A real-world characterization of a cohort with eosinophilic esophagitis: looking for severity biomarkers.

Summary: Background. Eosinophilic esophagitis (EoE) is an immune-mediated chronic esophageal disease, with frequent association with atopy. A validated non/minimally invasive biomarker of disease severity has not been identified. We aimed to determine if sensitization to airborne and food allergens correlates with disease severity, and to evaluate the association between clinical and laboratory characteristics with the severity of EoE. Methods. Retrospective study of EoE patients observed in a differentiated center, 2009-2021. The association between patients' diagnosis age, disease duration before diagnosis, sensitization to airborne/food allergens, serum total IgE and peripheral blood eosinophil values and severe clinical disease (presence of symptoms with a significant impact on quality of life and/or ≥ 1 hospital admission due to EoE complications, namely severe dysphagia, food impaction or esophageal perforation) and histological severe disease (≥ 55 eos/hpf and/or microabscesses in esophageal biopsies) was evaluated. Results. 92 patients were observed, 83% male, 87% atopic. There was a mean delay in diagnosis of 4 years (range 0-31). 84% had aeroallergen sensitization and 71% food sensitization. Food impaction and dysphagia were the most frequent symptoms, and severe clinical disease was observed in 55%. Histologically, 37% had severity criteria. Patients with severe clinical disease had a significantly longer mean disease duration before diagnosis than patients without severe clinical disease (79 vs 15 months, p = 0.021). Patients who described food impaction were significantly older at time of diagnosis than those who have never had impaction (18 vs 9 years, p less than 0.001). There was no significant association (p less than 0.05) between sensitization, serum total IgE and peripheral blood eosinophil values and clinical or histological severity. Conclusions. An older age at diagnosis and a longer disease duration before diagnosis appear to be useful for predicting EoE clinical severity. Despite having been demonstrated a high prevalence of allergic disease, the presence of sensitization to airborne and/or food allergens do not seem to be useful for predicting clinical or histological severity.

Clinical experience of a specialized urticaria outpatient clinic from a Portuguese UCARE.

Summary: Background. Chronic urticaria (CU) is a frequent disease, with a prevalence of at least 1%. It is characterized by pruritic wheals, angioedema or both for a period longer than 6 weeks. Objective. Identify the demographic, clinical, laboratory and therapeutic profile of patients treated in a Portuguese Urticaria Center of Reference and Excellence (UCARE) and compare it with international series. Methods. Retrospective analysis of database of patients observed in a specialized urticaria outpatient clinic, from January 2017 through September 2019, of a UCARE center in Portugal. Demographic and clinical features, laboratory findings and pharmacological treatment were obtained from the records. Descriptive analyses were performed for all variables. Chi square and fisher's exact tests were applied to analyze the independence of variables and the fit of distribution. P less than 0.05 was considered significant. Results. During this period, 477 patients were observed, of whom 429 (90%) were diagnosed with chronic urticaria. Mean age (years) at the onset of symptoms was 43.7 (standard deviation (SD) 17.6, range 6-88) and at diagnosis 46.7 (SD 17.8, range 6-88) resulting in an average diagnostic delay of 3 years (range 0-25). Median follow-up period since first attendance in the specialized outpatient clinic was 1.7 years (interquartile range (IQR) 0.79, range 0.1-2.75) . Concerning the whole group of CU patients, 347 (81%) had chronic spontaneous urticaria (CSU) - 79% female, 39 (9%) had isolated chronic inducible urticaria (CIndU) and 43 (10%) had CSU with CIndU. Autologous serum skin test (ASST) was done in 76 patients (positive in 24 (32%)) and basophil activation test (BAT) was done in 38 (positive in 13 (34%)). At the moment of study, 204 (48%) of CU patients were medicated with a second-generation H1-antihistamine (sgAH) daily (first-line therapy), 99 (23%) with sgAH up to four times the standard dose (second-line therapy) and 126 (29%) with omalizumab (third-line therapy). Additionally, 7 (2%) patients were completing a short course of systemic corticosteroids for management of disease exacerbation. Disease control was achieved in 316 of CSU patients (81%). Conclusions. Referral to a specialized urticaria outpatient clinic is important for a proper assessment of the disease and adequately symptom control.

