Razvoj definicije i reinterpretacija kardiovaskularne toksičnosti

SUMMARY One of the guiding principles of cardio-oncology practice is to minimize the unnecessary interruption of antineoplastic therapy. The overall goal of the specialty is to ensure that cancer patients receive the best possible anticancer therapy safely, while minimizing cancer therapy-related cardiovascular toxicity (CTR-CVT) during oncology care. In this paper, we describe prior and current definitions of CTR-CVT and briefly present the landmark CARDIOTOX registry, as well as corresponding parts of the recently published, first cardio-oncology guideline of the European Society of Cardiology. In our paper, we aim to provide insight into the cardio-oncology-related aspects of precision medicine.SAŽETAK Jedno od vodećih načela kardioonkološke prakse jest minimiziranje nepotrebnog prekidanja antitumorskog liječenja. Glavni je cilj ove specijalizacije osigurati da bolesnici s karcinomom dobiju najbolju moguću terapiju na siguran način, a pri tome na najmanju moguću mjeru svesti kardiovaskularnu toksičnost povezanu s onkološkom terapijom (CTR-CVT) tijekom skrbi. U ovom su radu opisane prethodne i trenutačne definicije CTR-CVT-a i ukratko predočeni ključni CARDIOTOX registar te odgovarajući dijelovi nedavno objavljenih prvih kardioonkoloških smjernica Europskoga kardiološkog društva. U radu nastojimo dati uvid u aspekte precizne medicine povezane s kardioonkologijom

Effect of genetic and environmental influences on hepatic steatosis: A classical twin study based on computed tomography

Background and aims: Non-alcoholic fatty liver disease (NAFLD) increases cardiovascular morbidity and mortality, and carries poor long-term hepatic prognosis. Data about the role of genetic and environmental factors in the hepatic lipid accumulation are limited. The aim of the study was to evaluate the genetic and environmental impact on the hepatic lipid accumulation within a cohort of adult twin pairs. Patients and methods: We investigated 182 twin subjects [monozygotic (MZ, n 5 114) and dizygotic (DZ, n 5 68) same-gender twins (age 56.0 ± 9.6 years; BMI 27.5 ± 5.0 kg/m2 ; females 65.9%)] who underwent computed tomography (CT) with a 256-slice scanner. Using nonenhanced CT-images, we calculated the average value of hepatic attenuation [expressed in Hounsfield unit (HU)] suggesting hepatic lipid content. Crude data were adjusted to age, sex, BMI and HbA1c values. Intra-pair correlations were established, and structural equation models were used for quantifying the contribution of additive genetic (A), common environmental (C) and unique environmental (E) components to the investigated phenotype. Results: The study cohort represented a moderately overweight, middle-aged Caucasian population. There was no significant difference between MZ and DZ twin subjects regarding hepatic CT-attenuation (57.9 ± 12.6 HU and 59.3 ± 11.7 HU, respectively; p 5 0.747). Age, sex, BMI and HbA1c adjusted co-twin correlations between the siblings showed that MZ twins have stronger correlations of HU values than DZ twins (rMZ 5 0.592, p < 0.001; rDZ 5 0.047, p 5 0.690, respectively). Using the structural equation model, a moderate additive genetic dependence (A: 38%, 95% CI 15–58%) and a greater unique environmental influence (E: 62%, 95% CI 42–85%) was found. Common environmental influence was not identified (C: 0%). Conclusion: The results of our classical CT-based twin study revealed moderate genetic and greater environmental influences on the phenotypic appearance of hepatic steatosis, commonly referred to as NAFLD. Favorable changes of modifiable environmental factors are of great importance in preventing or treating NAFLD

Environmental Factors Slightly Outweigh Genetic Influences in the Development of Pancreatic Lipid Accumulation: A Classical Twin Study

Background: Several studies showed that lipid accumulation in the pancreas (NAFPD: nonalcoholic fatty pancreas disease) may lead to different pancreatic disorders, including beta-cell dysfunction. The role of genetic and environmental factors in pancreatic lipid accumulation is unclear. We evaluated the magnitude of genetic and environmental impact on pancreatic lipid content within a cohort of adult twin pairs. Patients and Methods: We investigated 136 twin subjects [monozygotic (MZ, n = 86) and dizygotic (DZ, n = 50) same-gender twins (age 57.7 ± 9.1 years; body mass index [BMI] 28.0 ± 4.4 kg/m2; females 64.7%)] with a 256-slice computed tomography (CT)-scanner. Using nonenhanced CT images, we calculated the average value of pancreatic attenuation expressed in Hounsfield unit (HU) suggesting pancreatic lipid content. Crude data were adjusted to age, sex, BMI, and hemoglobinA1c values. Intrapair correlations were established, and structural equation models were used for quantifying the contribution of additive genetic (A), common environmental (C), and unique environmental (E) components to the investigated phenotype. Results: The study cohort represented a moderately overweight, middle-aged Caucasian population. Average pancreatic attenuation was 48.9 ± 11.9 HU in MZ and 49.0 ± 13.0 HU in DZ twins (P = 0.934). The intrapair correlation between HU values was stronger in MZ compared to DZ twins (rMZ = 0.536, P < 0.001; rDZ = 0.115, P = 0.580). Using the structural equation model, a greater unique environmental influence [E: 54%, 95% confidence interval (CI) 19%–66%] and a moderate additive genetic dependence (A: 46%, 95% CI 34%–81%) were found. Conclusions: The results of our classical twin study indicate that environmental (lifestyle) influences slightly outweigh genetic effects on the phenotypic appearance of pancreatic lipid accumulation known as NAFPD