Search

Abstract Background The SARS-CoV-2 pandemic led to unprecedented testing demands, causing major testing delays globally. One strategy used for increasing testing capacity was pooled-testing, using a two-stage technique first introduced during WWII. However, such traditional pooled testing was used in practice only when positivity rates were below 2%. Methods Here we report the development, validation and clinical application of P-BEST - a single-stage pooled-testing strategy that was approved for clinical use in Israel. Results P-BEST is clinically validated using 3636 side-by-side tests and is able to correctly detect all positive samples and accurately estimate their Ct value. Following regulatory approval by the Israeli Ministry of Health, P-BEST was used in 2021 to clinically test 837,138 samples using 270,095 PCR tests - a 3.1fold reduction in the number of tests. This period includes the Alpha and Delta waves, when positivity rates exceeded 10%, rendering traditional pooling non-practical. We also describe a tablet-based solution that allows performing manual single-stage pooling in settings where liquid dispensing robots are not available. Conclusions Our data provides a proof-of-concept for large-scale clinical implementation of single-stage pooled-testing for continuous surveillance of multiple pathogens with reduced test costs, and as an important tool for increasing testing efficiency during pandemic outbreaks.

Objetivos: O linfoma de Hodgkin (LH) é uma neoplasia hematológica caracterizada pela proliferação clonal de linfócitos nos linfonodos, com a presença de células de Reed-Sternberg. A extensão e localização do tumor define o estadiamento da doença, que segue a classificação de Lugano. O trabalho teve como objetivo caracterizar o perfil clínico-epidemiológico, imunohistoquímico e de resposta ao tratamento de pacientes adultos com LH. Material e métodos: Foi realizado um estudo descritivo observacional retrospectivo, empregando coleta de dados de prontuários médicos de pacientes adultos com diagnóstico de LH entre os anos de 2006 e 2018 no Centro de Oncologia Osvaldo Leite do Hospital de Urgência de Sergipe. Em um questionário semiestruturado foram coletados dados referentes a: idade, sexo, data de nascimento, data do diagnóstico e início do tratamento, sintomas, imunohistoquímica e reposta ao tratamento. Resultados: Foram analisados 54 prontuários, dos quais foram excluídos 23 por falta de informações, restando 31 para o estudo. A média de idade foi de 30,9 anos (18-67), sendo 51,6% do sexo masculino. Os sinais e sintomas mais comuns foram linfonodomegalia (81,5%), tosse (18,5%) e perda de peso (18,5%). A imunohistoquímica apresentou positividade para Ki-67 (100%), PAX5 (100%), CD30 (93,5%), CD15 (89,2%) e CD20 (36,7%). O tempo médio entre o diagnóstico e início do tratamento foi de 40 dias (2-125). Vinte e dois (70,9%) pacientes responderam bem ao esquema terapêutico com doxorrubicina, bleomicina, vimblastina e dacarbazina (ABVD) e continuam em remissão completa (RC) até a presente data. Nove pacientes (25,8%) foram refratários ou apresentaram remissão parcial (RP) ao ABVD, sendo submetidos a outra(s) linha(s) de tratamento e aos imunobiológicos brentuximabe e nivolumabe. Três pacientes foram submetidos ao transplante de medula óssea autólogo (TMO). Discussão: Estudos epidemiológicos demonstraram que a taxa de mortalidade por LH foi reduzida nos últimos anos devido à redução do tempo entre o diagnóstico e início do tratamento, melhoria na eficácia das técnicas diagnósticas e aprimoramento dos protocolos de tratamento. Neste estudo, apesar da média razoável, o tempo entre diagnóstico e tratamento variou bastante, em virtude de falta de medicamentos e não comparecimento dos pacientes na data estipulada, por vezes ocorrido por carência de recursos financeiros. A taxa de RC com ABVD ficou um pouco abaixo em relação aos dados da literatura (> 80%). O número de pacientes que fizeram uso dos imunobiológicos, geralmente administrados em pacientes com doença avançada, como terapia de salvamento ou antes do TMO, foi pequeno. Isso pode ser explicado pela janela temporal do estudo, visto que a aprovação dos imunobiológicos no Brasil ocorreu após o ano de 2014. Em conformidade com a literatura, o PAX-5 é o marcador imunohistoquímico mais sensível e confiável para o LH, tendo positividade de 100% nos pacientes. O CD20 pode estar relacionado à melhora ou piora do desenvolvimento clínico. No presente estudo, 75% dos pacientes CD20 positivos apresentaram um bom desfecho clínico, com RC. Conclusão: Conclui-se que o período entre a data do diagnóstico e a data do início do tratamento, bem como fatores socioeconômicos podem influenciar no prognóstico e resposta ao tratamento dos pacientes. Apesar disso, o esquema terapêutico ABVD continua tendo altas taxas de RC para o linfoma de Hodgkin.

