Mesenchymal stem cells-derived vascular smooth muscle cells release abundant levels of osteoprotegerin

Although several studies have shown that the serum levels of osteoprotegerin (OPG) are significantly elevated in patients affected with atherosclerotic lesions in coronary and peripheral arteries, the cellular source and the role of OPG in the physiopathology of atherosclerosis are not completely defined. Therefore, we aimed to investigate the potential contribution of mesenchymal stem cells in the production/release of OPG. OPG was detectable by immunohistochemistry in aortic and coronary atherosclerotic plaques, within or in proximity of intimal vascular smooth muscle cells (SMC). In addition, bone marrow mesenchymal stem cell (MSC)-derived vascular SMC as well as primary aortic SMC released in the culture supernatant significantly higher levels of OPG with respect to MSC-derived endothelial cells (EC) or primary aortic EC. On the other hand, in vitro exposure to full-length human recombinant OPG significantly increased the proliferation rate of aortic SMC cultures, as monitored by bromodeoxyuridine incorporation. Taken together, these data suggest that OPG acts as an autocrine/paracrine growth factor for vascular SMC, which might contribute to the progression of atherosclerotic lesions

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Serum VEGF, MMP-7 and CYFRA 21-1 as predictive markers of lung metastases from colorectal cancer

Background: Colorectal cancer (CRC) is one of the most common malignancy and the most frequent cause of cancer-related death in Western countries. In patients with CRC, the presence of liver or lung metastases (LMs) seriously affects survival, and the early diagnosis and resection of LMs significantly improves the outcome. Unfortunately, the sensitivity of imaging studies in detecting LMs is low, because the onset of solitary pulmonary nodules is common during follow-up, the most part of them are not malignant. The aim of this study was to evaluate the accuracy of serum carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-7 and cyrokeratin-19 fragment (CYFRA 21-1) as predictive markers of LMs from CRC. Methods: We retrospectively reviewed the medical charts of 21 patients with a history of CRC who developed histologically confirmed solitary or multiple PMs. There were 13 (61.9%) men and 8 (38.1%) women, with an overall median age of 65 years (range 31-82 years). Controls were 24 age-matched patients with CRC in whom the presence of PMs was excluded using 18F-FDG PET. The receiver operating characteristic (ROC) curve was used to obtain the optimal threshold value (cutoff point) for each TM. Results: The optimal cutoff was set at 5 ng/mL, 7.5 ng/mL, 250 pg/mL, and 2.8 ng/mL for CEA, VEGF, MMP-7, and CYFRA 21-1, respectively. The sensibility, specificity, positive (PPV) and negative (NPV) predictive value, and accuracy are reported in the Table. The logistic regression analysis excluded CYFRA 21-1 from the model, and thus we calculated the results also considering the combination of CEA+VEGF+MMP-7. The area under the ROC curve (AUC) was 0.712 (95% CI: 0.432-0.802). Conclusions: The periodic assay of CEA+VEGF+MMP-7 together may help to suspect the presence of LMs, suggesting the need to anticipate further evaluations

Choosing wisely: the list of the group of study Endocrinology and Metabolic Diseases of Italian Society of Clinical Pathology and Laboratory Medicine

Background.: The need to promote the appropriateness of diagnostic and therapeutic procedures increased in the recent years in the world and in Italy. Scientific societies participated from the beginning in defining modes and tools to support the members in the “translation” of this need in the clinical practice, for example defining lists of the diagnostic and therapeutic procedures with the highest risk of inappropriateness. The most relevant projects at international and national levels were, respectively, Choosing wisely e Slow Medicine. SIPMeL is supporting Slow Medicine and presented at 2015 SIPMel National Congress the list of the 5 procedures with the highest risk of inappropriateness in Laboratory Medicine. Methods.: In 2015 a survey has been carried out among the members of the Group of study Endocrinology-Metabolic diseases that were asked to vote (score 1–10) the five procedures with the highest risk of inappropriateness supporting their score with a short comment and essential references. Results.: The final list was obtained from the sum of the scores and includes: (1) optimal assessment of thyroid function; (2) optimal diagnostics of Cushing syndrome; (3) optimal diagnostics of pheocromocytoma; (4) optimal diagnostics for autoimmune thyroid disease; (5) assessment of 25 (OH) vitamin D. Conclusions.: The top five procedures have been presented at 2015 SIPMel National Congress and will be available in the Society website. We propose that also the other SIPMel groups of study prepare similar list and make them available within the Society and profession in a similar way

Sex-Differences in the Pattern of Comorbidities, Functional Independence, and Mortality in Elderly Inpatients: Evidence from the RePoSI Register.

BACKGROUND: The RePoSi study has provided data on comorbidities, polypharmacy, and sex dimorphism in hospitalised elderly patients. METHODS: We retrospectively analysed data collected from the 2010, 2012, 2014, and 2016 data sets of the RePoSi register. The aim of this study was to explore the sex-differences and to validate the multivariate model in the entire dataset with an expanded follow-up at 1 year. RESULTS: Among 4714 patients, 51% were women and 49% were men. The disease distribution showed that diabetes, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy were more frequent in men but that hypertension, anaemia, osteoarthritis, depression, and diverticulitis disease were more common in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment, mood disorders, and disability in daily life measured by the Barthel Index (BI) were worse in women. In the multivariate analysis, BI, CIRS, and malignancy significantly increased the risk of death in men at the 1-year follow-up, while age was independently associated with mortality in women. CONCLUSIONS: Our study highlighted the relevance and the validity of our previous predictive model in the identification of sex dimorphism in hospitalised elderly patients underscoring the need of sex-personalised health-care