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Summary: Output gaps that are estimated in real time can differ substantially from those estimated after the fact. We provide a comprehensive comparison of real‐time output gap estimates, with the aim of understanding this real‐time instability. Using a statistical decomposition, we find that including Okun's law relationship improves real‐time stability by alleviating the end‐point problem. Models that include the unemployment rate also produce output gaps with relevant economic content. [ABSTRACT FROM AUTHOR]

This work is aimed at illustrating one of the most engaging geoparks in Europe, the Gole della Breggia Geopark. By following its geotrail, the visitors can observe a great deal of features that encompass a wide variety of sedimentary, stratigraphic, tectonic and paleogeographic processes. Its contents are popularized by a comprehensive geotrail that encompasses 23 geostops, enriched with explanatory panels, which enable viewers to gain an overall picture of the complex processes that led to the present-day configuration of the outcrops encountered in the geopark. We have selected five significative outcrops, which we have regarded as fully-fledged geosites, and which encompass the whole 170-million-year interval, from Early Jurassic to Late Miocene times, during which the rocks of the geopark were deposited and deformed. We have performed an assessment of the five geosites, using the most common criteria that can be applied for geosite evaluation. The results of the assessment show that the most valuable geosites are the Lombardian Maiolica, and the Limestone with Pelagic Bivalves. All five geosites, thanks to a QR code added to each figure along the text, can be viewed as virtual geosites (VGs), integrated by 360° videos. [ABSTRACT FROM AUTHOR]

Summary: Heavy tails play an important role in modern macroeconomics and international economics. Previous work often assumes a Pareto distribution for firm size, typically with a shape parameter approaching Zipf's law. This convenient approximation has dramatic consequences for the importance of large firms in the economy. But we show that a lognormal distribution, or better yet, a convolution of a lognormal and a non‐Zipf Pareto distribution, provides a better description of the US economy, using confidential Census Bureau data. These findings hold even far in the upper tail and suggest that heterogeneous firm models should more systematically explore deviations from Zipf's law. [ABSTRACT FROM AUTHOR]

Aims: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic drugs, are nephroprotective in case of diabetes, but whether a similar beneficial effect may be detectable also in case of chronic non-diabetic kidney diseases remains still unknown. The aim of this study was to evaluate the effects of empagliflozin, a SGLT-2 inhibitor, on the progression of cyclosporine nephropathy, in the absence of diabetes. Methods: Sprague Dawley rats (n = 27) have been fed with low-salt diet starting 10 days before the beginning and finished at the end of the experimental period. Cyclosporine-A (CsA, 15 mg/kg/day, intraperitoneal injection, n = 8) and CsA plus empagliflozin (Empa, 10 mg/kg/day, per os, n = 7) were administered for 4 weeks. The control groups were treated with placebo (Control, n = 7) or empagliflozin (Control + Empa, n = 5). Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental period. At the end of the experimental protocol, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates (monocytes/macrophages), type I and type IV collagen expression, and tyrosine hydroxylase expression, used as marker of sympathetic nerve activity. Results: CsA-treated rats showed a significant increase (p < 0.01) in blood pressure, which was reduced by administration of empagliflozin (p < 0.05). CsA administration caused an increase in glomerular and tubulo-interstitial fibrosis (p < 0.05), renal inflammatory infiltrates (p < 0.05), type I and type IV collagen expression (p < 0.01), and tyrosine hydroxylase expression (p < 0.01) as compared to the control rats and control + Empa-treated rats. Treatment with empagliflozin in CsA-treated rats reduced glomerular (p < 0.01) and tubulo-interstitial fibrosis (p < 0.05), type I and type IV collagen expression (p < 0.01), inflammatory cell infiltration (p < 0.01) and tyrosine hydroxylase expression (p < 0.05), as compared to rats treated with CsA. Conclusion: Empagliflozin administration caused a reduction in blood pressure in CsA-treated rats and showed a protective effect on CsA nephropathy by decreasing renal fibrosis, type I and type IV collagen expression, macrophage infiltration and tyrosine hydroxylase expression. These data suggest that empagliflozin promotes nephroprotection also in non-diabetic kidney disease. [ABSTRACT FROM AUTHOR]

The impact of the COVID-19 pandemic has been dramatic worldwide, with China, Italy, and now US at its epicenter. Researchers and clinicians are studying and testing different approaches in the attempt to prevent the infection and minimize its severity. Major efforts are focused on optimizing mechanical ventilation, antiviral, and supportive treatment; however, the role of heparin and low molecular weight (LMW) heparin in this setting has been largely overlooked. This review summarizes the available evidence about the role of heparan sulfate as a key entry mechanism for SARS-CoV-2; the efficacy of heparin and LMW heparin in counteracting its entry into the cell, the recent experimental findings obtained in in vitro studies using the LMW heparin enoxaparin Inhixa®, the role of heparin and LMW heparin in modulating the cytokine storm, and the evidence for the use of LMW heparin in the prevention and treatment of the thromboembolic complications of COVID-19. The available evidence suggests that LMW heparin appears as a promising tool in the treatment of COVID-19. Whether its systematic use is associated with a reduction in complications and ultimately mortality of these patients is being tested in several studies starting worldwide. [ABSTRACT FROM AUTHOR]

