Perfil clínico, etiologia e escalas de avaliação funcional de pacientes com insuficiência cardíaca avançada: alocação para abordagem paliativa e desfechos hospitalares / Clinical profile, etiology and functional assessment scales of patients with advanced heart failure: allocation for palliative approach and hospital outcomes

INTRODUÇÃO: No conceito do Continuo da Doença Cardiovascular, a sequência de eventos seria iniciada por vários fatores de riscos progredindo por vias e processos fisiopatológicos até o desenvolvimento da lesão cardíaca final, no caso a Insuficiência Cardíaca (IC) em fase avançada. Cuidado Paliativo (CP) é uma abordagem interdisciplinar de tratamento que se concentra em melhorar a qualidade de vida dos pacientes nos diferentes estágios da IC.O racional para implementação de CP com planejamento avançado de cuidados por toda a progressão da doença e no luto , em pacientes com IC avançada ,inclui os seguintes: prognóstico limitado , elevada carga de sintomas , rehospitalizações, baixa qualidade de vida, comorbidades e estresse dos cuidadores OBJETIVOS: Caracterizar o perfil clínico dos pacientes cardiopatas incluídos para abordagem paliativa (AP), associado ao tratamento farmacológico da IC. MÉTODOS: Análise de 116 pacientes com IC incluídos para uma AP, entre fevereiro de 2017 a dezembro de 2018. RESULTADOS: Idade média de 74±12,7 anos, com 54% do sexo masculino. Diagnósticos etiológicos da miocardiopatia: incluíram: isquêmica 27%, valvar 25%, arritmogênica 13%, hipertensiva 8,6%, chagásica 8,6% e congênita 2,5%. Diagnósticos mas relevantes no momento da AP foram: insuficiência renal 78%, choque séptico 39,6%, IC 41,4%, choque cardiogênico 30,1%, acidente vascular cerebral 18,1% e pós parada cardiorrespiratória 9,4%, a média de fração de ejeção do VE por ecocardiograma 40%±16,5%. Performances nas atividades cotidianas: 64,6% com dependência total na escala Kartz, 37,9% com necessidade de suporte de vida na escala Karnofsky e 34,5% com alta dependência de cuidados pela Palliative Performance Scala. O intervalo de tempo entre a hospitalização e o óbito vario entre 3 e 405 dias (média de 29 dias). O intervalo de tempo entre a internação e a solicitação e indicação de uma AP variou entre 1 a 177 dias(média de 15 dias). Desfechos clínicos: 12% receberam alta hospitalar, e 7,7% estão em seguimento clínico. CONCLUSÃO: Os pacientes alocados e incluídos no programa de AP encontravam-se em estádios avançado da IC, em fase final de vida, mostrando que a AP foi iniciada tardiamente, caracterizado pelo tempo prolongado de internação , alta dependência de cuidados. DESCRITORES: Cuidados Paliativos, Cardiologia, Cuidados Paliativos na fase final de vida, Insuficiência Cardíaca. (AU)

Acompanhamento de familiares de pacientes cardiopatas sob assistência da equipe multidisciplinar de cuidados paliativos / Follow-up of relatives of cardiac patients assisted by the multidisciplinary palliative care team