Using a generative adversarial network to generate synthetic MRI images for multi-class automatic segmentation of brain tumors.

Challenging tasks such as lesion segmentation, classification, and analysis for the assessment of disease progression can be automatically achieved using deep learning (DL)-based algorithms. DL techniques such as 3D convolutional neural networks are trained using heterogeneous volumetric imaging data such as MRI, CT, and PET, among others. However, DL-based methods are usually only applicable in the presence of the desired number of inputs. In the absence of one of the required inputs, the method cannot be used. By implementing a generative adversarial network (GAN), we aim to apply multi-label automatic segmentation of brain tumors to synthetic images when not all inputs are present. The implemented GAN is based on the Pix2Pix architecture and has been extended to a 3D framework named Pix2PixNIfTI. For this study, 1,251 patients of the BraTS2021 dataset comprising sequences such as T1w, T2w, T1CE, and FLAIR images equipped with respective multi-label segmentation were used. This dataset was used for training the Pix2PixNIfTI model for generating synthetic MRI images of all the image contrasts. The segmentation model, namely DeepMedic, was trained in a five-fold cross-validation manner for brain tumor segmentation and tested using the original inputs as the gold standard. The inference of trained segmentation models was later applied to synthetic images replacing missing input, in combination with other original images to identify the efficacy of generated images in achieving multi-class segmentation. For the multi-class segmentation using synthetic data or lesser inputs, the dice scores were observed to be significantly reduced but remained similar in range for the whole tumor when compared with evaluated original image segmentation (e.g. mean dice of synthetic T2w prediction NC, 0.74 ± 0.30; ED, 0.81 ± 0.15; CET, 0.84 ± 0.21; WT, 0.90 ± 0.08). A standard paired t-tests with multiple comparison correction were performed to assess the difference between all regions (p < 0.05). The study concludes that the use of Pix2PixNIfTI allows us to segment brain tumors when one input image is missing.

Hereditary angioedema: 24 years of experience in a Portuguese Reference Center.

Summary: Hereditary angioedema (HAE) poses a high burden of disease, being its epidemiological and clinical data heterogeneous among countries, with no recent published studies concerning Portuguese patients. Therefore, we aimed to raise awareness of HAE and to contribute to clinical knowledge. An observational, descriptive, retrospective, and cross-sectional study was performed, that included a cohort of 126 patients followed in a single Portuguese Center. We observed a high prevalence of HAE-C1-INH type II (45.2% of patients). Most HAE patients (67.4%) presented the initial manifestations of the disease before adulthood, at a mean age of 12.6 ± 8.4 years. However, we found a long delay in HAE diagnosis, especially in those without family history (mean 20.7 ± 17.3 years). Stress was the most common trigger, followed by trauma and infection. Symptoms involving different systems were increasingly reported with increased disease duration. Cutaneous symptoms (95.0%) were more frequent, followed by gastrointestinal (80.7%), and respiratory symptoms (50.4%). HAE symptoms led to abdominal surgery in 22 (17.5%) patients and induced laryngeal edema requiring intubation/tracheostomy in 8 (6.3%) patients. Most patients were under long-term prophylaxis, mainly with attenuated androgens (62.7% of patients).The correct distinction between HAE and other common causes of angioedema is critical, allowing reduction of diagnostic delay, improvement of adequate management, and ultimately improving outcomes and quality of life of HAE patients.

Automated Detection and Segmentation of Brain Metastases in Malignant Melanoma: Evaluation of a Dedicated Deep Learning Model.