Background: Clinical trials have shown that empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, promotes nephroprotective effects in diabetic patients. The mechanisms underlying nephroprotection are not completely known and it is not known whether the renal beneficial action is present even in non-diabetic kidney disease. The aim of this study was to evaluate the effect of Empa administration on the development of renal fibrosis in an experimental model of angiotensin II (Ang II)-dependent hypertension.Methods: Sprague Dawley rats (n = 31) were divided into 4 experimental groups. Ang II (200 ng/kg/min, osmotic minipumps, s.c., n = 9) or Ang II + Empa (10 mg/kg/day, per os, n = 10) were administered for 2 weeks. Control rats were treated with placebo (physiological saline, n = 6), and another group was treated with placebo plus Empa (n = 6) for the same period. Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental protocol. After 2 weeks, the rats were euthanized and the kidneys were excised for histomorphometric evaluation of glomerular and tubulo-interstitial fibrosis and for the immunohistochemical evaluation of inflammatory infiltrates (monocytes/macrophages) and types I and IV collagen expression.Results: The administration of Ang II resulted in an increase in blood pressure (p < 0.01), glomerular (p < 0.05) and tubulo-interstitial (p < 0.01) fibrosis, renal inflammatory infiltrates (p < 0.01) and type I (p < 0.01) and type IV collagen expression (p < 0.05) compared to the control group. Treatment with Empa did not significantly modify the increase in blood pressure due to Ang II, but prevented the development of renal glomerular and tubulo-interstitial fibrosis, and the increase in inflammatory infiltrates and types I and IV collagen expression in Ang II-treated rats (p < 0.01).Conclusions: These data demonstrate that the treatment with Empa prevents the development of renal fibrosis in Ang II-dependent hypertension. In Ang II-dependent hypertension, the anti-fibrotic effect due to SGLT2 inhibition is caused by the reduction of inflammatory infiltrates and it is independent on the modulation of blood pressure increase. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Our objective was to report the outcomes of fenestrated/branched endovascular aneurysm repair of thoraco-abdominal aortic aneurysms (TAAAs) with endografts. METHODS Between January 2010 and April 2018, patients with TAAAs, considered at high surgical risk for open surgery and treated by Cook-Zenith fenestrated/branched endovascular aneurysm repair, were prospectively enrolled and retrospectively analysed. The early end points were 30-day/hospital mortality rate, spinal cord ischaemia and 30-day cardiopulmonary and nephrological morbidity. Follow-up end points were survival, patency of target visceral vessels and freedom from reinterventions. RESULTS Eighty-eight patients (male: 77%; mean age: 73 ± 7 years; American Society of Anesthesiologists 3/4: 58/42%) were enrolled. Using Crawford's classification, 43 (49%) were types I–III and 45 (51%) were type IV TAAAs. The mean aneurysm diameter was 65 ± 15 mm. Custom-made and off-the-shelf endografts were used in 60 (68%) and 28 (32%) cases, respectively. Five (6%) patients had a contained ruptured TAAA. The procedure was performed in multiple steps in 42 (48%) cases. There was 1 (1%) intraoperative death. Five (6%) patients suffered spinal cord ischaemia with permanent paraplegia in 3 (3%) cases. Postoperative cardiac and pulmonary complications occurred in 7 (8%) and 12 (14%) patients, respectively. Worsening of renal function (≥30% of baseline level) was detected in 11 (13%) cases, and 2 (2%) patients required haemodialysis. The 30-day and hospital mortality rates were 5% and 8%, respectively. The mean follow-up was 36 ± 22 months. Survival at 12, 24 and 36 months was 89%, 75% and 70%, respectively. The patency of target visceral vessels at 12, 24 and 36 months was 92%, 92% and 92%, respectively. Freedom from reinterventions at 12, 24 and 36 months was 85%, 85% and 83%, respectively. CONCLUSIONS The endovascular repair of TAAAs with fenestrated/branched endovascular aneurysm repair is feasible and effective with acceptable technical/clinical outcomes at early/midterm follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Incidental findings are common in presumed healthy volunteers but are infrequently studied in patients in a clinical context. Objective: To determine the prevalence, nature, and management implications of incidental findings on head MRI in patients presenting with cognitive symptoms, and to quantify and describe unexpected MRI abnormalities that are of uncertain relevance to the patient's cognitive symptoms. Methods: A single-centre retrospective review of patients attending a regional early-onset cognitive disorders clinic between March 2012 and October 2018. Medical records of consecutive patients who underwent head MRI were reviewed. Unexpected MRI findings were classified according to their severity and likelihood of being incidental. Markers of small vessel disease and cerebral atrophy were excluded. Results: Records of 694 patients were reviewed (median age 60 years, 49.9% female), of whom 514 (74.1%) underwent head MRI. 54% of the patients received a diagnosis of a neurodegenerative disorder. Overall 111 incidental findings were identified in 100 patients of whom 18 patients (3.5%, 95% CI 2.2–5.6%) had 18 incidental findings classified as requiring additional medical evaluation. 82 patients (16%, 95% CI 13.0–19.5%) had 93 incidental findings without clearly defined diagnostic consequences. 17 patients (3.3%) underwent further investigations, 14 patients (2.7%) were referred to another specialist clinic and 3 patients (0.6%) were treated surgically. Two patients had MRI findings of uncertain relevance to their cognitive symptoms, necessitating prolonged clinic follow-up. Conclusion: Incidental findings are common in patients with cognitive impairment from this large clinic-based series; however, few required additional medical evaluation. These data could help inform discussions between clinicians and people with cognitive symptoms regarding the likelihood and potential implications of incidental imaging findings. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate possible predictors of complications with flared iliac stent-graft limbs for ectatic common iliac arteries (CIAs) associated with abdominal aortic aneurysms treated with endovascular aneurysm repair (EVAR). Materials and Methods: A retrospective comparative analysis was conducted of 533 EVAR patients (mean age 75 years; 442 men) treated between 2012 and 2017 who had complications associated with the stent-graft limbs (n=1066). Complications, including type Ib endoleak, type IIIa endoleak, and limb occlusion, were compared between patients with nondilated (<16 mm) CIAs treated with standard iliac limbs (SLs, n=808) vs patients with ectatic CIAs treated with flared limbs (FLs, n=258). Follow-up included a duplex scan at 3, 6, and 12 months and yearly thereafter; computed tomography angiography was performed in case of iliac complications. Risk factors for iliac complications in FLs were investigated using Cox regression and Kaplan-Meier analyses; results of the regression analysis are presented as the hazard ratio (HR) and 95% confidence interval (CI). Results: Overall, no iliac complications occurred at 30 days, but over a mean follow-up of 38±8 months, there were 10 (1%) events (4 limb occlusions, 6 type Ib endoleaks): 7 (3%) in FLs and 3 (0.4%) in SLs (p=0.20). Kaplan-Meier analysis found no differences at 5 years in SLs vs FLs for freedom from limb occlusion (99%±1% vs 98%±1%, respectively; p=0.30) or type Ib endoleak (96%±3% vs 97%±1%, respectively; p=0.44). Similarly, the overall 5-year iliac complication rates were similar in SLs vs FLs (96%±3% vs 95%±2%, p=0.21). Regression analysis found CIA length =30 mm (HR 4.7, 95% CI 1.02 to 21.6, p=0.04) and a diameter =20 mm (HR 7.8, 95% CI 1.05 to 64.8, p=0.03) to be independent predictors of iliac complications in FLs. Kaplan-Meier estimates of iliac complication-free survival in FLs were significantly worse when the CIA length was =30 mm (79%±9% vs 98%±1%, p=0.003) or the diameter was =20 mm (85%±7% vs 99%±1%, p=0.02). The combination of both risk factors produced significantly poorer iliac complication-free survival compared with cases in which there was one or no risk factor (67%±19% vs 96%±2% vs 99%±1%, respectively; p<0.001). Conclusion: Iliac limb complications are infrequent in EVAR, regardless of the type of iliac limb chosen; however, CIAs =30 mm in length or =20 mm in diameter significantly increased the risk of late iliac complications in FLs. If both characteristics were present, this risk was further elevated. [ABSTRACT FROM AUTHOR]