Objetivos: O mieloma múltiplo (MM) é uma neoplasia hematológica caracterizada pela expansão clonal plasmocitária e produção de imunoglobulina monoclonal, com provável evolução de quadro para destruição óssea, falência renal, supressão hematopoética e infecções. O objetivo deste trabalho foi analisar casos de mieloma múltiplo a partir do diagnóstico e tratamento, relacionando-os aos seus respectivos marcadores imunofenotípicos. Material e métodos: Tratando-se de um estudo descritivo observacional retrospectivo, decorrente da análise e coleta de dados de prontuários dos pacientes do Centro de Oncologia Osvaldo Leite do Hospital de Urgência de Sergipe - HUSE, diagnosticados com MM no período de 2014 a 2018. As informações foram extraídas em questionário semiestruturado como idade, sexo, data de nascimento, data do diagnóstico e do início do tratamento, protocolo terapêutico e resposta ao tratamento com remissão completa (RC), remissão parcial (RP), recidiva e refratariedade, foram associadas ao perfil imunofenotípico. Resultados: Foram analisados 29 prontuários, a idade variou de 22 a 82 anos, com mediana de 58 anos, sendo 48,3% do sexo feminino. O perfil imunofenotípico revelou 89,7% dos pacientes com CD138+, 82,8% com CD38+, 69,0% com CD56+, 55,2% cadeia leve κ+ e 13,8% λ+. O CD56- foi observado em 13,8% dos pacientes. Dos quatro pacientes refratários/recidivados, três eram CD56+. O tempo médio entre o diagnóstico e o início do tratamento foi de 30,5 dias (1 a 81). O protocolo terapêutico mais utilizado foi o regime triplo VCd (velcade + ciclofosfamida + dexametasona), utilizado por 24,1% dos pacientes, seguido do regime duplo Cd = 20,7%, CTd (T para talidomida) = 13,8%, VTd = 10,3% e Cd + melfalano = 6,9%. Dentre os 16 prontuários com informações sobre resposta ao tratamento, observou-se RP em 62,5%, RC em 12,5%, recidivados e refratários, ambos 12,5%. Cinco pacientes foram elegíveis para o transplante autólogo de células tronco hematopoéticas (TCTH). Discussão: Os prontuários foram analisados mediante presença e acessibilidade de informações. A mediana 58 anos de idade para os pacientes com MM se aproxima dos dados da literatura (61 anos). A expressão do CD138 e CD38 é empregada no diagnóstico e acompanhamento da resposta ao tratamento. O CD56+ promove o crescimento das células do mieloma, diminuição da apoptose e adesão às células estromais. Quando a expressão do CD56 está diminuída pode reduzir a resposta ao tratamento, porém, há estudos que inferem resultados positivos. Um estudo empregando Cd ou CTd em pacientes CD56+ demonstrou alta taxa de RP e melhor prognóstico. A escolha pela dexametasona nos regimes é corroborada pela literatura por sua baixa toxicidade. A lenalidomida presente no protocolo atual padrão, foi somente aprovada em 2017 no Brasil. Logo, os regimes VTd ou VCd foram utilizados na época do estudo como melhor opção terapêutica disponível. Conclusão: O mieloma múltiplo acometeu igualmente ambos os sexos. Os protocolos VCd e Cd foram mais utilizados, mas outros regimes (VTd, CTd, e Cd + melfalano) foram aplicados em outros casos. Ademais, além dos CD38+ e CD38+, o CD56+ é o marcador imunofenotípico mais recorrente, não havendo consenso da sua expressão e influência na resposta ao tratamento. Por isso, monitorar as alterações imunofenotípicas em pacientes com MM pode ser benéfico para adaptar estratégias terapêuticas e melhorar o prognóstico.

