Agonistic CD40 monoclonal antibodies (mAb) have demonstrated some clinical activity, but with dose-limiting toxicity. To reduce systemic toxicity, we developed a bispecific molecule that was maximally active in the presence of a tumor antigen and had limited activity in the absence of the tumor antigen. LB-1 is a bispecific molecule containing single-chain Fv domains targeting mouse CD40 and the tumor antigen mesothelin. LB-1 exhibited enhanced activity upon binding to cell-surface mesothelin but was less potent in the absence of mesothelin binding. In a mouse model implanted with syngeneic 4T1 tumors expressing cell-surface mesothelin, LB-1 demonstrated comparable antitumor activity as an agonistic CD40 mAb but did not cause elevation of serum cytokines and liver enzymes, as was observed in anti-CD40-treated mice. The results from our study of LB-1 were used to develop a human cross-reactive bispecific molecule (ABBV-428) that targeted human CD40 and mesothelin. ABBV-428 demonstrated enhanced activation of antigen-presenting cells and T cells upon binding to cell-surface mesothelin, and inhibition of cultured or implanted PC3 tumor cell growth after immune activation. Although expression of cell-surface mesothelin is necessary, the bispecific molecules induced immunemediated antitumor activity against both mesothelin þ and mesothelin À tumor cells. ABBV-428 represents a class of bispecific molecules with conditional activity dependent on the binding of a tumor-specific antigen, and such activity could potentially maximize antitumor potency while limiting systemic toxicity in clinical studies.

Estudou-se a produção científica brasileira baseada em gênero na Saúde Coletiva, entre 1990-2008. Um total de 1.343 resumos de trabalhos de congressos e 251 artigos publicados foi examinado segundo: distribuição temporal, autoria, abordagem metodológica, áreas de conhecimento e temáticas abordadas. Os artigos foram também analisados quanto à coerência epistemológica entre a intenção e o uso efetivo de gênero ao longo do estudo e quanto à consistência metodológica de aplicação do conceito em termos do sentido completo ou parcial dado a gênero de acordo com sua construção teórica. Resultados mostraram que, embora com penetração crescente, 25,1% dos estudos reduzem gênero a sexo, uso considerado não coerente; 37,8% possuem uso coerente de gênero, mas lhe atribuíram um sentido parcial, e apenas 37,1% deram-lhe o sentido completo. Conclui-se que gênero tem importante presença no campo, mas é trabalhado de modo pouco preciso metodologicamente e inferior a seu potencial analítico.

Every year there are approximately 16,000 new cases of cervical cancer in Brazil. Novel screening technologies may reduce this number by expanding the population coverage but also by improving the detection rate of precursor lesions. We aimed to evaluate human papillomaviruses (HPV)-DNA testing in the context of routine cervical cancer screening in the public health system of the city of São Paulo, Brazil. Women participating in the primary screening program were invited to enroll. Liquid-based cytology samples were collected and cytology and Hr-HPV DNA testing were performed in parallel. Cytologists were blind to HPV results. Women older than 24 years with a positive high-risk HPV test and/or cytology class ! ASC-US were referred to colposcopy. From December 2014 to December 2016, 16,102 women joined the study. High-risk human papilloma-virus (HR HPV) DNA prevalence was 14.9%, whereas cytologic abnormalities were found in 7.2% of the women. Per protocol, 1,592 Hr-HPV þ women, in addition to 72 patients with cytologic classification > lowgrade squamous intraepithelial lesion (LSIL) were referred. A total of 80 cervical intraepithelial neoplasia (CIN2 þ) cases were diagnosed, 79 were Hr-HPV DNA þ and 18 had normal cytology. Hr-HPV DNA detected a significant number of patients with premalignant lesions missed by cytology and all 16 CIN3 þ cases were Hr-HPV DNA þ. HPV genotyping may be useful in the management of Hr-HPV þ women, reducing the burden of colposcopic referral for those harboring genotypes with a weaker association to CIN3 þ. Use of HPV-DNA testing was shown to be feasible and advantageous over current cytologic screening in the public health system.

Objective To investigate factors associated with colposcopy attendance in HPV‐positive women in São Paulo, Brazil. Methods We analyzed data from a prospective cohort of women positive for high‐risk HPV (hr‐HPV) undergoing cervical cancer screening in primary care services in São Paulo, Brazil. Non‐pregnant women attending routine screening between December 2014 and March 2016 were offered an hr‐HPV test, and those testing positive and aged 25 years or older were invited for colposcopy. Sociodemographic information was recorded at study enrollment. We compared variables between women who did and did not attend colposcopy within a logistic regression framework. Results Of 1537 hr‐HPV‐positive women, 1235 (80.4%) attended for colposcopy, with a median time from primary test to colposcopy of 132 days. Younger age (P<0.001) and concurrent negative cytology results (P=0.025) were associated with lower attendance. Women registered at units providing both the primary test and colposcopy were more likely to attend than those at units making external referrals (788/862 [91.4%] versus 447/675 [66.2%], P<0.001). Conclusion Non‐attendance for colposcopy may limit the success of future screening programs based on hr‐HPV testing in Brazil. Transfer of colposcopy services to primary care is a simple and effective facilitator of attendance.

