Circulating neuregulin-1 and galectin-3 can be prognostic markers in breast cancer

Background: It is important to identify novel plasmatic biomarkers that can contribute to assessing the prognosis and outcome of breast cancer patients. Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in breast cancer development and patient survival; therefore, we studied whether the serum concentration of these 2 proteins can be correlated to breast cancer progression. Methods: Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy controls and 50 breast cancer patients at baseline and at 3 and 6 months after treatment with anthracyclines and taxanes, with or without trastuzumab. Results: NRG1 and Gal-3 were significantly more elevated in cancer patients than in healthy controls; further- more, NRG1 and Gal-3 were significantly increased after chemotherapy and were predictive of mortality at 1 year. Conclusions: Circulating NRG1 and Gal-3 can be additional biomarkers indicative of prognosis and outcomes for breast cancer patients

Comparison between soluble ST2 and high-sensitivity troponin I in predicting short-term mortality for patients presenting to the Emergency Department with chest pain

Background: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. Methods: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. Results: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P35 ng/mL at ED arrival died during the 30-day follow-up. Conclusions: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value > 35 ng/mL at ED arrival showed the highest predictive power for short-term mortality

Serum Cystatin C for the diagnosis of acute Kidney Injury in Patients Admitted in the Emergency Department

BACKGROUND: Early diagnosis of acute kidney injury (AKI) at emergency department (ED) is a challenging issue. Current diagnostic criteria for AKI poorly recognize early renal dysfunction and may cause delayed diagnosis. We evaluated the use of serum cystatin C (CysC) for the early and accurate diagnosis of AKI in patients hospitalized from the ED. METHODS: In a total of 198 patients (105 males and 93 females), serum CysC, serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were calculated at 0, 6, 12, 24, 48, and 72 hours after presentation to the ED. We compared two groups according to the presence or absence of AKI. RESULTS: Serial assessment of CysC, sCr, and eGFR was not a strong, reliable tool to distinguish AKI from non-AKI. CysC > 1.44 mg/L at admission, both alone (Odds Ratio = 5.04; 95%CI 2.20-11.52; P < 0.0002) and in combination with sCr and eGFR (Odds Ratio = 5.71; 95%CI 1.86-17.55; P < 0.002), was a strong predictor for the risk of AKI. CONCLUSIONS: Serial assessment of CysC is not superior to sCr and eGFR in distinguishing AKI from non-AKI. Admission CysC, both alone and in combination with sCr and eGFR, could be considered a powerful tool for the prediction of AKI in ED patients

Proenkephalin, neutrophil gelatinase-associated lipocalin, and estimated glomerular filtration rates in patients with sepsis

Background: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (EGFR) in septic patients. Methods: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPICr, CDK-EPICysC, and CKD-EPICr-CysC. The PENK, NGAL, and EGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. Results: The PENK, NGAL, and EGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different EGFR equations, PENK showed constant and significant associations with all EGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. Conclusions: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis

Circadian blood pressure rhythm and intimal-medial thickness changes in non-dipper normotensive patients

We investigated 25 non-dipper normotensive vs 25 dipper normotensive patients. The aim of our study was to evaluate carotid intimal-medial thickness (IMT) in the two groups. At the admission patients underwent anamnesis and general examination, blood sampling for lipid profile measurement, glycemia, homocysteine, ambulatory blood pressure measurement to assess the circadian blood pressure profile, and Doppler ultrasound to measure carotid intimal-medial thickness (IMT). Our results showed that IMT is significantly higher in the non-dipper group (P&lt;0.006) vs dippers. Non-dipper status has been recognized in several studies a condition with increased risk for target organ damage in hypertensive and normotensive subjects. However, to our knowledge, a possible relationship between IMT and normotensive non-dipper patients has not yet clearly investigated. Our study instead has clearly demonstrated a significant relationship between IMT and the non-dipper status.</p

Soluble ST2 levels and left ventricular structure and function in patients with metabolic syndrome

Background: A biomarker that is of great interest in relation to adverse cardiovascular events is soluble ST2 (sST2), a member of the interleukin family. Considering that metabolic syndrome (MetS) is accompanied by a proinflammatory state, we aimed to assess the relationship between sST2 and left ventricular (LV) structure and function in patients with MetS. Methods: A multicentric, cross-sectional study was conducted on180 MetS subjects with normal LV ejection fraction as determined by echocardiography. LV hypertrophy (LVH) was defined as an LV mass index greater than the gender-specific upper limit of normal as determined by echocardiography. LV diastolic dysfunction (DD) was assessed by pulse-wave and tissue Doppler imaging. sST2 was measured by using a quantitative monoclonal ELISA assay. Results: LV mass index (β=0.337, P<0 .001, linear regression) was independently associated with sST2 concentrations. Increased sST2 was associated with an increased likelihood of LVH [Exp (B)=2.20, P=0.048, logistic regression] and increased systolic blood pressure [Exp (B)=1.02, P=0.05, logistic regression]. Comparing mean sST2 concentrations (adjusted for age, body mass index, gender) between different LV remodeling patterns, we found the greatest sST2 level in the group with concentric hypertrophy. There were no differences in sST2 concentration between groups with and without LV DD. Conclusions: Increased sST2 concentration in patients with MetS was associated with a greater likelihood of exhibiting LVH. Our results suggest that inflammation could be one of the principal triggering mechanisms for LV remodeling in MetS