Objective: Carotid stenosis with crescendo-transient-ischemic-attack (cTIA) requires a prompt intervention to reduce the stroke risk. Few data are reported in literature about cTIA suggesting a different perioperative risk compared with patients with single TIA (sTIA). This study aimed to compare the outcome of carotid endarterectomy (CEA) in patients with TIA (single/crescendo) and evaluate the outcome risk-factors.Methods: Data from two tertiary hospitals for vascular treatment were analyzed from 2007 to 2016. All patients with TIA subjected to CEA were considered, comparing the 30-day postoperative stroke and stroke/death in patients with cTIA and sTIA, particularly in the urgent (≤48 h) setting.Results: On a total of 3866 CEA, 888 (23%) were performed in symptomatic patients and 515 for TIA: 365 (71%) patients with sTIA and 150 (29%) with cTIA. When compared with sTIA, cTIA patients were younger and less frequently affected by coronary disease, dyslipidemia, and chronic pulmonary disease; however, contralateral carotid occlusion was more common (20% vs. 10%, P = .004; 56% vs. 46, P = .03; 16% vs. 7%, P = .01; >80 years 26% vs. 16%, P = .01 and 2% vs. 10%, P = .001; respectively). Postoperative stroke and stroke/death were significantly higher in cTIA compared with sTIA (5.3% vs. 1.6%, P = .02 and 6.0% vs. 2.2%, P = .03; respectively). Urgent CEA was performed in 58% ( n: 87) cTIA and in 11% ( n: 56) sTIA( P<.01). The urgent setting did not influence the stroke and stroke/death rate of CEA for sTIA (3.6% vs. 1.3%, P = .21 and 3.6% vs. 1.9%, P = .44, respectively), but was associated with lower rate of events in cTIA (1.1%vs. 11.1%, P = .01 and 2.3% vs. 11.1%, P = .03, respectively). This beneficial effect in patients with cTIA treated within 48-h was confirmed also by multivariate analysis (OR: 0.09, 95% CI: 0.76-0.01, P=.02).Conclusions: cTIA subjected to CEA have a higher stroke and stroke/death risk compared with patients with sTIA. The urgent setting seems to reduce the stroke/death rate cTIA; for sTIA with a stable neurological condition, the timing of CEA did not influence the outcome. [ABSTRACT FROM AUTHOR]

