Equatorial auroral records reveal dynamics of the paleo-West Pacific geomagnetic anomaly.

Localized regions of low geomagnetic intensity such as the South Atlantic Anomaly allow energetic particles from the Van Allen radiation belt to precipitate into the atmosphere and have been linked to a signature in the form of red aurora-like airglow visible to the naked eye. Smoothed global geomagnetic models predict a low-intensity West Pacific Anomaly (WPA) during the sixteenth to nineteenth centuries characterized by a simple time dependence. Here, we link the WPA to an independent database of equatorial aurorae recorded in Seoul, South Korea. These records show a complex fluctuating behavior in auroral frequency, whose overall trend from 1500 to 1800 AD is consistent with the locally weak geomagnetic field of the WPA, with a minimum at 1650 AD. We propose that the fluctuations in auroral frequency are caused by corresponding and hitherto unknown fluctuations in the regional magnetic intensity with peaks at 1590 and 1720 AD, a time dependence that has been masked by the smoothing inherent in regularized global geomagnetic models. A physical core flow model demonstrates that such behavior requires localized time-dependent upwelling flows in the Earth's core, possibly driven by regional lower-mantle anomalies.

Online Hemodiafiltration Inhibits Inflammation-Related Endothelial Dysfunction and Vascular Calcification of Uremic Patients Modulating miR-223 Expression in Plasma Extracellular Vesicles.

Decreased inflammation and cardiovascular mortality are evident in patients with end-stage chronic kidney disease treated by online hemodiafiltration. Extracellular vesicles (EV) are mediators of cell-to-cell communication and contain different RNA types. This study investigated whether mixed online hemodiafiltration (mOL-HDF) beneficial effects associate with changes in the RNA content of plasma EV in chronic kidney disease patients. Thirty bicarbonate hemodialysis (BHD) patients were randomized 1:1 to continue BHD or switch to mOL-HDF. Concentration, size, and microRNA content of plasma EV were evaluated for 9 mo; we then studied EV effects on inflammation, angiogenesis, and apoptosis of endothelial cells (HUVEC) and on osteoblast mineralization of vascular smooth muscle cells (VSMC). mOL-HDF treatment reduced different inflammatory markers, including circulating CRP, IL-6, and NGAL. All hemodialysis patients showed higher plasma levels of endothelial-derived EV than healthy subjects, with no significant differences between BHD and mOL-HDF. However, BHD-derived EV had an increased expression of the proatherogenic miR-223 with respect to healthy subjects or mOL-HDF. Compared with EV from healthy subjects, those from hemodialysis patients reduced angiogenesis and increased HUVEC apoptosis and VSMC calcification; however, all these detrimental effects were reduced with mOL-HDF with respect to BHD. Cell transfection with miR-223 mimic or antagomiR proved the role of this microRNA in EV-induced HUVEC and VSMC dysfunction. The switch from BHD to mOL-HDF significantly reduced systemic inflammation and miR-223 expression in plasma EV, thus improving HUVEC angiogenesis and reducing VSMC calcification.

A 5G-Enabled Smart Waste Management System for University Campus.

Future university campuses will be characterized by a series of novel services enabled by the vision of Internet of Things, such as smart parking and smart libraries. In this paper, we propose a complete solution for a smart waste management system with the purpose of increasing the recycling rate in the campus and provide better management of the entire waste cycle. The system is based on a prototype of a smart waste bin, able to accurately classify pieces of trash typically produced in the campus premises with a hybrid sensor/image classification algorithm, as well as automatically segregate the different waste materials. We discuss the entire design of the system prototype, from the analysis of requirements to the implementation details and we evaluate its performance in different scenarios. Finally, we discuss advanced application functionalities built around the smart waste bin, such as optimized maintenance scheduling.

Case series of six kidney transplanted patients with COVID-19 pneumonia treated with tocilizumab.

Few reports described the outcome of kidney transplanted patients (KTs) affected by COVID-19 treated with interleukin-6 receptor inhibitor tocilizumab (TCZ). We report our case series of 6 KTs with COVID-19 pneumonia who received TCZ: All were of male gender, with a mean age of 55.5 ± 8.4 years, a median time from transplantation of 3611 days (1465-5757); 5/6 had cardiovascular comorbidities, 1/6 had diabetes, and 3/6 have one or more previous KTs. Four out of six patients died, at an average time of 9.75 ± 2.4 days after tocilizumab administration, 3/6 due to a coexistent septic shock. Two patients improved after TCZ and were discharged at 20 and 21 days, respectively; in both patient, a significant increase of total lymphocyte count was observed. In conclusion, KTs, where the role of peculiar factors such as chronic immunosuppression is still undetermined, represent a high-risk group with significant COVID-19-associated mortality. The evaluation of the TCZ effect in COVID-19 pneumonia requires controlled studies (ideally RCTs) in this specific population.

