Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Interactions between coronary stenoses and microcirculation

“Coronary stenosis. Imaging, structure and physiology” has been designed as a clinically and research orientated reference for all cardiologists, physicians, cardiovascular imagers, trainees and investigators working in the field of ischemic heart disease. In the scenario of facilitated access to the coronary arteries provided by new diagnostic techniques, this book comes to fill an empty space in the medical literature: a textbook providing a comprehensive, multifaceted analysis of atherosclerotic and non-atherosclerotic coronary stenoses, addressing multiple issues that are of key importance in invasive and non-invasive diagnostic studies of the coronary vessels. Emphasis has been placed in integrating three separate aspects: imaging, structure and physiology. The chapters are written by top experts in invasive and non-invasive diagnostics, coronary anatomy, pathology and physiology, encouraged by the editors to adress each topic from a plural perspective to facilitate knowledge sharing between their respective disciplines. An associated website provides access to the electronic edition of the book, which includes moving images and updated material. This book is an indispensable companion for all those involved in the diagnosis and treatment of ischemic heart disease

Myocardial ischemia as a multifactorial: Disease: What is new?

Strategies for ischemic heart disease (IHD) focus almost exclusively on coronary atherosclerosis because access to interventional procedures is easy and gives gratifying angiographic results. This assumes that coronary artery disease and IHD are functionally identical. Recent reports, however, challenge the "plaque-centric" hypothesis of IHD. Alternative mechanisms, including coronary microvascular dysfunction, endothelial dysfunction, platelet dysfunction, coronary vasospasm, and inflammation, can precipitate myocardial ischemia (MI) in man. So, to assume that stenosis removal is a consistent cure for IHD is unwise, as is discounting MI because an angiogram appears "normal" after percutaneous coronary intervention or assuming MI is present because an atherosclerotic plaque is visible on angiography. © 2011 LLS SAS. All rights reserved

Integrated quadruple stress echocardiography

Stress echocardiography (SE) is an established diagnostic technique. For 40 years, the cornerstone of the technique has been the detection of regional wall motion abnormalities (RWMA), due to the underlying physiologically-relevant epicardial coronary artery stenosis. In the last decade, three new parameters (more objective than RWMA) have shown the potential to integrate and complement RWMA: 1) B-lines, also known as ultrasound lung comets, as a marker of extravascular lung water, measured using lung ultrasound with the 4-site simplified scan symmetrically of the antero-lateral thorax on the third intercostal space, from mid-axillary to anterior axillary and mid-clavicular line; 2) left ventricular contractile reserve (LV CR), assessed as the peak stress/rest ratio of left ventricular force, also known as elastance (systolic arterial pressure by cuff sphygmomanometer/end-systolic volume from 2D echocardiography); 3) coronary flow velocity reserve (CFVR) on left anterior descending coronary artery, calculated as peak stress/rest ratio of diastolic peak flow velocity assessed using pulsed-wave Doppler. The 4 parameters (RWMA, B-lines, LVCR and CFVR) now converge conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)-SE. IQ-SE optimizes the versatility of SE to include in a one-stop shop the core "ABCD" (asynergy+B-lines+contractile reserve+Doppler flowmetry) protocol. It allows a synoptic assessment of parameters mirroring the epicardial artery stenosis (RWMA), interstitial lung water (B-lines), myocardial function (LV CR) and small coronary vessels (CFVR). Each variable has a clear clinical correlate, different and complementary to all others: RWMA identify an ischemic vs. non-ischemic heart; B-lines a wet vs. dry lung; LV CR a strong vs. weak heart; CFVR a warm vs. cold heart. IQ-SE is highly feasible, with minimal increase in the imaging and analysis time, and obvious diagnostic and prognostic impact also beyond coronary artery disease - especially in heart failure. Large scale effectiveness studies with IQ-SE are now under way with the Stress Echo 2020 Study, and will provide the necessary evidence base prior to large scale acceptance of the technique

Effect of fatty acids on human bone marrow mesenchymal stem cell energy metabolism and survival.

Successful stem cell therapy requires the optimal proliferation, engraftment, and differentiation of stem cells into the desired cell lineage of tissues. However, stem cell therapy clinical trials to date have had limited success, suggesting that a better understanding of stem cell biology is needed. This includes a better understanding of stem cell energy metabolism because of the importance of energy metabolism in stem cell proliferation and differentiation. We report here the first direct evidence that human bone marrow mesenchymal stem cell (BMMSC) energy metabolism is highly glycolytic with low rates of mitochondrial oxidative metabolism. The contribution of glycolysis to ATP production is greater than 97% in undifferentiated BMMSCs, while glucose and fatty acid oxidation combined only contribute 3% of ATP production. We also assessed the effect of physiological levels of fatty acids on human BMMSC survival and energy metabolism. We found that the saturated fatty acid palmitate induces BMMSC apoptosis and decreases proliferation, an effect prevented by the unsaturated fatty acid oleate. Interestingly, chronic exposure of human BMMSCs to physiological levels of palmitate (for 24 hr) reduces palmitate oxidation rates. This decrease in palmitate oxidation is prevented by chronic exposure of the BMMSCs to oleate. These results suggest that reducing saturated fatty acid oxidation can decrease human BMMSC proliferation and cause cell death. These results also suggest that saturated fatty acids may be involved in the long-term impairment of BMMSC survival in vivo

OBSTRUCTIVE CORONARY ATHEROSCLEROSIS AND ISCHEMIC HEART DISEASE: AN ELUSIVE LINK!

Согласно современной патофизиологической модели хронической ишемической болезни сердца (ИБС), ишемия миокарда и стенокардия напряжения возникают в результате наличия атеросклеротической бляшки в коронарной артерии, в связи с чем клиническое лечение ИБС сосредоточено на выявлении и устранении стеноза. Хотя данный подход применяется на практике уже много лет , некоторые факты, включая недостаточное влияние этого подхода на прогноз, свидетельствуют о том, что такая прямая связь может представлять собой слишком упрощенный взгляд на ИБС. В частности, в многочисленных исследованиях было показано, что ИБС может быть как при наличии, так и в отсутствии коронарной болезни сердца, и что атеросклероз — всего лишь один из элементов в комплексном многофакторном патофизиологическом процессе, включающем также воспаление, нарушение микроциркуляции, эндотелиальную дисфункцию, тромбоз и ангиогенез. Более того, высокая частота рецидивов выделяет тот факт , что у пациентов со стабильной ИБС устранение стеноза не оказывает воздействия на лежащие в основе патологические механизмы, что ведет к прогрессированию других поражений. Предлагаемая в этом обзоре модель смещает фокус с обструктивного атеросклероза коронарных артерий на клетки миокарда, где, собственно, и возникает ишемия. Если клетку миокарда расположить в центре этой модели, появляется возможность учесть все возможные потенциальные патологические факторы и, как следствие, разработать стратегии для защиты кардиомиоцитов от ишемического повреждения, независимо от причинного механизма.</p