Acquired αSMA Expression in Pericytes Coincides with Aberrant Vascular Structure and Function in Pancreatic Ductal Adenocarcinoma.

The subpopulations of tumor pericytes undergo pathological phenotype switching, affecting their normal function in upholding structural stability and cross-communication with other cells. In the case of pancreatic ductal adenocarcinoma (PDAC), a significant portion of blood vessels are covered by an α-smooth muscle actin (αSMA)-expressing pericyte, which is normally absent from capillary pericytes. The DesminlowαSMAhigh phenotype was significantly correlated with intratumoral hypoxia and vascular leakiness. Using an in vitro co-culture system, we demonstrated that cancer cell-derived exosomes could induce ectopic αSMA expression in pericytes. Exosome-treated αSMA+ pericytes presented altered pericyte markers and an acquired immune-modulatory feature. αSMA+ pericytes were also linked to morphological and biomechanical changes in the pericyte. The PDAC exosome was sufficient to induce αSMA expression by normal pericytes of the healthy pancreas in vivo, and the vessels with αSMA+ pericytes were leaky. This study demonstrated that tumor pericyte heterogeneity could be dictated by cancer cells, and a subpopulation of these pericytes confers a pathological feature.

Real-world treatment patterns and clinical outcomes in patients with AML in Japan who were ineligible for first-line intensive chemotherapy.

Acute myeloid leukemia (AML) predominantly affects elderly adults, and its prognosis worsens with age. Treatment options for patients in Japan ineligible for intensive chemotherapy include cytarabine/aclarubicin ± granulocyte colony-stimulating factor (CA ± G), azacitidine (AZA), low-dose cytarabine (LDAC), targeted therapy, and best supportive care (BSC). The country's aging population and the evolving treatment landscape are contributing to a need to understand treatment pathways and associated outcomes. This retrospective chart review evaluated outcomes in patients across Japan with primary/secondary AML who were ineligible for intensive chemotherapy and began first-line treatment or BSC between 01/01/2015 and 12/31/2018. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and healthcare resource utilization (HRU). Of 199 patients (58% > 75 years), 121 received systemic therapy (38 CA ± G, 37 AZA, 7 LDAC, 39 other) and 78 received BSC. Median OS was 5.4, 9.2, 2.2, 3.8, and 2.2 months for CA ± G, AZA, LDAC, other systemic therapy, and BSC, respectively; median PFS was 3.4, 7.7, 1.6, 2.3, and 2.1 months, respectively. HRU rates were uniformly high, with > 80% patients hospitalized in each cohort. The poor clinical outcomes and high HRU among Japanese AML patients who are ineligible for intensive chemotherapy highlight an unmet need for novel therapies.

Real-world treatment patterns and clinical outcomes in patients with AML unfit for first-line intensive chemotherapy.

Acute myeloid leukemia (AML) predominantly affects the elderly, and prognosis declines with age. Induction chemotherapy plus consolidation therapy is standard of care for fit patients; options for unfit patients include hypomethylating agents (HMA), low-dose cytarabine (LDAC), targeted therapies, and best supportive care (BSC). This retrospective chart review evaluated clinical outcomes in unfit patients with AML who initiated first-line treatment or BSC 01/01/2015-12/31/2018. Overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), and response rates were assessed. Of 1762 patients, 1310 received systemic therapies: 809 HMA, 199 LDAC, and 302 other therapies; 452 received BSC. Median OS was 9.9, 7.9, 5.4, and 2.5 months for HMA, LDAC, other, and BSC, respectively. Median PFS was 7.5, 5.3, 4.1, and 2.1 months for HMA, LDAC, other, and BSC, respectively; median TTF was 4.9, 2.1, 2.2, and 2.1 months, respectively. Our findings highlight the unmet need for novel therapies for unfit patients.

Prehistoric baseline reveals substantial decline of oyster reef condition in a Gulf of Mexico conservation priority area.

The Gulf of Mexico (GoM) is home to the world's largest remaining wild oyster fisheries, but baseline surveys needed to assess habitat condition are recent and may represent an already-shifted reference state. Here, we use prehistoric oysters from archaeological middens to show that oyster size, an indicator of habitat function and population resilience, declined prior to the earliest assessments of reef condition in an area of the GoM previously considered pristine. Stable isotope sclerochronlogy reveals extirpation of colossal oysters occurred through truncated life history and slowed growth. More broadly, our study suggests that management strategies affected by shifting baselines may overestimate resilience and perpetuate practices that risk irreversible decline.

