Home administration of biological treatment in severe asthma in real-life experience: impact on asthma control and quality of life.

Summary: Introduction. Several biological agents for the treatment of severe asthma have been approved for self-administration on an outpatient basis in the last years. However, data on the impact of home administration in outcomes such as asthma control and quality of life in real-life settings are sparse. Being this knowledge crucial for clinical practice, this study aimed to assess asthma control and quality of life in patients who transitioned from day hospital administration of biological therapy to home administration. Methods. A single-center prospective analysis of 33 patients treated with biologics for severe asthma, who switched from hospital to home treatment was performed. Asthma Control Test (ACT), Control of Allergic Rhinitis and Asthma Test (CARAT), Asthma Life Quality (ALQ) and the number of exacerbations were assessed 3 months before and 3 and 6 months after of home-use. Results. ACT and CARAT did not show statistical differences comparing to the baseline values (21.8 ± 2.7 and 23.8 ± 5.5) within 3 months (22.1 ± 2.4, p = 0.609; 23.2 ± 5.3, p = 0.572) or 6 months (23.4 ± 0.9, p = 0.553; 23.7 ± 6.2, p = 0.149) of home administration. Also, ALQ score did not show meaningful variations between baseline (9.5 ± 3.2) and after 3 months (11.2 ± 4.4, p = 0.275) and 6 months (10.3 ± 3.8, p = 0.209) of home-use. Regarding asthma exacerbations, we did not record a significant difference comparing to the baseline values of 3 months/patient exacerbations (0.2 ± 0.4) and after 3 months (0.2 ± 0.5, p = 0.786) or 6 months (0.2 ± 0.4, p = 1.000) of change in modality treatment. There was no cases of anaphylaxis or other serious adverse effects in those patients treated at home. Conclusions. Transition of day hospital administration of biologic treatment for severe asthma to home administration did not lead to any deterioration of asthma control or quality of life. Our results emphasized the efficacy and safety of home administration of biologic treatment and provide support on changing the paradigm of the administration of biological treatment in severe asthma.

Two step calibration method for ozone low-cost sensor: Field experiences with the UrbanSense DCUs.

Urban air pollution is a global concern impairing citizens' health, thus monitoring is a pressing need for city managers. City-wide networks for air pollution monitoring based on low-cost sensors are promising to provide real-time data with detail and scale never before possible. However, they still present limitations preventing their ubiquitous use. Thus, this study aimed to perform a post-deployment validation and calibration based on two step methods for ozone low-cost sensor of a city-wide network for air pollution and meteorology monitoring using low-cost sensors focusing on the main challenges. Four of the 23 data collection units (DCUs) of the UrbanSense network installed in Porto city (Portugal) with low-cost sensors for particulate matter (PM), carbon monoxide (CO), ozone (O3), and meteorological variables (temperature, relative humidity, luminosity, precipitation, and wind speed and direction) were evaluated. This study identified post-deployment challenges related to their validation and calibration. The preliminary validation showed that PM, CO and precipitation sensors recorded only unreliable data, and other sensors (wind speed and direction) very few data. A multi-step calibration strategy was implemented: inter-DCU calibration (1st step, for O3, temperature and relative humidity) and calibration with a reference-grade instrument (2nd step, for O3). In the 1st step, multivariate linear regression (MLR) resulted in models with better performance than non-linear models such as artificial neural networks (errors almost zero and R2 > 0.80). In the 2nd step, the calibration models using non-linear machine learning boosting algorithms, namely Stochastic Gradient Boosting Regressor (both with the default and post-tuning hyper-parameters), performed better than artificial neural networks and linear regression approaches. The calibrated O3 data resulted in a marginal improvement from the raw data, with error values close to zero, with low predictability (R2 ∼ 0.32). The lessons learned with the present study evidenced the need to redesign the calibration strategy. Thus, a novel multi-step calibration strategy is proposed, based on two steps (pre and post-deployment calibration). When performed cyclically and continuously, this strategy reduces the need for reference instruments, while probably minimising data drifts over time. More experimental campaigns are needed to collect more data and further improve calibration models.

Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial.

