Association of anthropometric variables with therapy-induced cardiotoxicity in women with breast cancer: a pilot study for a randomized clinical trial.

BACKGROUND: Doxorubicin (DOX) has been widely used in the treatment of breast cancer, but it is directly associated with late-onset cardiovascular disease (CVD). Whether anthropometric, food intake or other risk factors together with DOX-based chemotherapy can increase the risk of developing cardiotoxicity remains uncertain. We examined the association between anthropometric variables with doxorubicin-induced cardiotoxicity in women with breast cancer. METHODS: Twenty-six women (53.7 ± 9.6 y) undergoing DOX-based chemotherapy (408.3 ± 66.7 mg/m2) participated in the study. We collected data on body composition (bioimpedance), dietary intake (24 h) and cardiac function (echocardiographic assessment of left ventricular ejection fraction, LVEF). All measurements were taken at baseline, one month of treatment completion and one-year follow-up after start of treatment. DOX-induced cardiotoxicity was defined as ≥ 10% absolute decrease in LVEF. Thus, the participants were then grouped as DOX-induced (DIC) or non-DOX-induced (non-DIC) cardiotoxicity. Data are shown as mean ± SD (standard deviation). We performed comparisons between the two groups using Student's t-test for independent samples or Generalized Estimating Equations (groups + 3 evaluation time points) with Bonferroni post-hoc test. Lastly, the correlations were analyzed using Pearson correlation; p < 0.05 for all tests. RESULTS: At baseline the participants' body mass index (BMI) was 29.9 ± 7.9 kg/m2 and LVEF was 67.4 ± 6.2%. Seven of them (26.9%) developed therapy-induced cardiotoxicity (ΔLVEF - 3.2 ± 2.6%; p < 0.001). Postmenopausal status and family history of CVD were more prevalent in the DIC group than non-DIC group. We found no consistent BMI changes in the groups over time. Interestingly, the non-DIC group showed a small increase in visceral fat at treatment completion and increased waist circumference at one-year follow-up compared to baseline. These same changes were not seen in the DIC group. We also observed a pattern of correlation of some anthropometric variables with LVEF: the more unfavorable the body composition the more pronounced the LVEF decrease at one-year follow-up, though not associated with cardiotoxicity. CONCLUSIONS: Our study did not provide sufficient evidence to support that anthropometric variables, food intake or other risk factors increase the risk of developing cardiotoxicity. However, there are apparent trends that need to be further investigated in larger samples.

Prospective cohort study of children exposed to hepatitis C virus through a pregnancy screening program.

OBJECTIVES: Porto Alegre, in south Brazil, has one of the highest hepatitis C virus (HCV) infection rates in the country (84.4 cases/100 000 in 2018). Prenatal screening of HCV, however, has not been routinely offered. METHODS: A longitudinal study of pregnant women with HCV and their infants was conducted between January 2014 and December 2018. Screening for HCV antibodies was offered to all women delivering at the study tertiary institution. HCV RT-PCR was performed if the woman was seropositive. Infants were followed prospectively. RESULTS: Among 18 953 pregnant women delivering infants during the study period, 17 810 were screened for HCV antibodies (93.9%) with 130 positive results (HCV seroprevalence 0.7%). HCV-RNA was detectable in 57/117 cases (48.7%). HCV viremia was associated with the use of injectable drugs (P = 0.03), inhaled/crack drug use (P = 0.02), having an HCV-seropositive partner, and ≥3 lifetime sexual partners (P < 0.01). Genotype 1 was most prevalent (68%) during pregnancy. Among 43 children with follow-up, six (13%) were HCV-infected (transmission rate 13.9%); 50% were infected with genotype 3. Two infants (33%) cleared their infection; the mothers had genetic polymorphisms associated with clearance. CONCLUSION: HCV vertical transmission was high in the study population, with HCV infection during pregnancy being vastly underdiagnosed. Public health efforts must focus on this vulnerable population for disease prevention and early treatment.

Are Liver Pericytes Just Precursors of Myofibroblasts in Hepatic Diseases? Insights from the Crosstalk between Perivascular and Inflammatory Cells in Liver Injury and Repair.

Cirrhosis, a late form of liver disease, is characterized by extensive scarring due to exacerbated secretion of extracellular matrix proteins by myofibroblasts that develop during this process. These myofibroblasts arise mainly from hepatic stellate cells (HSCs), liver-specific pericytes that become activated at the onset of liver injury. Consequently, HSCs tend to be viewed mainly as myofibroblast precursors in a fibrotic process driven by inflammation. Here, the molecular interactions between liver pericytes and inflammatory cells such as macrophages and neutrophils at the first moments after injury and during the healing process are brought into focus. Data on HSCs and pericytes from other tissues indicate that these cells are able to sense pathogen- and damage-associated molecular patterns and have an important proinflammatory role in the initial stages of liver injury. On the other hand, further data suggest that as the healing process evolves, activated HSCs play a role in skewing the initial proinflammatory (M1) macrophage polarization by contributing to the emergence of alternatively activated, pro-regenerative (M2-like) macrophages. Finally, data suggesting that some HSCs activated during liver injury could behave as hepatic progenitor or stem cells will be discussed.