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- Maternal Educational Level and the Risk of Persistent Post-Partum Glucose Metabolism Disorders in Women with Gestational Diabetes MellitusPublication . Gante, I; Ferreira, AC; Pestana, G; Pires, D; Amaral, N; Dores, J; Almeida, MC; Sandoval, JLAIMS: Gestational diabetes mellitus (GDM) occurs in 5-15% of pregnancies, and lower maternal educational attainment has been associated with higher risk of GDM. We aimed to determine if maternal education level is associated with persistent post-partum glucose metabolism disorders in women with GDM. METHODS: Retrospective cohort study of women with GDM followed in 25 Portuguese health institutions between 2008 and 2012. Educational attainment was categorised into four levels. Prevalence of post-partum glucose metabolism disorders (type 2 diabetes mellitus, increased fasting plasma glucose or impaired glucose tolerance) was compared and adjusted odds ratios calculated controlling for confounders using logistic regression. RESULTS: We included 4490 women diagnosed with GDM. Educational level ranged as follows: 6.8% (n = 307) were at level 1 (≤ 6th grade), 34.6% (n = 1554) at level 2 (6-9th grade), 30.4% (n = 1364) at level 3 (10-12th grade) and 28.2% (n = 1265) at level 4 (≥ university degree). At 6 weeks post-partum re-evaluation, 10.9% (n = 491) had persistent glucose metabolism disorders. Educational levels 1 and 2 had a higher probability of persistent post-partum glucose metabolism disorders when compared to level 4 (OR = 2.37 [1.69;3.32], p < 0.001 and OR = 1.39 [1.09;1.76], p = 0.008, for level 1 and 2, respectively), an association that persisted in multivariable logistic regression adjusting for confounders (level 1 OR = 2.25 [1.53;3.33], p < 0.001; level 2 OR = 1.43 [1.09;1.89], p = 0.01). CONCLUSIONS: Persistent post-partum glucose metabolism disorders are frequent in women with GDM and associated with lower maternal educational level. Interventions aimed at this risk group may contribute towards a decrease in prevalence of post-partum glucose metabolism disorders.
- Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber DiseasePublication . Bernardes, C; Santos, S; Loureiro, R; Borges, V; Ramos, GRendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events.
- Implications of Intrahepatic Cholangiocarcinoma Etiology on Recurrence and Prognosis after Curative-Intent Resection: a Multi-Institutional StudyPublication . Zhang, XF; Chakedis, J; Bagante, F; Beal, EW; Lv, Y; Weiss, M; Popescu, I; Pinto Marques, H; Aldrighetti, L; Maithel, SK; Pulitano, C; Bauer, TW; Shen, F; Poultsides, GA; Soubrane, O; Martel, G; Groot Koerkamp, B; Guglielmi, A; Itaru, E; Pawlik, TMBACKGROUND: We sought to investigate the prognosis of patients following curative-intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV-ICC), hepatolithiasis (Stone-ICC), and no identifiable cause (conventional ICC) etiologic subtype. METHODS: 986 patients with HBV-ICC (n = 201), stone-ICC (n = 103), and conventional ICC (n = 682) who underwent curative-intent resection were identified from a multi-institutional database. Propensity score matching (PSM) was used to mitigate residual bias. RESULTS: HBV-ICC patients more often had cirrhosis, earlier stage tumors, a mass-forming lesion, well-to-moderate tumor differentiation, and an R0 resection versus stone-ICC or conventional ICC patients. Five-year recurrence-free survival among HBV-ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence-free of only 8.3% among patients with stone-ICC. Similarly, 5-year overall survival among patients with stone-ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV-ICC and conventional ICC, respectively. On PSM, patients with stone-ICC group had equivalent long-term outcomes as HBV-ICC patients. In contrast, on PSM, stone-ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic-only recurrence among patients who had stone-ICC (6.0 months) was worse than OS among HBV-ICC (13.0 months) or conventional ICC (12.0 months) (p = 0.006 and p = 0.082, respectively). CONCLUSIONS: While HBV-ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage-for-stage differences in outcomes compared with stone-ICC or conventional ICC. In contrast, patients with stone-ICC had worse long-term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC.
- The Limitations of Standard Clinicopathologic Features to Accurately Risk-Stratify Prognosis after Resection of Intrahepatic CholangiocarcinomaPublication . Bagante, F; Merath, K; Squires, M; Weiss, M; Alexandrescu, S; Pinto Marques, H; Aldrighetti, L; Maithel, S; Pulitano, C; Bauer, T; Shen, F; Poultsides, G; Soubrane, O; Martel, G; Koerkamp, B; Guglielmi, A; Itaru, E; Pawlik, TBackground: The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence. Methods: Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence. Results: Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered "favorable." Conclusion: A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.