BACKGROUND: The phase III SANDPIPER study assessed taselisib (GDC-0032), a potent, selective PI3K inhibitor, plus fulvestrant in estrogen receptor-positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Postmenopausal women with disease recurrence/progression during/after an aromatase inhibitor were randomized 2 : 1 to receive taselisib (4 mg; taselisib arm) or placebo (placebo arm) plus fulvestrant (500 mg). Stratification factors were visceral disease, endocrine sensitivity, and geographic region. Patients with PIK3CA-mutant tumors (central cobas® PIK3CA Mutation Test) were randomized separately from those without detectable mutations. The primary endpoint was investigator-assessed progression-free survival (INV-PFS) in patients with PIK3CA-mutant tumors. Secondary endpoints included objective response rate, overall survival, clinical benefit rate, duration of objective response, PFS by blinded independent central review (BICR-PFS), safety, and time to deterioration in health-related quality of life. RESULTS: The PIK3CA-mutant intention-to-treat population comprised 516 patients (placebo arm: n = 176; taselisib arm: n = 340). INV-PFS was significantly improved in the taselisib {7.4 months [95% confidence interval (CI), 7.26-9.07]} versus placebo arm (5.4 months [95% CI, 3.68-7.29]) (stratified hazard ratio [HR] 0.70; 95% CI, 0.56-0.89; P = 0.0037) and confirmed by BICR-PFS (HR 0.66). Secondary endpoints, including objective response rate, clinical benefit rate, and duration of objective response, showed consistent improvements in the taselisib arm. Safety was assessed in all randomized patients who received at least one dose of taselisib/placebo or fulvestrant regardless of PIK3CA-mutation status (n = 629). Serious adverse events were lower in the placebo versus taselisib arm (8.9% versus 32.0%). There were more discontinuations (placebo arm: 2.3%; taselisib arm: 16.8%) and dose reductions (placebo arm: 2.3%; taselisib arm: 36.5%) in the taselisib arm. CONCLUSION: SANDPIPER met its primary endpoint; however, the combination of taselisib plus fulvestrant has no clinical utility given its safety profile and modest clinical benefit.

Assessing the effects of PMM2 variants on protein stability.

Phosphomannomutase 2 deficiency, PMM2-CDG, is the most frequent disorder of protein N-glycosylation. It is an autosomal recessive disease with a broad clinical and biochemical phenotype. Trying to predict the impact of novel variants is often a challenge due to the high number of variants and the difficulty to establish solid genotype-phenotype correlations. A potential useful strategy is to use computational chemistry calculations as a tool from which relevant information on the structural impact of novel variants may be deduced. Here we present our analyses based on four well-known PMM2 deleterious variants (p.(Leu32Arg), p.(Asp65Tyr), p.(Phe119Leu), p.(Arg141His)) and the polymorphic p.(Glu197Ala) for which we have predicted the effect on protein stability. Our work predicts the effect of different amino acid residues on the conformation and stability of PMM2. These computational simulations are, therefore, an extremely useful methodology which, in combination with routinely used in silico methods of pathogenicity prediction, may help to reveal the structural impact of novel variants at the protein level, potentially leading to a better understanding of target biological molecules.

The incidence of severe oral mucositis and its occurrence sites in pediatric oncologic patients.

BACKGROUND: Childhood cancer is one of the main causes of child mortality and its treatment has debilitating effects on the oral cavity. Several oral mucositis (SOM) is one of the most common and may cause undesirable symptoms such as pain and risk of systemic infection. MATERIAL AND METHODS: This was a longitudinal, retrospective, and observational study determining the incidence of severe oral mucositis (SOM) and its occurrence sites in pediatric oncologic patients, in João Pessoa, Brazil, between 2013 and 2018. Data from 56 patients aged 1 to 18 years were collected from their medical records and through an oral mucosa examination, from the 1st to 5th week of chemotherapy treatment (CT) using the modified Oral Assessment Guide, by previously calibrated examiners (Kappa index > 0.7). The data were analyzed by the Chi-square test, and Odds Ratios were calculated. RESULTS: Most patients were females (54.5%), aged 8.8 years (± 4.8), with hematologic tumors (73.2%), predominantly Acute Lymphoid Leukemia (50.0%). An increase in the occurrence of SOM was observed throughout the CT (P = 0.05), ranging from 12.5% in the 1st to 35.7% in the 5th CT week. In the 1st CT week, there was a predominance of alterations in the lips (5.5%) and saliva (5.5%), while in the 5th, the jugal / palate mucosa (21.4%) remained the most affected site by SOM. Differences in the severity of SOM in the jugal / palate mucosa (P = 0.01) and labial mucosa (P = 0.04) were observed over time. In the 5th CT week, the likelihood of developing SOM was 13.3-fold higher (95% CI: 1.5 - 105.6) in patients with hematologic tumors. CONCLUSIONS: The incidence of SOM was higher in the 5th CT week, most commonly affecting the jugal / palate mucosa, and patients with hematologic tumors were more prone to develop SOM.

