Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis.

In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolin-induced swelling and studied the correlation with in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and change in sweat chloride concentration. Receiver operating characteristic curves indicated good-to-excellent accuracy of the organoid-based test for defining clinical responses. This study indicates that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients and suggests that biobanked stem cell resources can be used to tailor individual treatments in a cost-effective and patient-friendly manner.

Interventions Guiding Advance Care Planning Conversations: A Systematic Review.

BACKGROUND: Advance care planning (ACP) is a communicative process of defining preferences for future medical care. Conversation guides support professionals to conduct ACP conversations, yet insight into essential components is limited. OBJECTIVES: To evaluate the content, rationale, and empirical evidence on the effect of ACP interventions based on conversation guides. METHODS: MEDLINE, Embase, PsycINFO, and CINAHL were searched from January 1, 1998, to February 23, 2018, to identify peer-reviewed articles describing or evaluating ACP interventions based on scripted conversation guides. A thematic analysis of the guides was performed. Data on intervention characteristics, underlying rationale, and empirical evidence were extracted by 2 authors independently using a predesigned form. Assessment of risk of bias and quality of reporting was performed using Cochrane tools and COREQ, respectively. RESULTS: Eighty-two articles reporting on 34 unique interventions met the inclusion criteria. Analysis of the conversation guides revealed a framework for ACP conversations consisting of 4 phases: preparation, initiation, exploration, and action. Exploration of patient's perspectives on illness, living well, end-of-life (EOL) issues, and decision making formed the core part of the guides. Their design was often expert-based, without an underlying theoretical background. Empirical evidence on the effect of the interventions was based on heterogeneous outcome measures. Dyad congruence and preference documentation rates increased among intervention subjects in most studies. The studies showed varying effects on knowledge of ACP, decisional conflict, quality of communication, and preferences-concordant care. Qualitative research showed that participants appreciate the importance and benefits of ACP conversations, yet perceive them as difficult and emotional. CONCLUSION: ACP conversation guides address a diversity of themes regarding illness, EOL issues, and decision making. There is a focus on the exploration of patient's perspectives and preferences. Evidence on the translation of explorative information into specific treatment preferences and consequences for care as provided is limited.

Young patients with cystic fibrosis demonstrate subtle alterations of the cardiovascular system.

BACKGROUND: As life expectancy increases in patients with cystic fibrosis, it is important to pay attention to extra-pulmonary comorbidities. Several studies have shown signs of myocardial dysfunction in adult patients, but little is known about onset and development of these changes over time. In this prospective study, cardiac function in children with cystic fibrosis was compared to that of healthy children. METHODS: 33 children, aged 3-12years, with cystic fibrosis were recruited from the Wilhelmina Children's hospital and 33 age-matched healthy children were selected from the WHISTLER study, a population-based cohort study. Measurements of lung function, arterial stiffness, and echocardiography (conventional measures and myocardial deformation imaging) were performed. RESULTS: There were no differences in anthropometrics, lung function and blood pressure between the two groups. The cystic fibrosis children had a higher arterial stiffness compared to the healthy children (pulse wave velocity respectively 5.76±0.57m/s versus 5.43±0.61m/s, p-value 0.049). Using conventional echocardiographic parameters for right ventricular function, Tricuspid Annular Plane Systolic Excursion) and Tissue Doppler Imaging, cystic fibrosis children had a reduced right ventricular systolic function when compared to the healthy children. After adjustment for lung function, global strains of both right and left ventricles were significantly lower in the cystic fibrosis group than in healthy children (linear regression coefficient 1.45% left ventricle, p-value 0.022 and 4.42% right ventricle, p-value <0.01). Systolic strain rate of basal segment of the left ventricle, the mid segment of the right ventricle and the apical septum were significantly lower in the cystic fibrosis children than in healthy controls. CONCLUSION: Our study suggests that already at a very young age, children with cystic fibrosis show an increased arterial stiffness and some signs of diminished both right and left ventricular function.

Feasibility and characteristics of arterial stiffness measurement in preschool children.

Background Arterial stiffness is an important predictor of cardiovascular risk in adult life. Increased arterial stiffness can also be present in children and may be associated with several other cardiovascular risk factors. Until now, however, we know little about measuring arterial stiffness in preschool children. In this study, we assessed the feasibility of measuring arterial stiffness in preschool children and explored possible determinants related to arterial stiffness at this age. Methods We studied 168 healthy children, aged 3.3-4.1 years, who were recruited from a prospective birth cohort. We measured arterial stiffness, expressed in aortic pulse wave velocity and augmentation index, using a non-invasive oscillometric device (Arteriograph). We measured anthropometry and recorded other determinants using a questionnaire. Results In 100 children (59.5%) at least one valid arterial stiffness measurement was obtained. Of these infants, 89 had at least two valid measurements and 73 infants had at least three valid measurements. The mean aortic pulse wave velocity was 5.56 m/s (SD 0.77), and the mean augmentation index of the aorta was 19.7 m/s (SD 7.0). The augmentation index was significantly inversely associated with body height, with a regression coefficient of -0.78 (m/s)/cm (95% confidence interval -1.13 to -0.42). The augmentation index was not significantly associated with age, sex or (birth) weight. Conclusion The feasibility of measuring arterial stiffness in preschool children using the Arteriograph is moderate. We identified height as the most important determinant of the augmentation index in preschool children.