Características socioculturales y de salud asociadas a enfermedad coronaria en mujeres. Estudio caso-control / Socio-cultural and healthcare characteristics associated with coronary artery disease in women. A case-control study / Características socioculturais e de saúde associadas à doença coronariana em mulheres. Estudo caso-controle

Resumen Introducción Las enfermedades cardiovasculares se constituyen un problema de salud pública, dentro de este grupo, la enfermedad coronaria ha mostrado incrementos especialmente en la prevalencia para infarto agudo de miocardio en mujeres de 35-54 años. La organización mundial de la salud propone estudiar el problema desde las diferencias regionales para encontrar soluciones al asunto. Objetivo Analizar la asociación entre características socioculturales y de salud con la enfermedad coronaria en mujeres de Nariño. Materiales y Métodos: Estudio de casos (mujeres con enfermedad coronaria) y controles (mujeres sin enfermedad coronaria) atendidas en instituciones de referencia para el departamento de Nariño. La muestra estuvo conformada por 35 casos y 105 controles por muestreo no probabilístico. Resultados Características como: ser fumadora, hipertensa y vivir en el área urbana mostraron mayor asociación con la enfermedad coronaria: Odd ratios= 21,11; IC 95% 3,97-112,26 y Odd ratios= 9,47; IC 95% 2,87-31,23 respectivamente. Se destaca la proporción de mujeres con enfermedad coronaria que culturalmente se caracterizan por callar su enfermedad para no preocupar. Discusión Ser fumadora e hipertensa se constituyen en determinantes para desarrollar enfermedad coronaria, situaciones que pueden ser inducidas por situaciones familiares, sociales, culturales, ocupacionales que la mujer debe enfrentar. Conclusiones La mujer con enfermedad coronaria se caracterizó por ser fumadora, hipertensa y vivir en el área urbana, lo anterior muestra que es necesario generar estrategias específicas de prevención y control en la mujer.

Abstract Introduction Cardiovascular diseases are a public health problem. In this group, coronary artery disease has shown an increase, in particular, in the prevalence of acute myocardial infarction in 35-54-year-old women. The World Health Organization suggests studying this issue based on regional differences to find solutions. Objective To analyze socio-cultural and healthcare characteristics associated with coronary artery disease in women from Nariño. Materials and Methods: Case study (women with coronary artery disease) and controls (women without coronary artery disease) served in reference institutions of Nariño. The sample was made of 35 cases and 105 controls through non-probability sampling. Results Features such as being a smoker, hypertensive and living in an urban area showed greater association with coronary artery disease: Odd ratios= 21.11; CI 95% 3.97-112.26 and Odd ratios= 9.47; CI 95% 2.87-31.23, accordingly. A proportion of women with coronary artery disease stand out as culturally characterized by keeping their illness a secret not to worry others. Discussion Being a smoker and hypertensive are key factors to develop coronary heart disease; these situations can be induced by family, social, cultural and occupational issues faced by women. Conclusions Women with coronary artery disease were characterized as being smokers, hypertensive and living in an urban area; it is thus necessary to generate specific prevention and control strategies for women.

Resumo Introdução As doenças cardiovasculares são um problema de saúde pública e, dentro desse grupo, a doença coronariana tem apresentado um aumento, principalmente, na prevalência de infarto agudo do miocárdio em mulheres de 35 a 54 anos. A Organização Mundial da Saúde propõe estudar o problema a partir de diferenças regionais para encontrar soluções ao problema. Objetivo Analisar a associação entre características socioculturais e de saúde com doença coronariana em mulheres de Nariño. Materiais e Métodos: Estudo de casos (mulheres com doença coronariana) e controles (mulheres sem doença coronariana) tratadas em instituições de referência no departamento de Nariño. A amostra foi composta por 35 casos e 105 controles por amostragem não probabilística. Resultados Características como: ser fumante, hipertensa e moradora da área urbana apresentaram maior associação com a doença coronariana: razão de possibilidades = 21,11; IC95% 3,97-112,26 e razão de possibilidades = 9,47; IC 95% 2,87-31,23, respectivamente. Destaca-se o número de mulheres com doença coronariana que são culturalmente caracterizadas por silenciarem sua doença para não preocupar. Discussão Ser fumante e hipertensa são fatores determinantes para o desenvolvimento da doença coronariana, situações que podem ser induzidas por situações familiares, sociais, culturais, ocupacionais que a mulher deve enfrentar. Conclusões A mulher com doença coronariana se caracterizou por ser tabagista, hipertensa e por morar em uma área urbana, o exposto anteriormente demonstra que é necessário gerar estratégias específicas de prevenção e de controle nas mulheres.