Large Abdominal Aortic Aneurysm in a High-Risk Surgical Patient: Combined Percutaneous Transfemoral TAVI and EVAR Procedure.

A 78-year-old man was referred for surgical treatment of a 55 x 59 mm abdominal aortic aneurysm (AAA). However, clinical and instrumental data revealed a more complex case than was initially thought, the patient having a large AAA in the setting of severe symptomatic aortic stenosis with multiple comorbidities. Following multidisciplinary discussion, a combined transcatheter aortic valve implantation and endovascular aneurysm repair was performed. The present case represents a good example of the importance of the heart team in the project of tailored operative strategies, and in the optimization of the interventional therapy for the individual patient.

Von Willebrand factor antigen predicts response to double dose of aspirin and clopidogrel by PFA-100 in patients undergoing primary angioplasty for ST elevation myocardial infarction.

Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P < 0.001). Delta of CEPI-CT (T1 - T0) was significantly related to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

Climatological predictions of the auroral zone locations driven by moderate and severe space weather events.

Auroral zones are regions where, in an average sense, aurorae due to solar activity are most likely spotted. Their shape and, similarly, the geographical locations most vulnerable to extreme space weather events (which we term 'danger zones') are modulated by Earth's time-dependent internal magnetic field whose structure changes on yearly to decadal timescales. Strategies for mitigating ground-based space weather impacts over the next few decades can benefit from accurate forecasts of this evolution. Existing auroral zone forecasts use simplified assumptions of geomagnetic field variations. By harnessing the capability of modern geomagnetic field forecasts based on the dynamics of Earth's core we estimate the evolution of the auroral zones and of the danger zones over the next 50 years. Our results predict that space-weather related risk will not change significantly in Europe, Australia and New Zealand. Mid-to-high latitude cities such as Edinburgh, Copenhagen and Dunedin will remain in high-risk regions. However, northward change of the auroral and danger zones over North America will likely cause urban centres such as Edmonton and Labrador City to be exposed by 2070 to the potential impact of severe solar activity.

Increase of continuous treatments and regional citrate anticoagulation during renal replacement therapy in the ICUs of the North-West of Italy from 2007 to 2015.

BACKGROUND: Few reports have addressed the change in renal replacement therapy (RRT) management in the Intensive care Units (ICUs) over the years in western countries. This study aims to assess the trend of dialytic practice in a 4.5-million population-based study of the northwest of Italy. METHODS: A nine-year survey covering all the RRT provided in the ICUs. Consultant nephrologists of the 26 Nephrology and Dialysis centers reported their activities in the years 2007, 2009, 2012, and 2015. RESULTS: From 2007 to 2015 the patients treated increased from 1042 to 1139, and the incidence of RRT from 254 to 263 cases/10^6 inhabitants. The workload for dialysis center was higher in the larger hub hospitals. RRT for acute kidney injury (AKI), continuation of treatment in chronically dialyzed patients, or extrarenal indications accounted for about the stable rate of 70, 25 and 5% of all RRT sessions, respectively. Continuous modality days increased from 2731 days (39.5%) in 2007 to 5076 (70.6%) in 2015, when the continuous+prolonged treatment days were 6880/7196 (95.6% of total days). As to RRT timing, in 2015 only the classical clinical criteria, and no K-DIGO stage were adopted by most Centers. As to RRT interruption, in 2015 urine volume was the first criterion. Implementation of citrate anticoagulation (RCA) for RRT patients significantly increased from 2.8% in 2007 to 30.9% in 2015, when it was applied in all 26 Centers. CONCLUSIONS: From 2007 to 2015, current practice has changed towards shared protocols, with increasing continuous modality and RCA implementation.

Prevalence and correlates of erectile dysfunction in men on chronic haemodialysis: a multinational cross-sectional study.