ASD patients were less hypoxemic at ICU admission; we can just speculate that, being less dyspnoeic, they possibly had more clear-headed experiences of their own condition and of the surrounding environment, including other patients' struggle and death. Many patients described nightmares, feeling of derealization and the initial belief of being in a fake hospital; this mainly affected the first patients of the pandemic. 10 patients (21.3%-ASD 4 (21.1%) vs. non-ASD patients 6 (21.4%); I p i = 0.975) wanted to see the ICU, both to meet the ICU staff and to help their memories' reconstruction process. [Extracted from the article]

Aims: Compound 21 (C21), selective AT2 receptor agonist, has cardioprotective effects in experimental models of hypertension and myocardial infarction. The aims of the study was to evaluate the effect of C21, losartan, or both in Zucker diabetic fatty (ZDF) rats (type 2 diabetes) on (1) the prevention of myocardial hypertrophy; (2) myocardial expression of phosphatase and tensin homolog (PTEN), a target gene of miR-30a-3p, involved in myocardial remodelling.Methods: Experiments were performed in ZDF (n = 33) and in control Lean (8) rats. From the 6th to the 20th week of age, we administered C21 (0.3 mg/kg/day) to 8 ZDF rats. 8 ZDF rats were treated with losartan (10 mg/kg/day), 8 rats underwent combination treatment, C21+ losartan, and 9 ZDF rats were left untreated. Blood glucose and blood pressure were measured every 4 weeks. At the end of the study the hearts were removed, the apex was cut for the quantification of PTEN mRNA and miR-30a-3p expression (realtime-PCR). Myocardial hypertrophy was evaluated by histomorphometric analysis, and nitrotyrosine expression (as marker of oxidative stress) by immunohistochemistry.Results: ZDF rats had higher blood glucose (p < 0.0001) with respect to control Lean rats, while blood pressure did not change. Both parameters were not modified by C21 treatment, while losartan and losartan + C21 reduced blood pressure in ZDF rats (p < 0.05). miR-30a-3p expression was increased in ZDF rats (p < 0.01) and PTEN mRNA expression was decreased (p < 0.05). ZDF rats developed myocardial hypertrophy (p < 0.01) and increased oxidative stress (p < 0.01), both were prevented by C21 or losartan, or combination treatment. C21 or losartan normalized the expression of miR-30a-3p and PTEN.Conclusions: Activation of AT2 receptors or AT1 receptor blockade prevents the development of myocardial hypertrophy in ZDF rats. This occurs through the modulation of the miR-30a-3p/PTEN interaction. [ABSTRACT FROM AUTHOR]

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Background: Medical therapy for asymptomatic carotid artery stenosis (ACAS) may obviate the carotid revascularization, according to recent literature reports, but many studies also considered moderate carotid artery stenosis (50–69% NASCET). This study reviews the most recent series of ACAS focusing on ipsilateral transient ischemic attack (TIA) stroke and annual risk of stroke in patients with ACAS ≥70%, thereby also evaluating the adherence to best medical therapy (BMT).Methods: A systematic review consisting of all the series of patients with ACAS being treated medically was performed, which was published after 2005. The annual pooled risk of ipsilateral TIA-stroke and stroke in patients with ACAS ≥70% was calculated. A subgroup of studies with BMT defined as ≥90% of the patients in antiplatelet and statin therapy was performed.Results: Eleven studies, with the enrolling period from 1996 to 2009, were reviewed. Overall, 2185 patients were considered, with a follow-up from 2 to 13 years, for a total of 6834 patients/year. The pooled risk was 3.4%/year for ipsilateral TIA-stroke and 1.6%/year for stroke. Five studies, published from 2014, had BMT adherence, for a total of 1665 patients/year. The pooled risk was 3.5%/year for ipsilateral TIA-stroke and for stroke.Conclusion: The most recent series of ACAS ≥70% and BMT had an overall stroke rate which is relatively low; however, the risk of developing symptoms is still relevant (3.4%/year). [ABSTRACT FROM PUBLISHER]

Objective: This systematic review and meta-analysis seeks to determine the validity of the anion gap to screen for hyperlactatemia in critically ill patients. We have previously shown that the anion gap does not predict 31-day and in-hospital mortality in critically ill patients. The present review aims to add confirmatory evidence to identify whether the anion gap is a suitable tool for risk stratification in low-resource countries. Results: Nine studies reporting on 4504 samples from 2111 patients were included. The anion gap failed to detect hyperlactatemia defined as lactate above 2.5 mmol/l but showed good discriminatory ability for the detection of severe hyperlactatemia defined as lactate over 4 mmol/l. At the 2.5 mmol/l threshold, the anion gap had high specificity but low sensitivity for the detection of hyperlactatemia. A meta-analysis of correlation coefficients yielded high statistical heterogeneity. Therefore, in keeping with our previous findings, the use of the anion gap for risk stratification as an alternative to lactate cannot be recommended. However, the strength of the evidence we have synthesised is adversely affected by the small number of studies included, inconsistency of effect measures and positivity thresholds reported, and selection bias within individual studies. PROSPERO Registration Number: CRD42015016470 (registered on the 4th February 2015). [ABSTRACT FROM AUTHOR]