Objetivos: O câncer de pâncreas é uma neoplasia maligna que apresenta altos índices de mortalidade, sendo frequentemente diagnosticada em sua fase avançada devido à ausência de sintomas precoces específicos. Esta neoplasia pode abranger indivíduos de todas as idades e sexo, sendo influenciadas por diversos fatores como ambiente e imunossenescência. Diversas pesquisas tem sido feitas para detectar fatores de risco que auxiliem na identificação do prognóstico destas neoplasias, como por exemplo, o fenótipo sanguíneo. Dessa forma, este trabalho teve como objetivo determinar o perfil fenotípico dos grupos sanguíneos ABO e Rh dos pacientes com câncer de pâncreas em um hospital de Sergipe. Material e métodos: Foi realizado um estudo descritivo observacional retrospectivo empregando coleta de dados de prontuários de pacientes adultos com diagnóstico câncer de pâncreas atendidos na Unidade Transfusional do Hospital Universitário da Universidade Federal de Sergipe – HU-UFS-Ebserh, no período de 2019 a 2024. Para a coleta dos dados, foi aplicado um questionário semiestruturado onde foram obtidos dados referentes a: idade, sexo, fenótipo ABO e Rh. Os dados dos controles foram obtidos de indivíduos sem histórico de neoplasias. Resultados: Foram analisados 35 prontuários, com média de idade de 55,6 anos (18 a 86), sendo 57,1% do sexo feminino. Do total dos pacientes, o grupo sanguíneo mais frequente foi o “O”com 62,9%, seguido de “A”com 22,9%, “B”com 8,5% e “AB”com 5,7%. O grupo controle sem neoplasia totalizou 5.836 indivíduos. Em comparação ao grupo controle, o grupo sanguíneo ‘’AB’’obteve maior risco de desenvolver neoplasia quando comparado aos outros grupos sanguíneos com 1,1% pacientes, seguido do ‘‘O’’com 0,7%, ‘‘B’’com 0,5% e ‘’A’’com 0,4%. Em relação ao sistema Rh antígeno D, 94,3% eram Rh positivos, e 5,7% Rh negativos. Analisando-se a combinação dos antígenos do fenótipo Rh estendido, o de maior predominância foi o “DCcee”com 17 (48,6%) indivíduos. Discussão: Os sistemas sanguíneos ABO e Rh tem sido associado ao risco de desenvolver cânceres incluindo câncer gástrico, câncer de pâncreas e câncer de colón. Observou-se que indivíduos do grupo do sanguíneo “O“apresentaram maior frequência de câncer de pâncreas quando comparado com os outros grupos sanguíneos ABO, em virtude que Sergipe tem uma predominância do grupo sanguíneo “O”em sua população. Em relação ao risco de desenvolver câncer de pâncreas, o grupo “AB'obteve um maior risco quando comparado com “A”, “B”e “O”. Estes resultados discordam de outros estudos realizados com objetivos semelhantes que demonstravam que o grupo sanguíneo “A”tinha maior risco de desenvolver câncer de pâncreas quando comparado com “B”, “AB”e “O”. Diferente do sistema ABO, os dados obtidos com o sistema Rh estão em concordância com a literatura existente, com maior predominância do fator Rh positivo em pessoas com câncer de pâncreas quando comparado com o Rh negativo, assim como o fenótipo Rh estendido “DCcee”já foi descrito em estudos com neoplasias hematológicas. Conclusão: O presente estudo sugere que indivíduos do grupo sanguíneo ”AB”, com o sistema Rh positivo e fenótipo ”DCcee”, apresentam maior incidência de câncer de pâncreas quando comparado aos outros grupos sanguíneos ABO.