Trend of hospitalized cases of oral cancer in Brazil and its relationship with oral health coverage in public health system between 2009 and 2017.

BACKGROUND: This study aimed to analyze the trend in the number of hospitalized cases of oral cancer in Brazil, according to the coverage of oral health services in public health system, and also investigate the influence of healthcare and clinical characteristics on the severity of oral cancer cases. MATERIAL AND METHODS: This retrospective study considered the period between 2009 and 2017. Data from the Hospital Registry of Cancer from the National Cancer Institute were used, considering the primary locations C00 to C06. Detailed information including sex, age, alcohol and tobacco use, year of first consultation, and the clinical stage of the cases were also collected. The frequency of hospitalized cases was correlated with the coverage of Primary Care Oral Health Teams (ESB) and the number of Dental Specialty Centers (CEO). It was also estimated the chance of advanced oral cancer cases, according to healthcare and clinical characteristics. Data were analyzed using Tweedie's multiple regression and multiple binary logistic regression (α<0.05). RESULTS: There was an increasing trend in the number of hospitalized cases of oral cancer in Brazil between 2009 and 2017 (B=0.043, p<0.001, PR=1.044). The increase in ESB coverage was associated with small increase in the number of hospitalized cases of oral cancer (B=0.001, p=0.003, PR=1.001). The increase in the number of CEO was associated with decrease in the number of hospitalized cases of oral cancer (B=-0.085, p<0.001, PR =0.918). The increase of ESB (OR=0.998) and CEO (OR=0.974) contributed for reducing the number of stage IV cases, whilst the history of alcohol and tobacco use (OR=1.574) was associated with an increase in the number of stage IV cases. CONCLUSIONS: Although an increasing trend was detected, the expansion of the public health system reduced the number of hospitalized cases and the frequency of advanced oral cancer cases in Brazil.

Primary melanoma of the oral cavity: A multi-institutional retrospective analysis in Brazil.

BACKGROUND: Melanoma is an aggressive malignant tumor, rarely observed in the oral cavity. The aim of this study was to describe the clinicopathologic features of a series of oral melanomas. MATERIAL AND METHODS: A retrospective descriptive study was performed. A total of 15,482 biopsy records from two oral and maxillofacial pathology services in Brazil were analyzed. All cases of oral melanomas were reviewed, and clinical, demographic, histopathological data, treatment, and follow-up status were collected. In addition, immunohistochemistry stains (pan-cytokeratin AE1/AE3, vimentin, α-SMA, CD45, S-100 protein, HMB-45, Melan A, and Ki-67) were performed. RESULTS: The series comprised of 5 males (71.4%) and 2 females (28.6%), with a mean age of 58.0 ± 9.2 years (range: 45-69 years) and a 2.5:1 male-to-female ratio. The gingiva (n = 3, 42.8%) and hard palate (n = 2, 28.6%) were the most common affected sites, presenting clinically as ulcerated swellings with a brown to black color. Cervical lymph node metastasis was detected in three patients during the first examination. Microscopically, 6 cases (85.7%) were melanotic, and one (14.3%) was amelanotic. Most cases (n = 4, 57.1%) presented a predominance of epithelioid cells. S-100 and HMB-45 were positive in all cases (n = 7, 100.0%). In contrast, only 4 cases (57.1%) were positive for Melan-A. The proliferative index with Ki-67 was high, with labeling index ranging from 70.0% to more than 90% of positive cells. Five patients died from complications of the tumors after a mean follow-up period of 7.8 months. CONCLUSIONS: Melanoma is an aggressive malignant tumor that rarely occurs in the oral cavity. It occurs mainly in adult and elderly patients and often is diagnosed in advanced stages. The current findings were similar to previous studies and reflected the characteristics of the services from where lesions were retrieved.

