The 99th percentile of reference population for cTnI and cTnT assay: Methodology, pathophysiology and clinical implications

According to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision â\u89¤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population "healthy"), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in "their quest to define normality". In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines

Convolutional Neural Networks for the segmentation of microcalcification in Mammography Imaging

Cluster of microcalcifications can be an early sign of breast cancer. In this paper we propose a novel approach based on convolutional neural networks for the detection and segmentation of microcalcification clusters. In this work we used 283 mammograms to train and validate our model, obtaining an accuracy of 98.22% in the detection of preliminary suspect regions and of 97.47% in the segmentation task. Our results show how deep learning could be an effective tool to effectively support radiologists during mammograms examination.Comment: 13 pages, 7 figure

Combined laparoscopic pyelolithotomy and endoscopic pyelolithotripsy for staghorn calculi. Long-term follow-up results from a case series

Purpose: Staghorn renal stones are a challenging field in urology. Due to their high recurrence rates, particularly those associated with an infective process, a complete removal is the ultimate goal in their management. We report our experience with a combined approach of laparoscopic pyelolithotomy and endoscopic pyelolithotripsy, the stone clearance rate, and long-term, follow-up outcomes. Methods: From June 2012 to October 2014, nine adult patients with large staghorn renal calculi (mean size, 7.2 cm; range, 6.2–9.0 cm) underwent a combined laparoscopic and endoscopic approach. The technique comprised laparoscopic pyelolithotomy and holmium-YAG laser stone fragmentation with the use of a flexible cystoscope introduced through a 12 mm trocar. Results: The average operative time was 140 min (range, 90–190 min). The mean estimated hemoglobin loss was 0.6 mmol/l (range 0.5–0.7 mmol/l). None of the patients required an open- surgery conversion. The mean hospital stay was 4 days (range, 2–6 days). A computed tomography urogram control at 6 months of follow up did not show any stone recurrence. Conclusions: Laparoscopic pyelolithotomy combined with endoscopic pyelolithotripsy could be a therapeutic option in cases where mini-invasive procedures, that is, extracorporeal shock wave lithotripsy, ureteroscopic lithotripsy, and percutaneous nephrolithotomy (PCNL) have failed. This technique has a high stone-clearance rate (75–100%) comparable with open surgery and PCNL. However, it could be technically demanding and should be performed by skilled laparoscopy surgeons

Compensatory Feto-Placental Upregulation of the Nitric Oxide System during Fetal Growth Restriction

Background: Fetal Growth Restriction is often associated with a feto-placental vascular dysfunction conceivably involving endothelial cells. Our study aimed to verify this pathogenic role for feto-placental endothelial cells and, coincidentally, demonstrate any abnormality in the nitric oxide system. Methods: Prenatal assessment of feto-placental vascular function was combined with measurement of nitric oxide (in the form of S-nitrosohemoglobin) and its nitrite byproduct, and of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Umbilical vein endothelial cells were also harvested to determine their gene profile. The study comprised term pregnancies with normal (n = 40) or small-for-gestational-age (n = 20) newborns, small-for-gestational-age preterm pregnancies (n = 15), and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12). Results: Umbilical blood nitrite (p<0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Fetal growth restriction umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Elevation in blood nitrite and S-nitrosohemoglobin persisted postnatally in the fetal growth restriction offspring. Conclusion: Fetal growth restriction is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptative event to sustain placental blood flow. However, its occurrence may modify the endothelial phenotype and may ultimately represent an element of risk for cardiovascular disease in adult life.Fil: Pisaneschi, Silvia. Università degli Studi di Pisa; Italia. Scuola Superiore Sant’Anna; ItaliaFil: Strigini, Francesca A. L.. Università degli Studi di Pisa; ItaliaFil: Sanchez, Angel Matias. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Begliuomini, Silvia. Università degli Studi di Pisa; ItaliaFil: Casarosa, Elena. Università degli Studi di Pisa; ItaliaFil: Ripoli, Andrea. National Research Council. Institute of Clinical Physiology, ; ItaliaFil: Ghirri, Paolo. Università degli Studi di Pisa; ItaliaFil: Boldrini, Antonio. Università degli Studi di Pisa; ItaliaFil: Fink, Bruno. Noxygen Science Transfer and Diagnostics; AlemaniaFil: Genazzani, Andrea R.. Università degli Studi di Pisa; ItaliaFil: Coceani, Flavio. Scuola Superiore Sant’Anna; ItaliaFil: Simoncini, Tommaso. Università degli Studi di Pisa; Itali

Glutamate/GABA co-release selectively influences postsynaptic glutamate receptors in mouse cortical neurons.

