HPV-related oropharyngeal carcinoma remains infrequent over 25 years in a Brazilian Oral Pathology Center: A cross-sectional study with literature review.

BACKGROUND: The aim was to evaluate the frequency, clinicopathological features, and HPV status of oropharyngeal squamous cell carcinoma (OP-SCC) and benign HPV-related epithelial lesions of the oropharynx over the last 25 years. Moreover, a literature review was performed to investigate HPV frequency in OP-SCC samples diagnosed in Brazilian Centers. MATERIAL AND METHODS: A cross-sectional study analyzed OP-SCC, squamous papilloma, verruca vulgaris, and condyloma accuminatum, diagnosed from 1997 to 2021. HPV status of OP-SCC was determined by immunohistochemistry and "in situ" hybridization. Bivariate statistics were performed (p≤0.05). For the literature review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. Two independent reviewers assessed the studies for eligibility. RESULTS: Cross-sectional: 211 OP-SCC (63.0%) and 124 benign lesions (37.0%) were included. OP-SCC frequency increased gradually over time, whereas benign lesions had steady trends. OP-SCC affected more males (n= 171; 81.0%), though the relative frequency in females rose over time. Smoking (n= 127; 60.2%) was common in OP-SCC. Nineteen OP-SCC (13.0%) were positive for HPV. HPV-positive and HPV-negative tumors had similar clinicopathological features (p>0.05). Benign lesions predominated in middle-aged (n= 32; 26.7%) women (n= 71; 57.3%), in the soft palate (n=101; 81.5%). LITERATURE REVIEW: 32 studies were included, and in 60% of them, HPV frequency in OP-SCC was less than 25%. CONCLUSIONS: OP-SCC prevalence has been increasing, and it was mostly associated with smoking and alcohol rather than with HPV infection in Brazil. Benign lesions had a stationary frequency over the evaluated period.

ALDH1 immunoexpression in epithelial and stromal cells of oral lichen planus and lesions with lichenoid inflammatory infiltrate.

BACKGROUND: Oral Lichen Planus is a potential malignant disorder and shares clinical and histopathological features with other similar lesions. ALDH1 is a specific biomarker for stem cells identification, however its role in stromal cells of immune inflammatory infiltrate has not been explored. The aim of this study was to investigate the ALDH1 immunoexpression in epithelial and stromal cells of Oral Lichen Planus and other lesions with lichenoid inflammatory infiltrate. MATERIAL AND METHODS: 64 samples of Oral Lichen Planus, Oral Lichenoid Lesions, Oral Leukoplakia and Unspecific Chronic Inflammation were included. ALDH1 was evaluated in both epithelium and stromal cells. ALDH1+ cells ≥ 5% were considered positive in epithelium. Stromal cells were evaluated semi quantitatively. Fields were ranked in scores, according to criteria: 1 (0 to 10%); 2 (11 to 50%) and 3 (>50%). The mean value of the sum of the fields was the final score. Statistical differences among groups were investigated, considering p < 0.05. RESULTS: ALDH1 expression in epithelium was low in all groups without difference among them. ALDH1+ cells in the lamina propria were higher for Lichen Planus [2.0], followed by Leukoplakia [1.3], Lichenoid lesions [1.2] and control [1.1] (p<0.05). CONCLUSIONS: ALDH1 immunoexpression in epithelium of lichenoid potential malignant disorders did not show a contributory tool, however ALDH1 in stromal cells of lichen planus might be involved in the complex process of immune regulation associated with the pathogenesis of this disease.

Oral amyloidosis: an update.

BACKGROUND: Amyloidosis is a disease characterized by the progressive deposition of abnormal proteins that can occur in any organ. In the oral cavity, the tongue is the most common affected site, usually causing macroglossia. Biopsy is essential for the diagnosis and the occurrence of its systemic form is mandatory to be investigated. This systematic review evaluated the existing information in the literature on Amyloidosis in the oral cavity to allow a more comprehensive and updated analysis of its clinicopathological characteristics, as well as to explore the main forms of treatment and prognostic factors. MATERIAL AND METHODS: Electronic searches were undertaken in five databases supplemented by manual scrutiny. RESULTS: A total of 111 studies were included with 158 individuals. CONCLUSIONS: The disease had a higher prevalence in women, the tongue was the most affected site, as well as the systemic form of the disease. The worst prognosis was for cases of systemic amyloidosis associated with multiple myeloma.