The effect of denudation and injection timing in the reproductive outcomes of ICSI cycles: new insights into the risk of in vitro oocyte ageing.

STUDY QUESTION: Does the time elapsed between oocyte pick-up (OPU) and denudation or injection affect the probability of achieving a live birth (LB) in ICSI cycles? SUMMARY ANSWER: Prolonged oocyte culture before denudation (>4 h) was associated with an increase in clinical pregnancy (CP), LB and cumulative LB (CLB) rates when compared with earlier denudation timings. WHAT IS KNOWN ALREADY: Oocyte maturation is a complex and dynamic process involving structural and biochemical modifications in the cell necessary to support fertilization and early embryo development. While meiotic competence is easily identifiable by the presence of an extruded first polar body, cytoplasmic maturation cannot be assessed microscopically. Culturing oocytes with their surrounding cumulus cells (CCs) prior to ICSI can enhance the completion of in vitro cytoplasmic maturation; conversely, prolonged culture may induce cell degeneration. The optimal culture intervals prior to oocyte denudation and/or injection have not yet been established and may prove relevant for the improvement of ICSI reproductive outcomes. STUDY DESIGN, SIZE, DURATION: This is a single-centre retrospective cohort analysis of 1378 ICSI cycles performed between January 2005 and October 2018. Data were categorized according to: (i) the time interval between OPU and denudation (<3 h, 3-4 h and ≥4 h), (ii) the time interval between denudation and ICSI (<1.5 h, 1.5-2 h, ≥2 h) and (iii) the time interval between OPU and ICSI (<5 h, 5-6 h and ≥6 h). The effect of these timings on fertilization, CP, LB and CLB rates were compared. The culture intervals between different procedures were dependent exclusively on laboratory workload. PARTICIPANTS/MATERIALS, SETTING, METHODS: ICSI cycles performed in women younger than 40 years old using autologous gametes with at least one metaphase II injected oocyte were included. The effect of oocyte culture duration prior to denudation and injection of the oocytes was compared using multivariable regression accounting for potential confounding variables. MAIN RESULTS AND THE ROLE OF CHANCE: Fertilization and oocyte damage rate after ICSI was found to be independent of the time interval to denudation (<3 h, 3-4 h and ≥4 h) and/or injection (<5 h, 5-6 h and ≥6 h). Extending oocyte culture before denudation significantly improved CP (29.5%, 42.7% and 50.6%, respectively), LB (25.1%, 34.4% and 40.7%, respectively) and CLB rates (26.0%, 36.1% and 42.2%, respectively), particularly if the time interval was at least 4 h. Additionally, LB (31.7%, 35.8% and 27.4%, respectively) and CLB rates (34.2%, 36.6% and 27.7%, respectively) were also dependent on the time from OPU to injection. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective nature and potential unmeasured confounding cannot be excluded. Furthermore, the effect of even shorter or longer periods of culture before denudation and/or injection were not evaluated and should not be extrapolated from these results. WIDER IMPLICATIONS OF THE FINDINGS: Our findings propose new evidence of a previously unrecognized protective effect of the CCs-oocyte interactions in human ART, raising the question of a possible downstream effect in embryogenesis which significantly affects LB rates. Additionally, this is the first study to suggest a negative effect of further extending culture before ICSI on LB and CLB rates, thus potentially allowing for the narrowing of an optimal ICSI time interval. Simple strategies such as the establishment of more effective time frames to perform these procedures and adjusting laboratory practice may prove beneficial, ultimately improving ICSI reproductive outcomes. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Epidemiologic analysis of salivary gland tumors over a 10-years period diagnosed in a northeast Brazilian population.

