Is low cerebral near infrared spectroscopy oximetry associated with neurodevelopment of preterm infants without brain injury?

OBJECTIVES: To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). METHODS: We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)<28 weeks or birth weight (BW)<1,000 g, with and without brain injury (BI). BI was defined as intraventricular haemorrhage, cystic periventricular leukomalacia or cerebellar haemorrhage. Univariate and multivariate analyses were used to study the association of rScO2<55% for more than 10 h in the first 3 days of life (NIRS<55%>10H) and the 24 months neurodevelopment. RESULTS: Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. NIRS<55%>10H in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p<0.05). NBI infants with NIRS<55%>10H were found to have lower systemic oxygenation than their counterparts with rScO2<55% for less than 10 h. CONCLUSIONS: NIRS<55%>10H in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values.

Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer.

BACKGROUND: First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial. METHODS: In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival and progression-free survival, as assessed by blinded, independent central radiologic review. RESULTS: After a median follow-up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the placebo-combination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64; P<0.001). Improvement in overall survival was seen across all PD-L1 categories that were evaluated. Median progression-free survival was 8.8 months (95% CI, 7.6 to 9.2) in the pembrolizumab-combination group and 4.9 months (95% CI, 4.7 to 5.5) in the placebo-combination group (hazard ratio for disease progression or death, 0.52; 95% CI, 0.43 to 0.64; P<0.001). Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group. CONCLUSIONS: In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck; KEYNOTE-189 ClinicalTrials.gov number, NCT02578680 .).

Mother's own milk and bronchopulmonary dysplasia in appropriate for gestational age preterm infants.

OBJECTIVE: To evaluate the association between mother's own milk (MOM) and bronchopulmonary dysplasia (BPD) in appropriate for gestational age (AGA) preterm infants <32 weeks. METHODS: Clinical data of AGA preterm infants (24+0/7-31+6/7 weeks) were reviewed. Infants with ≥66% of cumulative prescribed enteral volumes as MOM from birth to 36 weeks were allocated to the high provision of MOM group (H-MOM), whereas those with <66% were assigned to the low provision of MOM group (L-MOM). Multiple regressions were used to assess the association of H-MOM with BPD and oxygen saturation to fraction inspired oxygen ratio (SFR) at 36 weeks. RESULTS: A total of 1041 infants met the inclusion criteria, with a median provision of cumulative enteral nutrition volumes of 5721 (IQR 2616) mL/kg. Among them, 517 (49.7%) were H-MOM and 524 (50.3%) L-MOM infants. H-MOM showed a reduction in the incidence of BPD to 31.6% compared to L-MOM infants. H-MOM had a lower risk of BPD than L-MOM infants after the adjustment for gestational age, sex, cesarean section, mean SFR at the first hours of life, surfactant administration, patent ductus arteriosus, sepsis, prolonged ventilatory supports/oxygen exposure, and cumulative energy intakes from birth to 36 weeks [aOR: 0.613, p = 0.047]. H-MOM was also associated with a lower risk of SFR in the first quartile at 36 weeks [aOR: 0.616, p = 0.028] than L-MOM. CONCLUSION: A high provision (≥66%) of enteral volume as MOM from birth to 36 weeks is associated with a reduced risk of both BPD and low SFR at 36 weeks in AGA preterm infants <32 weeks.

Ten ways to get a grip on designing and implementing a competency-based medical education training program.

BACKGROUND: Globally there is a move to adopt competency-based medical education (CBME) at all levels of the medical training system. Implementation of a complex intervention such as CBME represents a marked paradigm shift involving multiple stakeholders. METHODS: This article aims to share tips, based on review of the available literature and the authors' experiences, that may help educators implementing CBME to more easily navigate this major undertaking and avoid "black ice" pitfalls that educators may encounter. RESULTS: Careful planning prior to, during and post implementation will help programs transition successfully to CBME. Involvement of key stakeholders, such as trainees, teaching faculty, residency training committee members, and the program administrator, prior to and throughout implementation of CBME is critical. Careful and selective choice of key design elements including Entrustable Professional Activities, assessments and appropriate use of direct observation will enhance successful uptake of CBME. Pilot testing may help engage faculty and learners and identify logistical issues that may hinder implementation. Academic advisors, use of curriculum maps, and identifying and leveraging local resources may help facilitate implementation. Planned evaluation of CBME is important to ensure choices made during the design and implementation of CBME result in the desired outcomes. CONCLUSION: Although the transition to CBME is challenging, successful implementation can be facilitated by careful design and strategic planning.

CONTEXTE: Partout dans le monde, on observe une tendance en faveur de l'éducation médicale axée sur les compétences (EMAC) à tous les niveaux du système d'éducation médicale. Une intervention complexe comme l'élaboration d'un programme d'EMAC représente un important changement de paradigme qui nécessite l'implication de plusieurs parties prenantes. MÉTHODE: L'objectif de cet article est de partager des conseils dégagés par les auteurs d'une revue de la littérature et de leur propre expérience afin d'aider les éducateurs à mieux s'orienter dans cette entreprise de taille qu'est la mise en œuvre de l'EMAC et à éviter les écueils. RÉSULTATS: Une planification minutieuse avant, pendant et après la transition des programmes vers l'EMAC contribue à garantir son succès. L'implication des principales parties prenantes, telles que les stagiaires, le corps enseignant, les membres du comité du programme de résidence et l'administrateur du programme, avant et pendant la mise en œuvre est essentielle. La sélection attentive des éléments clés, comme les activités professionnelles confiables, les évaluations et l'utilisation appropriée de l'observation directe, favorisera l'adoption de l'EMAC. Des tests pilotes peuvent permettre la participation du corps professoral et des apprenants, et à déceler les problèmes logistiques qui peuvent entraver la mise en œuvre. Les conseillers pédagogiques, le recours à la cartographie des programmes d'études et le repérage et la mobilisation de ressources locales peuvent faciliter la mise en œuvre des programmes d'EMAC. L'évaluation planifiée de ces programmes est importante pour garantir que les choix faits lors de leur conception et mise en œuvre aboutissent aux résultats souhaités. CONCLUSION: Puisque la transition vers l'EMAC peut comporter de nombreux défis, elle peut néanmoins être opérée avec succès grâce à une conception et une planification stratégique minutieuses.