BACKGROUND: Factors associated with erectile dysfunction in men on haemodialysis are incompletely identified due to suboptimal existing studies. We determined the prevalence and correlates of erectile dysfunction and identified combinations of clinical characteristics associated with a higher risk of erectile dysfunction using recursive partitioning and amalgamation (REPCAM) analysis. METHODS: We conducted a multinational cross-sectional study in men on haemodialysis within a collaborative network. Erectile dysfunction and depressive symptoms were evaluated using the erectile function domain of the International Index of Erectile Function questionnaire and the Center for Epidemiological Studies-Depression Scale, respectively. RESULTS: Nine hundred and forty-six (59%) of 1611 eligible men provided complete data for erectile dysfunction. Eighty-three per cent reported erectile dysfunction and 47% reported severe erectile dysfunction. Four per cent of those with erectile dysfunction were receiving pharmacological treatment. Depressive symptoms were the strongest correlate of erectile dysfunction [adjusted odds ratio 2.41 (95% confidence interval (CI) 1.57-3.71)]. Erectile dysfunction was also associated with age (1.06, 1.05-1.08), being unemployed (1.80, 1.17-2.79) or receiving a pension (2.05, 1.14-3.69) and interdialytic weight gain (1.9-2.87 kg, 1.92 [CI 1.19-3.09]; >2.87 kg, 1.57 [CI 1.00-2.45]). Married men had a lower risk of erectile dysfunction (0.49, 0.31-0.76). The prevalence of erectile dysfunction was highest (94%) in unmarried and unemployed or retired men who have depressive symptoms. CONCLUSIONS: Most men on haemodialysis experience erectile dysfunction and are untreated. Given the prevalence of this condition and the relative lack of efficacy data for pharmacological agents, we suggest that large trials of pharmacological and non-pharmacological interventions for erectile dysfunction and depression are needed.

Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation.

Introduction: Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev-Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosomes (pEXOs) are smallest nanovesicles exerting early postoperative cardioprotection. We hypothesized that late plasma exosomal microRNAs (miRs) contribute to Rev-Rem during the late postoperative period. Methods: Primary MR patients (n = 19; age, 45-71 years) underwent cardiac magnetic resonance imaging and blood sampling before (T0) and 6 months after (T1) MVR. The postoperative LV Rev-Rem was assessed in terms of a decrease in LV end-diastolic volume and patients were stratified into high (HiR-REM) and low (LoR-REM) LV Rev-Rem subgroups. Isolated pEXOs were quantified by nanoparticle tracking analysis. Exosomal microRNA (miR)-1, -21-5p, -133a, and -208a levels were measured by RT-qPCR. Anti-hypertrophic effects of pEXOs were tested in HL-1 cardiomyocytes cultured with angiotensin II (AngII, 1 µM for 48 h). Results: Surgery zeroed out volume regurgitation in all patients. Although preoperative pEXOs were similar in both groups, pEXO levels increased after MVR in HiR-REM patients (+0.75-fold, p = 0.016), who showed lower cardiac mass index (-11%, p = 0.032). Postoperative exosomal miR-21-5p values of HiR-REM patients were higher than other groups (p < 0.05). In vitro, T1-pEXOs isolated from LoR-REM patients boosted the AngII-induced cardiomyocyte hypertrophy, but not postoperative exosomes of HiR-REM. This adaptive effect was counteracted by miR-21-5p inhibition. Summary/Conclusion: High levels of miR-21-5p-enriched pEXOs during the late postoperative period depict higher LV Rev-Rem after MVR. miR-21-5p-enriched pEXOs may be helpful to predict and to treat incomplete LV Rev-Rem after successful early surgical MVR.

[Indications from the first audit on peritoneal dialysis in Piedmont and Aosta valley]. / Indicazioni dal primo audit sulla dialisi peritoneale in Piemonte e in Valle D'Aosta.

In March 2009 a clinical audit was held in Turin on peritoneal dialysis in order to analyze the problems that still hinder the effective deployment of the technique in Piedmont-Aosta Valley. Various data about epidemiological and clinical management were collected by means of a questionnaire that all 26 nephrology centers of the two regions responded to. The two major critical issues highlighted were the role of the outpatient facility dedicated to uremic patients and why the peritoneal technique was not chosen for new dialysis patients. With regard to the first issue, the presence of a well structured outpatient facility dedicated to chronic renal failure seems to direct more uremic patients to peritoneal dialysis, at the same time decreasing the rate of late referrals. Regarding the second issue, patient choice was the leading cause followed by problems related to the partner, while traditional clinical contraindications interfered to a lesser extent with the choice of dialysis technique. We therefore believe that it will be possible to increase the use of peritoneal dialysis by improving organizational aspects of the dialysis center and trying to remedy the lack of social support. Accurate information and early care of uremic patients by dedicated outpatient facilities are in fact able to lead more patients to choose peritoneal dialysis. The implementation of measures of support, such as financial incentives to dialysis patients following a recent decision of the Piedmont region, could help to overcome problems related to the lack or unhelpfulness of a partner.

Long-Term Preservation of Renal Function in Septic Shock Burn Patients Requiring Renal Replacement Therapy for Acute Kidney Injury.

