Medicine by Sfakianakis Alexandros: 06/25/18

Δευτέρα 25 Ιουνίου 2018

Immune checkpoint blockade therapy of mesothelioma: a clinical and radiological challenge

Abstract

Treatment of malignant pleural mesothelioma (MPM) represents a highly unmet medical need. Here, we discuss the results and therapeutic potential of first- and second-generation immunomodulatory antibodies targeting distinct immune checkpoints for the treatment of MPM, as well as their prospective therapeutic role in combination strategies. We also discuss the role of appropriate radiological criteria of response for MPM and the potential need of ad hoc criteria of disease evaluation in MPM patients undergoing treatment with immunotherapeutic agents.

https://ift.tt/2Kk4HE9

Atopic Dermatitis: Five Promising Targeted Therapies

Finally, patients with atopic dermatitis will have a range of treatment options.
Medscape Dermatology

https://ift.tt/2KoIWzX

Johns Hopkins Children’s Center Ranked Among Top U.S. Children’s Hospitals by U.S. News & World Report

BALTIMORE (June 26, 2018) – Johns Hopkins Children's Center ranked #8 in the nation on U.S. News & World Report's 2018-19 Best Children's Hospitals Honor Roll. Johns Hopkins Children's Center has the distinction of being the only children's hospital integrated with an adult facility to make the Honor Roll this year.

https://ift.tt/2tKJ0D1

Attitudes to local anaesthesia in radiofrequency thermotherapy sleep surgery: Our experience in a single centre with 42 adult patients

Clinical Otolaryngology, EarlyView.

https://ift.tt/2yIy0LZ

Three UTHealth Medical Students Invited to Present at Triological Society Meeting

Medical students José Ting, Margaret Engelhardt, and Brandon Esianor, BS, were invited to present the results of their research at...

https://ift.tt/2KoYFP9

5th Pediatric Allergy and Asthma Meeting (PAAM)

https://ift.tt/2Mj0jCs

The burden of chronic rhinosinusitis and its effect on quality of life among patients re-attending an otolaryngology clinic in south western Uganda

Worldwide, the burden of chronic rhinosinusitis (CRS) is variable, but not known in Uganda. CRS has significant negative impact on quality of life (QOL) and as such QOL scores should guide adjustments in treat...

https://ift.tt/2IrAa25

UTHealth Medical Students Make Presentations at International SENTAC Meeting

Nine posters were presented by medical students and residents from the McGovern Medical School Department of Otorhinolaryngology-Head and Neck Surgery...

https://ift.tt/2lycn7G

Precision medicine

https://ift.tt/2tEK6jg

How to avoid the inappropriate use of antibiotics in upper respiratory tract infections? A position statement from an expert panel

Abstract Introduction: Bacterial resistance burden has increased in the past years, mainly due to inappropriate antibiotic use. Recently it has become an urgent public health concern due to its impact on the prolongation of hospitalization, an increase of total cost of treatment and mortality associated with infectious disease. Almost half of the antimicrobial prescriptions in outpatient care visits are prescribed for acute upper respiratory infections, especially rhinosinusitis, otitis media, and pharyngotonsillitis. In this context, otorhinolaryngologists play an important role in orienting patients and non-specialists in the utilization of antibiotics rationally and properly in these infections. Objectives: To review the most recent recommendations and guidelines for the use of antibiotics in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, adapted to our national reality. Methods: A literature review on PubMed database including the medical management in acute otitis media, acute rhinosinusitis, and pharyngotonsillitis, followed by a discussion with a panel of specialists. Results: Antibiotics must be judiciously prescribed in uncomplicated acute upper respiratory tract infections. The severity of clinical presentation and the potential risks for evolution to suppurative and non-suppurative complications must be taken into 'consideration'. Conclusions: Periodic revisions on guidelines and recommendations for treatment of the main acute infections are necessary to orient rationale and appropriate use of antibiotics. Continuous medical education and changes in physicians' and patients' behavior are required to modify the paradigm that all upper respiratory infection needs antibiotic therapy, minimizing the consequences of its inadequate and inappropriate use.

Resumo Introdução: A resistência bacteriana a antibióticos nos processos infecciosos é um fato crescente nos últimos anos, especialmente devido ao seu uso inapropriado. Ao longo dos anos vem se tornando um grave problema de saúde pública devido ao prolongamento do tempo de internação, elevação dos custos de tratamento e aumento da mortalidade relacionada às doenças infecciosas. Quase a metade das prescrições de antibióticos em unidades de pronto atendimento é destinada ao tratamento de alguma infecção de vias aéreas superiores, especialmente rinossinusites, otite média aguda supurada e faringotonsilites agudas, sendo que uma significativa parcela dessas prescrições é inapropriada. Nesse contexto, os otorrinolaringologistas têm um papel fundamental na orientação de pacientes e colegas não especialistas, para o uso adequado e racional de antibióticos frente a essas situações clínicas. Objetivos: Realizar uma revisão das atuais recomendações de utilização de antibióticos nas otites médias, rinossinusites e faringotonsilites agudas adaptadas à realidade nacional. Método: Revisão na base PubMed das principais recomendações internacionais de tratamentos das infecções de vias aéreas superiores, seguido de discussão com um painel de especialistas. Resultados: Os antibióticos devem ser utilizados de maneira criteriosa nas infecções agudas de vias aéreas superiores não complicadas, a depender da gravidade da apresentação clínica e dos potenciais riscos associados de complicações supurativas e não supurativas. Conclusões: Constantes revisões a respeito do tratamento das principais infecções agudas são necessárias para que sejam tomadas medidas coletivas no uso racional e apropriado de antibióticos. Somente com orientação e transformações no comportamento de médicos e pacientes é que haverá mudanças do paradigma de que toda infecção de vias aéreas superiores deva ser tratada com antibióticos, minimizando por consequência os efeitos de seu uso inadequado.

https://ift.tt/2MVfbrU

Effects of distractors on upright balance performance in school-aged children with attention deficit hyperactivity disorder, preliminary study,

Abstract Introduction: Attention deficit hyperactivity disorder is a common impairing neuropsychiatric disorder with onset in early childhood. Almost half of the children with attention deficit hyperactivity disorder also experience a variety of motor-related dysfunctions ranging from fine/gross motor control problems to difficulties in maintaining balance. Objectives: The main purpose of this study was to investigate the effects of distractors two different auditory distractors namely, relaxing music and white noise on upright balance performance in children with attention deficit hyperactivity disorder. Methods: We compared upright balance performance and the involvement of different sensory systems in the presence of auditory distractors between school-aged children with attention deficit hyperactivity disorder (n = 26) and typically developing controls (n = 20). Neurocom SMART Balance Master Dynamic Posturography device was used for the sensory organization test. Sensory organization test was repeated three times for each participant in three different test environments. Results: The balance scores in the silence environment were lower in the attention deficit hyperactivity disorder group but the differences were not statistically significant. In addition to lower balance scores the visual and vestibular ratios were also lower. Auditory distractors affected the general balance performance positively for both groups. More challenging conditions, using an unstable platform with distorted somatosensory signals were more affected. Relaxing music was more effective in the control group, and white noise was more effective in the attention deficit hyperactivity disorder group and the positive effects of white noise became more apparent in challenging conditions. Conclusion: To the best of our knowledge, this is the first study evaluating balance performance in children with attention deficit hyperactivity disorder under the effects of auditory distractors. Although more studies are needed, our results indicate that auditory distractors may have enhancing effects on upright balance performance in children with attention deficit hyperactivity disorder.

Resumo Introdução: O transtorno do déficit de atenção e hiperatividade é um distúrbio neuropsiquiátrico comum que causa comprometimentos, com início na primeira infância. Quase metade das crianças com transtorno do déficit de atenção e hiperatividade também experimenta uma variedade de distúrbios relacionados às habilidades motoras, desde problemas de controle de habilidades motoras finas/grossas até dificuldades na manutenção do equilíbrio. Objetivos: O principal objetivo deste estudo foi investigar os efeitos de distrações, especificamente duas distrações auditivas diferentes, música relaxante e ruído branco, sobre o desempenho do equilíbrio vertical em crianças com transtorno de déficit de atenção e hiperatividade. Método: Comparamos o desempenho do equilíbrio vertical e o envolvimento de diferentes sistemas sensoriais na presença de distração auditiva entre crianças em idade escolar com transtorno do déficit de atenção e hiperatividade (n = 26) e controles com desenvolvimento típico (n = 20). O dispositivo Neurocom Smart Balance Master Dynamic Posturography foi utilizado para o teste de organização sensorial. O teste de organização sensorial foi repetido três vezes para cada participante em três ambientes de teste diferentes. Resultados: Os escores de equilíbrio no ambiente em silêncio foram menores no grupo com transtorno do déficit de atenção e hiperatividade, mas as diferenças não foram estatisticamente significativas. Além dos escores de equilíbrio mais baixos, as razões vestibulares e visuais também foram menores. As distrações auditivas afetaram positivamente o desempenho do equilíbrio geral para ambos os grupos. Condições mais desafiadoras, usando uma plataforma instável com sinais somatossensoriais distorcidos, foram mais afetados. Música relaxante foi mais eficaz no grupo de controle, e ruído branco foi mais eficaz no grupo de hiperatividade com déficit de atenção e os efeitos positivos do ruído branco se tornaram mais evidentes em condições desafiadoras. Conclusão: Que seja de nosso conhecimento, este é o primeiro estudo que avalia o desempenho do equilíbrio em crianças com transtorno do déficit de atenção e hiperatividade sob os efeitos de distrações auditivas. Embora mais estudos sejam necessários, os nossos resultados indicam que as distrações auditivas podem ter efeitos de aumento no desempenho do equilíbrio vertical em crianças com transtorno de déficit de atenção e hiperatividade.

https://ift.tt/2tK2tDR

Breaking paradigms in severe epistaxis: the importance of looking for the S-point

Abstract Introduction: Since the introduction of nasal endoscopy into the field of Otorhinolaryngology, the treatment paradigm for cases of severe epistaxis has shifted toward early and precise identification of the bleeding site. Although severe epistaxis is usually considered to arise from posterior bleeding, an arterial vascular pedicle in the superior portion of the nasal septum, around the axilla projection of the middle turbinate, posterior to the septal body, frequently has been observed. That vascular pedicle was named the Stamm's S-point. Objective: The aim of this study was to describe the S-point and report cases of severe epistaxis originating from it. Methods: A retrospective case series study was conducted. Nine patients with spontaneous severe epistaxis, where the S-point was identified as the source of bleeding, were treated between March 2016 and March 2017. Results: Male predominance (77.8%) with age average of 59.3 years old were reported. Most cases presented comorbidities (88.9%) and were not taking acetylsalicylic acid (66.7%). A predominance of left sided involvement (55.6%) and anteroposterior bleeding being the principal initial presentation (77.8%) was seen. Six patients (66.7%) presented with hemoglobin levels below 10 g/dL, and four (44.4%) required blood transfusion. Cauterization of S-point was performed in all patients, with complete resolution of bleeding. No patient experienced recurrence of severe epistaxis. Conclusion: The Stamm's S-point, a novel source of spontaneous severe epistaxis, is reported, and its cauterization was effective and safe. Otolaryngologists must actively seek this site of bleeding in cases of severe epistaxis.