Aging, immunity, and cancer.

Age is the most important risk factor for tumorigenesis. More than 60% of new cancers and more than 70% of cancer deaths occur in elderly subjects >65 years. The immune system plays an important role in the battle of the host against cancer development. Deleterious alterations occur to the immune response with aging, termed immunosenescence. It is tempting to speculate that this waning immune response contributes to the higher incidence of cancer, but robust data on this important topic are few and far between. This review is devoted to discussing state of the art knowledge on the relationship between immunosenescence and cancer. Emerging understanding of the aging process at the molecular level is viewed from the perspective of this increased tumorigenesis. We also consider some of the most recent means to intervene in the modulation of immunosenescence to increase the ability of the immune system to fight against tumors. Future research will unravel new aspects of the immune response against tumors which will be modulable to decrease the burden of cancer in elderly individuals.

Potential role of immunosenescence in cancer development.

The incidence and prevalence of most cancers increase with age. The reasons for this may include tumor escape mechanisms and decreased immunosurveillance, but most are caused by the time required for carcinogenesis, according to most scientists. The immune system is a unique mechanism of defense against pathogens and possibly cancers; however, there is a body of evidence that the immune system of the aged is eroded, a phenomenon termed immunosenescence. There is a growing interest in immunosenescence and how it may contribute to the increased number of cancers with aging. Each arm of the immune system, innate and adaptive, is altered with aging, contributing to increased tumorigenesis. Understanding the contribution of immunosenescence to cancer development and progression may lead to better interventions for the elderly.

Manifestaçöes clínicas associadas ao parvovírus humano B19, incluindo a anemia persistente na AIDS e em outras formas de imunodepressäo / Clinical problems related to human parvovírus B19, including protracted anemia in AIDS and other forms of immunodeficiency

A descoberta acidental do parvovírus humano B19 em 1974 levou ao esclarecimento da etiologia de algumas síndromes clínicas já desde há muito desconhecidas, e hoje comprovadamente associadas à infecçäo por este vírus. Com base na revisäo da literatura, säo descritas estas síndromes, bem como os eventos que permitiram associá-las ao parvovírus B19, na ordem aproximada em que ocorreram. A literatura brasileira foi também revista. O texto aborda também a infecçäo por pavovírus B19 no contexto de Aids e de outras formas de imunodepressäo

Pesquisa de chlamydia trachomatis em mulheres do município de Piraí-Rio de Janeiro / Research on chlamydia trachomatis in women from the municipal district of Piraí-Rio de Janeiro

A chlamydia trachomatis é um importante agente causador de endocervicite em mulheres sexualmente ativas. esta pode ser assintomática ou apresentar sintomas inespecíficos. A ausência de diagnóstico e tratamento representa um grave problema de saúde pública, já que pode evoluir para sérias complicaçöes como endometrite, doença inflamatória pélvica, esterilidade e infecçöes neonatais, pulmonares e oftálmicas. Contudo,säo escassos osdados em relaçäo a sua prevalência entre as mulheres brasileiras. Objetiva determinar a frequência de endocervicite por CT em mulheres atendidas no ambulatório de ginecologiade posto de saúde e clínica privada da cidade de Piraí-RJ, e identificar o perfilsocioeconomico e os dados da história sexual das mulheres com diagnósticos confirmados. Estudo prospectivo com mulheres sexualmente ativas com idade entre 13 e 49 anos que procuraram atendimento ginecológico por motivos diversos e que näo fizeram uso de medicaçäo até quinze dias antes. O estudo envolveu dados como: anamnese, exame ginecológico para colpocitologia oncótica e coleta de material endocervical com swab específico. As amostras do endocérvice foram submetidas ao ELISA pelo sistema Elfa-Vidas para detecçäo de antígenos clamídiais no laboratório do Setor de Doenças Sexualmente Transmissíveis da Universidade Federal Fluminense, Niterói, RJ. A amostra constituiu-se de 108 pacientes. Detectou-se antígenos clamidiais em 20 mulheres, sendo a positividade 18,8, 16/69, na rede pública e 18 por cento, 7/39, no serviço particular. Os principais motivos da consulta foram: rotina e corrimento vaginal e/ou dor pélvica. Das pacientes com resultado positivo 28 por cento apresentaram exame clínico sugestivo de infecçäo por chlamydia. A positividade geral para pesquisa de CT na endocérvice foi de 18,5 por cento, 10/108; näo foi significativa a diferença de positividade entre os grupos estudados. Basear-se apenas nos achados clínicos e colpocitológicos para diagnóstico desta infecçäo pode ser um equívoco

Ocorrências de doenças sexualmente transmissíveis antes e depois do carnaval no Rio de Janeiro / Occurrence of sexually transmitted diseases before and after carnival in Rio de Janeiro

Estudo retrospectivo de análise de 2000 prontuários de pacientes que procuraram o Setor de DST da Universidade Federal Fluminense, 30 dias antes e 30 dias depois do Carnaval, nos anos de 1994, 95, 96, 97 e 1998. A partir daí, selecionou-se 1005 prontuários de pacientes que chegaram ao Setor pela primeira vez e que tiveram diagnóstico clínico e/ou laboratorial de DST ou infecçäo genital de possível envolvimento sexual