Two-stage transposed brachiobasilic arteriovenous fistula is a common procedure after brachiobasilic fistula (BBF) creation. Different techniques can be used for basilic vein transposition but few comparative literature reports are available. The aim of our study was to compare two different techniques for basilic vein transposition. The first maintains the BBF anastomosis and the basilic vein is placed in a subcutaneous pocket (BBAVF). The second transects the basilic vein at the BBF anastomosis and tunnels it superficially, with a new BBF in the brachial artery (BBAVFTn). From 2009 to 2014, all patients who underwent basilic vein superficialization were treated by one of the two techniques, recorded in a dedicated database and retrospectively reviewed. The surgeon chose the technique on the basis of personal preference. The two techniques were compared in terms of perioperative complications, length of hospital stay, time of cannulation, ease of cannulation, and long-term patency. Eighty patients were included in the study: 40 (50%) BBAVF and 40 (50%) BBAVFTn. Length of hospital stay was similar in the two groups (median [interquartile range-IQR] 3(2) [BBAVF] vs. 2(1) [BBAVFTn], P = 0.52, respectively). BBAVFTn was associated with a lower hematoma incidence (1/40 [2.5%] vs. 15/40 [37.5%], P = 0.01), shorter first cannulation time (median IQR: 11(10) vs. 23(8) days, P = 0.01) and easier cannulation compared with BBAVF (32/40 [80%] vs. 15/40 [37.5%], P < 0.001). Median (IQR) follow-up was 16(7) months. No statistical differences in terms of primary and assisted primary patency were found in BBAVFTn vs. BBAVF (at 24 months 91(5) vs. 71(7), P = 0.21 and 93(6) vs. 78(8), P = 0.33, respectively). Patients who underwent BBAVFTn surgery showed fewer surgical complications, better dialytic performance, and easier cannulation compared with those submitted to BBAVF. [ABSTRACT FROM AUTHOR]

Background: Human mesenchymal stem cells (MSCs) possess well-known reparative abilities, but any defect of the immunomodulatory activity and/or the differentiation process may determine the development of human diseases, including those affecting the vascular wall. MSCs residing within the human aortic wall represent a potential cell mediator of atherosclerotic aneurysm development. Methods: MSCs isolated from healthy and aneurysm aortas were characterized by flow cytometer and tested for differentiation properties. Healthy aorta (ha)-MSCs were then subjected to inflammatory stimuli to evaluate the microenvironmental impact on their function and involvement in vascular remodelling. Results: Abdominal aortic aneurysm (AAA)-MSCs were isolated from calcified and inflamed aortas of 12 patients with high serum levels of MMP-9 protein. AAA-MSCs expressed typical mesenchymal markers and, in line with the histological analysis, elevated levels of OPN, an osteogenic marker also involved in vascular remodelling. AAA-MSCs were highly osteogenic and underwent intense calcium deposition under proper stimulation; moreover, AAA-MSCs were able to differentiate into tubule-like structures in Matrigel, even if the lack of CD146 and the reduced structural stability suggested an inefficient maturation process. We further demonstrated an association between osteogenesis and inflammation; indeed, ha-MSCs cultured with either cytokines (TNF-α,IL-1β) or AAA-PBMCs showed increased expression of MMP-9 and osteogenic markers, to the detriment of the adipogenic regulator PPAR-γ. Interestingly, the culture with inflammatory cells highly stimulated ha-MSCs towards the osteogenic commitment. Conclusions: AAA-MSCs displayed high osteogenic potential and pathological angiogenesis that represent crucial steps for AAA progression; we showed that the inflammatory process critically addresses human vascular MSCs towards a pathological behaviour, inducing vascular bone matrix deposition and remodelling. Inhibition of this pathway may represent a pharmacological approach against arterial calcification. [ABSTRACT FROM AUTHOR]

Background/Aims: This study aimed to evaluate total and sudden death (SD) in a cohort of dialysis patients, comparing hemodialysis (HD) vs. peritoneal dialysis (PD). Methods: This is a multicenter retrospective cohort study. Results: Deaths were 626 out of 1,823 in HD and 62 of 249 in PD patients. HD patients had a greater number of comorbidities (p < 0.05). PD patients had a lower risk of death than HD patients (p < 0.001); however, the advantage decreased with time (p < 0.001). Mortality predictors were left ventricular ejection fraction (LVEF) ≤ 35%, older age, ischemic heart disease, diabetes mellitus, previous stroke, and atrial fibrillation (p < 0.03). SDs were 84: 71 in HD and 13 in PD population (12.1 and 22.8% of all causes of death, respectively). A non-significant risk of SD among PD compared to HD patients was detected. SD predictors were older age, ischemic heart disease, and LVEF ≤ 35% (p < 0.05). Conclusions: HD patients showed a greater presence of comorbidities and reduced survival compared to PD patients; however, the incidence of SD does not differ in the 2 populations. [ABSTRACT FROM AUTHOR]