BACKGROUND: Salivary gland tumors (SGT) correspond to a heterogeneous group of lesions with variable biological behavior. The present study aimed to determine the distribution and demographic findings of salivary gland neoplasms in a northeast Brazilian population. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. A total of 588 cases of SGT were diagnosed between 2006 and 2016 of 4 pathology services in the state of Sergipe, Brazil. All cases were reviewed, and data such as sex, age, anatomical location, and histopathological diagnosis were collected. RESULTS: A total of 470 (79.9%) tumors were benign and 118 (20.1%) were malignant. The majority of the patients were females (n=328, 55.8%) with an overall female:male ratio of 1.2:1. The major salivary glands were affected more than the minor glands (69.5% vs. 30.5%). Pleomorphic adenoma (n=419, 71.3%) and mucoepidermoid carcinoma (n=29, 4.9%) were the most frequent benign and malignant tumors, respectively. In addition, both benign and malignant tumors occurred more frequently in the parotid gland (n=300, 51%, p<0.05). CONCLUSIONS: The epidemiologic profile and clinical characteristics of SGT were similar to those described in other countries and other regions of Brazil. Epidemiological studies of SGT help to understand their clinical and pathological features and are essential to establish the proper management and prognosis.

Quantifying indoor air quality determinants in urban and rural nursery and primary schools.

Poor indoor air quality can adversely affect children's health, comfort and school performance, but existing literature on quantifying indoor air pollutants (IAP) determinants' in nursery and primary schools is limited. Following previous studies, this study mainly aimed to quantify determinants of selected IAP, in nursery and primary schools from both urban and rural sites, accounting for seasonal variations. In 101 indoor microenvironments (classrooms, bedrooms and canteens) from 25 nursery and primary schools, CO2, CO, HCOH, NO2, O3, total volatile organic compounds, PM1, PM2.5, PM10, total suspended particles (TSP), and meteorological/comfort parameters were continuously sampled (occupancy and background levels), from at least 24 h to 9 consecutive days (not simultaneously) in each studied room; in some cases weekend was also considered. Children faced thermal discomfort and inadequate humidity, respectively in 60.1% and 44.1% of the studied classrooms. They were also exposed to high levels of IAP, namely PM2.5 and CO2 respectively in 69.0% and 41.3% of the studied classrooms, mostly in urban sites, depending on season and on occupancy and activity patterns (different amongst age groups). As PM2.5 and CO2 were the major concerning IAP, multivariate linear regression models were built to quantify (explained variability and relative importance) their main determinants, in both occupancy and non-occupancy (background) periods. Models for occupancy periods showed higher explained variability (R2 = 0.64, 0.57 and 0.47, respectively, for CO2, PM2.5 and PM10) than for non-occupancy. Besides background concentrations (43.5% of relative importance), relative humidity (21.1%), flooring material (17.0%), heating (6.7%) and age group of the occupants (5.3%), adjusted for season of sampling (6.4%) were predictors in CO2 occupancy model. In the cases of PM2.5 and PM10 occupancy concentrations, besides background concentrations (71.2% and 67.2% of relative importance, respectively for PM2.5 and PM10), type of school management (8.8% and 15.2%) and flooring material (13.9% and 13.9%), adjusted for season of sampling (6.1% and 3.8%), were the main predictors. These findings support the need of mitigation measures to reduce IAP levels, and prevention actions to avoid children's exposure. Reducing the time spent indoors in the same microenvironment by doing more and/or longer breaks, improving ventilation and cleaning actions, and avoiding or making a better maintenance hardwood flooring materials, chalkboard use and VOC emitting materials, are practices that should be implemented and their impacts quantified.

Street food research worldwide: a scoping review.

BACKGROUND: Street foods vary with respect to their nutritional value and safety characteristics and contribute to a sizable proportion of food intake in many populations worldwide. Therefore, the present study aimed to describe the coverage in the scientific literature of different health-related and socio-economic aspects of street food consumption and trading. METHODS: Three electronic databases (searched from inception to 16 October 2017), a hand-search of relevant journals and backward citation tracking were used to identify eligible scientific articles with a main objective of investigating or reporting specific results on health-related or socio-economic aspects of street food. Papers published in English, Portuguese, French, Spanish or Italian, as well as English abstracts of papers published in other languages, were assessed. The selected articles were evaluated by two independent researchers and described according to year of publication, geographical distribution, definition of street food, main topics addressed and target population. RESULTS: In total, 441 papers were selected. The number of publications has increased in recent years, almost half of them being published after 2012. Almost three-quarter of the articles were from Africa or Asia. Most studies addressed food safety (85.5%), whereas street food availability and consumption were much less frequently investigated (30.3%). The focus of the studies was usually the food (mostly its microbiological contamination) and the vendors (mostly their food handling), whereas consumers and vending sites were seldom evaluated. More than half of the studies did not specify a definition for street food. CONCLUSIONS: Efforts are needed for a more widespread and comprehensive assessment of different issues related to street food availability and consumption in different settings, especially regarding street food offer, nutritional composition, and patterns of purchase and consumption by the population.

