Effect of comorbidity and multimorbidity on adherence to follow-up recommendations among long-term breast cancer survivors.

OBJECTIVES: To study the impact of comorbidities, multimorbidity, and multimorbidity clusters on adherence to recommended follow-up guidelines among long-term breast cancer survivors. STUDY DESIGN: Retrospective cohort study based on 2078 women diagnosed with breast cancer from 2000 to 2006 and followed up from 2012 to 2016. MAIN OUTCOME MEASURES: Adherence to breast cancer follow-up recommendations (annual medical visit and imaging) was determined. Comorbidities were classified as acute/chronic. Multimorbidity was defined as the presence of two or more chronic comorbidities aside from breast cancer. Five multimorbidity clusters were considered. Multivariate logistic regression models were fitted to determine the relationship between adherence to recommendations and the presence of comorbidities and multimorbidity, considering both sociodemographic and clinical characteristics. RESULTS: Overall adherence to recommendations was 79.5 %. Adherence was lower among long-term breast cancer survivors with no comorbidities (75.8 %). Among multimorbidity clusters, adherence was highest in the anxiety and fractures cluster (84.3 %) and was lowest in the musculoskeletal and cardiovascular cluster (76.4 %). In adjusted multivariate models, multimorbidity was associated with higher levels of adherence (OR = 1.52 95 %CI 1.16-1.99), and adherence was highest in the metabolic and degenerative cluster (OR = 2.2 95 %CI 1.4-3.5). CONCLUSION: Adherence to follow-up recommendations was higher among long-term breast cancer survivors with multimorbidity than among those without. Adherence also differed by multimorbidity cluster. These results suggest suboptimal adherence to the current follow-up recommendations in certain groups, suggesting the need to adapt clinical practice guidelines to reflect patients' comorbidities and different characteristics.

Adherence of long-term breast cancer survivors to follow-up care guidelines: a study based on real-world data from the SURBCAN cohort.

PURPOSE: To identify adherence to follow-up recommendations in long-term breast cancer survivors (LTBCS) of the SURBCAN cohort and to identify its determinants, using real-world data. METHODS: We conducted a retrospective study using electronic health records from 2012 to 2016 of women diagnosed with incident breast cancer in Spain between 2000 and 2006 and surviving at least 5 years. Adherence to basic follow-up recommendations, adherence according to risk of recurrence, and overall adherence were calculated based on attendance at medical appointments and imaging surveillance, by year of survivorship. Logistic regression models were fitted to depict the association between adherence and its determinants. RESULTS: A total of 2079 LTBCS were followed up for a median of 4.97 years. Of them, 23.6% had survived ≥ 10 years at baseline. We estimated that 79.5% of LTBCS were overall adherent to at least one visit and one imaging test. Adherence to recommendations decreased over time and no differences were found according to recurrence risk. Determinants of better overall adherence were diagnosis in middle age (50-69 years old), living in a more-deprived area, having fewer years of survival, receiving primary treatment, and being alive at the end of follow-up. CONCLUSION: We identified women apparently not complying with surveillance visits and tests. Special attention should be paid to the youngest and eldest women at diagnosis and to those with longer survival.

Use of health services among long-term breast cancer survivors in Spain: longitudinal study based on real-world data.

PURPOSE: This study aimed to evaluate health service utilization in Spain among long-term breast cancer survivors and to compare it with that among women with no history of breast cancer. METHODS: Study based on the SURBCAN cohort includes a sample of long-term breast cancer survivors and a sample of women without breast cancer from 5 Spanish regions. Healthcare utilization was assessed through primary care, hospital visits, and tests during the follow-up period (2012 to 2016) by using electronic health records. Annual contact rates to healthcare services were calculated, and crude and multivariate count models were fitted to estimate the adjusted relative risk of healthcare services use. RESULTS: Data were obtained from 19,328 women, including 6512 long-term breast cancer survivors. Healthcare use was higher among breast cancer survivors (20.9 vs 16.6; p < 0.0001) and decreased from >10 years of survival. Breast cancer survivors who underwent a mastectomy were more likely to have a primary care visit (RR = 3.10 95% CI 3.08-3.11). Five to ten years survivors were more likely to have hospital inpatient visits and imaging test compared to women without breast cancer (RRa = 1.35 95% CI 1.30-1.39 and RRa = 1.27 95% CI 1.25-1.29 respectively). CONCLUSION: This study shows higher use of health services in long-term breast cancer survivors than in women without breast cancer regardless of survival time. IMPLICATIONS FOR CANCER SURVIVORS: These results help to estimate the health resources needed for the growing group of breast cancer survivors and to identify risk factors that drive higher use of health services.

Development of Chocolates with Improved Lipid Profile by Replacing Cocoa Butter with an Oleogel.