Abstract Cultured rat cortical neurons co-expressing VGLUT1 and VGAT (mixed synapses) co-release Glu and GABA. Here, mixed synapses were studied in cultured mouse cortical neurons to verify whether in mice mixed synapses co-release Glu and GABA, and to gain insight into how they may influence excitation/inhibition balance. Results showed the existence of synapses and autapses that co-release Glu and GABA in cultured mouse cortical neurons, and the ability of both neurotransmitters to evoke postsynaptic responses mediated by ionotropic receptors. We studied the short-term plasticity of glutamatergic, GABAergic, and mixed responses and we found that the kinetics of mixPSC amplitude depression was similar to that observed in EPSCs, but it was different from that of IPSCs. We found similar presynaptic release characteristics in glutamatergic and mixed synapses. Analysis of postsynaptic features, obtained by measuring AMPAR- and NMDAR-mediated currents, showed that AMPAR-mediated currents were significantly higher in pure glutamatergic than in mixed synapses, whereas NMDAR-mediated currents were not significantly different from those measured in mixed synapses. Overall, our findings demonstrate that glutamatergic and mixed synapses share similar electrophysiological properties. However, co-release of GABA and Glu influences postsynaptic ionotropic glutamatergic receptor subtypes, thus selectively influencing AMPAR-mediated currents. These findings strengthen the view that mixed neurons can play a key role in CNS development and in maintaining the excitation-inhibition balance

Systematic differences between BNP immunoassays: Comparison of methods using standard protocols and quality control materials

Background: Recent studies suggested that there are marked systematic differences among BNP immunoassays. In this study we compared the BNP data and clinical results obtained with different immunoassays, including a new method (ST-AIA-PACK, TOSOH Corporation). Methods: BNP was measured on plasma-EDTA samples of healthy subjects (HS, n = 126) and patients with heart failure (HF, n = 31 NYHA I, II; n = 46 NYHA III, IV) using the ST-AIA-PACK and the Triage Biosite (Beckman Coulter) methods. Control samples distributed in the CardioOrmoCheck external quality assessment were also measured with TOSOH and the most used BNP immunoassays in Italy. Results: TOSOH method showed a good correlation (R = 0.976; n = 327) but a mean bias (−46.9%) compared to Triage Biosite. On the base of the results obtained in 10 samples of the CardioOrmoCheck study, TOSOH method showed a strict agreementwith ADVIA Centaur, while it underestimated BNP in comparisonwith Triage (−52.5%) and ARCHITECT methods (−39.4%). The agreement of ST-AIA-PACK and Triage Biosite methods for classification of HF patients was tested using 100 ng/L of BNP; the positive agreement between methods was 65%, overall agreement was 73%. Conclusions: Our results confirm that there are marked differences in measured values among commercial methods for BNP assay

Low-T3 Syndrome

Background— Clinical and experimental data have suggested a potential negative impact of low-T3 state on the prognosis of cardiac diseases. The aim of the present prospective study was to assess the role of thyroid hormones in the prognosis of patient population with heart disease. Methods and Results— A total of 573 consecutive cardiac patients underwent thyroid function profile evaluation. They were divided in two subgroups: group I, 173 patients with low T3, ie, with free T3 (fT3) <3.1 pmol/L, and group II, 400 patients with normal fT3 (≥3.1 pmol/L). We considered cumulative and cardiac death events. During the 1-year follow-up, there were 25 cumulative deaths in group I and 12 in group II (14.4% versus 3%, P <0.0001); cardiac deaths were 13 in group I and 6 in group II (7.5% versus 1.5%, P =0.0006). According to the Cox model, fT3 was the most important predictor of cumulative death (hazard ratio [HR] 3.582, P <0.0001), followed by dyslipidemia (HR 2.955, P =0.023), age (HR 1.051, P <0.005), and left ventricular ejection fraction (HR 1.037, P =0.006). At the logistic multivariate analysis, fT3 was the highest independent predictor of death (HR 0.395, P =0.003). A prevalence of low fT3 levels was found in patients with NYHA class III-IV illness compared with patients with NYHA class I-II (χ 2 5.65, P =0.019). Conclusions— Low-T3 syndrome is a strong predictor of death in cardiac patients and might be directly implicated in the poor prognosis of cardiac patients