What is the preferred concentration of ethanolamine oleate for sclerotherapy of oral vascular anomalies?

BACKGROUND: This study compared three different concentrations of EO (1.25%, 2.5% and 5%) for the treatment of oral vascular anomalies (OVAs). MATERIAL AND METHODS: This was a retrospective comparative analysis of patients with OVAs treated with EO. Anomalies smaller than 20 mm were included. The patients were treated with 1.25% (G1), 2.5% (G2), and 5% (G3) and clinical data were obtained. The number of sessions, the final volume and dose of EO were statistically analyzed to verify effectiveness and safety of the treatment. The different concentrations of EO were compared considering the number of sessions, the final volume and total dose of EO. Analysis of covariance (ANCOVA) was used to evaluate the influence of covariates on the outcomes. A p-value < 0.05 was considered significant. RESULTS: Nineteen women and 11 men with a median age of 54 years were included. The OVAs were most frequent in the lip (n=14) and cheek (n=9). All lesions exhibited complete clinical healing within 28 days. Patients of G3 required fewer sessions than those of G2 (p=0.017), a lower final volume compared to the other groups (p<0.001), and a lower total dose than G1 (p<0.001). Patients of G1 used a lower total dose than G2 (p=0.003). CONCLUSIONS: The concentration of 5% EO performed better than 1.25% and 2.5% for sclerotherapy of OVAs measuring up to 20 mm. This preliminary result should be the preferred concentration of EO to provide an effective and safe treatment of OVAs.

Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study.

BACKGROUND AND AIMS: Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. METHODS: This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. RESULTS: A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 µg/mL vs 1.3 µg/mL, p = 0.0013; and 3.1 µg/mL vs 1.7 µg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 µg/mL vs 1.7 µg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. CONCLUSIONS: A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.

Proactive therapeutic drug monitoring of infliximab: a comparative study of a new point-of-care quantitative test with two established ELISA assays.

BACKGROUND: Therapeutic drug monitoring is a powerful strategy known to improve the clinical outcomes and to optimise the healthcare resources in the treatment of autoimmune diseases. Currently, most of the methods commercially available for the quantification of infliximab (IFX) are ELISA-based, with a turnaround time of approximately 8 h, and delaying the target dosage adjustment to the following infusion. AIM: To validate the first point-of-care IFX quantification device available in the market - the Quantum Blue Infliximab assay (Buhlmann, Schonenbuch, Switzerland) - by comparing it with two well-established methods. METHODS: The three methods were used to assay the IFX concentration of spiked samples and of the serum of 299 inflammatory bowel diseases (IBD) patients undergoing IFX therapy. RESULTS: The point-of-care assay had an average IFX recovery of 92%, being the most precise among the tested methods. The Intraclass Correlation Coefficients of the point-of-care IFX assay vs. the two ELISA-based established methods were 0.889 and 0.939. Moreover, the accuracy of the point-of-care IFX compared with each of the two reference methods was 77% and 83%, and the kappa statistics revealed a substantial agreement (0.648 and 0.738). CONCLUSIONS: The Quantum Blue IFX assay can successfully replace the commonly used ELISA-based IFX quantification kits. This point-of-care IFX assay is able to deliver the results within 15 min makes it ideal for an immediate target concentration adjusted dosing. Moreover, it is a user-friendly desktop device that does not require specific laboratory facilities or highly specialised personnel.

Tunable DNA cleavage activity promoted by copper(ii) ternary complexes with N-donor heterocyclic ligands.

Several small molecules have the capacity to cleave DNA promptly at high yields, even under mild conditions. Usually, this activity has no constraints, occurring without external or user control. Here, we demonstrate that UV-light exposure can greatly enhance the DNA cleavage activity promoted by four ternary copper(ii) complexes. A remarkable photocontrolled activity was achieved, which may be interesting for chemical and biochemical applications.

Estimating the prevalence of inflammatory bowel disease in Portugal using a pharmaco-epidemiological approach.