BACKGROUND AND PURPOSE: Malignant melanoma is an aggressive skin cancer in which brain metastases are common. Our aim was to establish and evaluate a deep learning model for fully automated detection and segmentation of brain metastases in patients with malignant melanoma using clinical routine MR imaging. MATERIALS AND METHODS: Sixty-nine patients with melanoma with a total of 135 brain metastases at initial diagnosis and available multiparametric MR imaging datasets (T1-/T2-weighted, T1-weighted gadolinium contrast-enhanced, FLAIR) were included. A previously established deep learning model architecture (3D convolutional neural network; DeepMedic) simultaneously operating on the aforementioned MR images was trained on a cohort of 55 patients with 103 metastases using 5-fold cross-validation. The efficacy of the deep learning model was evaluated using an independent test set consisting of 14 patients with 32 metastases. Manual segmentations of metastases in a voxelwise manner (T1-weighted gadolinium contrast-enhanced imaging) performed by 2 radiologists in consensus served as the ground truth. RESULTS: After training, the deep learning model detected 28 of 32 brain metastases (mean volume, 1.0 [SD, 2.4] cm3) in the test cohort correctly (sensitivity of 88%), while false-positive findings of 0.71 per scan were observed. Compared with the ground truth, automated segmentations achieved a median Dice similarity coefficient of 0.75. CONCLUSIONS: Deep learning-based automated detection and segmentation of brain metastases in malignant melanoma yields high detection and segmentation accuracy with false-positive findings of <1 per scan.

Abacavir usage patterns and hypersensitivity reactions in the EuroSIDA cohort.

OBJECTIVES: Five to eight per cent of HIV-positive individuals initiating abacavir (ABC) experience potentially fatal hypersensitivity reactions (HSRs). We sought to describe the proportion of individuals initiating ABC and to describe the incidence and factors associated with HSR among those prescribed ABC. METHODS: We calculated the proportion of EuroSIDA individuals receiving ABC-based combination antiretroviral therapy (cART) among those receiving cART after 1 January 2009. Poisson regression was used to identify demographic, and current clinical and laboratory factors associated with ABC utilization and discontinuation. RESULTS: Between 2009 and 2016, of 10 076 individuals receiving cART, 3472 (34%) had ever received ABC-based cART. Temporal trends of ABC utilization were also heterogeneous, with 28% using ABC in 2009, dropping to 26% in 2010 and increasing to 31% in 2016, and varied across regions and over time. Poisson models showed lower ABC utilization in older individuals, and in those with higher CD4 cell counts, higher cART lines, and prior AIDS. Higher ABC utilization was associated with higher HIV RNA and poor renal function, and was more common in Central-East and Eastern Europe and lowest during 2014. During 779 person-years of follow-up (PYFU) in 2139 individuals starting ABC after 1 January 2009, 113 discontinued ABC within 6 weeks of initiation for any reason [incidence rate (IR) 14.5 (95% confidence interval (CI) 12.1, 17.5) per 100 PYFU], 13 because of reported HSR [IR 0.3 (95% CI 0.1, 1.0) per 100 PYFU] and 35 because of reported HSR/any toxicity [IR 4.5 (95% CI 3.2, 6.3) per 100 PYFU]. There were no factors significantly associated with ABC discontinuation because of reported HSR/any toxicity. CONCLUSIONS: ABC remains commonly used across Europe and the incidence of discontinuation because of reported HSR was low in our study population.

Composição de ácidos graxos do queijo e leite de vacas alimentadas com casca de banana / Fatty acid composition of cheese and milk of cows fed with banana peel

Objetivou-se avaliar os níveis de casca de banana seca ao sol na dieta de vacas F1 Holandês x Zebu sobre o perfil de ácidos graxos do leite e do queijo minas frescal. Os tratamentos foram constituídos de 0, 15, 30, 45 e 60% de substituição da silagem de sorgo pela casca de banana. O delineamento experimental foi em dois quadrados latinos 5 x 5 simultâneos. As amostras de leite e queijo foram analisadas quanto ao perfil de ácidos graxos por cromatografia gasosa. Observou-se efeito quadrático para o somatório de ácidos graxos poli-insaturados do leite, com valor máximo no nível de 23,54% de substituição. Houve efeito linear decrescente para os ácidos graxos C15:0 iso e C16:0 iso. Os ácidos graxos heneicosanoico, linoleico, linoleico conjugado e araquidônico apresentaram efeito quadrático. Não houve efeito das dietas sobre os ácidos graxos no queijo. A substituição de até 60% da silagem de sorgo por casca de banana na dieta de vacas em lactação pode ser alternativa para produção e processamento do leite, quando se considera a melhora no valor nutricional da fração lipídica do leite e o aumento dos teores de ácido linoleico conjugado.(AU)