Environmental and social valuation of shipping emissions on four ports of Portugal.

Maritime sector is expected to continue growing significantly in line with world trade, however its impacts on environmental, social and human health are not yet fully known. Thus, this study aimed to estimate the external costs of in-port shipping emissions (NOx, SO2, CO2, VOCs and PM2.5) and accomplish a comprehensive eco-efficiency evaluation of four ports in Portugal (Leixões, Setúbal, Sines and Viana do Castelo) during 2013. External costs were based on the external cost factors from BeTa, CAFE and NEEDS projects and from Song (2014). Eco-efficiency evaluation was based on environmental, social and economic criteria. Results showed higher externalities for Sines and Setúbal (2.0E+02 million €), followed by Leixões (1.8E+02 million €), and Viana do Castelo (6.3 million €). NOx, SO2, and PM2.5 were the pollutants with the highest externalities. Sines port showed the best overall eco-efficiency. Although Setúbal port showed higher performance than Viana do Castelo port based on the economic data, when social and environmental aspects were considered the results changed. This shows the importance of performing a more comprehensive analysis using social and environmental indicators. The combination of all these indicators is highly important to support the implementation of policies for the abatement of shipping in-port emissions.

Clinical, laboratory and epidemiological aspects of HPV infection in a low-income population from South Bahia, Brazil.

The aim of this study was to determine the prevalence and risk factors for human papillomavirus (HPV) infection in the Southern region of the State of Bahia, evaluating the performance of alternative complementary methods for cervical lesion detection. Cervical samples from women who attended healthcare units were collected and diagnosed by visual inspection, cervical cytology and nested polymerase chain reaction (PCR). Moreover, hemi-nested PCR was performed to detect different HPV genotypes. The prevalence of HPV infection was 47·7%, with genotype 16 detected in most cases. Infection was associated with dyspareunia and bleeding (P < 0·001, odds ratio (OR) 5·6, 95% confidence interval (CI) 2·815-11·14) and hormonal contraceptive use (P = 0·007, OR 2·33, 95% CI 1·25-4·34). There was a positive correlation between positive PCR and positive visual inspection, cervical cytology and symptoms reported. Furthermore, visual inspection was twice as specific, and had a greater positive predictive value than cytology. We showed a high prevalence of HPV infection in Southern Bahia, with HPV 16 being the most common type, and visual inspection being most effective at detecting HPV lesions, corroborating the suggestion that it can be applied in routine gynecologic examinations for low-income populations.

Allelic loss in amalgam-associated oral lichenoid lesions compared to oral lichen planus and mucosa.

BACKGROUND: The amalgam-associated oral lichenoid lesion (AAOLL) shows clinical and histopathological features similar to oral lichen planus (OLP). Molecular researches to improve knowledge of pathogenesis and clinical behavior of AAOLL are still scarce. OBJECTIVE: We investigated for the first time the use of loss of heterozygosity (LOH) as a molecular approach for genetic characterization of AAOLL in comparison with OLP and evaluated the cell proliferation index. MATERIALS AND METHODS: The sample comprised nine AAOLLs, 10 OLPs, and eight NOMs matched by patients' gender and age. LOH was assessed using polymorphic microsatellite markers at chromosomes 9p (D9S157, D9S162, D9S171), 11q (D11S1369), and 17p (TP53, AFM238WF2). Cell proliferation was assessed by immunohistochemical expression of Ki-67 (MIB-1). The association between LOH and Ki-67 was investigated. RESULTS: Loss of heterozygosity occurred in 5/9 AAOLLs and in 2/10 OLPs in at least one marker each, while NOM showed no LOH. Cell proliferation index in AAOLL ranged from 2 to 23%. There was no association between cell proliferation and LOH, independent of the marker. CONCLUSION: Our study shows that the profile of molecular changes in AAOLL and OLP, evaluated by LOH and Ki-67 expression, is similar. Additional studies including larger samples should be performed to confirm or to refute our findings.

Extra-tongue oral granular cell tumor: Histological and immunohistochemical aspect.