Resumo Introdução: Desde a introdução da endoscopia nasal no campo de otorrinolaringologia, o paradigma de tratamento para casos graves de epistaxe voltou-se para a identificação precoce e correta do local de sangramento. Embora a epistaxe grave seja geralmente considerada uma hemorragia posterior, um pedículo vascular arterial tem sido frequentemente observado na porção superior do septo nasal, ao redor da projeção da axila da concha média, posterior ao tubérculo septal. Esse pedículo vascular foi chamado de Stamm's S-point. Objetivo: Descrever o S-point e relatar casos graves de epistaxe que se originam nesse local. Método: Um estudo retrospectivo de série de casos foi conduzido. Nove pacientes com epistaxe grave espontânea, na qual o S-point foi identificado como a fonte do sangramento, foram tratados de março de 2016 a março de 2017. Resultados: Houve predominância do sexo masculino (77,8%) com média de 59,3 anos. A maioria dos casos apresentava comorbidades (88,9%), mas sem uso de ácido acetilsalicílico (66,7%). Observou-se predominância do lado esquerdo (55,6%) com sangramento anteroposterior como a principal apresentação inicial (77,8%). Seis pacientes (66,7%) apresentaram níveis de hemoglobina inferiores a 10 g/dL e quatro (44,4%) necessitaram de transfusão sanguínea. Cauterização do S-point foi feita em todos os pacientes, com resolução completa do sangramento. Nenhum paciente apresentou recorrência de epistaxe grave. Conclusão: O Stamm's S-point é relatado como uma nova região de origem de epistaxe grave espontânea e o tratamento feito com cauterização foi eficaz e seguro. Os otorrinolaringologistas devem buscar ativamente esse local de sangramento em casos de epistaxe grave.

https://ift.tt/2MVGSAR

Obstructive sleep apnea is associated with increased QT corrected interval dispersion: the effects of continuous positive airway pressure

Abstract Introduction: Severe obstructive sleep apnea is associated with increased QT corrected interval dispersion and continuous positive airway pressure is thought to improve this arrhythmogenic marker. Objective: The aim of the study was to determine the decrease of ratio of cardiovascular risk in patients with obstructive sleep apnea. Methods: The study included 65 patients with severe obstructive sleep apnea who had an apnea-hypopnea index score of >30. Each patient underwent 12-channel electrocardiogram monitoring and polysomnography. Patients with an apnea-hypopnea index score of <5 were used as the control group. The control group also underwent electrocardiogram monitoring and polysomnography testing. The QT corrected interval dispersion levels of both groups were calculated. Three months after continuous positive airway pressure treatment, electrocardiogram recordings were obtained from the 65 patients with severe obstructive sleep apnea again, and their QT corrected interval dispersion values were calculated. Results: There were 44 male and 21 female patients with severe obstructive sleep apnea syndrome. The age, gender, body mass index, initial saturation, minimum saturation, average saturation, and desaturation index were determined in both groups. The QT corrected intervals of the obstructive sleep apnea patients (62.48 ± 16.29 ms) were significantly higher (p = 0.001) than those of the control group (29.72 ± 6.30 ms). There were statistically significant differences between the QT corrected values before and after the continuous positive airway pressure treatment, with pretreatment QT corrected intervals of 62.48 ± 16.29 ms and 3-month post-treatment values of 41.42 ± 16.96 ms (p = 0.001). There was a positive and significant correlation between QT corrected interval dispersion periods and the apnea-hypopnea index and hypopnea index in obstructive sleep apnea patients (p = 0.001; r = 0.71; p = 0.001; r = 0.679, respectively). Conclusion: Continuous positive airway pressure treatment reduced the QT corrected interval dispersion in patients with severe obstructive sleep apnea. In addition, shortening the QT corrected interval dispersion periods in patients with severe obstructive sleep apnea may reduce their risk of arrhythmias and cardiovascular disease.

Resumo Introdução: A apneia obstrutiva do sono grave está associada a uma maior dispersão do intervalo QT corrigido e acredita-se que a pressão positiva contínua nas vias aéreas melhore esse marcador arritmogênico. Objetivo: Determinar a diminuição da razão de risco cardiovascular em pacientes com apneia obstrutiva do sono. Método: O estudo incluiu 65 pacientes com apneia obstrutiva do sono grave que apresentavam índice de apneia-hipopneia > 30. Cada paciente foi submetido à monitoração por eletrocardiograma de 12 derivações e polissonografia. Os pacientes com escore de índice de apneia-hipopneia < 5 foram utilizados como o grupo de controle. O grupo de controle também foi submetido à monitoração por eletrocardiograma e teste de polissonografia. Os níveis de dispersão do intervalo QT corrigido dos dois grupos foram calculados. Três meses após o tratamento com pressão positiva contínua nas vias aéreas, os registros de eletrocardiograma foram novamente obtidos dos 65 pacientes com apneia obstrutiva do sono grave e seus valores de dispersão do intervalo QT corrigido foram calculados. Resultados: Havia 44 pacientes do sexo masculino e 21 do feminino com síndrome de apneia obstrutiva do sono grave. Idade, sexo, índice de massa corporal, saturação inicial, saturação mínima, saturação média e índice de dessaturação foram determinados em ambos os grupos. Os intervalos QT corrigido dos pacientes com apneia obstrutiva do sono (62,48 ± 16,29 ms) foram significativamente maiores (p = 0,001) do que os do grupo controle (29,72 ± 6,30 ms). Houve diferenças estatisticamente significativas entre os valores de QT corrigido antes e após o tratamento com pressão positiva contínua nas vias aéreas, com intervalos QT corrigido pré-tratamento de 62,48 ± 16,29 ms e três meses pós-tratamento, de 41,42 ± 16,96 ms (p = 0,001). Houve uma correlação positiva e significativa entre os períodos de dispersão do intervalo QT corrigido e o índice de apneia-hipopneia e índice de hipopneia em pacientes com apneia obstrutiva do sono (p = 0,001; r = 0,71; p = 0,001; r = 0,679, respectivamente). Conclusão: O tratamento com pressão positiva contínua nas vias aéreas reduziu a dispersão do intervalo QT corrigido em pacientes com apneia obstrutiva do sono grave. Além disso, o encurtamento de dispersão do intervalo QT corrigido em pacientes com apneia obstrutiva do sono grave pode reduzir o risco de arritmias e doenças cardiovasculares.

https://ift.tt/2tK2cRl

Peritonsillar and deep neck infections: a review of 330 cases

Abstract Introduction: Deep neck infections are defined as suppurative infectious processes of deep visceral spaces of the neck. Objective: The aim of this study is to review different factors that may influence peritonsillar and deep neck infections and may play a role as bad prognosis predictors. Methods: We present a retrospective study of 330 patients with deep neck infections and peritonsillar infections who were admitted between January 2005 and December 2015 in a tertiary referral hospital. Statistical analysis of comorbidities, diagnostic and therapeutic aspects was performed with Excel and SPSS. Results: There has been an increase in incidence of peritonsilar and deep neck infections. Systemic comorbidities such as diabetes or hepatopathy are bad prognosis factors. The most common pathogen was S. viridans (32.1% of positive cultures). 100% of the patients received antibiotics and corticosteroids, 74.24% needed surgical treatment. The most common complications were mediastinitis (1.2%) and airway obstruction (0.9%). Conclusion: Systemic comorbidities are bad prognosis predictors. Nowadays mortality has decreased thanks to multidisciplinary attention and improvements in diagnosis and treatment.

Resumo Introdução: Infecções cervicais profundas são definidas como processos infecciosos supurativos dos espaços viscerais profundos do pescoço. Objetivo: Analisar diferentes fatores que podem influenciar as infecções peritonsilares e cervicais profundas que podem desempenhar um papel como preditores de mau prognóstico. Método: Apresentamos um estudo retrospectivo de 330 pacientes portadores de infecções cervicais profundas e de infecções peritonsilares admitidos entre janeiro de 2005 e dezembro de 2015 em um hospital terciário de referência. A análise estatística de comorbidades, aspectos diagnósticos e terapêuticos foi realizada utilizando-se os programas Excel e o SPSS. Resultados: Houve um aumento na incidência de infecções peritonsilares e infecções cervicais profundas. Comorbidades sistêmicas como diabetes ou doença hepática são fatores de mau prognóstico. O patógeno mais comum foi S. viridans (32,1% das culturas positivas). 100% dos pacientes receberam antibióticos e corticosteroides, e 74,24% necessitaram de tratamento cirúrgico. As complicações mais comuns foram mediastinite (1,2%) e obstrução das vias aéreas (0,9%). Conclusão: Comorbidades sistêmicas são preditores de mau prognóstico. Atualmente, a mortalidade diminuiu graças ao cuidado multidisciplinar e melhorias no diagnóstico e tratamento.

https://ift.tt/2trV1xO

Nasal mucociliary transportability of male and female smokers

Abstract Introduction: Female smoker's present increased susceptibility to several diseases when compared to the opposite gender. However, there are no studies showing differences in nasal mucociliary transport behavior between male and female smokers. Objective: To compare the nasal mucociliary transportability in male and female smokers and non-smokers, taking into consideration age, anthropometric data, smoking load and pulmonary function. Methods: The analysis included 139 individuals (33 men and 37 women smokers and 32 men and 37 women non-smokers). All participants answered an initial interview to obtain personal data and smoking load. Anthropometric data and carbon monoxide in the exhaled air were assessed. Individuals also performed pulmonary function test and Saccharin Transit Time test. To compare saccharin transit time values between men and women, smokers and non-smokers, stratification of all independent variables was performed (sociodemographic, smoking and respiratory variables) into two categories: below and above the median values. Results: There was no difference between men and women, smokers and non-smokers, regarding nasal mucociliary transportability. Significant differences were only observed between non-smokers. Among those with less forced vital capacity values (<97.37% of predicted), women presented mucociliary transport faster than men. Moreover, it was observed influence of BMI and COex (women smokers), FCV and FEV1 (men non-smokers) and FEF25-75% (women non-smokers) on saccharin transit time values. Conclusion: Based on the findings of this study, nasal mucociliary transport in male and female adult smokers, apparently healthy, are similar.