INTRODUÇÃO: O processo de doença e terminalidade do indivíduo com insuficiência cardíaca estende-se em toda estrutura familiar. Com a proximidade da morte, o modo de enfrentamento dos familiares é moldado pelo conjunto de crenças, experiências de perda e luto, somado as demandas sociais, espirituais, físicas, psicológicas. OBJETIVO: Avaliar a perspectiva do familiar de pacientes cardiopatas em assistência paliativa, durante a finitude da vida. MÉTODO: Trata-se de um estudo transversal. A amostra foi constituída por familiares de pacientes cardíacos que foram encaminhados para a equipe de cuidados paliativos de um hospital especializado em cardiologia, no período de janeiro de 2017 a julho de 2018. Por meio de contato telefônico, os familiares responderam questões relacionadas ao atendimento da equipe de cuidados paliativos durante a internação de seu ente querido. Na análise descritiva utilizou-se valor de média e percentuais das variáveis. RESULTADOS: A amostra foi constituída por 58 familiares. Desses familiares, 100% referiram que a abordagem paliativa foi importante e essencial para o paciente e que a comunicação da equipe foi efetiva; 39(68,4%) referiram ficar muito satisfeitos e 18(31,6%) satisfeitos com os cuidados prestados e acolhimento recebido. Entre as preocupações que os familiares mais referiram foram: 27(47,4%) que o paciente não sentisse dor, 7(12,3%) tinham medo que a equipe retirasse ou diminuísse cuidados ao paciente, outros 7(12,3%) que se ausentasse no processo de finitude do paciente e 5(8,8%) demonstraram medo sobre o momento exato da morte. E 15(26,3%) agradeceram a equipe após a finalização da entrevista. CONCLUSÃO: Foi possível observar que a presença da equipe de cuidados paliativos influenciou na compreensão e aceitação da doença, no planejamento dos cuidados ao familiar internado, com o objetivo de que a família deve receber assistência durante todo o período de acompanhamento do paciente. Assim, é importante que a equipe multidisciplinar fortaleça os laços com os familiares, para reduzir a ansiedade e o sofrimento dos envolvidos nesse processo de terminalidade da doença cardíaca. (AU)

Photocytotoxicity of a cyanine dye with two chromophores toward melanoma and normal cells.

BACKGROUND: Due to high optical absorption, triplet quantum yield and affinity to biological structures bichromophoric cyanine dyes (BCDs) can be considered promising sensitizers for application in photodynamic therapy (PDT). In this work, we report on the study of the BCD photocytotoxicity toward melanoma and normal cells in comparison with that of commercial photosensitizer Photogem®. METHODS: The cytotoxic and phototoxic effects were measured by standard tests of cell viability. The drug uptake was obtained by the flow cytometry and optical absorption techniques. The BCD intracellular distribution was obtained by the fluorescence image microscopy using specific organelle markers. RESULTS: Both drugs demonstrated increased cytotoxicity under irradiation, while in darkness their cytotoxic effect at concentrations lower than 20 µM after 24 h of incubation did not exceed 20%. For 5 h of incubation, BCD photocytotoxicity in relation to melanoma cells reached 100% already at concentrations below 5 µM, while for normal cells the effect did not exceed 70% even for the 20 µM concentration. It is shown that BCD penetrates into the cells and is located predominantly in perinuclear cytoplasmic structures. CONCLUSIONS: The BCD photosensitizing characteristics appear more adequate for application in PDT than that of the actually applied commercial photosensitizer Photogem®. Higher light absorption by BCD in the near IR region and its preferential localization in mitochondria can explain its high photocytotoxicity. GENERAL SIGNIFICANCE: BCD can be considered as a new promising photosensitizer class for cancer PDT.

Role of cardiac troponin I in the evaluation of myocardial injury.

Cardiac troponin I (cTnl) is highly specific for cardiac muscle. In this study, we compared the utility of CK and CK-MB index versus cTnl in the assessment of myocardial infarction in 155 patients being evaluated for myocardial damage. As a cardiac marker for MI, Troponin I seems to be superior to CK-MB. In the subset of patients with renal disease, cTnl has definite advantages over CK-MB. In addition, the use of cTnl has the potential to replace the measurement of lactate dehydrogenase isoenzymes.

Ca2+ modulation of cis-unsaturated fatty acid-induced mutant protein kinase C activity: indication of inhibitory Ca2+-binding site in protein kinase C-alpha.

