Detecting heart failure using novel bio-signals and a knowledge enhanced neural network.

BACKGROUND: Clinical decisions about Heart Failure (HF) are frequently based on measurements of left ventricular ejection fraction (LVEF), relying mainly on echocardiography measurements for evaluating structural and functional abnormalities of heart disease. As echocardiography is not available in primary care, this means that HF cannot be detected on initial patient presentation. Instead, physicians in primary care must rely on a clinical diagnosis that can take weeks, even months of costly testing and clinical visits. As a result, the opportunity for early detection of HF is lost. METHODS AND RESULTS: The standard 12-Lead ECG provides only limited diagnostic evidence for many common heart problems. ECG findings typically show low sensitivity for structural heart abnormalities and low specificity for function abnormalities, e.g., systolic dysfunction. As a result, structural and functional heart abnormalities are typically diagnosed by echocardiography in secondary care, effectively creating a diagnostic gap between primary and secondary care. This diagnostic gap was successfully reduced by an AI solution, the Cardio-HART™ (CHART), which uses Knowledge-enhanced Neural Networks to process novel bio-signals. Cardio-HART reached higher performance in prediction of HF when compared to the best ECG-based criteria: sensitivity increased from 53.5% to 82.8%, specificity from 85.1% to 86.9%, positive predictive value from 57.1% to 70.0%, the F-score from 56.4% to 72.2%, and area under curve from 0.79 to 0.91. The sensitivity of the HF-indicated findings is doubled by the AI compared to the best rule-based ECG-findings with a similar specificity level: from 38.6% to 71%. CONCLUSION: Using an AI solution to process ECG and novel bio-signals, the CHART algorithms are able to predict structural, functional, and valve abnormalities, effectively reducing this diagnostic gap, thereby allowing for the early detection of most common heart diseases and HF in primary care.

Impact of telemedicine on the management of heart failure patients during coronavirus disease 2019 pandemic.

AIMS: Chronic heart failure (HF) is a major comorbidity accounting for an increased severity and mortality related to coronavirus disease 2019 (COVID-19). To reduce the risk of COVID-19 in HF patients, telemedicine has been encouraged. METHODS AND RESULTS: During the COVID-19 pandemic, telemedical management with mainly over-the-phone appointments became a major strategy of follow-up of our HF clinic patients. Previously, the large majority of patients have been seen in the hospital with direct patient-provider contact. We compared both strategies of follow-up, in pre-pandemic (PPP) and pandemic (PP) periods, regarding total mortality and hospitalizations/emergency department (ED) visits due to HF exacerbation. We prospectively studied a cohort of 196 patients. The mean follow-up time in PPP was 1.4 years. In this period, 20 patients died. In PP (follow-up of 71 days), there was one additional death. Total mortality in the first year of follow-up was 12.0%, matching the mortality predicted by the Meta-Analysis Global Group in Chronic Heart Failure score. Considering hospitalizations/ED visits due to decompensated HF, there was no statistically significant difference between PPP and PP. Only one patient was diagnosed with COVID-19. CONCLUSIONS: In the light of an increase in telemedical management of this cohort of HF patients, we were able to maintain a low rate of admissions due to HF decompensation, without an increment in mortality. Regarding these results, we encourage the incremental use of telemedicine in HF patients in the context of this or future pandemics and also in situations in which physical consultation might not be possible due to logistic issues.

Cell Competition, the Kinetics of Thymopoiesis, and Thymus Cellularity Are Regulated by Double-Negative 2 to 3 Early Thymocytes.

Cell competition in the thymus is a homeostatic process that drives turnover. If the process is impaired, thymopoiesis can be autonomously maintained for several weeks, but this causes leukemia. We aimed to understand the effect of cell competition on thymopoiesis, identify the cells involved, and determine how the process is regulated. Using thymus transplantation experiments, we found that cell competition occurs within the double-negative 2 (DN2) and 3 early (DN3e) thymocytes and inhibits thymus autonomy. Furthermore, the expansion of DN2b is regulated by a negative feedback loop that is imposed by double-positive thymocytes and determines the kinetics of thymopoiesis. This feedback loop affects the cell cycle duration of DN2b, in a response controlled by interleukin 7 availability. Altogether, we show that thymocytes do not merely follow a pre-determined path if provided with the correct signals. Instead, thymopoiesis dynamically integrates cell-autonomous and non-cell-autonomous aspects that fine-tune normal thymus function.

Silicates of Potassium and Aluminium (Kaolin); Comparative Foliar Mitigation Treatments and Biochemical Insight on Grape Berry Quality in Vitis vinifera L. (cv. Touriga National and Touriga Franca).