Resumo Introdução: Mulheres tabagistas apresentam maior susceptibilidade à diversas doenças quando comparadas ao sexo masculino. No entanto, não há estudos mostrando diferenças no comportamento do transporte mucociliar nasal entre tabagistas do sexo masculino e feminino. Objetivo: Comparar a transportabilidade mucociliar nasal em homens e mulheres fumantes e não fumantes, levando em consideração idade, dados antropométricos, carga tabágica e função pulmonar. Método: A análise incluiu 139 indivíduos (33 homens e 37 mulheres fumantes e 32 homens e 37 mulheres não fumantes). Todos os participantes responderam a uma entrevista inicial para a obtenção de dados pessoais e a carga tabágica. Dados antropométricos e monóxido de carbono no ar expirado foram avaliados. Os indivíduos também fizeram teste de função pulmonar e o teste de trânsito de sacarina. Para comparar os valores do teste de trânsito de sacarina entre homens e mulheres, fumantes e não fumantes, foi feita a estratificação de todas as variáveis independentes (variáveis sociodemográficas, tabágicas e respiratórias) em duas categorias: abaixo e acima dos valores médios. Resultados: Não houve diferenças entre homens e mulheres, fumantes e não fumantes, em relação à transportabilidade mucociliar nasal. Diferenças significativas foram observadas apenas entre não fumantes. Entre os que apresentaram valores menores de capacidade vital forçada (< 97,37% do previsto), as mulheres apresentaram transporte mucociliar mais rápido do que os homens. Além disso, observou-se influência do IMC e COex (mulheres fumantes), CVF e VEF1 (homens não fumantes) e FEF25%-75% (mulheres não fumantes) sobre os valores do teste de trânsito de sacarina. Conclusão: Com base nos achados deste estudo, o transporte mucociliar nasal em tabagistas masculinos e femininos adultos, aparentemente saudáveis, são semelhantes.

https://ift.tt/2tHODlo

Comparison between clinical and audiological results of tympanoplasty with modified sandwich technique and underlay technique

Abstract Introduction: Surgical repair of the tympanic membrane, termed a type one tympanoplasty is a tried and tested treatment modality. Overlay or underlay technique of tympanoplasty is common. Sandwich tympanoplasty is the combined overlay and underlay grafting of tympanic membrane. Objective: To describe and evaluate the modified sandwich graft (mediolateral graft) tympanoplasty using temporalis fascia and areolar fascia. To compare the clinical and audiological outcome of modified sandwich tympanoplasty with underlay tympanoplasty. Methods: A total of 88 patients of chronic otitis media were studied. 48 patients (Group A) underwent type one tympanoplasty with modified sandwich graft. Temporalis fascia was underlaid and the areolar fascia was overlaid. 48 patients (Group B) underwent type one tympanoplasty with underlay technique. We assessed the healing and hearing results. Results: Successful graft take up was accomplished in 47 patients (97.9%) in Group A and in 40 patients (83.3%) Group B. The average Air-Bone gap closure achieved in Group A was 24.4 ± 1.7 dB while in Group B; it was 22.5 ± 3.5 dB. Statistically significant difference was found in graft healing rate. Difference in hearing improvement was not statistically significant. Conclusion: Double layered graft with drum-malleus as a 'meat' of sandwich maintains a perfect balance between sufficient stability and adequate acoustic sensitivity.

Resumo Introdução: O reparo cirúrgico da membrana timpânica, denominado timpanoplastia tipo 1, é uma modalidade de tratamento já bem estabelecida. As técnicas overlay ou underlay de timpanoplastia são comuns. A timpanoplastia "sanduíche" é a técnica de enxerto de membrana timpânica overlay e underlay combinadas. Objetivo: Descrever e avaliar a timpanoplastia com a técnica "sanduíche" modificada (timpanoplastia mediolateral) utilizando fáscia temporal e fáscia aureolar. Comparar o desfecho clínico e audiológico da timpanoplastia com a técnica "sanduíche" modificada com o da timpanoplastia com a técnica underlay. Método: Foram estudados 88 pacientes com otite média crônica, 48 (Grupo A) foram submetidos à timpanoplastia tipo 1 com enxerto "sanduíche" modificado. A fáscia temporal foi utilizada na técnica underlay e a fáscia areolar na técnica overlay. 48 pacientes (Grupo B) foram submetidos à timpanoplastia tipo 1 com a técnica underlay. Foram avaliados os resultados da cicatrização e da audição. Resultados: O sucesso do enxerto ocorreu em 47 pacientes (97,9%) no Grupo A e em 40 (83,3%) do Grupo B. O fechamento médio do gap aéreo-ósseo no Grupo A foi de 24,4 ± 1,7 dB, enquanto no Grupo B foi de 22,5 ± 3,5 dB. Houve diferença estatisticamente significativa na taxa de cicatrização do enxerto. A diferença na melhora auditiva não foi estatisticamente significante. Conclusão: O enxerto de camada dupla e o tímpano-martelo posicionados como o "recheio" do sanduíche mantém um equilíbrio perfeito entre a estabilidade necessária e adequada sensibilidade acústica.

https://ift.tt/2MZd8Dq

Retrospective analysis of skin complications related to bone-anchored hearing aid implant: association with surgical technique, quality of life, and audiological benefit

Abstract Introduction: The bone-anchored hearing aid is an effective form of auditory rehabilitation. Due to the nature of the implant, the most common complications are skin related. A number of alternative surgical implantation techniques have been used to reduce the frequency and severity of skin complications, including the U-shaped graft and the linear incision. Objective: To assess skin complications and their association with surgical technique, quality of life, and audiological benefit in patients with bone-anchored hearing aids. Methods: This was a retrospective study conducted in a tertiary referral center in Bogotá, Colombia. Patients who had been fitted with a bone-anchored hearing aid implant (unilaterally or bilaterally) for at least 6 months were included in the study. The Holgers classification was used to classify skin complications (Grade 0 = none; Grade 1 = erythema; Grade 2 = erythema and discharge; Grade 3 = granulation tissue; and Grade 4 = inflammation/infection resulting in the removal of the abutment). The Glasgow Benefit Inventory questionnaire was used to determine quality of life, and the Abbreviated Profile of Hearing Aid Benefit questionnaire was used to determine the subjective audiological benefit. Results: A total of 37 patients were included in the study (30 with unilateral implants and 7 with bilateral implant). Of the 44 implants evaluated, 31 (70.3%) were associated with skin complications (7 [15.9%] Grade 1; 4 [9.1%] Grade 2; 15 [34.1%] Grade 3, 5 [11.4%] Grade 4). The U-shaped graft was statistically associated with major complications (Grades 3 and 4) compared with the linear incision technique (p = 0.045). No statistically significant differences were found between Abbreviated Profile of Hearing Aid Benefit scores and severity of complications. Similarly, no differences were found between Glasgow Benefit Inventory physical health questions and skin complications. Conclusion: Despite the high frequency, skin complications did not seem to affect quality of life or subjective audiological benefits of patients with bone-anchored hearing aids.

Resumo Introdução: A prótese auditiva óssea (BAHA, do inglês Bone-Anchored Hearing Aid) é uma forma eficaz de reabilitação auditiva. Devido à natureza do implante, as complicações mais comuns são relacionadas à pele. Várias técnicas opcionais de implantação cirúrgica têm sido usadas para reduzir a frequência e a gravidade das complicações cutâneas, inclusive o enxerto em forma de U e a incisão linear. Objetivo: Avaliar as complicações cutâneas e sua associação com a técnica cirúrgica, qualidade de vida e benefício audiológico em pacientes com BAHAs. Método: Estudo retrospectivo feito em um centro terciário de referência em Bogotá, Colômbia. Os pacientes que receberam um implante de BAHA (unilateral ou bilateralmente) durante pelo menos seis meses foram incluídos no estudo. A classificação de Holgers foi usada para classificar as complicações cutâneas (Grau 0 = nenhuma, Grau 1 = eritema, Grau 2 = eritema e secreção, Grau 3 = tecido de granulação e Grau 4 = inflamação/infecção, resultou na remoção da estrutura de apoio). O questionário Glasgow Benefit Inventory (GBI) foi usado para determinar a qualidade de vida e o questionário Abbreviated Profile of Hearing Aid Benefit (APHAB) foi usado para determinar o benefício audiológico subjetivo. Resultados: Foram incluídos 37 pacientes (30 com implantes unilaterais e sete com implantes bilaterais). Dos 44 implantes avaliados, 31 (70,3%) foram associados às complicações cutâneas (sete [15,9%] Grau 1; quatro [9,1%] Grau 2; 15 [34,1%] Grau 3 e cinco [11,4%] Grau 4). O enxerto em forma de U foi estatisticamente associado a complicações maiores (Graus 3 e 4) em comparação com a técnica de incisão linear (p = 0,045). Não foram encontradas diferenças estatisticamente significativas entre os escores APHAB e gravidade das complicações. Do mesmo modo, não foram encontradas diferenças entre as questões de saúde física pelo questionário GBI e complicações cutâneas. Conclusão: Apesar da alta frequência, as complicações cutâneas não parecem afetar a qualidade de vida ou os benefícios audiológicos subjetivos de pacientes com BAHAs.

https://ift.tt/2yDxmPM

Ototoxicity of boric acid powder in a rat animal model

Abstract Introduction: Boric acid, which has antiseptic and acidic properties, is used to treat external and middle ear infections. However, we have not found any literature about the effect of boric acid powder on middle ear mucosa and inner ear. Objective: The purpose of this study is to investigate possible ototoxic effects of boric acid powder on cochlear outer hair cell function and histological changes in middle ear mucosa in a rat animal model. Methods: Twenty healthy, mature Wistar albino rats were used in this study. The rats were divided into two groups, Group A and Group B, each of which consisted of 10 rats. Initially, the animals in each group underwent distortion product otoacoustic emissions testing of their right and left ears. After the first distortion product otoacoustic emissions test, a surgical microscope was used to make a small perforation in both ears of the rats in each group, and a second distortion product otoacoustic emissions test was used to measure both ears in all of the rats. Boric acid powder was applied to the right middle ear of the rats using tympanic membrane perforation, and the distortion product otoacoustic emissions were measured immediately after the boric acid powder application. The histological changes and distortion product otoacoustic emissions were evaluated three days later in Group A and 40 days later in Group B. Results: No significant differences were found at all of the distortion product otoacoustic emissions frequencies. In Group A, mild inflammation of the middle ear mucosa was found on the third day after boric acid powder application. In Group B, boric acid powder caused mild inflammatory changes on the 40th day, which declined over time. Those changes did not lead to significant fibrosis within the mucosa. Conclusion: In rats, boric acid powder causes mild inflammation in middle ear mucosa and it has no ototoxic effects on cochlear outer hair cell function in the inner ear of rats.