PURPOSE: To estimate inflammatory bowel disease (IBD) prevalence in Portugal from 2003 to 2007, and to obtain disease, sex and age specific estimates. METHODS: A pharmaco-epidemiological approach based on intestinal anti-inflammatory (IAI) drugs consumption was used. Proportion of patients taking IAI drugs and mean prescribed daily dose (PDD) were estimated from a sample of 513 IBD patients. Assumptions were made about unknown parameters and sensitivity analysis performed: drug compliance (80% in base case; range 70-85%) and proportion of sulphasalazine used in IBD (52%; range 40-80%). Sex and age specific estimates were based on a proposed methodological extension and results from a nationwide (n = 5893) cross-sectional study. RESULTS: IBD prevalence increased from 86 patients per 100 000 in 2003 to 146 in 2007. Regions more affected were Lisboa and Porto (173 and 163 per 100 000 in 2007, respectively). Prevalence increased from 42 and 43 per 100 000 in 2003 to 71 and 73 in 2007, respectively for ulcerative colitis (UC) and Crohn's disease (CD). In 2007, prevalence was higher in the 40-64 age stratum for UC (99 per 100 000) and in the 17-39 stratum for CD (121). Prevalence was consistently higher in females. CONCLUSIONS: Portugal is half way between countries with the highest and lowest IBD prevalence, but is steeply making the road to the highest-level group. Despite limitations of the proposed methods, assumptions were reasonable and estimates seem to be valid. Feasibility and comparability of this methodology makes it an interesting tool for future studies on IBD epidemiology.

Teores de proteína para vacas lactantes em pastejo de capim-elefante / Protein contents for lactating dairy cows grazing elephant grass

Avaliou-se o efeito da utilização de concentrados com diferentes teores de proteína bruta (PB) para vacas em lactação sob pastejo rotacionado de capim-elefante, distribuídas em três quadrados latinos (3x3). Os tratamentos foram concentrados suplementares contendo 15,2; 18,2 ou 21,1 por cento de PB. Foram oferecidos 3kg de concentrado por vaca, duas vezes ao dia. A disponibilidade de matéria seca (MS)/ha de capim-elefante foi de 1.873kg ou de 17,4kg de MS/vaca dia-1. A MS do capim-elefante foi de 19,6 por cento, contendo 13,9 por cento de PB e 66,1 por cento de fibra detergente neutro (FDN) e 67,4 por cento de digestibilidade in vitro da MS (DIVMS). Não houve diferença (P>0,05) entre os tratamentos quanto ao consumo diário de MS da dieta total (21,5; 21,6 e 20,8kg/d), MS do capim-elefante (16,1; 16,3 e 15,5kg/d) e FDN do capim-elefante (10,7; 10,7 e 10,3kg/d). As produções de leite (17,5; 17,2 e 17,6kg/d) e os teores de gordura (3,4; 3,5 e 3,5 por cento), proteína (2,9; 2,9 e 2,9 por cento), lactose (4,4; 4,4 e 4,4 por cento) e N-ureia no leite (14,1; 14,6 e 15,8mg/dL) não diferiram (P>0,05) entre os tratamentos (respectivamente, para 15,2; 18,2 ou 21,1 por cento de PB). O teor de N-ureia no plasma foi maior (P<0,05) em vacas alimentadas com concentrado com 21,1 por cento de PB (na ordem citada: 11,5; 12,2 e 14,4mg/dL). Nas condições experimentais, o concentrado suplementar com 15,2 por cento de PB pode ser utilizado na alimentação de vacas em lactação em pastagem de capim-elefante.

To evaluate the effect of feeding concentrate with different crude protein (CP) contents, lactating dairy cows grazing elephant grass were distributed in a 3x3 latin square. Three kg/cow of concentrates (15.2, 18.2, or 21.1 percent CP) were offered twice a day. Elephant grass dry matter (DM) availability was 1,873kg/ha; with a daily offer of 17.4kg/cow. The elephant grass DM content was 19.6 percent with 13.9 percent CP, 66.1 percent neutral detergent fiber (NDF), and 67.4 percent in vitro DM digestibility. There was no difference among treatments regarding total diet DM daily intake (21.5, 21.6, and 20.8kg/cow), elephant grass DM (16.1, 16.3, and 15.5kg/cow), and elephant grass NDF (10.7, 10.7, and 10.3kg/cow). Milk yield (17.5, 17.2, and 17.6kg/d) fat (3.4, 3.5, and 3.5 percent), protein (2.9, 2.9, and 2.9 percent), lactose (4.4, 4.4, and 4.4 percent), and N-urea (14.1, 14.6, and 15.8mg/dL) did not differ among concentrates (P>0.05). Plasma N-urea was higher in cows fed concentrate with 21.1 percent CP (11.5 = 12.2<14.4mg/dL, P<0.05). According to these results, concentrate with 15.2 percent CP can be used to lactating dairy cows grazing elephant grass, without affecting milk production as compared to concentrate with 18.2 or 21.1 percent of CP.