Grapevine physiology is influenced by several environmental factors, such as temperature, precipitation, potential evapotranspiration, and sunshine hours. Due to climatic changes, effects in grapevine physiology and consequently on the grape berry composition and quality have been observed. This work aims to make a comparative study of the effect of foliar mitigation treatment with kaolin (5%) and potassium silicates (0.1% and 0.05%) on the grape berry quality; namely on berry weight, pH, probable alcohol, total phenolics, tannins, total anthocyanins, monomeric anthocyanins, calcium, potassium, and magnesium composition from Portuguese grapevines (Vitis vinifera L. cv. Touriga Nacional and Touriga Franca). The results suggested that the phenolic composition and anthocyanin content differs between treatments while other parameters showed distinct behavior among the different applications. Qualitative parameters observed in the present study suggested non-significant changes upon both the applications.

Sixteen properties of Eucalyptus Tereticornis wood for structural uses / Dezesseis propriedades da madeira de Eucalyptus Tereticornis para usos estruturais

Forest Red Gum eucalypt provides a versatile wood and is converted into different purposes. However, such wood is somewhat limited in structural ends, which highlights the need to exploit this gap through diffusion of mechanical properties of suchtimber. This study aimed to evaluate the effect of moisture content reduction, from 30 to 12%, in physical and mechanical properties of Eucalyptus tereticornis, using Brazilian and American documents, to reinforce the structural potential wood and assisting engineers and architects in decision-making for its best building application. We evaluated two physical and fourteen mechanical properties of Eucalyptus tereticornis at two different moisture contents, following the prescriptions of Brazilian (ABNT NBR 7190: 1997) and North American (ASTM D-143-14: 2014) standards. Thus, 1091 repeats were carried out for all properties. By a moisture reduction, the bulk density and eleven strength properties statistically showed changes such as modulus of rupture (static bending, parallel and perpendicular compressions), modulus of elasticity (perpendicular compression and static bending), shear stress, tangential cleavage, and parallel and perpendicular hardnesses. Then, the Eucalyptus tereticornis timber could be better usable if is further applied for structural construction uses.

Eucalipto de goma vermelha prove uma madeira versátil e é convertido para diferentes propósitos. Porém, essa madeira é um pouco limitada para fins estruturais, o que destaca a necessidade de explorar essa lacuna mediante à difusão das propriedades mecânicas de tal madeira. Os resultados obtidos deverão auxiliar os engenheiros e arquitetos na tomada de decisão para a sua melhor aplicação construtiva. Esse artigo estudou a avaliação de duas propriedades físicas e catorze propriedades mecânicas do Eucalyptus tereticornis em dois teores de umidade, seguindo as prescrições dos documentos normativos brasileiro (ABNT NBR 7190: 1997) e norte-americano (ASTM D-143-14: 2014). Assim, 1091 repetições foram conduzidas para todas essas propriedades. Pela redução de umidade de 30% para 12%, a densidade aparente e onze propriedades de resistência demonstraram estatisticamente mudanças, tais como módulos de ruptura (flexão estática ecompressões paralela e perpendicular), módulos de elasticidade (compressão perpendicular e flexão estática), cisalhamento, fendilhamento e as durezas perpendicular e paralela. Então, a madeira de Eucalyptus tereticornispoderia ser melhor utilizável se for também aplicada para usos construtivos estruturais.

Mercury and methylmercury transport and fate in the water column of Tagus estuary (Portugal).

Six campaigns were performed in North Channel (CNOR), Barcas Channel (BC) and lower zones (EZ) of Tagus estuary to better understand methylmercury (MMHg) and mercury (Hg) transport and fate. Highest concentrations of particulate and dissolved MMHg were observed in CNOR in bottom waters and in the warmest months. The MMHg distribution coefficients between particulate and dissolved fractions were mainly influenced by particulate matter and dissolved organic carbon. The values were slightly higher in summer than in winter and in CNOR. Overall, results established that the tidal effect is a main driver on the transport and fate of Hg and MMHg from CNOR to outer areas, evidenced by the exportation of the Hg species from CNOR to the upstream station in high tide and to the downstream one in low tide. Therefore, CNOR may be considered a source of Hg and MMHg to the outer estuary.

ProACS risk score: An early and simple score for risk stratification of patients with acute coronary syndromes.