Resumo Introdução: O ácido bórico, que tem propriedades antissépticas e ácidas, é usado para tratar infecções de orelha externa e média. No entanto, não encontramos literatura sobre o efeito do ácido bórico em pó sobre a mucosa da orelha interna e da orelha média. Objetivo: Investigar possíveis efeitos ototóxicos do ácido bórico em pó sobre a função das células ciliadas externas cocleares e alterações histológicas na mucosa da orelha média em um modelo animal de rato. Método: Vinte ratos Wistar albinos maduros e saudáveis foram usados neste estudo. Os ratos foram divididos em dois grupos, Grupo A e Grupo B, cada um dos quais com 10 ratos. Inicialmente, os animais de cada grupo foram submetidos a testes de emissões otoacústicas - produto de distorção, nas orelhas direita e esquerda. Após o primeiro teste de emissões otoacústicas - produto de distorção, utilizou-se um microscópio cirúrgico para fazer uma pequena perfuração em ambas as orelhas dos ratos em cada grupo, e um segundo teste de emissões otoacústicas - produto de distorção foi utilizado para medir e avaliar as orelhas em todos os ratos. O ácido bórico em pó foi aplicado na orelha média direita dos ratos utilizando perfuração da membrana timpânica e as emissões otoacústicas - produto de distorção foram medidas imediatamente após a aplicação de ácido bórico em pó. As alterações histológicas e emissões otoacústicas - produto de distorção foram avaliadas três dias depois no Grupo A e 40 dias depois no Grupo B. Resultados: Não foram encontradas diferenças significativas em todas as frequências da emissões otoacústicas - produto de distorção. No Grupo A, foi observada uma ligeira inflamação da mucosa da orelha média no terceiro dia após a aplicação de ácido bórico em pó. No Grupo B, o ácido bórico em pó causou leves alterações inflamatórias após 40 dias, que diminuíram ao longo do tempo. Essas alterações não levaram à fibrose significativa da mucosa. Conclusão: Em ratos, o ácido bórico em pó causa inflamação leve na mucosa da orelha média e não tem efeitos ototóxicos na função das células ciliadas externas da cóclea na orelha interna.

https://ift.tt/2tvhdH9

The analysis of expression of p16 protein in group of 53 patients treated for sinonasal inverted papilloma

Abstract Introduction: Sinonasal inverted papilloma constitute relevant therapeutic problem due to destructive character of growth, tendency to recur and the possibility of malignant transformation. Therefore, many attempts to identify risk factors for inverted papilloma occurrence have been undertaken, as well as research to find markers that would allow for the earlier detection of tumors and the application of adequate therapy. A widely known risk factor of inverted papilloma is HPV infection. One of the markers of HPV infection and the ongoing effect of this change (although arousing some controversy) is the expression of the p16 protein. Objective: The aim of the study was to analyze the correlation between the expression of p16 as a surrogate of HPV infection in analyzed histopathological material and epidemiological variables, recurrences or malignant transformation. Methods: The retrospective study includes a group of 53 patients (18 women and 35 men) undergoing treatment for sinonasal inverted papilloma in the period of 2002-2012. The intensity of the p16 protein in histopathological material was scored as: 0 - no expression, 1 - diffuse expression (borderline) and 2 - positive expression; or 0 - no expression/diffuse expression (borderline); 1 - positive expression. The Ethics Committee agreement was obtained (1089/12; 245/13). Results and conclusion: There was no statistically significant relationship between the expression of p16 and the age of patients, cigarette smoking, tumor location, tumor staging according to the Krouse and Cannady classification, the presence of dysplasia or the occurrence of relapse.

Resumo Introdução: Papiloma invertido nasossinusal constitui um problema terapêutico relevante devido ao caráter destrutivo do crescimento, a tendência à recorrência e a possibilidade de transformação maligna. Assim, muitas tentativas têm sido realizadas para identificar fatores de risco para ocorrência de papiloma invertido, bem como pesquisas para encontrar marcadores que permitam a detecção precoce de tumores e a utilização de terapia adequada. Um fator de risco amplamente conhecido de papiloma invertido é a infecção pelo HPV. Um dos marcadores da infecção por HPV e do efeito contínuo dessa alteração (embora suscite alguma controvérsia) é a expressão da proteína p16. Objetivo: Analisar a correlação entre a expressão de p16 como um substituto da infecção pelo HPV no material histopatológico analisado e as variáveis epidemiológicas, recorrências ou transformação maligna. Método: O estudo retrospectivo inclui um grupo de 53 pacientes (18 mulheres e 35 homens) submetidos a tratamento para papiloma invertido nasossinusal de 2002 a 2012. A intensidade da expressão da proteína p16 no material histopatológico foi pontuada como: 0 - sem expressão, 1 - expressão difusa (limite) e 2 - expressão positiva; ou 0 - sem expressão/expressão difusa (limite); 1 - expressão positiva. O Comitê de Ética aprovou o estudo (1.089/12; 245/13). Resultados e conclusão: Não houve relação estatisticamente significante entre a expressão de p16 e a idade dos pacientes, o tabagismo, a localização tumoral e o estadiamento tumoral de acordo com a classificação de Krouse e Cannady, presença de displasia ou ocorrência de recidiva.

https://ift.tt/2yEziHG

Translation and adaptation of the Radiotherapy Edema Rating Scale to Brazilian Portuguese

Abstract Introduction: Internal lymphedema is one of the sequelae of head and neck cancer treatment that can lead to varying degrees of swallowing, speech, and respiration alterations. The Radiotherapy Edema Rating Scale, developed by Patterson et al., is a tool used to evaluate pharyngeal and laryngeal edema. Objective: To translate into Brazilian Portuguese, to culturally adapt and test this scale in patients undergoing treatment for head and neck cancer. Methods: The process followed the international guidelines and translation steps by two head and neck surgeons and back-translation performed independently by two North-American natives. The final version of the test was evaluated based on the assessment of 18 patients by two head and neck surgeons and two speech therapists using the scales in Brazilian Portuguese. Results: The translation and cultural adaptation were satisfactorily performed by the members of the committee in charge. Conclusion: The translation and adaptation into Brazilian Portuguese of the Radiotherapy Edema Rating Scale was successfully performed and showed to be easy to apply.

Resumo Introdução: O linfedema interno é uma das sequelas do tratamento para o câncer de cabeça e pescoço, pode levar a alterações de grau variado na deglutição, voz e respiração. A Escala do Edema da Radioterapia (Radiotherapy Edema Rating Scale), elaborada por Patterson et al., é uma ferramenta de avaliação do edema de faringe e laringe. Objetivo: Traduzir, para o português brasileiro, adaptar culturalmente e testar essa escala em pacientes submetidos ao tratamento para o câncer de cabeça e pescoço. Método: O processo seguiu as diretrizes internacionais e as etapas de tradução por dois cirurgiões de cabeça e pescoço e a retrotradução de forma independente por dois nativos norte-americanos. O teste da versão final para avaliação foi realizado a partir da avaliação de 18 pacientes por dois médicos cirurgiões de cabeça e pescoço e duas fonoaudiólogas por meio da aplicação das escalas em português. Resultados: A tradução e a adaptação cultural foram executadas satisfatoriamente pelos membros do comitê responsável. Conclusão: A tradução e adaptação da Escala do Edema da Radioterapia para o português foi bem-sucedida e de fácil aplicação.

https://ift.tt/2MZuCQ6

Evaluation of pre- and post-pyriform plasty nasal airflow

Abstract Introduction: Nasal obstruction is a frequent complaint in otorhinolaryngology outpatient clinics, and nasal valve incompetence is the cause in most cases. Scientific publications describing surgical techniques on the upper and lower lateral cartilages to improve the nasal valve are also quite frequent. Relatively few authors currently describe surgical procedures in the piriform aperture for nasal valve augmentation. We describe the surgical technique called pyriform plasty and evaluate its effectiveness subjectively through the NOSE questionnaire and objectively through the rhinomanometry evaluation. Objective: To compare pre- and post-pyriform plasty nasal airflow variations using rhinomanometry and the NOSE questionnaire. Methods: Eight patients submitted to pyriform surgery were studied. These patients were screened in the otorhinolaryngology outpatient clinic among those who complained of nasal obstruction, and who had a positive response to Cottle maneuver. They answered the NOSE questionnaire and were submitted to preoperative rhinomanometry. After 90 days, they were reassessed through the NOSE questionnaire and the postoperative rhinomanometry. The results of these two parameters were compared pre- and postoperatively. Results: Regarding the subjective measure, the NOSE questionnaire, seven patients reported improvement, of which two reported marked improvement, and one patient reported an unchanged obstructive condition. Regarding the rhinomanometry assessment, of 96 comparative measurements between the preoperative and postoperative periods, we obtained 68 measurements with an increase in nasal airflow in the postoperative period, 26 negative results, and two cases that remained unaltered between the preoperative and postoperative periods. Conclusion: When analyzing the results obtained in this study, we can conclude that the piriform plasty surgical procedure resulted in nasal airflow improvement in most of the obtained measurements.

Resumo Introdução: A obstrução nasal é queixa frequente nos ambulatórios de otorrinolaringologia, e a incompetência da válvula nasal é responsável em grande parte dos casos. São bastante frequente também as publicações de trabalhos científicos descrevendo técnicas cirúrgicas sobre as cartilagens laterais superiores e inferiores para melhorar a válvula nasal. Relativamente poucos autores descrevem atualmente procedimentos cirúrgicos na abertura piriforme para incremento da válvula nasal. Descrevemos a técnica cirúrgica chamada piriformeplastia e avaliamos a sua eficácia de forma subjetiva através do questionário NOSE e de forma objetiva através do exame rinomanometria. Objetivo: Comparar as variações do fluxo aéreo nasal pré e pós-piriformeplastia através da rinomanometria e do questionário NOSE. Método: Foram estudados 8 pacientes submetidos à piriformeplastia. Estes pacientes foram triados no ambulatório de otorrinolaringologia, pacientes estes que se queixavam de obstrução nasal, e que apresentavam resposta positiva a manobra de Cottle. Responderam ao questionário NOSE e foram submetidos a rinomanometria no pré-operatório. Após 90 dias foram reavaliados pelo questionário NOSE e pela rinomanometria pós-operatória. Os resultados desses dois parâmetros foram comparados pré e pós-operatoriamente. Resultados: Em relação a medida subjetiva, questionário NOSE, sete pacientes referiram melhora, sendo que dois deles referiram melhora acentuada, e um paciente referiu quadro obstrutivo inalterado. Em relação ao exame rinomanometria, de 96 medidas comparativas entre o pré e o pós-operatório, obtivemos 68 medidas com incremento ao fluxo aéreo nasal no pós-operatório, 26 resultados negativos, e dois casos inalterados entre pré e pós-operatório. Conclusão: O procedimento cirúrgico piriformeplastia conferiu melhoria do fluxo aéreo nasal na maioria das medidas obtidas.