BACKGROUND: Granular cell tumor (GCT) is an uncommon benign tumor founded in any part of the body but mainly in the tongue. Extra-tongue oral granular cell tumor (ETOGCT) is rare with few cases reported. Here we describe seven cases of oral GCT located in sites other then the tongue and discuss histopathological and immunohistochemical differences between differential diagnoses. MATERIAL AND METHODS: We retrieved all cases diagnosed with oral granular cell tumor, from the Oral Pathology Service at the School of Dentistry/ University of São Paulo, and excluded the ones sited in the tongue. Immunohistochemical staining anti-S100 was also performed. RESULTS: The presented cases of Extra-tongue Oral Granular Cell Tumor (ETOGT) are composed by granular cells with intimately association with the adjacent tissue. Atypia and mitoses were not seen, and in most cases, the typical pseudoepitheliomatous hyperplasia was not observed. CONCLUSIONS: The importance of an adequate attention is to avoid misdiagnoses, since ETOGT is rare and the tricking histopathological findings could induce to it. All the cases can be differentiated from the tumors that has a granular cell proliferation through a morphological analysis and when needed, immunohistochemistry stain.

Oral Thrombus: Report of 122 cases with clinically descriptive data.

BACKGROUND: The aim of the present study was to assess the frequency and characterize clinic-pathologic aspects of thrombus occurring as a single lesion or in association with other oral pathologies. MATERIAL AND METHODS: 122 cases of thrombus from the oral cavity were retrieved. Information regarding site of the lesion, age, sex and clinical diagnosis or hypothesis and associated lesions were collected from the patients' records. RESULTS: The lesions occurred in a wide age range but the 5th decade was the most prevalent and female patients were more affected. The most frequent site for the lesion was the lip, followed by tongue, buccal mucosa, alveolar ridge, gingiva, floor of the mouth and vestibule. Thirty-five cases were associated with other vascular anomalies or actinic cheilitis. Microscopically, typical thrombus morphology was present. Organized thrombus presented neovascularization and fibroblasts, associated with hemorrhagic areas. CONCLUSIONS: Only 4 cases of oral thrombus have been described in the oral cavity. Given the limited number of cases reported, the importance of a thrombus in the oral cavity is not well established. This study contributes to establishing the profile of patients presenting oral thrombus, a lesion not rare but not well documented.

Clinical features and long-term outcomes of systemic lupus erythematosus: comparative data of childhood, adult and late-onset disease in a national register.

Systemic lupus erythematosus (SLE) affects predominantly women at reproductive age but may present at any age. Age at disease onset has a modulating effect on presentation and course of disease, but controversies persist regarding its impact on long-term outcome. Our aims were to characterize clinical features, co-morbidities and cumulative damage in childhood-onset, adult-onset and late-onset SLE. Patients with childhood-onset SLE fulfilling ACR 1997 criteria were identified in a nationwide register-Reuma.pt/SLE (N = 89) and compared with adult-onset and late-onset counterparts matched 1:1:1 for disease duration. 267 SLE patients with mean disease duration of 11.9 ± 9.3 years were analyzed. Skin (62 %), kidney (58 %), neurological (11 %) and hematologic involvement (76 %) were significantly more common in childhood-onset SLE and disease activity was higher in this subset than in adult- and late-onset disease (SLEDAI-2K 3.4 ± 3.8 vs. 2.2 ± 2.7 vs. 1.6 ± 2.8, respectively; p = 0.004). Also, more childhood-onset patients received cyclophosphamide (10 %) and mycophenolate mofetil (34 %). A greater proportion of women (96 %), prevalence of arthritis (89 %) and anti-SSA antibodies (34 %) were noted in the adult-onset group. There was a significant delay in the diagnosis of SLE in older ages. Co-morbidities such as hypertension, diabetes and thyroid disease were significantly more frequent in late-onset SLE, as well as the presence of irreversible damage evaluated by the SLICC/ACR damage index (20 vs. 26 vs. 40 %; p < 0.001). Greater organ involvement as well as the frequent need for immunosuppressants supports the concept of childhood-onset being a more severe disease. In contrast, disease onset is more indolent but co-morbidity burden and irreversible damage are greater in late-onset SLE, which may have implications for patients' management.

Self-declared ethnicity and genomic ancestry in prostate cancer patients from Brazil.