The C2 domain in protein kinase C (PKC) is homologous to equivalent domains in a number of important cytoplasmic proteins. Except for its implied function in Ca2+ and phospholipid binding, the precise role of this domain is not well understood. We examined the role of the C2 domain of PKC-alpha using a mutant enzyme in which 80% of this domain has been deleted. This mutant can be activated by phospholipid and diacylglycerol, but is independent of Ca2+. In this regard, its characteristics are similar to those of the novel PKCs (nPKCs), consistent with the notion that the C2 domain of PKC confers its Ca2+ responsiveness. However, when the C2 deletion mutant is activated by cis-unsaturated fatty acid, the activity is strongly inhibited by Ca2+ at micromolar concentrations. The Ca2+ inhibition is dose-dependent and is specific to cis-unsaturated fatty acids. The deletion mutant can also be activated synergistically by diacylglycerol and cis-fatty acid, but again activation is inhibited by Ca2+. Our results indicate that a PKC lacking the C2 domain is Ca2+-responsive and there exists an additional site for Ca2+ that modulates the sensitivity of the enzyme to cis-unsaturated fatty acid but not to diacylglycerol. This modulatory Ca2+-binding site appears to be suppressed by the C2 domain because the presence of the domain reverses the direction of PKC activity induced by cis-unsaturated fatty acid. These results suggest that the modulatory Ca2+-binding site could act as a molecular switch selective for fatty acid activation by sensing the changes in the Ca2+ levels in a cell, serving a possible mechanism of differential activation of cPKC with a C2 domain and nPKC lacking this domain.

Polysialylated neural cell adhesion molecule and plasticity of ipsilateral connections in Xenopus tectum.

The optic tectum of Xenopus offers a readily manipulated system for testing the hypothesis that polysialylation of the neural cell adhesion molecule is associated with axonal plasticity. Axons relaying input to the tectum from the ipsilateral eye employ visual input to establish a topographic map in register with the contralateral map, despite naturally-occurring or surgically-induced repositioning of the eyes. This capacity for activity-dependent refinement or re-organization of the ipsilateral map is normally confined to a period between about one and four months postmetamorphosis but can be restored in adults by local application of N-methyl-D aspartate to the tectum. In addition, dark-rearing prolongs plasticity indefinitely. We have used immunohistochemical staining with antibodies to polysialic acid to determine whether conditions of high plasticity are correlated with high levels of polysialylated neural cell adhesion molecule in the tectum. We find that the staining level is high in tecta from one to three month postmetamorphic frogs but is low both before and after this period. Thus, in normal Xenopus frogs, anti-polysialic acid staining is heavier in the period of high plasticity than in the preceding or following postmetamorphic periods. As a further test of this relationship, we examined brains of adults with experimentally-induced plasticity. Tecta of N-methyl-D-aspartate-treated adults and of dark-reared adults showed higher levels of staining than did the tecta of normally-reared adults. These results also support the hypothesis that the presence of high levels of polysialic acid on neural cell adhesion molecules is causally related to activity-related changes in axonal growth patterns.

Problems in determining levels of free digoxin in patients treated with digoxin immune FAb.

Determination of free digoxin levels in patients treated with digoxin immune FAb has long been a problematic area in clinical laboratory testing. The older radioimmunoassays resulted in inaccurate and variable results due to the competition of the administered drug with the radioactively labelled forms. The 1995 Physicians' Desk Reference continues to state that digoxin immune FAb will interfere with digitalis immunoassay measurements. This statement, however, is based primarily on the RIA methods. We evaluated the Stratus digoxin assay and the TDX digoxin II assay. Increasing amounts of immune FAb were added in a stepwise fashion to 12 patient samples containing high normal to elevated digoxin levels. Results showed a progressive decrease in digoxin levels when assayed with the Stratus kit. However, five patient samples tested with the TDX kit resulted in constant digoxin values despite the presence of increasing digibind levels. These results suggest that the Stratus method measures free digoxin, whereas the TDX method measures the total digoxin. Measurement of digoxin by the Stratus method is simple and quick. The Stratus digoxin assay may be an accurate and objective way of measuring free digoxin levels in patients on digoxin immune FAb.