Objetivos: As neoplasias hematológicas compreendem um grupo heterogêneo de doenças malignas que afetam o sangue periférico e/ou a medula óssea, abrangendo diferentes idades, variações geográficas, diversidade genética e molecular. Estudos sugerem que estas neoplasias podem ser influenciadas por diversos fatores como idade, ambiente, imunossenescência, e possivelmente a distribuição dos fenótipos sanguíneos. Com isso, o trabalho teve como objetivo determinar a distribuição dos fenótipos dos grupos sanguíneos ABO, Rh e Kell dos pacientes com neoplasias hematológicas em um hospital de Sergipe. Material e métodos: Foi realizado um estudo descritivo, observacional e retrospectivo, empregando coleta de dados de prontuários médicos de pacientes adultos com diagnóstico neoplasias hematológicas, atendidos na Unidade Transfusional do Hospital Universitário da Universidade Federal de Sergipe – HU-UFS-Ebserh, no período de 2019 a 2024. Para a coleta dos dados, foi aplicado um questionário semiestruturado onde foram obtidos dados referentes a: idade, sexo, data de nascimento, fenótipo ABO e Rh. Os dados dos controles foram obtidos de indivíduos sem histórico de neoplasia. Resultados: Foram analisados 78 prontuários, dos quais 23 foram excluídos por falta de informações, restando 55 pacientes para o estudo. A média de idade dos pacientes foram 58,9 (variando de 21 a 88), sendo 54,5% do sexo masculino e 45,5% do sexo feminino. Do total de pacientes, 19 (34,5%) tinham o diagnóstico de leucemias, 17 (30,9%) de mieloma, 12 (21,8%) de linfoma e 7 (12,8%) de SMD. O grupo sanguíneo predominante foi “O”com 49%, seguido do “A”com 44%, “B”com 7% e “AB”com 0%. O grupo controle sem neoplasia totalizou 5.836 indivíduos. Em comparação ao grupo controle, o grupo sanguíneo ‘’A’’obteve maior risco de desenvolver neoplasia quando comparado aos outros grupos sanguíneos, com 11,8% pacientes, seguido do ‘’O’’, com 8,6%, o ‘’B’’, com 0,7% e ‘’AB’’, com 0,0%. Em relação ao sistema Rh, pôde-se constatar que 44 pacientes possuem Rh positivo (75,0%) e 11 pacientes possuem Rh negativo (25,0%), o fenótipo ‘’DCcee’’apresentou maior frequência, sendo encontrado em 16 (29,0%) pacientes. Discussão: Dados da literatura são semelhantes em relação ao risco associado aos sistemas ABO/Rh e neoplasias hematológicas. Um estudo que avaliou as neoplasias hematológicas demostrou que o risco foi maior no grupo “A”quando comparados com o “B”, “O”e “AB”. No presente trabalho, observou-se um maior risco em pacientes do grupo sanguíneo ‘’A’’. Em relação ao sistema Rh, foi observada maior incidência do Rh positivo, corroborando com as evidências científicas em outros estudos de objetivos similar na literatura. assim como o fenótipo Rh estendido “DCcee”já foi descrito em estudos com neoplasias hematológicas. Conclusão: O presente estudo sugere que indivíduos do grupo sanguíneo ”A’, com o sistema Rh positivo e Rh e o fenótipo ”DCcee”, apresentam maior incidência de neoplasias hematológicas quando comparado aos outros grupos sanguíneos ABO.

This article reconsiders the much-discussed second divine council at the beginning of Book 5 of the Odyssey (5.1-42). It is demonstrated that this assembly is not a case of successive narration of simultaneous actions, as many scholars have maintained, but that the second council is necessary because Zeus, in order to avoid interdivine conflicts, has not kept his promise to initiate Odysseus' repatriation as announced in the first council. It is further argued that Athene's speech to Zeus (5.7-20), with its minacious tone and its cento-like composition, serves to put pressure on Zeus and to display Athene's intellectual superiority. [ABSTRACT FROM AUTHOR]

Abstract The brown honeyeater (Lichmera indistincta) is a common bird species in Australia and is a pollinator of many native plant species but there are no records demonstrating evidence of effective pollination by honeyeaters in commercial cropping systems. We observed L. indistincta visiting rabbiteye blueberry flowers at a commercial berry orchard on the Mid North Coast of New South Wales and evaluated their capacity to transfer pollen. We did this by bagging flowers to prevent visitation prior to anthesis; after anthesis, we unbagged the flowers and waited for L. indistincta visits. After a single visit, we collected the stigma and mounted it on a slide to evaluate stigmatic pollen load. We observed the birds visiting blueberry flowers and foraging on nectar. We also found that L. indistincta deposited similar amounts of pollen to other common insect pollinator species, such as honeybees and stingless bees. As the commercial berry orchard blocks are surrounded by diverse remnant vegetation, we hypothesize that the vegetation is likely providing habitat for these birds. Our results indicate that berry growers with management practices that protect and support remnant vegetation surrounding blueberry orchard blocks may benefit from higher blueberry pollination services by supporting diverse pollinators within fields.