https://ift.tt/2yH6Yo6

Hearing in Noise Test, HINT-Brazil, in normal-hearing children

Abstract Introduction: The auditory processing is related to certain skills such as speech recognition in noise. The HINT-Brazil test allows the measurement of the Speech/Noise ratio however there are no studies in the national literature that establish parameters for the child population. Objective: To analyze the performance of normal-hearing subjects aged 8-10 years old in tasks for speech recognition in noise using HINT test. Methods: Sixty schoolchildren were evaluated. They were between 8 and 10 years of age, of both genders, and had no auditory and school complaints, with results ranking within normality for the Basic Audiological Assessment and the Dichotic Digits Test. HINT-Brazil test was applied with headphones, with the Speech/Noise ratio in conditions of frontal noise, noise to the right, and noise to the left being investigated. The software calculated the Composite Noise, which corresponds to the weighted mean of the tested conditions. Results: There was no statistically significant difference between the ears, nor between the genders. There was a statistically significant difference for age ranges of 8 and 10 years, in situations with noise, and for Composite Noise. The age group of 10 years showed better performance than the age group of 8; the age group of 9 years did not show statistically significant difference regarding the other age ranges. We suggest the values of mean and standard deviation of the Speech/Noise ratio, considering the age ranges of: 8 years - Frontal Noise: −2.09 (±1.09); Right Noise: −7.64 (±1.72); Left Noise: −7.53 (±2.80); Composite Noise: −4.86 (±1.31); 9 years - Frontal Noise: −2.82 (±0.74); Right Noise: −8.49 (±2.24); Left Noise: −8.41 (±1.75); Composite Noise: −5.63 (±1.02); 10 years - Frontal Noise: −3.01 (±0.95); Right Noise: −9.47 (±1.43); Left Noise: −9.16 (±1.65); Composite Noise: −6.16 (±0.91). Conclusion: HINT-Brazil test is a simple and fast test, and is not difficult to performed with normal-hearing children. The results confirm that it is an efficient test to be used with the age range evaluated.

Resumo Introdução: O processamento auditivo está relacionado a determinadas habilidades, como o reconhecimento de fala no ruído. O teste HINT-Brasil permite a mensuração da relação Fala/Ruído, porém, não há na literatura nacional estudos que estabeleçam parâmetros para a população infantil. Objetivo: Analisar o desempenho de normo-ouvintes, de 8 a 10 anos, nas tarefas de reconhecimento de fala no ruído, por meio do teste HINT. Método: Avaliados 60 escolares, entre 8 e 10 anos, de ambos os gêneros, sem queixas auditivas e escolares, e com resultados dentro da normalidade para a Avaliação Audiológica Básica e o Teste Dicótico de Dígitos. O teste HINT-Brasil foi aplicado com fones de ouvido, sendo pesquisada a relação Fala/Ruído nas condições Ruído Frontal, Ruído à Direita e Ruído à Esquerda. O software calculou o Ruído Composto, que corresponde à média ponderada das condições testadas. Resultados: Não houve diferença estatisticamente significante entre as orelhas, nem entre os gêneros. Houve diferença estatisticamente significante para as faixas de 8 e 10 anos, nas situações com ruído e para o Ruído Composto. A faixa etária de 10 anos apresentou desempenho melhor do que a faixa etária de 8; a faixa etária de 9 anos não apresentou diferença estatisticamente significante com relação as outras faixas etárias. Sugerimos os valores de Média e Desvio Padrão da relação F/R, considerando as faixas: 8 anos - RF: -2,09 (± 1,09); RD: -7,64 (± 1,72); RE: -7,53 (± 2,80); RC: -4,86 (± 1,31); 9 anos - RF: -2,82 (± 0,74); RD: -8,49 (± 2,24); RE: -8,41 (± 1,75); RC: -5,63 (± 1,02); 10 anos - RF: -3,01 (± 0,95); RD: -9,47 (± 1,43); RE: -9,16 (± 1,65); RC: -6,16 (± 0,91). Conclusão: O teste HINT-Brasil é um teste simples e rápido e não oferece dificuldades em seu uso com crianças normo-ouvintes; os resultados mostram se tratar de um teste eficaz para ser utilizado com a faixa etária avaliada.

https://ift.tt/2tvgNAz

Effect of antioxidant supplementation on the auditory threshold in sensorineural hearing loss: a meta-analysis

Abstract Introduction: Hearing loss is conceptualized as any impairment of the ability to hear and/or detect speech or environment sounds, regardless of cause, type, or degree. It may occur at different stages of life; during pregnancy or childbirth, in childhood, adulthood or old age. It should be noted that aging is the most common cause of sensorineural hearing loss followed by noise-induced hearing loss, and both are closely related to the formation of reactive oxygen species. Dietary antioxidant supplementation has been employed as a therapeutic strategy to prevent and/or delay the risks of major human diseases. Objective: To assess randomized clinical trials to determine the effect of antioxidant supplementation on the auditory thresholds in patients of different age groups with sensorineural hearing loss. Methods: This systematic review consisted of a search in the following databases: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO and ClinicalTrials.gov. Additionally, the gray literature was also searched. The search strategy included terms related to the intervention (antioxidant supplementation), primary outcome (sensorineural hearing loss), as well as terms related to randomized clinical trials to improve search sensitivity. Results: Based on 977 potentially relevant records identified through the search in the databases, ten full-text publications were retrieved for further evaluation. The increase in threshold at the 4 kHz frequency was statistically higher in the control group (1.89 [1.01-2.78], p < 0.0001) when compared to the NAC group and the ginseng group, whereas at 6 kHz, the threshold increase was higher in the control group (1.42 [−1.14-3.97], p = 0.28), but no statistically significant differences were found between groups. Conclusion: Ginseng was the antioxidant agent that showed the best effect in preventing auditory threshold worsening at the frequency of 4 kHz, but not at 6 kHz in patients with sensorineural hearing loss caused by exposure to high sound pressure levels. There was no improvement in the thresholds with vitamin E supplementation.

Resumo Introdução: A perda auditiva é conceituada como qualquer diminuição da capacidade de ouvir e/ou detectar sons da fala ou do ambiente, independentemente da causa, tipo ou grau e pode ocorrer em diversos estágios da vida, durante a gestação ou parto, na infância, vida adulta ou na terceira idade. Convém destacar que o envelhecimento é a primeira causa de perda auditiva do tipo sensorioneural e em segundo lugar a perda auditiva induzida pelo ruído, ambas estão intimamente relacionadas com a formação de espécies reativas de oxigênio. Evidências têm sido acumuladas indicando que a suplementação com antioxidantes via alimentação tornou-se estratégia terapêutica para prevenir e/ou retardar os riscos das principais doenças humanas. Objetivo: Avaliar ensaios clínicos aleatórios para determinar qual o efeito da suplementação com antioxidantes sobre o limiar auditivo na perda auditiva sensorioneural em pacientes de diversas faixas etárias. Método: A formulação desta revisão sistemática consistiu na busca dos estudos nas seguintes bases de dados: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO e ClinicalTrials.gov. Adicionalmente, a literatura cinzenta também foi pesquisada. A estratégia de busca incluiu termos relacionados à intervenção (suplementação de antioxidantes), o desfecho primário (perda auditiva sensorioneural), bem como termos relacionados aos ensaios clínicos randomizados para melhorar e a sensibilidade da busca. Resultados: A partir de 977 registros potencialmente relevantes identificados através da busca nas bases de dados, dez publicações em texto completo foram recuperadas para avaliação mais aprofundada. O aumento no limiar na frequência de 4 kHz foi estatisticamente maior no Grupo Controle (1,89 [1,01-2,78], p < 0,0001) quando comparados com o Grupo NAC e o Grupo Ginseng, já na frequência de 6 kHz o aumento no limiar foi maior no Grupo Controle (1,42 [-1,14-3,97], p = 0,28), porém, não foram encontradas diferenças estatisticamente significativas entre grupos. Conclusão: O Ginseng foi o antioxidante que evitou a piora do limiar auditivo na frequência de 4 kHz, mas não em 6 kHz, em pacientes com perda auditiva sensorioneural causada por exposição a elevados níveis de pressão sonora. Não foi observada melhora nos limiares com a suplementação com Vitamina E.

https://ift.tt/2tHNIBs

Effect of caffeine on vestibular evoked myogenic potential: a systematic review with meta-analysis

Abstract Introduction: Caffeine can be considered the most consumed drug by adults worldwide, and can be found in several foods, such as chocolate, coffee, tea, soda and others. Overall, caffeine in moderate doses, results in increased physical and intellectual productivity, increases the capacity of concentration and reduces the time of reaction to sensory stimuli. On the other hand, high doses can cause noticeable signs of mental confusion and error induction in intellectual tasks, anxiety, restlessness, muscle tremors, tachycardia, labyrinthine changes, and tinnitus. Objective: Considering that the vestibular evoked myogenic potential is a clinical test that evaluates the muscular response of high intensity auditory stimulation, the present systematic review aimed to analyze the effects of caffeine on vestibular evoked myogenic potential. Methods: This study consisted of the search of the following databases: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO and ClinicalTrials.gov. Additionally, the gray literature was also searched. The search strategy included terms related to intervention (caffeine or coffee consumption) and the primary outcome (vestibular evoked myogenic potential). Results: Based on the 253 potentially relevant articles identified through the database search, only two full-text publications were retrieved for further evaluation, which were maintained for qualitative analysis. Conclusion: Analyzing the articles found, caffeine has no effect on vestibular evoked myogenic potential in normal individuals.