This study aimed to evaluate the inclusion levels of dry banana peel in the sun in the diet of F1 Holstein x Zebu cows on the profile of fatty acids of milk and Minas fresh cheese. The diets were composed of 0, 15, 30, 45, and 60% replacement of sorghum silage by banana peel. The experimental design was Latin squares, simultaneous, 5 x 5. Samples of milk and cheese were analyzed for fatty acid composition by gas chromatography. Quadratic effect for the sum of milk polyunsaturated fatty acids, with the maximum level of 23,54% replacement. There was a decreasing linear effect for C15:0 iso fatty acids and C16: 0 iso. The heneicosanoic fatty acids, linoleic, conjugated linoleic and arachidonic presented quadratic effect. There was no effect of diets on fatty acids in cheese. Replacement of up to 60% of the sorghum silage of a banana peel in the diet of cows can be an alternative to milk production and processing when considering the improvement in the nutritional value of the milk lipid fraction and increase of the levels of conjugated linoleic acid.(AU)

Evolving epidemiology of carbapenemase-producing Enterobacteriaceae in Portugal: 2012 retrospective cohort at a tertiary hospital in Lisbon.

Despite great efforts to enhance European epidemiological surveillance on carbapenemase-producing Enterobacteriaceae (CPE), information from several countries remains scarce. To address CPE epidemiology in Portugal, we have undertaken a retrospective cohort study of adults with CPE cultures identified in the microbiology laboratory of a tertiary hospital, in 2012. Sixty patients from 25 wards or intensive care units were identified. This is, to the best of our knowledge, the first report of clinical data on CPE in Portugal. It shows a hospital-wide CPE dissemination and alerts us to an evolving epidemiological situation not previously described.

Extração de DNA e avaliação da composição espécie-específica de queijos / DNA extraction and evaluation of the specie-specific composition of cheeses

Foram testados três métodos de extração de DNA em amostras de queijo, com o objetivo de identificar uma técnica eficiente para extração de DNA em amostras com várias limitações, como alto teor de gordura, alto grau de degradação do DNA e grande concentração de impurezas. A técnica que faz uso do tiocianato de guanidina mostrou-se mais adequada para identificação de adição intencional não declarada de leite bovino em queijos bubalinos, podendo ser empregada para certificação de produto específico (selo de Identidade de Espécie).

Three methods of DNA extraction were tested in cheese samples. The objective of this study was to identify an efficient technique for DNA extraction in different samples with several limitations, such as high fat tenor, high degree of DNA degradation and great sludge concentration. The technique using Guanidine thiocyanate was more appropriate for identification of intentional undeclared addition of bovine milk in buffalo cheeses. This technique can be used for certification of a specific product (stamp of Identity of Species).

Influência do período de armazenamento na qualidade do ovo integral pasteurizado refrigerado / Influence of storage period on refrigerated pasteurized whole egg quality

Avaliaram-se o pH e a qualidade microbiológica de ovos integrais pasteurizados refrigerados obtidos de dois tipos de matéria-prima: o ovo in natura (comercial ) e o ovo galado (ovo fértil). Os tratamentos foram dispostos no delineamento inteiramente ao acaso, em parcelas subdivididas, sendo na parcela dois tipos de ovos integrais pasteurizados, o comercial e o galado, e na subparcela quatro períodos de estocagem sob temperatura de refrigeração, um, sete, 14 e 21 dias. Não foi observada a presença de Salmonella spp. em nenhuma amostra analisada, e para os ovos comerciais, o período de estocagem não contribuiu para o aumento (P>0,05) da contaminação por mesófilos aeróbios, coliformes a 35ºC, Staphylococcus spp. e bolores e leveduras. Para as amostras de ovos galados, o período de armazenamento influenciou no aumento (P<0,05) da contagem de mesófilos aeróbios, coliformes a 35ºC, bolores e leveduras, e Staphylococcus spp. Os valores de pH aumentaram durante os primeiros dias do armazenamento e depois voltaram a diminuir. Concluiu-se que os ovos integrais galados pasteurizados apresentam pior qualidade em relação aos ovos integrais comerciais pasteurizados, e que o período de validade sob refrigeração desses tipos de ovos poderia ser de sete e 14 dias, respectivamente.