- Population Genetics of IFITM3 in Portugal and Central Africa Reveals a Potential Modifier of Influenza SeverityPublication . David, S; Correia, V; Antunes, L; Faria, R; Ferrão, J; Faustino, P; Nunes, B; Maltez, F; Lavinha, J; Rebelo de Andrade, HInfluenza epidemics are a serious global public health and economic problem. The IFITM3 allele (rs12252-C) was suggested as a population-based genetic risk factor for severe influenza virus infection by A(H1N1)pdm09. We analyzed the population genetics of IFITM3 variants in the Portuguese general population (n = 200) and Central Africans (largely Angolan) (n = 148) as well as its association to influenza severity in Portuguese patients (n = 41). Seven SNPs, within the 352 bp IFITM3 amplicon around rs12252, were identified. SNP distributions in the Portuguese appeared at an intermediate level between the Africans and other Europeans. According to HapMap, rs34481144 belongs to the same linkage disequilibrium (LD) block as rs12252 and is in strong LD with rs6421983. A negative association with severe relative to mild disease was observed for allele rs34481144-A, indicating a protective effect under the dominant model. Moreover, haplotype Hap4 with rs34481144-A, not including rs12252-C, was significantly associated to mild influenza. Conversely, although with borderline significance, haplotype Hap1 with rs34481144-G, not including rs12252-C, was associated to severe disease. Moreover, in comparison to the general Portuguese population, statistical significant differences in the frequencies of the protective allele rs34481144-A in the severe disease group, the deleterious Hap1 in the mild disease group, and the protective Hap4 in the severe disease group were observed. The population attributable risk (PAR) for the targeted rs34481144 allele or genotype was of 55.91 and 64.44% in the general population and the mildly infected individuals, respectively. Implication of these variants in disease phenotype needs further validation, namely through functional analysis as is discussed.
- Piperacillin-Tazobactam Anaphylaxis: a Rare Cause of Occupational DiseasePublication . Gaspar-Marques, J; Finelli, E; Martins, PC; Prates, S; Leiria-Pinto, PPiperacillin is a beta-lactam antibiotic of penicillin family. Some penicillins were report-ed as occupational diseases cause, but piperacillin anaphylaxis with occupational sensi-tization is rare. We describe the case of a female nurse with recurrent anaphylaxis in last few months without apparent cause, only in work environment. Latex allergy was excluded after negative latex glove provocation. Later during diagnostic workup, the patient reported a similar reaction minutes after piperacillin preparation. She denied any previous antibiotic therapeutic exposure. Skin prick tests (SPT) to beta-lactams were positive to piperacillin, penicillin G and major and minor determinants. SPT to cefuroxime was negative but intradermic test was positive. The patient has indication for beta-lactams eviction and for adrenaline auto-injector kit. No further reactions occurred after patient's transfer to another department with minimum possible exposure. Allergic risk prevention is essential and must be rapidly implemented to avoid incapacitating occupational diseases development.
- Hidradenocarcinoma do Escroto com Metastização GanglionarPublication . Simões, MI; Marcão, I; Toscano, M; Borges, LO hidradenocarcinoma é uma neoplasia rara das células écrinas das glândulas sudoríparas, geralmente assintomática e de crescimento lento, com maior incidência entre os 50 e os 80 anos, atingindo ambos os sexos e com localização preferencial nas regiões palmar, plantar, frontal, axilar e nuca. Tem um comportamento agressivo, com alta taxa de recorrência local e metastização à distância, associando-se a mau prognóstico. Apresentamos um caso raro de hidradenocarcinoma do escroto manifestado por metastização ganglionar justificando exercício de diagnóstico diferencial clínico e histológico de adenopatia inguinal num adulto jovem.
- Hepatitis E Virus Genotype 1 Cases Imported to Portugal from India, 2016Publication . Mesquita, JR; Almeida-Santos, M; Fernandes, M; Maltez, F; Lino, S; Alves, L; Abreu-Silva, J; Oliveira, R; Curran, M; Nascimento, MHepatitis E in industrialized countries is mainly associated with genotype 3 hepatitis E virus (HEV) and normally causes a sporadic self-limiting disease in immunocompetent individuals. Unlike genotype 3, genotypes 1 and 2 circulate in developing countries, produce severe disease and occur in the epidemic form. Hepatitis E occurring in travellers returning from endemic areas in developing countries is not a novel epidemiological occurrence, however the vast majority of cases remain to be genetically studied. The present study describes two cases of severe acute hepatitis E that required hospitalization for 6 and 9 days in two individuals of Indian nationality that had recently migrated to Portugal to work. The retrieved HEV sequences both belonged to genotype 1 and had a high degree of nucleotide sequence identity, clustering with strains isolated in India and Nepal, in 2013 and 2014. Confirmed HEV genotypes of increased pathogenicity like genotype 1 are being introduced into otherwise naïve populations of industrialized countries such as European countries with consequences difficult to predict. As far as we know the present study is the first in Portugal to describe and genetically characterize imported cases of hepatitis E infection caused by HEV genotype 1.
- Retinopathy and Bone Marrow Failure Revealing Coats Plus SyndromePublication . Painho, T; Conceição, C; Kjöllerström, P; Batalha, S