Resumo Introdução: A cafeína pode ser considerada a droga mais consumida por adultos em nível mundial, podendo ser encontrada em inúmeros alimentos, como no chocolate, café, chá, refrigerante e outros. Em geral, a cafeína em doses moderadas, produz ótimos rendimentos físico e intelectual, aumenta a capacidade de concentração e diminui o tempo de reação aos estímulos sensoriais. Por outro lado, doses elevadas podem causar sinais perceptíveis de confusão mental e indução de erros em tarefas intelectuais, ansiedade, nervosismo, tremores musculares, taquicardia, alterações labirínticas e zumbido. Objetivo: Considerando que o potencial evocado miogênico vestibular é um teste clínico que avalia a resposta muscular decorrente de estimulação auditiva de alta intensidade, a presente revisão sistemática objetivou analisar o efeito da cafeína sobre o potencial evocado miogênico vestibular. Método: A formulação deste trabalho consistiu na busca dos estudos nas seguintes bases de dados: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO e Clinical-Trials.gov. Adicionalmente, a literatura cinzenta também foi pesquisada. A estratégia de busca incluiu termos relacionados à intervenção (consumo de cafeína ou café) e ao desfecho primário (potencial evocado miogênico vestibular). Resultados: A partir de 253 registros potencialmente relevantes identificados através da busca nas bases de dados, apenas duas publicações em texto completo foram recuperadas para avaliação mais aprofundada, sendo estas mantidas para a análise qualitativa. Conclusão: Diante dos artigos encontrados a cafeína não tem efeito sobre o potencial evocado miogênico vestibular em sujeitos normais.

https://ift.tt/2tvgANN

Undifferentiated high-grade pleomorphic sarcoma of ethmoid sinus: a case report and literature review

Genomic profile of a squamous cell carcinoma ex pleomorphic adenoma compared to a head and neck squamous cell carcinoma

Unusual coexisting thyroglossal duct cyst and second branchial cleft fistula in an adult

Two cases of extranasopharyngeal angiofibroma mimicking choanal polyp in patients with chronic paranasal sinusitis

Extranasopharyngeal angiofibroma (ENA) is an angiofibroma that occurs in the extranasopharynx. It shows pathologic findings, such as juvenile angiofibroma (JNA), which accounts for 0.5% of head and neck mass. However, compared with JNA, the prevalence, affected site, and clinical characteristics are completely different, which leads some physicians to classify ENA as a disease different from JNA. ENA of the nasal turbinate origin are rarely reported in the literature. In addition, choanal polyp originating from the posterior part of the nasal turbinate is uncommonly reported.

https://ift.tt/2MXliMp

Binaural sensitivity to temporal fine structure and lateralization ability in children with suspected (central) auditory processing disorder

Previous studies have shown that a subgroup of children with suspected (central) auditory processing disorder (SusCAPD) have insufficient ability to use binaural cues to benefit from spatial processing. Thus, they experience considerable listening difficulties in challenging auditory environments, such as classrooms. Some researchers have also indicated the probable role of binaural temporal fine structure (TFS) in the perceptual segregation of target signal from noise and hence in speech perception in noise.

https://ift.tt/2Mqy459

Heat-induced necrosis after bronchial thermoplasty: a new concern?

Bronchial thermoplasty (BT) is an endoscopic procedure for the treatment of severe refractory asthma, based on the local airways delivery of radio-frequency at 65 °C. Several controlled clinical studies demons...

https://ift.tt/2Ir782B

Ultrastructural changes of Trichophyton rubrum in tinea unguium after itraconazole therapy in vivo observed using scanning electron microscopy

Clinical and Experimental Dermatology, EarlyView.

https://ift.tt/2yK1zwI

Utility of a minimal skin incision laparotomy technique for removing uterine leiomyomas at a regional core hospital: a retrospective study

We present a minimal skin wound abdominal myomectomy performed in our hospital and attempt to identify the optimal range of this technique by considering the characteristics of target leiomyomas. In this proce...

https://ift.tt/2IpU1Pn

Osteolytic lesions (brown tumors) of primary hyperparathyroidism misdiagnosed as multifocal giant cell tumor of the distal ulna and radius: a case report

Brown tumors represent a rare clinical manifestation reported in approximately 3% of patients with primary hyperparathyroidism and correspond to radiologically osteolytic lesions with well-defined borders in d...

https://ift.tt/2lxUplK

Issue Information ‐ TOC

Allergy, Volume 73, Issue 7, Page 1357-1358, July 2018.

https://ift.tt/2tuUSth

Issue Information ‐ Cover and Editorial Board

Allergy, Volume 73, Issue 7, Page 1355-1355, July 2018.

https://ift.tt/2Kmt1SB

The influence of ‘moral disengagement’ on conflict of interest: insights for dermatology from social psychology and qualitative research

British Journal of Dermatology, EarlyView.

https://ift.tt/2K85mJF

Detection of anti‐BP180 NC16A autoantibodies after the onset of dipeptidyl peptidase‐IV inhibitor‐associated bullous pemphigoid: a report of three patients

British Journal of Dermatology, EarlyView.

https://ift.tt/2MVZxNb

The Orotomide Olorofim is Efficacious in an Experimental Model of Central Nervous System Coccidioidomycosis [PublishAheadOfPrint]

Olorofim (formerly F901318) is an advanced analog of the orotomide class that inhibits fungal pyrimidine biosynthesis. We evaluated the in vitro and in vivo activity of olorofim against Coccidioides species. In vitro activity was assessed against 59 clinical Coccidioides isolates. Central nervous system infection was established in mice via intracranial inoculation with C. immitis arthroconidia. Oral therapy began 48 hours post-inoculation and consisted of vehicle control, olorofim daily doses of 20 mg/kg (6.67 mg/kg TID or 10 mg/kg BID), and 40 mg/kg (13.3 mg/kg TID or 20 mg/kg BID), or fluconazole (25 mg/kg BID). Treatment continued for 7 and 14 days in the fungal burden and survival arms, respectively. Fungal burden was assessed by colony-forming unit counts in brains. Olorofim demonstrated potent in vitro activity (MIC range ≤ 0.008 - 0.06 μg/ml). Survival was significantly enhanced in mice treated with olorofim. Reductions in brain tissue fungal burden were also observed on day 9 in the olorofim groups. Improvements in survival and reductions in fungal burden also occurred with fluconazole. More frequent dosing of olorofim was associated with enhanced survival and greater reductions in fungal burden. In the olorofim 13.3 mg/kg TID group, fungal burden remained low on day 30, 15 days after treatment stopped, and was undetectable in 7 of 10 mice. In contrast, elevated fungal burden rebounded in all other groups after therapy stopped. Olorofim was highly active in vitro and in vivo against Coccidioides. These results demonstrate that olorofim may have a role in the treatment of coccidioidomycosis.

https://ift.tt/2K7MZEu

Screening and characterization of multidrug-resistant Gram-negative bacteria from a remote African area, Sao Tome and Principe [PublishAheadOfPrint]

Occurrence of resistance to last-resort antibiotics was evaluated among Enterobacteriaceae isolates recovered from hospitalized children in a remote African archipelago, São Tomé and Príncipe, where there is limited access to those antibiotics. Fifty patients were screened for colonization by carbapenem-, pan-aminoglycoside-, or polymyxin-resistant Enterobacteriaceae. A total of 36 isolates (including 30 Escherichia coli and 4 Klebsiella pneumoniae) were recovered from 23 patients, including 26 isolates harboring the bla_OXA-181 carbapenemase gene, a single isolate harboring the 16S rRNA methylase gene rmtB encoding pan-resistance to aminoglycosides, and 8 isolates co-harboring both genes. A single isolate possessed the plasmid-borne colistin resistance gene mcr-1. A high clonal relationship was found for OXA-181-producing E. coli (4 clones), and conversely three out of the four OXA-181-producing K. pneumoniae isolates were clonally unrelated. This study overall showed a high prevalence of resistance to last-resort antibiotics in this country where no epidemiological data was previously available.

https://ift.tt/2IsdTBj

Population Pharmacokinetics and Dosing Optimization of Azithromycin in Children with Community-Acquired Pneumonia [PublishAheadOfPrint]

Background: Azithromycin is extensively used in children acquired with community-acquired pneumonia (CAP). Currently, the intravenous azithromycin was used off-label in children partly due to lacking of pharmacokinetic data. Our objective was to evaluate the population pharmacokinetics (PPK) and optimize dose strategy in order to improve treatment in this distinctive population.

Methods: This was a prospective, multi-center, open-labeled pharmacokinetic study. Blood samples were collected from hospitalized pediatric patients and concentrations were determined by LC-MS/MS. PPK analysis was conducted using NONMEM software.

Results: The pharmacokinetic data from 95 pediatric patients (age range 2.1 – 11.7 years) were available for analysis. The PPK was best fitted by two-compartment model with linear elimination. Covariate analysis verified body weight and alanine aminotransferase (ALT) had significant effect on azithromycin pharmacokinetics, yielding a 24% decrease of clearance in patients with ALT>40. Monte Carlo simulation showed that for children with normal liver function, a loading dose strategy (a loading dose of 15mg/kg followed by maintenance doses of 10 mg/kg) would achieve the ratio of the area under free drug plasma concentration-time curve over 24 hours (fAUC) to MIC₉₀ (fAUC/MIC) target of 3 h in 53.2% hypothetical patients, using normative MIC susceptibility breakpoint of 2 mg/L. For children with ALT>40, the proposed dose needed to decrease by 15% to achieve comparable exposure. The corresponding risk of overdose for the recommended dosing regimen was less than 5.8%.

Conclusion: The PPK of azithromycin was evaluated in CAP children and an optimal dosing regimen was constructed based on developmental pharmacokinetic-pharmacodynamic modeling and simulation.

https://ift.tt/2Kk15lv

Acquisition of beta-lactamase by Neisseria meningitidis through possible horizontal gene transfer [PublishAheadOfPrint]

We report the detection in France of a beta-lactamase producing invasive meningococcal isolate. Whole genome sequencing of the isolate revealed ROB-1 type beta-lactamase gene that is frequently encountered in Haemophilus influenzae suggesting horizontal transfer between isolates of these bacterial species. Beta-lactamases are exceptional in meningococci with no reports from more than two decades. This report is worrying as the expansion of such isolates may jeopardize the effective treatment against invasive meningococcal disease.

https://ift.tt/2MmdVgl

Quantification of Cefepime, Meropenem, Piperacillin and Tazobactam in Human Plasma using a Sensitive and Robust LC-MS/MS Method- Part II. Stability Evaluation [PublishAheadOfPrint]

Although the stability of β-lactam antibiotics is a known issue, none of the previously reported bioanalytical methods had an adequate evaluation on their stability. In the current study, the stability of cefepime, meropenem, piperacillin, and tazobactam under various conditions was comprehensively evaluated. The evaluated parameters include stock solution stability, short-term stability, long-term stability, freeze-thaw stability, processed sample stability and whole blood stability. When stored at -20 °C, the stock solution of meropenem in methanol is stable for up to 3 weeks, and the stock solutions of cefepime, piperacillin, and tazobactam are stable for up to 6 weeks. All four antibiotics were stable in human plasma for up to 3 months when stored at -80 °C and stable in whole blood for up to 4 hours at room temperature. Short-term stability results indicated that all four β-lactams are stable at room temperature for 2 hours, but substantial degradation was observed when their plasma samples were stored at room temperature for 24 hours, with the degradation of cefepime, meropenem, piperacillin and tazobactam being 30.1 %, 75.6 %, 49.0 % and 37.7 %, respectively. As the stability information is method-independent, our stability results can be used as a reference by other research groups that work with these antibiotics.