The reformulation of chocolates seeks to find innovative alternatives to cocoa butter (CB) that are more economical and adhere to nutritional recommendations to replace saturated fats with unsaturated ones. In this research, chocolates were elaborated by substituting CB with an oleogel (OG) formulated with hydroxypropyl methylcellulose (HPMC) as an entrapper of sunflower oil by using the foam-templated approach. Four different CB/OG blends were prepared and characterized as potential CB substitutes (100/0 control), at replacement levels of 30%, 50%, 70% and 100% (70/30, 50/50, 30/70 and 0/100 blends), and subsequently, CB/OG-based chocolates (CB/OG-Ch) were formulated (100/0-Ch, 70/30-Ch, 50/50-Ch, 30/70-Ch and 0/100-Ch). Both the CB/OG blends and the CB/OG-Ch counterparts were characterized by dynamic and stationary rheology, hardness, thermal parameters, microstructure, and oil-binding capacity; in addition, the lipid profile of the chocolates was analyzed, and a sensory analysis was performed. Increasing the OG proportion in the CB/OG blend weakens the rigidity and strength of the fat-crystal network conferred by the CB, and decreases both its viscoelasticity and thermal parameters, but the differences between all the different properties and parameters of the CB/OG-Ch samples diminished in presence of the other ingredients used in the chocolate formulation. Sensory analysis evidenced that it is possible to replace up to 70% of CB with the OG, although from a technological point of view a replacement level of 50% would seem more appropriate. As compared to 100/0-Ch, 50/50-Ch and 30/70-Ch involve saturated fat reductions of 55% and 37%, respectively.

Thermorheological Characterization of Healthier Reduced-Fat Cocoa Butter Formulated by Substitution with a Hydroxypropyl Methylcellulose (HPMC)-Based Oleogel.

Cocoa butter (CB) is a main ingredient in pastry due to the unique functional properties of its fat, which is high in saturated fatty acids (SFAs). However, excessive consumption of SFAs is associated with the occurrence of several chronic diseases. This study researched the partial or total replacement of CB by an oleogel (OG) formulated with a healthier lipid profile, for mixed systems that would allow a partial substitution of CB in confectionery products. The "emulsion-templated approach" was used to develop a sunflower oil-HPMC-based OG. Different CB:OG ratios were formulated increasing the percentage replacement of CB by OG from 50 to 100%. Rheological and textural properties were determined and compared with a CB control at 20 and 10 °C. Oil-binding capacity was also analyzed. The systems showed a solid-like behavior, with higher elastic than viscous modulus, which increased with CB concentration. Compared with 20 °C, at 10 °C there was an increase in connectivity, viscoelasticity, and consistency of the systems, in response to a more complete CB crystallization. The replaced systems also presented a better lipid profile than CB. This evidence suggests that formulated CB:OG system at 50:50 ratio could become useful as a CB equivalent in chocolate products.

Development of Structured Sunflower Oil Systems for Decreasing Trans and Saturated Fatty Acid Content in Bakery Creams.

In this work, the design of low moisture (10%) oil/water emulsions based on sunflower oil were investigated, as well as their application in a bakery cream as a conventional fat replacer. The emulsions were dehydrated to reach 10% moisture content, achieving highly concentrated vegetable oil gel emulsions of different consistencies and qualities. Physical properties of the dried emulsions were evaluated by texture, microstructure, and oil loss determination. The reformulated bakery creams with the dried emulsions obtained from 47% oil showed better spreadability, viscosity, and viscoelasticity properties. A shortening replacement with the dried emulsion obtained from 70% initial oil caused a negative impact on the creams' consistency, with lower viscosity and lower hysteresis area, revealing a weakness of structure. This research provided new knowledge about the structuration of vegetable oils through concentrated emulsions and their application as a source of healthy fat in creams for bakery applications.

Maximizing the oil content in polysaccharide-based emulsion gels for the development of tissue mimicking phantoms.

Formulations based on agar and κ-carrageenan were investigated for the production of emulsion gels applicable as tissue mimicking phantoms. The effects of the polysaccharide matrix, the oil content and the presence of surfactants on the micro-/nanostructure, rheology, and mechanical and dielectric properties were investigated. Results showed a high capacity of the agar to stabilize oil droplets, producing gels with smaller (10-21 µm) and more uniform oil droplets. The addition of surfactants allowed increasing the oil content and reduced the gel strength and stiffness down to 57 % and 34 %, respectively. The permittivity and conductivity of the gels were reduced by increasing the oil content, especially in the agar gels (18.8 and 0.05 S/m, respectively), producing materials with dielectric properties similar to those of low-water content tissues. These results evidence the suitability of these polysaccharides to design a variety of tissue mimicking phantoms with a broad range of mechanical and dielectric properties.

Use of Milk Fat/Cellulose Ether Emulsions in Spreadable Creams and the Effect of In Vitro Digestion on Texture and Fat Digestibility.

This study investigated the texture properties and fat digestibility of new spreadable chocolate creams formulated with an emulsion composed of milk fat and a cellulose ether as a fat source. The spreadability was analysed at 20 °C and compared with a commercial spreadable cream formulated with palm fat. Structural changes in the creams after the in vitro oral and gastric digestion stages were evaluated; lipid digestibility was determined by titration with NaOH during intestinal digestion. Spreadability tests showed the spreads were similar. After oral digestion, the commercial spread showed an increase in extrusion force because of flocculation induced by saliva, an effect not observed in spreads with cellulose ether. Digestibility determination showed lower values for the reformulated spreads. Therefore, milk fat-cellulose ether based emulsions offer an alternative to achieve reformulated spreadable creams, with physical properties similar to those of commercial products but providing reduced fat content and lower lipid digestibility, without compromising the quality of the final product.