INTRODUCTION: There are barriers to proper implementation of risk stratification scores in patients with acute coronary syndromes (ACS), including their complexity. Our objective was to develop a simple score for risk stratification of all-cause in-hospital mortality in a population of patients with ACS. METHODS: The score was developed from a nationwide ACS registry. The development and internal validation cohorts were obtained from the first 31829 patients, randomly separated (60% and 40%, respectively). The external validation cohort consisted of the last 8586 patients included in the registry. This cohort is significantly different from the other cohorts in terms of baseline characteristics, treatment and mortality. Multivariate logistic regression analysis was used to select four variables with the highest predictive potential. A score was allocated to each parameter based on the regression coefficient of each variable in the logistic regression model: 1 point for systolic blood pressure ≤116 mmHg, Killip class 2 or 3, and ST-segment elevation; 2 points for age ≥72 years; and 3 points for Killip class 4. RESULTS: The new score had good discriminative ability in the development cohort (area under the curve [AUC] 0.796), and it was similar in the internal validation cohort (AUC 0.785, p=0.333). In the external validation cohort, there was also excellent discriminative ability (AUC 0.815), with an adequate fit. CONCLUSIONS: The ProACS risk score enables easy and simple risk stratification of patients with ACS for in-hospital mortality that can be used at the first medical contact, with excellent predictive ability in a contemporary population.

Risk factor paradox in the occurrence of cardiac arrest in acute coronary syndrome patients. / Paradoxo dos fatores de risco na ocorrência de parada cardiorrespiratória em pacientes com síndrome coronária aguda.

OBJECTIVE:: To compare patients without previously diagnosed cardiovascular risk factors) and patients with one or more risk factors admitted with acute coronary syndrome. METHODS:: This was a retrospective analysis of patients admitted with first episode of acute coronary syndrome without previous heart disease, who were included in a national acute coronary syndrome registry. The patients were divided according to the number of risk factors, as follows: 0 risk factor (G0), 1 or 2 risk factors (G1 - 2) and 3 or more risk factors (G ≥ 3). Comparative analysis was performed between the three groups, and independent predictors of cardiac arrest and death were studied. RESULTS:: A total of 5,518 patients were studied, of which 72.2% were male and the mean age was 64 ± 14 years. G0 had a greater incidence of ST-segment elevation myocardial infarction, with the left anterior descending artery being the most frequently involved vessel, and a lower prevalence of multivessel disease. Even though G0 had a lower Killip class (96% in Killip I; p < 0.001) and higher ejection fraction (G0 56 ± 10% versus G1 - 2 and G ≥ 3 53 ± 12%; p = 0.024) on admission, there was a significant higher incidence of cardiac arrest. Multivariate analysis identified the absence of risk factors as an independent predictor of cardiac arrest (OR 2.78; p = 0.019). Hospital mortality was slightly higher in G0, although this difference was not significant. By Cox regression analysis, the number of risk factors was found not to be associated with mortality. Predictors of death at 1 year follow up included age (OR 1.05; p < 0.001), ST-segment elevation myocardial infarction (OR 1.94; p = 0.003) and ejection fraction < 50% (OR 2.34; p < 0.001). CONCLUSION:: Even though the group without risk factors was composed of younger patients with fewer comorbidities, better left ventricular function and less extensive coronary disease, the absence of risk factors was an independent predictor of cardiac arrest.

Paradoxo dos fatores de risco na ocorrência de parada cardiorrespiratória em pacientes com síndrome coronária aguda / Risk factor paradox in the occurrence of cardiac arrest in acute coronary syndrome patients

RESUMO Objetivo: Comparar pacientes admitidos com síndrome coronariana aguda sem prévia identificação de fatores de risco cardiovascular com pacientes que portavam um ou mais fatores de risco. Métodos: Análise retrospectiva dos pacientes admitidos com o primeiro episódio de síndrome coronariana aguda sem cardiopatia prévia, incluídos em um registro nacional de síndrome coronariana aguda. Os pacientes foram divididos segundo o número de fatores de risco: nenhum fator de risco (G0), um ou dois fatores de risco (G1 - 2) e três ou mais fatores de risco (G ≥ 3). Realizou-se uma análise comparativa entre os três grupos e se estudaram os preditores independentes de parada cardíaca e óbito. Resultados: O total apurado foi de 5.518 pacientes, 72,2% deles do sexo masculino, com média de idade de 64 ± 14 anos. O G0 teve uma incidência maior de infarto do miocárdio com elevação do segmento ST, sendo o vaso mais frequentemente envolvido a artéria descendente anterior esquerda, e menor prevalência de envolvimento de múltiplos vasos. Embora o G0 tivesse uma classe Killip mais baixa (96% Killip I; p < 0,001) e maior fração de ejeção (G0: 56 ± 10% versus G1 - 2 e G ≥ 3: 53 ± 12%; p = 0,024) na admissão, houve incidência significantemente maior de parada cardíaca. A análise multivariada identificou ausência de fatores de risco como um fator independente para parada cardíaca (OR 2,78; p = 0,019). A mortalidade hospitalar foi ligeiramente maior no G0, embora sem significância estatística. Segundo a análise de regressão de Cox, o número de fatores de risco não se associou com mortalidade. Os preditores de óbito em 1 ano de seguimento foram infarto do miocárdio com elevação do segmento ST (OR 1,05; p < 0,001) e fração de ejeção inferior a 50% (OR 2,34; p < 0,001). Conclusão: Embora o grupo sem fatores de risco fosse composto de pacientes mais jovens e com menos comorbidades, melhor função ventricular esquerda e coronariopatia menos extensa, a ausência de fatores de risco foi um preditor independente de parada cardíaca.