Level and correlates of physical activity and sedentary behavior in patients with type 2 diabetes: a cross-sectional analysis of the italian diabetes and exercise study-2

OBJECTIVE: Patients with type 2 diabetes usually show reduced physical activity (PA) and increased sedentary (SED)-time, though to a varying extent, especially for low-intensity PA (LPA), a major determinant of daily energy expenditure that is not accurately captured by questionnaires. This study assessed the level and correlates of PA and SED-time in patients from the Italian Diabetes and Exercise Study_2 (IDES_2). METHODS: Three-hundred physically inactive and sedentary patients with type 2 diabetes were enrolled in the IDES_2 to be randomized to an intervention group, receiving theoretical and practical exercise counseling, and a control group, receiving standard care. At baseline, LPA, moderate-to-vigorous-intensity PA (MVPA), and SED-time were measured by accelerometer. Physical fitness and cardiovascular risk factors and scores were also assessed. RESULTS: LPA was 3.93±1.35 hours∙day-1, MVPA was 12.4±4.6 min∙day-1, and SED-time was 11.6±1.2 hours∙day-1, with a large range of values (0.89-7.11 hours∙day-1, 0.6-21.0 min∙day-1, and 9.14-15.28 hours∙day-1, respectively). At bivariate analysis, LPA and MVPA correlated with better cardiovascular risk profile and fitness parameters, whereas the opposite was observed for SED-time. Likewise, values of LPA, MVPA, and SED-time falling in the best tertile were associated with optimal or acceptable levels of cardiovascular risk factors and scores. At multivariate analysis, age, female gender, HbA1c, BMI or waist circumference, and high-sensitivity C reactive protein (for LPA and SED-time only) were negatively associated with LPA and MPA and positively associated with SED-time in an independent manner. CONCLUSIONS: Physically inactive and sedentary patients with type 2 diabetes from the IDES_2 show a low level of PA, though values of LPA, MVPA, and SED-time vary largely. Furthermore, there is a strong correlation of these measures with glycemic control, adiposity and inflammation, thus suggesting that even small improvements in LPA, MVPA, and SED-time might be associated with significant improvement in cardiovascular risk profile

Vitamin D: From measurement problems to clinical implications

La vitamina D svolge un ruolo cruciale nel metabolismo fosfo-calcico, e molti altri importanti effetti protettivi su diversi distretti ed organi si sono evidenziati negli ultimi anni, tanto da farla considerare un vero e proprio ormone. La sua azione si svolge tramite una serie di metaboliti che vengono attivati attraverso vari passaggi. È molto importante quindi poterne misurare i livelli. La scelta dei valori di riferimento non può essere effettuata considerando un campione della cosiddetta popolazione “normale”, perché gli stati carenziali sono molto diffusi. La determinazione della vitamina D, però, presenta diverse problematiche, legate sia alla scelta del metabolita da valutare, sia al sistema con cui viene trasportata in circolo. Infatti il metabolita più rappresentativo dello stato vitaminico, la 25(OH) vitamina D, circola strettamente legato ad una proteina di trasporto (VDBP), che ne ostacola il dosaggio. Si sono sviluppati, alla luce della sempre maggior importanza che il suo ruolo sembra rivestire, molti metodi di misurazione, sia indiretti (immunochimici) che diretti (HPLC, spettrometria di massa MS). I metodi indiretti presentano il grande vantaggio della possibilità dell’automazione, ma tendono in generale a sottostimare, mentre i metodi diretti sono più accurati, ma soggetti a maggiori interferenze. La valutazione clinica del paziente non può prescindere dalla conoscenza di queste problematiche, anche se molto si sta facendo per ridurre le differenze tra metodi e giungere ad una loro standardizzazione, che permetterà di ridurre la variabilità e quindi l’incertezza del dato.Vitamin D plays a crucial role in phospho-calcic metabolism, and in recent years many other important protective effects have been highlighted, so it could be considered a true hormone. Its action is due to a series of metabolites that are activated through various steps. It is very important therefore to measure levels of this vitamin. The choice of the reference values cannot be done by taking a sample of the socalled “normal” population, because deficiency states are very prevalent. The determination of vitamin D, however, presents difficulties, related both to the choice of the metabolite to be evaluated, and to the system by which it is transported into the circulation. In fact, the most representative metabolite of vitamin status, 25 (OH) vitamin D, circulates tightly bound to a carrier protein (VDBP), which hinders the assay. In light of the increasing importance of vitamin D many methods of measurement, both indirect (immunochemical) and direct (HPLC, mass spectrometry-MS) have been developed. Indirect methods have the advantage of automation, but generally tend to underestimate, while direct methods are more accurate, but subject to greater interference. The correct clinical evaluation of a patient cannot ignore these issues, although much is being done to reduce the differences between methods and come to a standardization