The pH and microbiological quality of refrigerated pasteurized whole eggs at 4ºC obtained from two types of raw materials, in nature (commercial) egg and the fertile egg were evaluated. The treatments were arranged in a completely randomized split plot design, the two types of pasteurized whole eggs (commercial and fertile) were alloted to the plots and four periods of storage under refrigeration (one, seven, 14 and 21 days) to the split plot. The presence of Salmonella spp. was not observed in the samples and the commercial pasteurized whole egg storage period did not contribute to the increase (P>0.05) in mesophilic aerobic coliforms at 35ºC, Staphylococcus spp and mold and yeast contamination. For samples of fertile pasteurized whole eggs, the storage period influenced the increased (P<0.05) count of mesophilic aerobic, coliforms at 35ºC, mold and yeast and Staphylococcus spp. The pH values rose during the first days of storage and then decreased again. It was concluded that fertile pasteurized whole eggs have lower quality than the commercial pasteurized whole eggs, and that the shelf life of these could be seven and 14 days, respectively.

Critical analysis about solutions and models of solar shades in non-residential buildings from tropical regions.

Whereas the non-residential buildings consume a significant percentage of the total energy produced by the city, is important that these buildings have for such consumption is reduced or consumed in a conscious way. To do so, using concepts of energy efficiency, this work is to explain passive strategies with the use of flexible solar shades that help to get a favorable outcome with respect to the performance of the building right in the initial stages of planning and design. Once initial gains can be obtained and the architecture constants that value at the same time provide better working conditions and indoor comfort.

High resolution BrainPET combined with simultaneous MRI.

UNLABELLED: After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Jülich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. MATERIAL, METHODS: The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. RESULTS: Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. DISCUSSION, CONCLUSION: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.

Cardiac autonomic responses to repeated shuttle sprints.

Team sport match play requires athletes to perform a number of repeated shuttle sprints. However, the acute effects of these repeated sprint sequences on lactic acidosis and resulting autonomic state perturbation are not known. The aim of this study was to observe and compare the blood lactate and post-exercise cardiac autonomic responses of a repeated shuttle-sprint ability test with the 30-15 Intermittent Fitness Test (30-15 (IFT)); the latter test representing a standard for exhaustive supramaximal effort. Thirteen adult team sport players performed the repeated shuttle-sprint ability test and the 30-15 (IFT) on separate days in a counter-balanced order. The repeated shuttle-sprint ability test consisted of six repetitions of maximal 2x15 m shuttle sprints ( approximately 5 s) departing every 20 s, while the 30-15 (IFT) involved progressive 30 s shuttle runs interspersed with 15 s of passive recovery until exhaustion. Blood lactate was measured before and after the tests, while autonomic responses were assessed using immediate heart rate recovery and heart rate variability indices. Peak blood lactate (10.6+/-2.1 vs. 10.2+/-2.8 mM) and heart beats recovered in one minute after exercise cessation (36.4+/-7.8 vs. 39.3+/-7.9 bpm) were similar after both the repeated shuttle-sprint ability test and the 30-15 (IFT). With the exception of the vagal-related time-varying root mean square of successive R-R interval differences at each 30 s, which recovered earlier after the repeated shuttle-sprint ability test compared with 30-15 (IFT), all heart rate variability indices decreased similarly after both tests in comparison to baseline values. In conclusion, the repeated shuttle-sprint ability test was shown to induce comparable levels of lactic acidosis and post-exercise autonomic state as the 30-15 (IFT). These levels of metabolic and autonomic states are likely to occur during team sport match play.