ABSTRACT Objective: To compare patients without previously diagnosed cardiovascular risk factors) and patients with one or more risk factors admitted with acute coronary syndrome. Methods: This was a retrospective analysis of patients admitted with first episode of acute coronary syndrome without previous heart disease, who were included in a national acute coronary syndrome registry. The patients were divided according to the number of risk factors, as follows: 0 risk factor (G0), 1 or 2 risk factors (G1 - 2) and 3 or more risk factors (G ≥ 3). Comparative analysis was performed between the three groups, and independent predictors of cardiac arrest and death were studied. Results: A total of 5,518 patients were studied, of which 72.2% were male and the mean age was 64 ± 14 years. G0 had a greater incidence of ST-segment elevation myocardial infarction, with the left anterior descending artery being the most frequently involved vessel, and a lower prevalence of multivessel disease. Even though G0 had a lower Killip class (96% in Killip I; p < 0.001) and higher ejection fraction (G0 56 ± 10% versus G1 - 2 and G ≥ 3 53 ± 12%; p = 0.024) on admission, there was a significant higher incidence of cardiac arrest. Multivariate analysis identified the absence of risk factors as an independent predictor of cardiac arrest (OR 2.78; p = 0.019). Hospital mortality was slightly higher in G0, although this difference was not significant. By Cox regression analysis, the number of risk factors was found not to be associated with mortality. Predictors of death at 1 year follow up included age (OR 1.05; p < 0.001), ST-segment elevation myocardial infarction (OR 1.94; p = 0.003) and ejection fraction < 50% (OR 2.34; p < 0.001). Conclusion: Even though the group without risk factors was composed of younger patients with fewer comorbidities, better left ventricular function and less extensive coronary disease, the absence of risk factors was an independent predictor of cardiac arrest.

Percutaneous closure of a giant left ventricular wall pseudoaneurysm: Anterograde approach with a double snare technique.

Left ventricular pseudoaneurysm is a rare complication of acute myocardial infarction, cardiac surgery, trauma or infection. Since surgical repair is associated with high morbidity and mortality, percutaneous closure has been described as an alternative. In this regard, we present a case in which a symptomatic large left ventricular pseudoaneurysm was treated by percutaneous closure due to the patient's high surgical risk, using a double snare technique. Despite the technical difficulties, this procedure had a good final result followed by clinical success, confirming that this procedure is an effective alternative to surgery in high-risk patients.

External validation of the ProACS score for risk stratification of patients with acute coronary syndromes. / Validação externa do score de risco ProACS para estratificação de risco de doentes com síndrome coronária aguda.

INTRODUCTION: The ProACS risk score is an early and simple risk stratification score developed for all-cause in-hospital mortality in acute coronary syndromes (ACS) from a Portuguese nationwide ACS registry. Our center only recently participated in the registry and was not included in the cohort used for developing the score. Our objective was to perform an external validation of this risk score for short- and long-term follow-up. METHODS: Consecutive patients admitted to our center with ACS were included. Demographic and admission characteristics, as well as treatment and outcome data were collected. The ProACS risk score variables are age (≥72 years), systolic blood pressure (≤116 mmHg), Killip class (2/3 or 4) and ST-segment elevation. We calculated ProACS, Global Registry of Acute Coronary Events (GRACE) and Canada Acute Coronary Syndrome risk score (C-ACS) risk scores for each patient. RESULTS: A total of 3170 patients were included, with a mean age of 64±13 years, 62% with ST-segment elevation myocardial infarction. All-cause in-hospital mortality was 5.7% and 10.3% at one-year follow-up. The ProACS risk score showed good discriminative ability for all considered outcomes (area under the receiver operating characteristic curve >0.75) and a good fit, similar to C-ACS, but lower than the GRACE risk score and slightly lower than in the original development cohort. The ProACS risk score provided good differentiation between patients at low, intermediate and high mortality risk in both short- and long-term follow-up (p<0.001 for all comparisons). CONCLUSIONS: The ProACS score is valid in external cohorts for risk stratification for ACS. It can be applied very early, at the first medical contact, but should subsequently be complemented by the GRACE risk score.

A Rare Case of Transfusion Transmission of Hepatitis A Virus to Two Patients with Haematological Disease.