Compound 21 (C21), selective agonist of angiotensin type-2 (AT-2) receptors, shows anti-inflammatory effects in experimental models of hypertension and nephroprotection in diabetes. The aim of the present study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague-Dawley rats. Cyclosporine-A (CsA; 15 mg/kg per day, intraperitoneal injection) and CsA plus C21 (0.3 mg/kg per day, intraperitoneal injection) were administered for 1 and 4 weeks. Control groups were left without any treatment. Blood pressure (plethysmographic method) and 24 h urinary albumin excretion were measured once a week. At the end of the experimental protocols, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and type I and type IV collagen expression. After 1 and 4 weeks, the rats treated with CsA showed a significant increase (P<0.01) in blood pressure, no significant changes in urinary albumin excretion and a significant increase (P<0.01) in glomerular and tubulo-interstitial fibrosis and inflammatory infiltrates as compared with the control rats. Treatment with C21 did not modify the CsA dependent increase of blood pressure, which was higher than in control rats, but after 4 weeks of treatment significantly reduced (P<0.01) glomerular and tubulo-interstitial fibrosis, type 1 collagen expression and macrophage infiltration, as compared with rats treated with cyclosporine. The administration of C21 showed a protective effect on cyclosporine nephropathy, decreasing renal fibrosis and macrophage infiltration. These data suggest that C21 may counteract tubulo-interstitial fibrosis, the most potent predictor of the progression of renal diseases. [ABSTRACT FROM AUTHOR]

Hyperuricemia: from the evolution of species to cardiovascular risk In this review we analyze the cardiorenal effects of hyperuricemia and try to answer the eternal question of whether it is or is not to be considered a true risk factor in addition to a well-established marker of cardiovascular, cerebrovascular and renal risk. [ABSTRACT FROM AUTHOR]

Background: Lactate concentration is a robust predictor of mortality but in many low resource settings facilities for its analysis are not available. Anion gap (AG), calculated from clinical chemistry results, is a marker of metabolic acidosis and may be more easily obtained in such settings. In this systematic review and meta-analysis we investigated whether the AG predicts mortality in adult patients admitted to critical care settings. Methods: We searched Medline, Embase, Web of Science, Scopus, The Cochrane Library and regional electronic databases from inception until May 2016. Studies conducted in any clinical setting that related AG to in-hospital mortality, in-intensive care unit mortality, 31-day mortality or comparable outcome measures were eligible for inclusion. Methodological quality of included studies was assessed using the Quality in Prognostic Studies tool. Descriptive meta-analysis was performed and the I² test was used to quantify heterogeneity. Subgroup analysis was undertaken to identify potential sources of heterogeneity between studies. Results: Nineteen studies reporting findings in 12,497 patients were included. Overall, quality of studies was poor and most studies were rated as being at moderate or high risk of attrition bias and confounding. There was substantial diversity between studies with regards to clinical setting, age and mortality rates of patient cohorts. High statistical heterogeneity was found in the meta-analyses of area under the ROC curve (I² = 99 %) and mean difference (I² = 97%) for the observed AG. Three studies reported good discriminatory power of the AG to predict mortality and were responsible for a large proportion of statistical heterogeneity. The remaining 16 studies reported poor to moderate ability of the AG to predict mortality. Subgroup analysis suggested that intravenous fluids affect the ability of the AG to predict mortality. Conclusion: Based on the limited quality of available evidence, a single AG measurement cannot be recommended for risk stratification in critically ill patients. The probable influence of intravenous fluids on AG levels renders the AG an impractical tool in clinical practice. Future research should focus on increasing the availability of lactate monitoring in low resource settings. PROSPERO registration number: CRD42015015249. Registered on 4th February 2015. Abbreviations: AG, Anion gap; APACHE II, Acute physiology and chronic health evaluation ii; AUC, Area under the ROC curve; AVPU, Alert, verbal, pain, unresponsive; CIs, Confidence intervals; DKA, Diabetic ketoacidosis; ENT, Ear nose and throat; GCS, Glasgow coma scale; ICCU, Intensive cardiac care unit; ICU, Intensive care unit; IQR, Interquartile range; ISS, Injury severity score; Mdn, Median; MI, Myocardial infarction; OR, Odds ratio; PCI, Percutaneous coronary intervention; PRISMA, Preferred reporting items for systematic reviews and meta-analyses; Pro, Prospective; QUIPS, Quality in prognostic studies; Retro, Retrospective; SAPS, Simplified acute physiology score; SD, Standard deviation; SE, Standard error; SOFA, Sequential organ failure assessment; STEMI, ST-elevation myocardial infarction [ABSTRACT FROM AUTHOR]