Abstract We observed the brown honeyeater, Lichmera indistincta, visiting blueberry orchards in eastern Australia. L. indistincta is considered to be a nectarivorous bird, feeding almost entirely on nectar. However, we report observations of this species as both a nectarivore and insectivore in blueberry crops and as an insectivore in raspberry crops. Brown honeyeaters may be acting as biological control agents when feeding on leaf‐roller caterpillars (Lepidoptera: Tortricidae) in blueberry orchards and on brown blowflies (Calliphora stygia) in raspberry orchards. Although most blueberry growing regions use managed honey bees as the main pollinator, more studies on the complex tritrophic interactions occurring in these crops are needed to better understand the costs and benefits of different farm management practices upon alternative pollinators.

Abstract Background Although medical students have a duty to seek advice for their health conditions, they tend to avoid disclosure and help-seeking behaviours, therefore potentially posing a risk to themselves and their patients. The literature regarding their decisions to seek help or disclose health conditions is limited. The study’s purpose was to explore the factors that determine disclosure and help-seeking decision processes by medical students who have health conditions with or without disability. Methods We recruited by purposive sampling and conducted in-depth semi-structured interviews with 11 male and female medical students from a UK medical school, who had physical or mental health disorders. Thematic analysis was used to identify themes. A mix of inductive and deductive techniques was used while using an organising framework proposed by Llewellyn-Thomas (1995). Results The impact of individuals’ features, such as personality traits on medical students’ disclosure and help-seeking decisions were identified. Different aspects of the condition, such as its type and severity were found to influence these decisions. Participants made an evaluation of the potential receiver of a disclosure, consisting of factors such as the receiver’s characteristics and attitudes. The culture of the medical environment, such as role models, had a major impact on their decisions. Finally, systemic factors, such as the lack of clarity of policies influenced students’ decisions. Conclusion Medical students’ disclosure and help-seeking decision processes are influenced by risk-benefit evaluations and factors in interlinked spheres of their lives. They tend to avoid or postpone disclosure and seeking help, especially when the university is involved, due to a perceived risk to their future. Future research should examine the role of personality traits and the medical culture. Medical schools should encourage earlier help-seeking and disclosure behaviours by clarifying procedures and building trust via online and confidential platforms; interpersonal channels and normalisation processes within the medical education and the profession as a whole.

In-depth analysis of SARS-CoV-2 quasispecies is pivotal for a thorough understating of its evolution during infection. The recent deployment of COVID-19 vaccines, which elicit protective anti-spike neutralizing antibodies, has stressed the importance of uncovering and characterizing SARS-CoV-2 variants with mutated spike proteins. Sequencing databases have allowed to follow the spread of SARS-CoV-2 variants that are circulating in the human population, and several experimental platforms were developed to study these variants. However, less is known about the SARS-CoV-2 variants that are developed in the respiratory system of the infected individual. To gain further insight on SARS-CoV-2 mutagenesis during natural infection, we preformed single-genome sequencing of SARS-CoV-2 isolated from nose-throat swabs of infected individuals. Interestingly, intra-host SARS-CoV-2 variants with mutated S genes or N genes were detected in all individuals who were analyzed. These intra-host variants were present in low frequencies in the swab samples and were rarely documented in current sequencing databases. Further examination of representative spike variants identified by our analysis showed that these variants have impaired infectivity capacity and that the mutated variants showed varied sensitivity to neutralization by convalescent plasma and to plasma from vaccinated individuals. Notably, analysis of the plasma neutralization activity against these variants showed that the L1197I mutation at the S2 subunit of the spike can affect the plasma neutralization activity. Together, these results suggest that SARS-CoV-2 intra-host variants should be further analyzed for a more thorough characterization of potential circulating variants.