BACKGROUND: This paper describes the transmission of hepatitis A virus (HAV) to two blood recipients from a healthy donor that later presented to the blood bank with jaundice. METHODS: The RNA of HAV was detected by qualitative nested reverse transcription polymerase chain reaction (nested RT-PCR) and quantified by real-time RT-PCR. HAV RNA samples were genotyped by direct sequencing of PCR products. A sequence from a fragment of 168 bp from the VP1/2A HAV region was used to construct a phylogenetic tree. CASE REPORT: A 31-year-old male donor accepted for donation of a whole blood unit returned to the blood bank with clinical jaundice 20 days after donation. His serological and NAT tests were negative for HBV and HCV. Serological tests for HAV IgM and IgG were negative on donation sample but positive on follow-up sample, confirming donor's HAV acute infection. Both recipients of red blood cells (R1) and platelet concentrate (R2) from the same implicated donation were HAV IgM-negative and IgG-positive. Qualitative PCR was positive on samples from all three individuals and phylogenetic analysis of viruses proved HAV transmission to the two recipients of blood products. HAV viral load on donor follow-up sample and the platelet recipient was 1.3 and 1.5 × 10(3) IU/ml, respectively. The RBC recipient, also infected by HCV, was undergoing bone marrow transplantation and died from fulminant hepatitis, 26 days after the implicated HAV transfusion. CONCLUSION: The blood donor, a garbage collector, spontaneously returned to the blood bank when developing jaundice. This highlights the importance of donor education to immediately report to blood banks of any signs and symptoms related to infectious disease developed after blood donation. The fact that one immunocompromised patient with HCV infection died from fulminant hepatitis after receiving a HAV-contaminated platelet transfusion underpins the importance of a HAV vaccination program for these group of patients.

Seasonal variation of methylmercury in sediment cores from the Tagus Estuary (Portugal).

Seasonal and spatial variations of dissolved and particulate methylmercury were evaluated for the first time in sediment cores from the Tagus Estuary. Results showed the highest MeHg concentrations in summer months indicating that the "seasonally" methylation process occurs not only at the topmost layers of the sediments but also in the deeper layers of the sediment column. The proportion of MeHg (up to 92%) in some of our pore water samples was higher than values reported in the literature for other estuaries suggesting that the sedimentary environment in the Tagus tends to favour Hg methylation. This work points to the importance of seasonal variation of the MeHg production in sediment cores. In physically dominated estuaries this enhances seasonal MeHg production in deeper sediments that can have serious ecological impacts due to resuspension or advection processes under extreme events by the increase of MeHg transported to the water column.

Percutaneous closure of a large ascending aortic pseudoaneurysm.

Pseudoaneurysm of the ascending aorta is a rare complication, usually after thoracic surgery or trauma. Since surgical repair is associated with very high morbidity and mortality, percutaneous closure has been described as an alternative. In this regard, we present a case in which a symptomatic large pseudoaneurysm of the ascending aorta was treated percutaneously due to the high surgical risk. Despite the technical difficulties, this procedure had a good final result followed by clinical success.

Role of intra-aortic balloon pump counterpulsation in the treatment of acute myocardial infarction complicated by cardiogenic shock: Evidence from the Portuguese nationwide registry.

BACKGROUND: In previous guidelines, intra-aortic balloon pump (IABP) use was strongly recommended in the treatment of cardiogenic shock in the context of acute myocardial infarction. The recent IABP-SHOCK II trial demonstrated no benefit in short- and medium-term mortality with the use of IABP. It was our objective to evaluate in a real life nationwide population of patients with acute myocardial infarction the impact of IABP in short- and medium-term mortality. METHODS: We included patients admitted with acute myocardial infarction in Killip class IV in the first 24 hours, all submitted to urgent coronary angiography. Our study objective was the occurrence of hospital and six-month all-cause mortality. RESULTS: From the 33,300 patients included in the registry, 4.2% presented with Killip class IV in the first 24 hours and 646 (43.6%) were submitted to urgent coronary angiography. IABP was implanted in 19.8% of these patients. The IABP group was younger, had higher admission heart rate, more multivessel disease and more left main disease. There were 260 hospital deaths (40.2%), similar between groups (46.1% vs. 38.8%, p=0.132). IABP use was associated with a deleterious effect in patients with previous MI and beneficial effect in patients with mechanical complications. IABP use had a neutral effect on mortality (hazard ratio 1.14, 95% confidence interval 0.84-1.56). This was further confirmed in a propensity score matching analysis. CONCLUSIONS: In a real life population of patients with acute myocardial infarction, the use of IABP for the treatment of cardiogenic shock was associated with a neutral effect.