Some studies of polymorphisms in prostate cancer (PCa) analyze individuals in a uniform manner, regardless of genetic ancestry. However, PCa aggressiveness differs between subjects of African descent and those of European extraction. Thus, genetic ancestry analysis may be used to detect population stratification in case-control association studies. We genotyped 11 ancestry informative markers to estimate the contributions of African, European, and Amerindian ancestries in a case-control sample of 213 individuals from Bahia State, Northeast Brazil, including 104 PCa patients. We compared this data with self-reported ancestry and the stratification of cases by PCa aggressiveness according to Gleason score. A larger African genetic contribution (44%) was detected among cases, and a greater European contribution (61%) among controls. Self-declaration data revealed that 74% of PCa patients considered themselves non-white (black and brown), and 41.3% of controls viewed themselves as white. Our data showed a higher degree of European ancestry among fast-growing cancer cases than those of intermediate and slow development. This differs from many previous studies, in which the prevalence of African ancestry has been reported for all grades. Differences were observed between degrees of PCa aggressiveness in terms of genetic ancestry. In particular, the greater European contribution among patients with high-grade PCa indicates that a population's genetic structure can influence case-control studies. This investigation contributes to our understanding of the genetic basis of tumor aggressiveness among groups of different genetic ancestries, especially admixed populations, and has significant implications for the assessment of inter-population heterogeneity in drug treatment effects.

Clinico-biochemical characteristics of 229 Portuguese infertile women with polycystic ovary syndrome: clinical relevance and relationship with fertility treatment results.

PURPOSE: Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-age women. The authors aimed to evaluate the characteristics of PCOS women and its relationship with fertility treatment outcomes. MATERIALS AND METHODS: The authors reviewed records of PCOS women assisted at Hospital Santa Maria. Fertility treatment results were assessed as pregnancy rate, number of cycles, and miscarriage rate. RESULTS: They identified 229 PCOS women, 179 (78.2%) had waist circumference > 80 cm, 72 (31.4%) had type 2 diabetes mellitus (T2DM) familial history and glucose abnormalities, hypertriglyceridemia and low cholesterol-HDL were detected in 23(10.1%), 15 (6.6%) and 103 (45.0%), respectively. Pregnancy was achieved in 164 women. The mean number of cycles to achieve pregnancy was 2.7 (±2.2). Statistical analysis identified factors associated with longer/higher number of treatments: primary infertility, T2DM familial history, hypertriglyceridemia, and low cholesterol-HDL. Waist circumference > 80 cm, older age, and increased LH level were associated with miscarriage. CONCLUSIONS: Primary infertility, T2DM familial history, hypertriglyceridemia, low cholesterol-HDL, older age, waist circumference > 80 cm, and high LH may confer poorer fertility treatment results.

Characterization of damage in Portuguese lupus patients: analysis of a national lupus registry.

BACKGROUND: Although the survival rate has considerably improved, many patients with systemic lupus erythematosus (SLE) develop irreversible organ damage. OBJECTIVES: The objectives of this paper are to characterize cumulative damage in SLE patients and identify variables associated with its presence and severity. METHODS: A cross-sectional analysis of SLE patients from the Portuguese Lupus register Reuma.pt/SLE in whom damage assessment using the SLICC/ACR-Disability Index (SDI) was available was performed. Predictor factors for damage, defined as SDI ≥ 1, were determined by logistic regression analyses. A sub-analysis of patients with severe damage (SDI ≥ 3) was also performed. RESULTS: In total, 976 patients were included. SDI was ≥1 in 365 patients, of whom 89 had severe damage. Musculoskeletal (24.4%), neuropsychiatric (24.1%) and ocular (17.2%) domains were the most commonly affected. Older age, longer disease duration, renal involvement, presence of antiphospholipid antibodies and current therapy with steroids were independently associated with SDI ≥ 1. The subpopulation with severe damage had, in addition, a greater interval between the first manifestation attributable to SLE and the clinical diagnosis as well as and more frequently early retirement due to SLE. CONCLUSIONS: This large lupus cohort confirmed that demographic and clinical characteristics as well as medication are independently associated with damage. Additionally, premature retirement occurs more often in patients with SDI ≥ 3. Diagnosis delay might contribute to damage accrual.