Inflammatory bowel disease: a patient's and caregiver's perspective.

The purpose of this study was to conduct a survey examining the impact of inflammatory bowel disease (IBD) on patients' and their caregivers' daily activities. Questionnaires were distributed to patients registered in the APDI (Portuguese Association for IBD) database and their respective caregivers in 2007. Of 422 patient respondents, 251 had Crohn's disease (CD) and 171 had ulcerative colitis (UC), with the majority of patients being women (58.1%) and aged over 40 years (37.4%). The number of disease flares experienced by IBD patients was slightly higher for patients with CD than for patients with UC (2.64 vs. 2.34), and surgery was more often required in CD patients as compared to UC patients (42.4 vs. 7%). Sixty percent (60%) of patients reported having no problems with mobility, daily activities, or personal hygiene; however, over half of all patients experienced some pain and anxiety. Adult patients and children and adolescents respectively experienced time off work or school due to their disease but caregivers were not affected in this regard. The caregivers life (N=324) was affected by anxiety, with the major concern reported as the risk of the patient developing cancer. Both IBD patients and caregivers thought that the provision of information on new drugs and contact time with a doctor would have the biggest impact on improving care. The symptoms and complications of IBD have a considerable impact on the lives of patients and their caregivers, and several actions could be taken to improve their care.

Inflammatory myofibroblastic tumor of the alveolar mucosa of the mandible.

Inflammatory myofibroblastic tumor is a rare lesion composed of myofibroblastic spindle cells accompanied by inflammatory infiltrate. The objective of this paper is to report an uncommon case of inflammatory myofibroblastic tumor located in the alveolar mucosa of the mandible. A 33-year-old male presented an asymptomatic tumoral lesion, firm, pedunculated, pink-colored, covered by smooth mucosa, with focal ulceration, measuring 30x20x20 mm, located in the left posterior alveolar mucosa. Clinical diagnosis was soft tissue tumor. An excisional biopsy was made. Microscopic examination showed compact fascicular spindle cells proliferation with a diffuse inflammatory infiltrate of plasma cells, lymphocytes, and eosinophils. Large ganglion-like cells were observed. The lesional cells were immunopos-itive to vimentin, a-smooth muscle actin, muscle specific actin, and CD68. Negative immunostain was observed to S-100, Bcl-2, Ki-67, desmin, CD34, and cytokeratin. A diagnosis of inflammatory myofibroblastic tumor was performed. After 28 months of follow-up there was no recurrence. Although no evidence of oral inflammatory myofibroblastic tumor recurrence or malignant transformation has been reported, it has been observed that in inflammatory myofibroblastic tumor of other regions a prolonged follow-up is necessary after surgical excision.

A situação do aleitamento materno em Montes Claros, Minas Gerais: estudo de uma amostra representativa / Breastfeeding in Montes Claros, Minas Gerais: a representative sample study

Objetivo: Avaliar a situação do aleitamento materno em Montes Claros, entre crianças menores de dois anos de idade, e determinar variáveis associadas a maior risco de desmame precoce. Métodos: Neste estudo transversal foram realizadas entrevistas, por equipe treinada, com 602 mães selecionadas aleatoriamente na área urbana de Montes Claros, de setembro a novembro de 1996. A análise de sobrevivência foi o método utilizado para o cálculo da prevalência e da duração mediana do aleitamento materno. O teste do qui-quadrado foi empregado para comparação das proporções, admitindo-se um nível de confiança de 95 por cento. A análise de regressão logístiva foi utilizada para identificar os fatores de risco para o desmame precoce. Resultados: A duração mediana do aleitamento materno em geral foi de 8,7 meses; entretanto, a duração mediana do aleitamento materno exclusivo foi de apenas 27 dias. Os fatores de risco para o desmame precoce foram baixo peso ao nascimento (OR=2,65; IC95 por cento=1,10-6,40), dificuldades iniciais para amamentar (OR=1,86; IC95 por cento=1,21-2,85) e falta de incentivo para amamentação nas consultas médicas de pueriicultura (OR=1,75; IC95 por cento=1,15-2,66). Conclusões: Para o aleitamento materno em geral, existe uma siituação melhor do que aquela apresentada por outros estudos nacionais, mais ainda aquém do que recomenda a OMS. Existe uma situação crítica em relação ao padrão de amamentação exclusiva. Os fatores associados ao desmame precoce denotam um precário apoio dos serviços de saúde materno-infantil ao aleitamento materno