Leishmania parasites cycle between sand fly vectors and mammalian hosts, transforming from extracellular promastigotes that reside in the vectors’ alimentary canal to obligatory intracellular non-motile amastigotes that are harbored by macrophages of the mammalian hosts. The transition between vector and host exposes them to a broad range of environmental conditions that induces a developmental program of gene expression, with translation regulation playing a key role. The Leishmania genome encodes six paralogs of the cap-binding protein eIF4E. All six isoforms show a relatively low degree of conservation with eIF4Es of other eukaryotes, as well as among themselves. This variability could suggest that they have been assigned discrete roles that could contribute to their survival under the changing environmental conditions. Here, we describe LeishIF4E-5, a LeishIF4E paralog. Despite the low sequence conservation observed between LeishIF4E-5 and other LeishIF4Es, the three aromatic residues in its cap-binding pocket are conserved, in accordance with its cap-binding activity. However, the cap-binding activity of LeishIF4E-5 is restricted to the promastigote life form and not observed in amastigotes. The overexpression of LeishIF4E-5 shows a decline in cell proliferation and an overall reduction in global translation. Immuno-cytochemical analysis shows that LeishIF4E-5 is localized in the cytoplasm, with a non-uniform distribution. Mass spectrometry analysis of proteins that co-purify with LeishIF4E-5 highlighted proteins involved in RNA metabolism, along with two LeishIF4G paralogs, LeishIF4G-1 and LeishIF4G-2. These vary in their conserved eIF4E binding motif, possibly suggesting that they can form different complexes.

This paper presents the goals of teacher-parent cooperation, various potential models for establishing mutual cooperation, and the conditions required to achieve quality interactive cooperation. The partnership model is highlighted as an optimal model of interactive cooperation between teachers and parents, as it includes the distribution of expertise and control with the purpose of ensuring optimal education for children. It enables the creation of an interactive working relationship in which all of those involved are respected and recognised in their efforts to achieve common goals. The second part presents the findings of an empirical study carried out on a representative sample of Slovene primary schools. Teachers (N = 467) and parents (N = 1,690) were asked to express their opinions about the need for mutual cooperation, their view of each other when fulfilling their respective roles, and where they perceive the main obstacles to mutual cooperation. It became evident that teachers and parents have doubts about each other’s competence. This does not form a solid base on which to establish and build the necessary partner relationship, and along with it mutual cooperation. Yet both groups to a large extent agree that teacher-parent cooperation is both necessary and useful. This gives rise to the question as to how to ensure that schools adopt policies promoting opportunities for better understanding, for building quality mutual relations and for parents to become more actively involved.

Background: Accurate bleeding risk stratification after percutaneous coronary intervention (PCI) is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of high bleeding risk patients. We derived and validated a novel bleeding risk score by augmenting the PRECISE-DAPT score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria., Methods: The derivation cohort comprised 29,188 patients undergoing PCI, of whom 1136 (3.9%) had a Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from four contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis (p<0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial and 5970 patients from the STOPDAPT-2 total cohort., Results: The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white-blood-cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in the MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in the STOPDAPT-2, with superior discrimination than the PRECISE-DAPT (cross-validation: Δ AUC, 0.01; p=0.02; MASTER DAPT: Δ AUC, 0.05; p=0.004; STOPDAPT-2: Δ AUC, 0.02; p=0.20) and other risk scores. In the derivation cohort, a cut-off of 23 points identified 11,414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white-blood-cell count, showed similar predictive ability., Conclusions: The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after PCI, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.