Safety, reactogenicity and immunogenicity of the human rotavirus vaccine in preterm European Infants: a randomized phase IIIb study.

BACKGROUND: Rotavirus disease is more severe in preterm infants than in full-term infants. This study assessed the safety, reactogenicity and immunogenicity of a human rotavirus vaccine, RIX4414, in European preterm infants. METHODS: A total of 1009 preterm infants were randomized (2:1, vaccine:placebo) and stratified into 2 groups: 20% of early (27-30 weeks, group 1) and 80% of late (31-36 weeks, group 2) gestational age preterm infants in each group. Two doses of RIX4414/placebo were administered to these preterm infants according to the recommended chronologic age for full-term infants with an interval of 30-83 days between doses. Serious adverse events were recorded throughout the study period. Solicited and unsolicited adverse events were recorded for 15 and 31 days post-each dose. Antirotavirus IgA concentrations (enzyme-linked immunosorbent assay cutoff = 20 U/mL) and geometric mean concentration were determined pre-dose 1 and 30-83 days post-dose 2 in a subset of 300 infants. This study is registered with ClinicalTrials.gov, number NCT00420745 (eTrack106481). RESULTS: Serious adverse events were reported at a similar frequency in both groups (P = 0.266). Fifty-seven infants reported at least 1 serious adverse event (5.1% [3.5-7.0] in the RIX4414 group and 6.8% [4.3-10.0] in the placebo group). During the 15-day postvaccination follow-up period, diarrhea, vomiting and fever occurred at a similar frequency in both groups; fever could have been due to concomitant vaccines. Five cases (RIX4414 = 3, Placebo = 2) of rotavirus gastroenteritis were reported. The onset of rotavirus gastroenteritis in the RIX4414 group was 1-5 days after vaccination (vaccine strain identified in all cases) and in the placebo group it was 3-4 days after receiving placebo (wild-type rotavirus identified from both cases). Antirotavirus IgA seroconversion rates at 30-83 days post-dose 2 were 85.7% (79.0-90.9) in the RIX4414 group and 16.0% (8.8-25.9) in the placebo group. Geometric mean concentrations were 202.2 U/mL (153.1-267.1) in the RIX4414 group and <20 U/mL in the placebo group. Seroconversion rate in groups 1 and 2 in RIX4414 recipients were 75.9% (95% confidence interval [CI]: 56.5-89.7%) and 88.1% (95% CI: 80.9-93.4%), respectively; the geometric mean concentrations in the respective groups were 110.2 U/mL (95% CI: 56.1-216.5) and 234.8 U/mL (95% CI: 173.4-318.0; exploratory analysis). CONCLUSIONS: Two doses of RIX4414 were immunogenic and well-tolerated in European preterm infants.

Mercury in sediments and vegetation in a moderately contaminated salt marsh (Tagus Estuary, Portugal).

Depth variations of total mercury (Hg) and methylmercury (MeHg) concentrations were studied in cores from non-colonized sediments, sediments colonized by Halimione portulacoides, Sarcocorniafruticosa and Spartina maritima and belowground biomass, in a moderately contaminated salt marsh (Tagus Estuary, Portugal). Concentrations in belowground biomass exceeded up to 3 (Hg) and 15 (MeHg) times the levels in sediments, and up to 198 (Hg) and 308 (MeHg) times those found in aboveground parts. Methylmercury in colonized sediments reached 3% of the total Hg, 50 times above the maximum values found in non-colonized sediments. The absence of correlations between total Hg concentrations in sediments and the corresponding MeHg levels suggested that methylation was only dependent on the environmental and microbiological factors. The analysis of belowground biomass at high-depth resolution (2 cm) provided evidence that Hg and MeHg were actively absorbed from sediments, with higher enrichment factors at layers where higher microbial activity was probably occurring. The results obtained in this study indicated that the biotransformation of Hg to the toxic MeHg could increase the toxicity of plant-colonized sediments.

Transplante de célula-tronco hematopoética para síndrome mielodisplásica / Bone marrow transplantation in myelodysplastic syndromes