Oil-in-water emulsions stabilised by cellulose ethers: stability, structure and in vitro digestion.

The effect of cellulose ethers in oil-in-water emulsions on stability during storage and on texture, microstructure and lipid digestibility during in vitro gastrointestinal digestion was investigated. All the cellulose ether emulsions showed good physical and oxidative stability during storage. In particular, the methylcellulose with high methoxyl substituents (HMC) made it possible to obtain emulsions with high consistency which remained almost unchanged during gastric digestion, and thus could enhance fullness and satiety perceptions at gastric level. Moreover, the HMC emulsion slowed down lipid digestion to a greater extent than a conventional protein emulsion or the emulsions stabilised by the other cellulose ethers. Therefore, HMC emulsions could be used in weight management to increase satiation capacity and decrease lipid digestion.

A case report of a round cystic tumor in the left ventricular outflow tract.

We report a case of a patient who was admitted to our hospital complaining of angina pectoris. On auscultation, a systolic ejection murmur was heard at the right upper sternal border. Transthoracic echocardiography displayed regional wall motion abnormalities and detected a mobile mass in the left ventricular outflow tract, causing mild obstruction during systole. The mass appeared as an unilocular cystic tumor. Coronary angiography showed a significant lesion in the left anterior descending artery. Surgical treatment was indicated for coronary artery disease and for the unpredictable behaviour of the neoplasm. The mass was identified as arising from the top of the anterior papillary muscle. Histopathological examination revealed that the tumor was a cavernous hemangioma. Cardiac hemangiomas are rare, benign vascular tumors of the heart. This is an unusual case of left ventricular hemangioma incidentally discovered, which raised an interesting differential diagnosis.

Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury.

AIMS: Currently available non-invasive imaging methods frequently fail to detect alterations in left ventricular (LV) function despite histological evidence of injury. Tissue Doppler imaging (TDI) can detect subtle LV dysfunction. The aim of this study was to investigate whether TDI indices can predict LV systolic dysfunction and mortality following exposure to doxorubicin (DOX) in mice. METHODS AND RESULTS: TDI-derived peak endocardial systolic velocity (V(ENDO)) and strain rate (SR), as well as M-mode and two-dimensional indices of LV systolic function, were measured serially in mice after receiving DOX as a single dose (20 mg/kg). Haemodynamic measurements were obtained invasively before and at 1, 2, 4, and 5 days after the single DOX dose. Cardiac apoptosis was measured before and at 1 day after DOX. V(ENDO) and SR decreased after 1 and 2 days, respectively, whereas changes in fractional shortening (FS) and LV ejection fraction (LVEF) were not detected before 5 days. The reduction in both V(ENDO) and SR correlated with the decrease in dP/dt(MAX), and the change in V(ENDO) correlated with the early increase in cardiac cell apoptosis. In a subsequent experiment, DOX was administered at 4 mg/kg/week for 5 weeks, and LV function was followed serially for 16 weeks. In this chronic experiment, TDI indices decreased before FS and LVEF, correlated with late LV dysfunction, and predicted DOX-induced mortality. CONCLUSION: In a murine model of DOX-induced cardiac injury, TDI detects LV dysfunction prior to alterations in conventional echocardiographic indices and predicts mortality. This study suggests that TDI may be a reliable tool to detect early subtle changes in DOX-induced cardiac dysfunction.

Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling.

The glycoprotein VI (GPVI)-Fc receptor (FcR) gamma-chain complex, a key activatory receptor for collagen on platelet surface membranes, is constitutively associated with the Src family kinases Fyn and Lyn. Molecular cloning of GPVI has revealed the presence of a proline-rich domain in the sequence of GPVI cytoplasmic tail which has the consensus for interaction with the Src homology 3 (SH3) domains of Fyn and Lyn. A series of in vitro experiments demonstrated the ability of the SH3 domains of both Src kinases to bind the proline-rich domain of GPVI. Furthermore, depletion of the proline-rich domain in GPVI (Pro(-)-GPVI) prevented binding of Fyn and Lyn and markedly reduced phosphorylation of FcR gamma-chain in transiently transfected COS-7 cells, but did not affect the association of the gamma-chain with GPVI. Jurkat cells stably transfected with wild type GPVI show robust increases in tyrosine phosphorylation and intracellular Ca2+ in response to the snake venom convulxin that targets GPVI. Importantly, convulxin is not able to activate cells transfected with Pro(-)-GPVI, even though the association with the immunoreceptor tyrosine-based activation motif-containing chains is maintained. These findings demonstrate that the proline-rich domain of GPVI mediates the association with Fyn/Lyn via their SH3 domain and that this interaction initiates activation signals through GPVI.