Atherosclerosis is initiated by injury or damage to the vascular endothelial cell monolayer. Therefore, the early repair of the damaged vascular endothelium by a proliferation of neighbouring endothelial cells is important to prevent atherosclerosis and thrombotic events. Arthrospira platensis (AP) has been used as a dietary supplement, mainly due to its high content of vitamins, minerals, amino acids, and pigments such as chlorophylls, carotenoids, and phycocyanin, ingredients with antioxidant, anti-inflammatory, and anti-thrombotic properties. Therefore, in this prospective, placebo-controlled, data-driven, sample-size-estimated in vitro study, we tested whether an aqueous extract of AP at different concentrations (50, 100, and 200 µg/mL) had an effect on the different cellular parameters of human umbilical vein endothelial cells. Therefore, cell impedance measurement and cell proliferation were measured to investigate the monolayer formation. In addition, cell viability, integrity, and metabolism were analysed to evaluate singular cellular functions, especially the antithrombotic state. Furthermore, cell-cell and cell-substrate interactions were observed. The highest proliferation was achieved after the addition of 100 µg/mL. This was consistently confirmed by two independent optical experiments in cell cultures 48 h and 85 h after seeding and additionally by an indirect test. At this concentration, the activation or dysfunction of HUVECs was completely prevented, as confirmed by prostacyclin and interleukin-6 levels. In conclusion, in this study, AP induced a significant increase in HUVEC proliferation without inducing an inflammatory response but altered the hemostasiological balance in favour of prostacyclin over thromboxane, thereby creating an antithrombotic state. Thus, APE could be applied in the future as an accelerator of endothelial cell proliferation after, e.g., stent placement or atherosclerosis.

Background: Investigations of very long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) according to clinical presentation are scarce. Here, we investigated the 10-year clinical outcomes of patients undergoing DES-PCI according to clinical presentation., Methods: Patient-level data from five randomized trials with 10-year follow-up after DES-PCI were pooled. Patients were dichotomized into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) groups as per clinical presentation. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST) and repeat revascularization involving the target lesion (TLR), target vessel (TVR) or non-target vessel (nTVR)., Results: Of the 9700 patients included in this analysis, 4557 presented with ACS and 5143 with CCS. Compared with CCS patients, ACS patients had a higher risk of all-cause death and nTVR in the first year, but comparable risk thereafter. In addition, ACS patients had a higher risk of MI [adjusted hazard ratio 1.21, 95% confidence interval (1.04-1.41)] and definite ST [adjusted hazard ratio 1.48, 95% confidence interval (1.14-1.92)], while the risk of TLR and TVR was not significantly different up to 10-year follow-up., Conclusions: Compared to CCS patients, ACS patients treated with PCI and DES implantation have an increased risk of all-cause death and repeat revascularization of remote vessels up to 1 year, with no significant differences thereafter and up to 10-year follow-up. ACS patients have a consistently higher risk of MI and definite ST. Whether these differences persist with current antithrombotic and secondary prevention therapies requires further investigation., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Among patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCT ischemia ) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCT ischemia among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion., Methods: AI-QCT ischemia was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream 15 O-H 2 O-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCT ischemia . Absolute stress myocardial blood flow ≤2.3 ​ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4-8.3] years., Results: 662 of 768 (86%) patients had conclusive AI-QCT ischemia result. In patients with normal 15 O-H 2 O-PET perfusion, an abnormal AI-QCT ischemia result (n ​= ​147/331) vs. normal AI-QCT ischemia result (n ​= ​184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17-5.21, p ​= ​0.018). This did not pertain to patients with abnormal 15 O-H 2 O-PET perfusion (abnormal AI-QCT ischemia result (n ​= ​269/331) vs. normal AI-QCT ischemia result (n ​= ​62/331); adjusted HR 1.09, 95% CI 0.58-2.02, p ​= ​0.794) (p-interaction ​= ​0.039)., Conclusion: Among patients with obstructive CAD on coronary CTA referred for downstream 15 O-H 2 O-PET perfusion imaging, AI-QCT ischemia showed incremental prognostic value among patients with preserved perfusion by 15 O-H 2 O-PET imaging, but not among those with reduced perfusion., Competing Interests: Declaration of competing interest Dr. Bär received research grants to the institution from Medis Medical Imaging Systems, Bangerter-Rhyner Stiftung (Basel, Switzerland) and Abbott, outside the submitted work. Dr. Saraste received consultancy fees from Astra Zeneca and Pfizer, and speaker fees from Abbott, Astra Zeneca, Janssen, Novartis and Pfizer. Dr. Bax received speaker fees from Abbott. Drs Earls and Min are employees of and hold equity in Cleerly Inc. Dr. Knuuti received consultancy fees from GE Healthcare and Synektik and speaker fees from Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer and Siemens, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)