As síndromes mielodisplásicas (SMD) constituem um grupo de doenças hematológicas caracterizadas por citopenias crônicas, associadas a uma maturação celular anormal. A melhor forma de classificação atual destas patologias é o International Prognostic Scoring System (IPSS), que se baseia no grau de citopenia, número de mieloblastos na medula óssea e alterações citogenéticas. Há quatro estágios: baixo risco, riscos intermediário-1 e 2 e alto risco. Um grupo destes pacientes pode ser curado com o transplante de células-tronco hematopoéticas (TCTH). Esta forma de tratamento pode ser considerada para pacientes com idade inferior a 60 anos, que possuam um doador familiar HLA-idêntico. A opção por esta modalidade terapêutica depende de alguns critérios, que incluem o IPSS, o risco de progressão de doença, o risco de infecção e o estado geral do paciente. O TCTH autólogo pode ser considerado em pacientes que alcancem uma remissão completa citogenética e que não disponham de doador HLAidêntico. Em pacientes não candidatos ao TCTH mieloablativo, uma possibilidade é o transplante com regimes de intensidade reduzida. Estudos recentes têm demonstrado resultados favoráveis com esta opção terapêutica, pois, apesar do alto rico de recaída, as taxas de mortalidade associada ao procedimento são menores. Os pacientes com SMD devem ser dispostos em ensaios clínicos que considerem as comorbidades, DECH e riscos de recaída.

The myelodysplastic syndrome (MDS) encompasses a series of hematological conditions characterized by chronic cytopenias with abnormal cellular maturation. Based on the cytopenias, number of blast cells in bone marrow and cytogenetic abnormalities, MDS may be best classified by the International Prognostic Scoring System (IPSS) in four groups: low risk, intermediate 1, intermediate 2 risks and high risk. A subset of patients can be cured following allogeneic hematopoietic stem cell transplantation (SCT). This therapy should be considered for under 60-year-old patients with an HLA-matched sibling donor. The decision in favor of this aggressive therapy depends upon a number of criteria including the IPSS score, risk of disease progression, risk of infection, and the overall health of the patient. Autologous HCT can be considered for those rare patients who are successfully induced into complete remission and do not have an HLA-matched donor. Non-myeloablative allogeneic HCT appears promising for patients with MDS who are not candidates for myeloablative allogeneic HCT. Early results are encouraging. Despite an increased relapsed rate, the treatment-related mortality is lower. Patients should be enrolled in well-designed clinical trials attempting to address the important issues of patient comorbidities, GVHD, and relapse risk.

Spatial and seasonal variation of water quality in an impacted coastal lagoon (Obidos Lagoon, Portugal).

The spatial distribution of silicate, ammonium, nitrate, nitrite, phosphate, chlorophyll a and dissolved oxygen in Obidos lagoon was obtained by surveying five sites in eight campaigns, between October 2004 and October 2006. A confined inner branch of the lagoon showed higher availability of ammonium (1.2-81 micromol l(-1)), phosphate (1.9-17 micromol l(-1)), silicate (0.85-86 micromol l(-1)) and chlorophyll a (0.30-18 microg l(-1)) than other sites (0.47-25 micromol l(-1), 0.10-3.9 micromol l(-1), 0.47-25 micromol l(-1), 0.25-11 microg l(-1), respectively). According to several trophic classification tools, that branch is considered eutrophic to polytrophic, emphasising its deteriorated conditions, while the rest of the lagoon is of better quality. In autumn/winter nutrients were inversely correlated to salinity (r > 0.93) reflecting the freshwater inputs enriched in nitrogen and phosphorous compounds to the inner branch. In warmer periods, dissolved oxygen concentrations dropped during the night, and sediments of the branch become an important source of ammonium and phosphate. The low DIN:P ratio (median = 10) obtained in the branch, which suggests an excess of phosphate, that increased in warmer periods and changed the limiting nutrient in the entire lagoon. These results emphasize the spatial heterogeneity of water quality in Obidos lagoon, its seasonal variability, and the importance of recognising these distributions before defining homogenous water body on the scope of Water Framework Directive.

Estudo comparativo entre manutenção com ganciclovir e observação em receptores de transplante alogeneico de células-tronco hematopoéticas preemptivamente tratados com ganciclovir devido à reativação da infecção por citomegalovírus