No abstract

Objective: The aim of this study was to compare the performance of the current conventional Pap smear with liquid-based cytology (LBC) preparations. Study Design: Women routinely undergoing their cytopathological and histopathological examinations at Fundação Oncocentro de São Paulo (FOSP) were recruited for LBC. Conventional smears were analyzed from women from other areas of the State of São Paulo with similar sociodemographic characteristics. Results: A total of 218,594 cases were analyzed, consisting of 206,999 conventional smears and 11,595 LBC. Among the conventional smears, 3.0% were of unsatisfactory preparation; conversely, unsatisfactory LBC preparations accounted for 0.3%. The ASC-H (atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion) frequency did not demonstrate any differences between the two methods. In contrast, the incidence of ASC-US (atypical squamous cells of undetermined significance) was almost twice as frequent between LBC and conventional smears, at 2.9 versus 1.6%, respectively. An equal percentage of high-grade squamous intraepithelial lesions were observed for the two methods, but not for low-grade squamous intraepithelial lesions, which were more significantly observed in LBC preparations than in conventional smears (2.2 vs. 0.7%). The index of positivity was importantly enhanced from 3.0% (conventional smears) to 5.7% (LBC). Conclusions: LBC performed better than conventional smears, and we are truly confident that LBC can improve public health strategies aimed at reducing cervical lesions through prevention programs.

SALA, A. et al. Avaliação do processo de atendimento a pacientes portadores de doença crônico-degenerativa em uma unidade básica de saúde. Rev. Saúde Pública, 27: 463-71, 1993. Avalia-se o desempenho de ações de saúde desenvolvidas em uma unidade básica de saúde, relativas ao controle da hipertensão arterial sistêmica (HAS) enquanto estratégia de redução de morbi-mortalidadc por doença cardiovascular baseada no "enfoque de risco". Estas ações estruturam-se a partir da detecção da hipertensão arterial na população adulta atendida no serviço e do controle dos níveis pressóricos nos indivíduos portadores de HAS, incluindo outros fatores de risco conhecidos, bem como tratamento de eventuais complicações. Analisaram-se 3.793 usuários que compareceram pelo menos uma vez à consulta médica no serviço de Assistência ao Adulto de um Centro de Saúde-Escola, do Município de São Paulo (Brasil), no período de l o de junho de 1990 a 31 de maio de 1991. Para cada um dos usuários foram considerados os diagnósticos realizados, bem como a concentração de cada modalidade de consulta realizada (pronto-atendimento e consulta agendada). Destes, 839 eram portadores de hipertensão arterial e/ou diabete e foram agrupados em quatro categorias: os exclusivamente hipertensos, os hipertensos com outra doença crônica associada (exceto diabete), os diabéticos e os diabéticos com hipertensão arterial. Os resultados deste estudo mostraram: 1) baixa cobertura de indivíduos hipertensos e diabéticos em atendimento no serviço, quando se considera a população atendida pelo Centro de Saúde; 2) a existência de pacientes diagnosticados como hipertensos em consultas de pronto-atendimento, que não retornaram ao Centro de Saúde para seguimento médico programático, apontando para dificuldades na captação efetiva destes indivíduos. Esta "perda" deveu-se tanto a faltas dos pacientes às consultas agendadas para seu seguimento quanto ao não agendamento de consultas de seguimento por parte do serviço; 3) para os pacientes que aderiram ao seguimento, a concentração de consultas médicas e a concentração de faltas apresentaram números compatíveis com a proposta de agendamento trimestral; 4) a categoria dos exclusivamente hipertensos apresentou, quando comparada com as demais, menor concentração de consultas e maior proporção de faltas por consulta agendada. Discutem-se os limites das ações baseadas no "enfoque de risco" para controle de doenças crónico-degenerativas em população.Descritores: Avaliação de processos e resultados (cuidados de saúde). Hipertensão, prevenção. Avaliação de programas. IntroduçãoJá há algum tempo, a magnitude das doenças cardiovasculares como causa de óbito e morbidade tem suscitado estudos que relacionam certos fat0ores (tabagismo, alcoolismo, hipercolesterolemia, obesidade, "stress", diabetes melitus, hiper- tensão arterial e outros), ao aparecimento dessas doenças 5 .No intuito de tentar evitar a morte precoce e a morbidade por essas citadas doenças, em sua maior parte incapacitantes, tem-se formulado duas estratégias básicas: a do "enf...

Our data indicate that cytology interpreted with prior knowledge of the HPV status provides higher sensitivity for CIN 2+ lesions while marginally reducing the overall specificity compared with HPV status blinded cytology.