has two common polymorphic forms encoding either proline or arginine, at position 72, and the presence of homozygous arginine has been reported as a risk factor for cervical cancer in many populations. We evaluated the effect of this TP53 polymorphism in a northern Portuguese population. We analyzed blood samples of 385 women; 20 with low-grade squamous intraepithelial lesion (SIL), 56 with high-grade SIL, 164 with invasive cervical cancer, and 145 healthy controls, using allele specific-polymerase chain reaction methodology. We observed an increased frequency of the Arg/Arg genotype in the cancer group, but no statistical significance was found between cases and controls ( P > 0.05). Our results indicate that there is no association between the presence of the Arg allele in codon 72 of TP53 polymorphism and risk of cervical cancer in our population.

Allele Frequencies of 15 Loci Using AmpFℓSTR Identifiler Kit in a Northern Portuguese Population

Abstract 250 unrelated and healthy individuals from Portugal

Analysis of Penta D and Penta E STR loci in a Northern Portuguese population

Allele and genotype frequency data for two STR loci, Penta D and Penta E, were obtained from a sample of 291 unrelated inhabitants from Northern Portugal, with a commercial PCR-based typing kit. No significant deviations from Hardy–Weinberg equilibrium were found. There was no evidence for correlation between alleles of the two loci. Appropriate statistical evaluations revealed that these systems have a high forensic efficiency and can be very useful for personal identification among the Northern Portuguese population.

Y-chromosome STR defined haplotypes in North Portugal

The Y-specific STR loci, DYS19, DYS385, DYS389I and II, DYS390, DYS391, DYS392, DYS393, DYS434, DYS437, DYS438, DYS439 and GATA A10, were studied in the Northern Portuguese population. In a sample of 212 individuals, it was possible to define 196 different haplotypes of which 182 were found only once, 12 were found in two samples and the 2 most frequent haplotypes were shared by three individuals. The observed haplotype diversity value was 0.9992. The usefulness of the inclusion of each of these new markers for forensic purposes is discussed, comparing expected and observed increase in haplotype diversity.