https://ift.tt/2K6SNxX

TEM-184: a novel TEM-derived ESBL with enhanced activity against aztreonam [PublishAheadOfPrint]

TEM-184, a novel TEM-derived ESBL, was isolated from an Escherichia coli ST354 clinical strain. Compared to TEM-1, TEM-184 contains the following mutations: Q6K, E104K, I127V, R164S and M182T. Kinetic analysis of this enzyme revealed extended-spectrum activity in particular against aztreonam. TEM-184 was also susceptible to inhibitors including clavulanic acid, tazobactam and avibactam.

https://ift.tt/2Mosn7E

Quantification of Cefepime, Meropenem, Piperacillin and Tazobactam in Human Plasma using a Sensitive and Robust LC-MS/MS Method- Part I. Assay Development and Validation [PublishAheadOfPrint]

The highly variable pharmacokinetics of β-lactam antibiotics and β-lactamase inhibitors poses a significant challenge to clinicians in ensuring appropriate antibiotic doses in critically ill patients. Therefore, routine monitoring of their plasma concentrations is important for individualization of antimicrobial therapy. Accordingly, a simple and robust analytical method for the simultaneous determination of multiple β-lactam antibiotics and β-lactamase inhibitors is highly desirable to ensure quick decisions on dose adjustments. In this study, a sensitive, simple and robust method for the simultaneous quantification of cefepime, meropenem, piperacillin and tazobactam in human plasma was developed and rigorously validated according to the FDA guidance. Sample extraction was accomplished by simple protein precipitation. Chromatographic separation of analytes was achieved using a step-wise gradient elution. Analytes were monitored using MS/MS with a turbo ion spray source in positive multiple reaction monitoring mode. The calibration curve ranged from 0.5-150 μg/mL for cefepime, 0.1-150 μg/mL for meropenem and piperacillin, and 0.25-150 μg/mL for tazobactam. The inter- and intra-day precision and accuracy, sensitivity, selectivity, dilution integrity, matrix effect, extraction recovery and hemolysis effect were investigated for all four analytes and the results met the acceptance criteria. Compared with other reported methods, our method is more robust because of the combination of following features: a) simple sample extraction procedure, b) short sample run time, c) wide dynamic range, and d) small plasma sample volume needed. Since our method already covers β-lactams and a β-lactamase inhibitor with high heterogeneity of physico-chemical properties, further antibiotic candidates could be easily incorporated in this multi-analyte method.

https://ift.tt/2K5vftv

Variability of daptomycin minimum inhibitory concentrations for Enterococcus faecium when measured by reference broth microdilution and gradient diffusion tests [PublishAheadOfPrint]

Daptomycin has become a mainstay therapy for the treatment of serious vancomycin-resistant Enterococcus faecium infections. However, concern exists that current testing methods do not accurately predict clinical success of daptomycin therapy. We evaluated a collection of 40 isolates of E. faecium across 3 centers by reference broth microdilution (BMD), and two gradient strips, to determine the precision of daptomycin MICs by these methods and the correlation of daptomycin MIC testing with mutations in the liaFSR system, one of the primary daptomycin resistance mechanisms among the enterococci. Daptomycin MICs spanned 3 log₂ dilutions by BMD for 60.0% of isolates, 17.5% spanned 4 dilutions, 2.5% spanned 5 dilutions, and 20.0% spanned 6 or more dilutions. Fifteen isolates had MICs interpreted as susceptible by some tests, and nonsusceptible by others. Neither BMD not gradient diffusion tests could reliably differentiate isolates with or without mutations in liaFSR, resulting in a 59.8% very major error rate compared to genotype by BMD, 63.5% by Etest and 68.5% by MIC Test Strip. Imprecision in daptomycin MIC determination for E. faecium make establishment of a revised breakpoint challenging. Clinicians should be aware of this testing variability when making treatment decisions for patients with serious infections caused by this organism.

https://ift.tt/2Mo1Uao

Ceftaroline resistance by clone-specific polymorphism in penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus [PublishAheadOfPrint]

A total of 281 non-duplicated Staphylococcus aureus blood isolates were collected from January to May 2017 from eight hospitals in South Korea to investigate the epidemiological traits of ceftaroline resistance in methicillin-resistant S. aureus (MRSA). Cefoxitin-disk diffusion tests and mecA gene PCR revealed that 56.6% (159/281) of S. aureus was MRSA and mostly belonged to ST5 (50.3%, 80/281) and ST72 (41.5%, 66/281). Of the MRSA isolates, 44.0% (70/159) was non-susceptible to ceftaroline (MIC ≥2 mg/L), whereas all of the methicillin-susceptible S. aureus isolates were susceptible to the drug. Eight amino acid substitutions in penicillin-binding protein 2a (PBP2a), including four (L357I, E447K, I563T, and S649A) in penicillin-binding domain (PBD) and four (N104K, V117I, N146K, and A228V) in non-PBD (nPBD) of PBP2a, were associated with ceftaroline resistance. The accumulation of substitutions in PBP2a resulted in the elevation of ceftaroline MICs: one substitution at 1-2 mg/L, two or three substitutions at 2-4 mg/L, and five substitutions at 4 or 16 mg/L. Ceftaroline resistance in MRSA might be the result of clone-specific PBP2a polymorphism, along with substitutions both in PBD and in nPBD, and the elevated ceftaroline MICs were associated with the substitution sites and accumulation of substitutions.

https://ift.tt/2K8qwax

Reversal of chloroquine resistance of Plasmodium vivax in Aotus monkeys [PublishAheadOfPrint]

Chloroquine resistant (CQR) vivax malaria has emerged as a threat to the malaria elimination agenda. The objective of this study was to assess if a combination of chloroquine (CQ) and prochlorperazine was able to reverse CQ resistance of the Plasmodium vivax AMRU-1 strain from Papua New Guinea in infected Aotus monkeys. For this purpose, in two independent experimental drug efficacy trials, a total of eighteen Aotus monkeys infected with blood obtained from donor animals, were randomly assigned into treatment and control groups and administered CQ at 10 mg/kg or prochlorperazine at 20 mg/kg orally for five consecutive days alone or in combination. Reversal of CQR was achieved in animals that received the drug combination, whereas neither drug alone produced cures. This same drug combination reverses CQR in P. falciparum and could be an alternative for treatment in humans with chloroquine resistance P. vivax infections.

https://ift.tt/2MneEhz

Combination of amino acid substitutions leading to CTX-M-15-mediated resistance to the ceftazidime-avibactam combination [PublishAheadOfPrint]

Single amino-acid substitutions in the -loop of KPC β-lactamases are known to lead to resistance to the ceftazidime-avibactam combination. Here, we investigate this mechanism of resistance in CTX-M enzymes, which are the most widely spread extended-spectrum β-lactamases worldwide. Nine single amino acid polymorphisms were identified in the -loop of the 172 CTX-M sequences present in the Lahey database. The corresponding modifications were introduced in CTX-M-15 by site-directed mutagenesis. None of the nine substitutions was associated with ceftazidime-avibactam resistance in Escherichia coli TOP10. However, two substitutions led to 4-fold (P¹⁶⁷S) and 16-fold (L¹⁶⁹Q) increases in the MIC of ceftazidime. We determined whether these substitutions favor the in vitro selection of mutants resistant to ceftazidime-avibactam. The selection provided mutants for the L¹⁶⁹Q substitution but not for the P¹⁶⁷S substitution or for the parental enzyme CTX-M-15. Resistance to the drug combination (MIC of ceftazidime = 16 μg/ml in the presence of 4 μg/ml of avibactam) resulted from the acquisition of the S¹³⁰G substitution by CTX-M-15 L¹⁶⁹Q. Purified CTX-M-15 with the two substitutions, L¹⁶⁹Q and S¹³⁰G, was only partially inhibited by avibactam at concentrations as high as 50,000 μM but retained ceftazidime hydrolysis activity with partially compensatory decreases in k_cat and K_m. These results indicate that emergence of resistance to the ceftazidime-avibactam combination requires more than one mutation in most CTX-M-encoding genes. Acquisition of resistance could be restricted to rare variants harboring predisposing polymorphisms such as Q at position 169 detected in a single naturally-occurring CTX-M enzyme (CTX-M-93).

https://ift.tt/2KcGosE

Genistein and Ascorbic Acid reduce oxidative stress-derived DNA damage induced by antileishmanial meglumine antimoniate [PublishAheadOfPrint]

Meglumine antimoniate (Glucantime) is an antimonial pentavalent used to treat leishmaniasis, despite its acknowledged toxic effects, such as its ability to cause oxidative damage to lipids and proteins. Recently, our group demonstrated that meglumine antimoniate causes oxidative stress-derived DNA damage. Acknowledging that antioxidants modulate reactive oxygen species, we evaluated the capacity of genistein and ascorbic acid for preventing genotoxicity caused by meglumine antimoniate. For that, mice (n=5/group) received genistein (via gavage) in doses of 5, 10 and 20mg/kg for three consecutive days. After this period, they were treated with 810mg/kg meglumine antimoniate via intraperitoneal (i.p.). Furthermore, mice (n=5/group) received, simultaneously, ascorbic acid (i.p.) in doses of 30, 60 and 120mg/kg and 810mg/kg meglumine antimoniate. We also conducted post- and pre-treatment assays, in which animals received ascorbic acid (60mg/kg) 24 hours prior to or after receiving meglumine antimoniate. Genomic instability and mutagenicity were analyzed through conventional Comet assay and enzymatic assay using Formamidepyrimidine-DNA-glycosylase (Fpg) enzyme, as well as the Micronucleus Test, respectively. Meglumine antimoniate induced an increase in the DNA damage after digestion with Fpg, reinforcing its mutagenic potential by oxidizing DNA bases, which was prevented by genistein. Similarly, ascorbic acid proved itself capable of reducing mutagenic effects in simultaneous treatment, as well as in post-treatment. Therefore, our results demonstrate that both compounds are efficient in preventing mutations in mammalian cells treated with meglumine antimoniate.

https://ift.tt/2IuQmzA

Validating a 14-drug microtitre plate containing bedaquiline and delamanid for large-scale research susceptibility testing of Mycobacterium tuberculosis [PublishAheadOfPrint]