Receiving a positive HIV test result: the experience of patients in Europe.

OBJECTIVE: To describe HIV-infected people's experience of the HIV test procedure in Europe. METHODS: Between August 1996 and September 1997, anonymous self-administered questionnaires were distributed to HIV-infected people in 11 European countries. RESULTS: A total of 1366 people completed the questionnaire (50% response rate). Of these, 194 (16%) had more than five negative HIV tests before being diagnosed as HIV positive, 179 (14%) were tested without consent and 192 (15%) were informed about the HIV positive test result by mail or by telephone. Of the 963 people who received a positive test result during a consultation, 247 (26%) reported that this visit lasted less than 10 min, 336 (35%) between 10 and 20 min, and 289 (30%) more than 20 min. Over half the total respondents (591, 54%) felt they did not receive adequate support when they were informed about being HIV positive, with 249 (19%) experiencing feelings of rejection. People who were diagnosed as HIV positive after 1994 reported more frequently receiving adequate support, information and understanding when the positive test result was revealed compared with those diagnosed before 1990. CONCLUSION: A large number of our study participants did not endorse the way HIV tests were conducted and positive test results revealed. Although there was an improvement over time in the way HIV tests were conducted, they often did not conform to international guidelines.

Effect of oral washes on the diagnosis of Pneumocystis carinii pneumonia with a low parasite burden and on detection of organisms in subclinical infections.

This study was designed to assess the efficacy of using oral washes (OWs) to diagnose Pneumocystis carinii pneumonia (PCP) in patients with a low parasite burden and to detect cases of subclinical infection. A total of 104 paired induced sputum (IS) samples and OWs from 104 HIV-seropositive patients and 32 OWs from immunocompetent healthy controls were studied. All of the control samples were negative. Fifty-two IS specimens were positive for Pneumocystis carinii, and 26 of these cases were also detected in the OWs using conventional stain or polymerase chain reaction. Twenty-four of the PCP cases had a high or a moderate parasite load and 28 had a low parasite load; among them, Pneumocystis carinii was detected in the OWs of 15 and 11 cases, respectively. Fifteen of the 104 IS samples studied belonged to patients who were asymptomatic carriers or who had a subclinical infection, and Pneumocystis carinii was detected in the OWs of 4 of these cases. The parasite was not detected in 37 IS samples and in 74 OWs. The results of this study indicate that in patients with a low pulmonary parasite burden, the number of organisms reaching the oral cavity is insufficient for reliable detection in OWs. Thus, OWs are less useful than IS samples for detecting Pneumocystis carinii in cases of pneumonia in which a low parasite burden and/or subclinical infection are present.

Candida albicans meningitis: clinical case.

Candida spp. meningitis is still a rare clinical situation, although it is becoming more frequent. Literature references to it and therapeutic options are scarce. We present a case of a young male, HIV-positive drug addict, with Candida albicans meningitis which was treated with oral fluconazole, having a good outcome.

Utilization of healthcare services by people living with HIV/AIDS in Europe. Eurosupport Group.

Our objective was to compare the utilization of healthcare/support services for people with HIV infection in Europe. Between August 1996 and September 1997 self-administered anonymous questionnaires were distributed by reference HIV treatment centres and HIV support organizations. The questionnaire was completed by 1366 people living with HIV/AIDS. A small number of people had received influenza or pneumococcal vaccinations (34% and 19% respectively). Many patients did not receive dental care (48% of participants from the southern countries) and only 72% of the women had a gynaecological examination. More participants from the south reported insufficient access to healthcare/support services, particularly for nursing care (19%), psychological support (33%), nutritional advice (45%), access to support organizations (36%), and legal advice (46%). In conclusion, many people living with HIV/AIDS in Europe do not benefit from certain annual medical procedures proposed by international guidelines and consider themselves to have insufficient access to health/support services.