A infecção por citomegalovírus (CMV) é uma complicação freqüente no período pós-transplante de células-tronco hematopoéticas(TCTH); seu diagnóstico pode ser realizado por antignemia ou PCR. A infecção pelo CMV é definida como a presença do vírus circulante e a doença como a presença deste vírus associada à lesão tecidual e sintomatologia clínica. A doença pelo CMV tem elevadas taxas de mortalidade, sendo importante sua prevenção e tratamento. Há duas formas de prevenção da doença: a profilaxia e o tratamento preemptivo; a profilaxia se caracteriza pelo uso do ganciclovir até o dia 100 do TCTH e o tratamento preemptivo no início do antiviral a partir de uma documentação de infecção pelo CMV em um paciente assintomático. O CDC recomenda o trtamento preemptivo baseado em uma antigenemia ou dois PCRs positivos consecutivos para o DNA viral. A droga de escolha é o ganciclovir, por via intravenosa. A duração do tratamento preemptivo anti-CMV é variável. Alguns estudos sugerem que cursos curtos, de 2 a 3 semanas baseados em um marcador viral negativo ao final do tratamento seriam eficazes. Porém, nesses casos há um risco de reativação da infecção por CMV em 30% dos pacientes, que requerem, então, um novo curso de tratamento. O estudo visa determinar o valor da manutenção com ganciclovir na prevenção da reativação e da progressão para doença pelo CMV. Secundariamente este estudo visa determinar o valor do PCR na detecção da infecção pelo CMV e avaliar a toxicidade do ganciclovir. Trata-se de um ensaio clínico randomizado, comparando a manutenção com ganciclovir e a observação em pacientes preventivamente tratados com ganciclovir por infecção pelo CMV. De 15 de agosto de 2005 a 18 de abril de 2007, 29 pacientes foram recrutados pelo estudo. Foram realizadas antigenemias e PCRs para o CMV semanalmente em todos os pacientes. O tratamento preemptivo foi baseado em uma antigenemia positiva e realizado com ganciclovir por via intravenosa por 14 dias. Após este tratamento inicial os pacientes foram randomizados e acompanhados com dosagens de creatinina e hemograma com plaquetas 3 vezes por semana. Quinze dos 29 pacientes (51,7%) apresentaram reativação do CMV e foram randomizados: 5 para o grupo manutenção e 10 para o grupo observação. Quatro dos 15 tiveram uma segunda reativação da infecção pelo CMV ( 1 no grupo manutenção e 3 no grupo observação); um paciente do grupo observação desenvolveu cistite hemorrágica atribuída ao CMV e outro desenvolveu quadro de esofagite com biópsia positiva para o CMV(doença pelo CMV). Seis de dez pacientes no grupo observação e 4/5 no grupo manutenção desenvolveram neutropenia, com duração de 2 a 20 dias no grupo observação (mediana: 8,5) e 4 a 17 dias no grupo manutenção (mediana: 12); trombocitopenia ocorreu em 6/10 pacientes no grupo observação e em 5/5 no grupo manutenção. Oito pacientes desenvolveram infecção bacteriana, sendo 5/10 no grupo observação e 3/5 no manutenção. Um paciente em cada grupo apresentou infecção fúngica...

Cytomegalovirus infection is a frequent complication of hematopoietic stem cell transplantation (HSCT). It may be diagnosed by antigenemia or PCR. CMV infection is defined as circulating virus, and disease as the presence of virus causing organic lesion and symptoms. Given that CMV disease has great mortality, treatment and prevention of CMV infection is fundamental. There are two major forms of disease prevention: prophylaxis and preemptive treatment. Prophylaxis is defined as the use of ganciclovir until day 100 of HSCT; preemptive treatment is the treatment based on the detection of CMV infection in an asymptomatic patient. The CDC recommend preemptive treatment based on an antigenemia or two consecutive positive PCRs for CMV DNA. The drug of choice is intravenous ganciclovir. The duration of anti-CMV preemptive treatment is variable. Some studies suggest that shorter treatments based on a negative PCR test by the end of two or three weeks of treatment will be enough. However, in these cases, reactivation occurred in 30 percent of patients, who ultimately required additional treatment. The objective of this study is to determine the value of ganciclovir maintenance on the prevention of CMV reactivation and progression to disease. As a secondary objective, this study aimed to determine the value of PCR in preventing CMV disease and ganciclovir toxicity. It is a randomized clinical trial, comparing ganciclovir maintenance versus observation in patients preemptively treated for CMV infection. From august 15, 2005 until april 18, 2007, 29 patients were included in the study. Antigenemia and PCRs for CMV were done weekly in all patients. Preemptive treatment was started with intravenous ganciclovir for 14 days after one positive antigenemia. Thereafter, patients were randomized. All had creatinine levels and blood counts thrice a week. Fifteen of 29 patients (51.7%) had CMV reactivation and were randomized: 5 to the maintenance and 10 to the observational group. Four of 15 had a second CMV reactivation (1 in the maintenance and 3 in the observational group); one patient in the observational group developed hemorrhagic cystitis attributed to CMV and another had esophagitis with positive biopsy for CMV (CMV disease). Six of 10 patients in the observational group and 4/5 in the maintenance group developed neutropenia, with a duration of 2 to 20 days in the observational (median: 8.5) and 4 to 17 days in the maintenance group (median: 12); thrombocytopenia occurred in 6/10 patients in the observational and 5/5 in the maintenance group. Overall, 8 patients developed infectious complications: 3/5 in the maintenance and 5/10 in the observational group. One patient in each group had fungal infection. Creatinine levels varied from 1.0 to 2.44 times the baseline level in the observational (median: 1.59), versus 1.08 to 2.36 times the baseline level in the experimental group (median: 1.82). Resistance to ganciclovir was not observed...