Background: Calcifications of atherosclerotic plaques represent a controversial issue as they either lead to the stabilization or rupture of the lesion. However, the cellular key players involved in the progression of the calcified plaques have not yet been described. The primary reason for this lacuna is that decalcification procedures impair protein and nucleic acids contained in the calcified tissue. The aim of our study was to preserve the cellular content of heavily calcified plaques with a new rapid fixation in order to simplify the study of calcifications. Methods: Here we applied a fixation method for fresh calcified tissue using the Carnoy's solution followed by an enzymatic tissue digestion with type II collagenase. Immunohistochemistry was performed to verify the preservation of nuclear and cytoplasmic antigens. DNA content and RNA preservation was evaluated respectively with Feulgen staining and RT-PCR. A checklist of steps for successful image analysis was provided. To present the basic features of the F-DNA analysis we used descriptive statistics, skewness and kurtosis. Differences in DNA content were analysed with Kruskal-Wallis and Dunn's post tests. The value of P < 0.05 was considered significant. Results: Twenty-four vascular adult tissues, sorted as calcified (14) or uncalcified (10), were processed and 17 fetal tissues were used as controls (9 soft and 8 hard). Cells composing the calcified carotid plaques were positive to Desmin, Vimentin, Osteocalcin or Ki-67; the cellular population included smooth muscle cells, osteoblasts and osteoclasts-like cells and metakaryotic cells. The DNA content of each cell type found in the calcified carotid artery was successfully quantified in 7 selected samples. Notably the protocol revealed that DNA content in osteoblasts in fetal control tissues exhibits about half (3.0 ng) of the normal nuclear DNA content (6.0 ng). Conclusion: Together with standard histology, this technique could give additional information on the cellular content of calcified plaques and help clarify the calcification process during atherosclerosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of the angiotensin II (Ang II) induced-differential mi RNA expression in renal glomerular and tubulo-interstitial fibrosis in an experimental model of Ang II-dependent hypertension. To clarify this issue, Sprague Dawley rats were treated with Ang II (200 ng/kg per minute, n = 15) or physiological saline ( n = 14) for 4 weeks. Systolic blood pressure and albuminuria were measured every 2 weeks. At the end of the experimental period, renal glomerular and tubulo-interstitial fibrosis was evaluated by histomorphometric analysis, after Sirius-Red and Masson's trichrome staining. Ang II increased systolic blood pressure ( P < 0.0001), albuminuria ( P < 0.01) and both glomerular and tubulo-interstitial fibrosis ( P < 0.01). Using laser capture microdissection and mi RNA microarray analysis this study showed that miR-29a-3p was down-regulated in renal tubules and up-regulated in glomeruli. Real-time polymerase chain reaction ( PCR) experiments confirmed in Ang II-treated rats a down-regulation of miR-29a-3p in tubules ( P < 0.01), while no significant changes were observed in glomeruli. Matrix metalloproteinase-2 ( MMP-2) was identified as putative miR-29a-3p target (by TargetScan, miRanda, Tarbase software) and functionally confirmed by luciferase activity assay. These data demonstrate that the effects of Ang II on miR-29a-3p expression in renal tubules is different from the one exerted in the glomeruli and that miR-29a-3p targets MMP-2. These results suggest that the development of renal fibrosis at glomerular and tubulo-interstitial level depends on different molecular mechanisms. [ABSTRACT FROM AUTHOR]

Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs). hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL) from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki–67 assay), migration (scratch and transwell assays), and angiogenesis (Matrigel) were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR). The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers. [ABSTRACT FROM AUTHOR]

Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs). hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL) from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki–67 assay), migration (scratch and transwell assays), and angiogenesis (Matrigel) were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR). The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers. [ABSTRACT FROM AUTHOR]

Background: Portal-superior mesenteric vein (PV/SMV) resection during pancreatic resection has been widely applied in clinical practice. Methods: From a prospective data base of pancreatic resections, patients undergoing PV/SMV resection and reconstruction with a cryopreserved arterial homograft were extracted with the aim of evaluating the safety, feasibility and reproducibility of the procedure. Data regarding patient demographics, preoperative staging, surgery, histopathology and postoperative outcomes were analyzed. Results: Five patients were extracted in the last year. Indications for this technique were type IV-V degree of vein involvement and a 3.5 cm median length of vein infiltration. Median operative and clamping times were satisfactory (385 and 27 min, respectively), postoperative outcomes were good and there was no graft infection, thrombosis or stenosis occurred postoperatively and during the follow-up period. Conclusion: The use of a cryopreserved arterial homograft for PV/SMV reconstruction after pancreatic resection seems to be a feasible, safe and easily reproducible surgical technique in high-volume specialized centers and can be added to the pool of surgical solutions in selected patients. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Neoangiogenesis is crucial in plaque progression and instability. Previous data from our group showed that Nestin-positive intraplaque neovessels correlated with histological complications. The aim of the present work is to evaluate the relationship between neoangiogenesis, plaque morphology, and clinical instability of the plaque. Materials and Methods. Seventy-three patients (53 males and 20 females, mean age 71 years) were consecutively enrolled. Clinical data and 14 histological variables, including intraplaque hemorrhage and calcifications, were collected. Immunohistochemistry for CD34 and Nestin was performed. RT-PCR was performed to evaluate Nestin mRNA (including 5 healthy arteries as controls). Results. Diffusely calcified plaques (13/73) were found predominantly in females (P=0.017), with a significantly lower incidence of symptoms (TIA/stroke (P=0.019) than noncalcified plaques but with the same incidence of histological complications (P=0.156)). Accordingly, calcified and noncalcified plaques showed similar mean densities of positivity for CD34 and Nestin. Nestin density, but not CD34, correlated with the occurrence of intraplaque hemorrhage. Conclusions. Plaques with massive calcifications show the same incidence of histological complications but without influencing symptomatology, especially in female patients, and regardless of the amount of neoangiogenesis. These results can be applied in a future presurgical identification of patients at major risk of developing symptoms. [ABSTRACT FROM AUTHOR]