UKMYC5 is a 96-well microtitre plate designed by the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) to enable the measurement of minimum inhibitory concentrations (MICs) of 14 different anti-TB compounds for >30,000 clinical tuberculosis isolates. Unlike the MYCOTB plate, on which UKMYC5 is based, the plate included two new (bedaquiline and delamanid) and two repurposed (clofazimine and linezolid) compounds. UKMYC5 plates were tested by seven laboratories on four continents using a panel of 19 external quality assessment (EQA) strains, including H37Rv. To assess the optimal combination of reading method and incubation time, MICs were measured from each plate by two readers using three methods (mirrored-box, microscope and Vizion™ Digital viewing system) after 7, 10, 14 and 21 days incubation. In addition, all EQA strains were whole-genome sequenced and phenotypically characterized by 7H10/7H11 agar proportion method (APM) and MGIT960. We conclude that the UKMYC5 plate is optimally read using the Vizion™ system after 14 days incubation, achieving an inter-reader agreement of 97.9% and intra- and inter-laboratory reproducibility of 95.6% and 93.1%, respectively. The mirrored-box had similar reproducibility. Strains classified as resistant by APM, MGIT960 or the presence of mutations known to confer resistance consistently record elevated MICs compared with those strains classified as susceptible. Finally, the UKMYC5 plate records intermediate MICs for one strain which the APM measured MICs close the applied critical concentration, providing early evidence that the UKMYC5 plate can quantitatively measure the magnitude of resistance to anti-TB compounds due to specific genetic variation.

https://ift.tt/2KbSDFB

UCT943, a next generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria [PublishAheadOfPrint]

The 2-aminopyridine MMV048 was the first drug candidate inhibiting Plasmodium phosphatidylinositol 4-kinase (PI4K), a novel drug target for malaria, to enter clinical development. In an effort to identify the next generation of PI4K inhibitors, the series was optimized to improve properties such as solubility and antiplasmodial potency across the parasite lifecycle, leading to the 2-aminopyrazine UCT943. The compound displayed higher asexual blood stage, transmission-blocking, and liver stage activity than MMV048 and was more potent against resistant P. falciparum and P. vivax clinical isolates. Excellent in vitro antiplasmodial activity translated into high efficacy in P. berghei and humanized P. falciparum NOD-scid IL-2R^null mouse models. The high passive permeability and high aqueous solubility of UCT943, combined with low to moderate in vitro intrinsic clearance, resulted in sustained exposure and high bioavailability in preclinical species. In addition, the predicted human dose for a curative single administration using monkey and dog pharmacokinetics was low, ranging from 50 to 80 mg. As a next generation Plasmodium PI4K inhibitor, the combined preclinical data suggest that UCT943 has the potential to form part of a single-exposure radical cure and prophylaxis (SERCaP) to treat, prevent and block the transmission of malaria.

https://ift.tt/2Mo1iS8

Molecular analysis of resistance and detection of non-wild type strains using ECV values of Etest for amphotericin B and echinocandins for bloodstream Candida infections from a tertiary hospital in Qatar. [PublishAheadOfPrint]

A total number of 301 Candida bloodstream isolates were evaluated from 289 patients collected over five years at a tertiary hospital in Qatar. Out of all Candida infections, 53% were diagnosed in patients admitted to the ICUs. Steady increases in non-albicans Candida species were reported from 2009 to 2014 (30.2% C. albicans vs. 69.8% for other Candida species). Etest antifungal susceptibility testing was performed on all recovered clinical isolates to determine echinocandin (micafungin and anidulafungin) and amphotericin B susceptibilities and assess non-wild type (WT) strains (MICs above the epidemiological cutoff values). DNA sequence analysis was performed on all isolates to assess the presence of FKS mutations, which confer echinocandin resistance in Candida species. A total of 3.9% of isolates (12/301) contained FKS hot spot mutations including heterozygous mutations in FKS1 among strains of C. albicans and C. orthopsilosis. For C. tropicalis, the Etest appeared to overestimate non-WT for micafungin, anidulafungin, and amphotericin B, as 14%, 11%, and 35% of strains were above the ECV. However, no FKS mutations were identified in this species. For all other species, micafungin best reported echinocandin non-WT strains relative to FKS genotype, as anidulafungin tended to overestimate non-wild type. Besides C. tropicalis, few strains were classified as non-WT towards amphotericin B.

https://ift.tt/2KbSoKH

Surveillance of genetic variations associated with antimalarial resistance of Plasmodium falciparum from returned migrant workers in Wuhan, Central China [PublishAheadOfPrint]

Antimalarial drug resistance developed in Plasmodium falciparum has become a problem for malaria control. Evaluation of drug resistance is the first step for effective malaria control. In this study, we investigated the gene mutations of P. falciparum using blood samples from the Chinese returned migrant workers in order to identify drug resistance-associated molecular markers. These workers returned from Africa and Southeast Asia (SEA) during 2011-2016. The polymorphisms in pfcrt, pfmdr1, and k13-propeller genes and the haplotype patterns of Pfcrt and Pfmdr1 were analyzed. The results showed the presence of four haplotypes of Pfcrt codons 72-76, including CVMNK (wild type), SVMNT, and CVIET (mutation type), CV M/I N/E K/T (mixed type), with 50.57%, 1.14%, 25.00%, and 23.30% prevalence, respectively. For Pfmdr1, N86Y (22.28%) and Y184F (60.01%) were the main prevalent mutations. The prevalence of mutation at position 550, 561, 575, and 589 of K13-propeller were 1.09%, 0.54%, 0.54% and 0.54%, respectively. These data suggested that Pfcrt, Pfmdr1, and K13-propeller polymorphisms are the potential markers to assess drug resistance of P. falciparum in China, Africa and SEA.

https://ift.tt/2MjxmGH

Molecular identification and susceptibility testing of molds isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 study) [PublishAheadOfPrint]

Antifungal resistance is increasing by the emergence of intrinsically resistant species and by the development of secondary resistance in susceptible species. A previous study performed in Spain revealed levels of azole resistance in molds between 10 to 12.7% but secondary resistance in A. fumigatus was not detected. We used itraconazole supplemented media to select resistant strains. A total of 500 plates supplemented with 2 mg/L of ITZ were sent to 10 Spanish tertiary hospitals, molecular identification and antifungal susceptibility testing were performed. In addition, cyp51A gene was sequenced in those A. fumigatus strains showing azole resistance. A total of 493 isolates were included in the study. Sixteen strains were isolated from patients with an infection classified as proven, 104 as probable and 373 as colonization. Aspergillus was the most frequent genera isolated with 80.3% followed by Scedosporium/Lomentospora (7.9%), Penicillium/Talaromyces (4.5%), Fusarium (2.6 %) and the order Mucorales (1 %). Antifungal resistance was detected in Scedosporium/Lomentospora species, Fusarium, Talaromyces and Mucorales. Three strains of A. fumigatus senso stricto were resistant to azoles, two of them harbored TR₃₄+L98H mechanism of resistance and the other one had no mutations in cyp51A. The level of azole resistance in A. fumigatus remains low but cryptic species represent over 10% of the isolates and have broader but overall higher range of antifungal resistance

https://ift.tt/2K4UfRs

Functional characterization of AbaQ, a novel efflux pump mediating quinolone resistance in Acinetobacter baumannii. [PublishAheadOfPrint]

Acinetobacter baumannii has emerged as an important multidrug-resistant nosocomial pathogen. In previous work, we identified a putative MFS transporter, AU097_RS17040, involved in the pathogenicity of A. baumannii (Pérez-Varela et al., Infect Immun. 2017). In this study, we analyzed the susceptibility to diverse antimicrobial agents of A. baumannii cells defective in this transporter, referred to herein as AbaQ. Our results showed that AbaQ is mainly involved in the extrusion of quinolone-type drugs in A. baumannii.

https://ift.tt/2IrLQ4P

Pharmacokinetics and Comprehensive Analysis of the Tissue Distribution of Eravacycline in Rabbits [PublishAheadOfPrint]

Eravacycline (7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline or TP-434) is a novel, fully synthetic broad-spectrum fluorocycline with potent activity against Gram positive bacteria, anaerobes, and MDR Enterobacteriaciae. We characterized the plasma pharmacokinetics and conducted a comprehensive analysis of eravacycline tissue distribution in rabbits after multiple day dosing. Eravacycline for single-dose-pharmacokinetics was administered to NZW rabbits at 1, 2, 4, 8 & 10 mg/kg intravenously (IV) QD (n = 20). Eravacycline for multi-dose-pharmacokinetics was administered at 0.5, 1, 2, and 4 mg/kg IV QD (n = 20) for 6 days. Eravacycline concentrations in plasma and tissues were analyzed by LC/MS/MS assay. Mean AUCs following a single eravacycline dose ranged from 5.39 μg·h/ml to 183.53 μg·h/ml. Within the multi-dose study, mean AUCs ranged from 2.53 μg·h/ml to 29.89 μg·h/ml. AUCs correlated linearly within the dosage range (r=0.97; p=0.0001). In the cardiopulmonary system, concentrations were greatest in lung>heart>PAMs>BAL fluid; for the intraabdominal system: bile>liver>gall bladder>spleen>pancreas; for the renal system: urine>renal cortex>renal medulla; for musculoskeletal tissues: muscle psoas>bone marrow>adipose, for the CNS system: cerebrum>aqueous humor>CSF>choroid>vitreous. Concentrations in prostate and seminal vesicles demonstrated relatively high mean concentrations. The plasma pharmacokinetic profile of 0.5 to 4 mg/kg in NZW rabbits yields comparable exposure to that of humans (1 or 2 mg/kg Q12h) and demonstrates target tissue concentrations in most sites.

https://ift.tt/2MmU54I

Leishmania parasites are inhibited by the benzoxaborole AN2690 targeting leucyl-tRNA synthetase [PublishAheadOfPrint]

Visceral Leishmaniasis is an important public health threat in parts of India. It is caused by a protozoan parasite, Leishmania donovani. Currently, available drugs manifest severe side effects. Hence, there is a need to identify new drug targets and drugs. Aminoacyl-tRNA synthetases required for protein synthesis are known drug targets for bacterial and fungal pathogens. The aim of the present study was to obtain essentiality data for Leishmania donovani leucyl-tRNA synthetase (LdLRS) by gene replacement. Gene replacement studies indicate that this enzyme plays an essential role in the viability of this pathogenic organism and appears to be indispensable for its survival in vitro. The heterozygous mutant parasites demonstrated a growth deficit and reduced infectivity in mouse macrophages as compared to the wild type cells. We also report that Leishmania donovani recombinant LRS displayed aminoacylation activity and the protein localized to both the cytosol and mitochondrion. A broad-spectrum antifungal 5-fluro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690) was found to inhibit parasite growth in both the promastigote and amastigote stages in vitro as well as in vivo in BALB/c mice. This compound exhibited low toxicity to mammalian cells. AN2690 was effective in inhibiting the aminoacylation activity of the recombinant LdLRS. We provide preliminary chemical validation of LdLRS as a drug target by showing that AN2690 is an inhibitor both of L. donovani LRS and of L. donovani cell growth.

https://ift.tt/2KkhPt0

Αρχειοθήκη ιστολογίου

Ετικέτες

Δευτέρα 25 Ιουνίου 2018

Abstract