A novel 3-D integral formulation for solving eddy currents in thin conductors of any shape and topology is presented. The field problem is formulated with the cell method in terms of mesh currents in order to minimize the number of unknowns and, thus, computing requirements. We prove that additional degrees of freedom, globally defined, are required with complex topologies. [ABSTRACT FROM PUBLISHER]

…the issue of whether to anticoagulate or not is far from resolved and this prospective study by Genovesi et al. teaches us that although haemodialysis patients with atrial fibrillation treated with warfarin are at high risk of bleeding…the net clinical benefit of warfarin use in HD patients is not yet established, and the debate will only be resolved when a randomized controlled trial clarifies this conundrum.Background Oral anticoagulation therapy (OAT) is the choice treatment for thromboembolism prevention in atrial fibrillation (AF), although data about OAT use in haemodialysis (HD) patients with AF are contradictory. Methods The effect of OAT on the risk of mortality, stroke and bleeding was prospectively evaluated in a population of HD patients with AF. All the patients of 10 HD Italian centres alive on 31 October 2010 with documented AF episode(s) were recruited and followed-up for 2 years. OAT and antiplatelet intake, age, dialytic age, comorbidities and percentage time in the target international normalized ratio (INR) range (target therapeutic range; TTR) were considered as predictors of hazard of death, thromboembolic and bleeding events. Results At recruitment, 134 patients out of 290 were taking OAT. During the follow-up, 115 patients died (4 strokes, 3 haemorrhagic and 1 thromboembolic). Antiplatelet therapy, but not OAT, was associated with increased mortality (HR 1.71, CI 1.10–2.64, P = 0.02). The estimated survival of patients always taking OAT tended to be higher than that of patients who stopped taking (68.6 versus 49.6%, P = 0.07). OAT was not correlated to a significant decreased risk of thromboembolic events (HR 0.12, CI 0.00–3.59, P = 0.20), while it was associated with an increased risk of bleeding (HR 3.96, CI 1.15–13.68, P = 0.03). Higher TTR was associated with a reduced bleeding risk (HR 0.09, CI 0.01–0.76, P = 0.03), while previous haemorrhagic events were associated with higher haemorrhagic risk (HR 2.17, CI 1.09–4.35, P = 0.03). Conclusions In our population of HD patients with AF, the mortality is very high. OAT is not associated with increased mortality, while antiplatelet drugs are. OAT seems, on the contrary, associated with a better survival; however, it does not decrease the incidence of ischaemic stroke, whereas it increases the incidence of bleeding. Bleeding risk is lower in subjects in whom the INR is kept within the therapeutic range. [ABSTRACT FROM AUTHOR]

Vascular access-related complications are still one of the leading causes of morbidity in hemodialysis patients. The aim of this study was to compare polytetrafluoroethylene (PTFE) grafts versus tunneled cuffed permanent catheters (TCCs) in terms of vascular access and patients’ survival. An observational study was carried out with a 2-year follow-up. Eighty-seven chronic hemodialysis patients were enrolled: 31 with a PTFE graft as vascular access for hemodialysis versus 56 with a TCC. Patients’ mean age was 63.8 ± 14.6 (grafts) versus 73.5 ± 11.3 years (TCCs), P = 0.001. Significantly more patients with TCC had atrial fibrillation than patients with grafts (30.3% versus 6.5%, P = 0.01). In an unadjusted Kaplan–Meier analysis, median TCC survival at 24 months was 5.4 months longer than that of PTFE grafts but not significantly (log-rank test = 1.3, P = ns). In a Cox regression analysis adjusted for age, gender, number of previous vascular accesses, diabetes, atrial fibrillation, smoking, and any complication, this lack of significant difference in survival of the vascular access between TCC and PTFE groups was confirmed and diabetes proved to be an independent risk factor for the survival of both vascular accesses considered (P = 0.02). In an unadjusted Kaplan–Meier analysis, a higher mortality was found in the TCC group than in the PTFE group at 24 months (log-rank test = 10.07, P < 0.01). The adjusted Cox regression analysis showed that patients with TCC had a 3.2 times higher risk of death than patients with PTFE grafts. When an arteriovenous fistula (AVF) is not possible, PTFE grafts can be considered the vascular access of second choice, whereas TCCs can be used when an AVF or PTFE graft are not feasible or as a bridge to AVF or PTFE graft creation. [ABSTRACT FROM AUTHOR]