BACKGROUND: The real impact of septic shock-associated acute kidney injury (AKI) on the long-term renal outcome is still debated, and little is known about AKI-burn patients. In a cohort of burn survivors treated by continuous renal replacement therapy (CRRT) and sorbent technology (CPFA-CRRT), we investigated the long-term outcome of glomerular and tubular function. METHODS: Out of 211 burn patients undergoing CRRT from 2001 to 2017, 45 survived, 40 completed the clinical follow-up (cumulative observation period 4067 months, median 84 months, IR 44-173), and 30 were alive on 31 December 2020. Besides creatinine and urine albumin, in the 19 patients treated with CPFA-CRRT, we determined the normalized GFR by 99mTc-DTPA (NRI-GFR) and studied glomerular and tubular urine protein markers. RESULTS: At the follow-up endpoint, the median plasma creatinine and urine albumin were 0.99 (0.72-1.19) and 0.0 mg/dL (0.0-0.0), respectively. NRI-GFR was 103.0 mL/min (93.4-115). Four patients were diabetic, and 22/30 presented at least one risk factor for chronic disease (hypertension, dyslipidemia, and overweight). Proteinuria decreased over time, from 0.47 g/day (0.42-0.52) at 6 months to 0.134 g/day (0.09-0.17) at follow-up endpoint. Proteinuria positively correlated with the peak of plasma creatinine (r 0.6953, p 0.006) and the number of CRRT days (r 0.5650, p 0.035) during AKI course, and negatively with NRI-GFR (r -0.5545, p 0.049). In seven patients, urine protein profile showed a significant increase of glomerular marker albumin and glomerular/tubular index. CONCLUSIONS: Burn patients who experienced septic shock and AKI treated with CRRT had a long-term expectation of preserved renal function. However, these patients were more predisposed to microalbuminuria, diabetes, and the presence of risk factors for intercurrent comorbidities and chronic renal disease.

Plesio-geostrophy for Earth's core: I. Basic equations, inertial modes and induction.

An approximation is developed that lends itself to accurate description of the physics of fluid motions and motional induction on short time scales (e.g. decades), appropriate for planetary cores and in the geophysically relevant limit of very rapid rotation. Adopting a representation of the flow to be columnar (horizontal motions are invariant along the rotation axis), our characterization of the equations leads to the approximation we call plesio-geostrophy, which arises from dedicated forms of integration along the rotation axis of the equations of motion and of motional induction. Neglecting magnetic diffusion, our self-consistent equations collapse all three-dimensional quantities into two-dimensional scalars in an exact manner. For the isothermal magnetic case, a series of fifteen partial differential equations is developed that fully characterizes the evolution of the system. In the case of no forcing and absent viscous damping, we solve for the normal modes of the system, called inertial modes. A comparison with a subset of the known three-dimensional modes that are of the least complexity along the rotation axis shows that the approximation accurately captures the eigenfunctions and associated eigenfrequencies.

Procalcitonin, white blood cell count and C-reactive protein as predictors of S. aureus infection and mortality in infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is characterized by high rates of in-hospital death, and Staphylococcus aureus infection predicts a worse prognosis. We aimed to assess if admission inflammatory biomarkers (white blood cell - WBC - count, C-reactive protein - CRP, and procalcitonin) are informative on microbiological etiology and short-term outcomes. METHODS: Data from 236 patients admitted for IE from January 2013 to June 2018 were retrieved from a multicenter registry. RESULTS: Fifty-two patients (22%) were infected by S. aureus. WBC, CRP and procalcitonin had area under the curve (AUC) values for S. aureus infection of 0.595, 0.675, and 0.727, respectively. Adding procalcitonin to WBC improved discrimination over WBC alone (p = 0.045), and procalcitonin predicted S. aureus infection independently from the other inflammatory biomarkers and patient characteristics. Patients with WBC ≥ 12,800/mm3, CRP ≥ 130 mg/L, and procalcitonin ≥ 1.7 ng/mL had an almost 20-fold higher risk of S. aureus infection than patients with all biomarkers < cut-offs. AUC values for in-hospital death were 0.702, 0.725 and 0.727 for the WBC, CRP, and procalcitonin, respectively. Among inflammatory biomarkers, WBC and procalcitonin independently predicted in-hospital death. Procalcitonin refined risk stratification when added to WBC, and to the combination of WBC and CRP. Patients with WBC ≥ 10,535/mm3, CRP ≥ 85 mg/dL, and procalcitonin ≥ 0.4 ng/mL had a 27-fold higher risk of in-hospital death than patients with all biomarkers < cut-offs. CONCLUSIONS: Among patients with IE, high levels of inflammatory biomarkers on admission, particularly procalcitonin, are associated with a higher likelihood of S. aureus infection, and a higher risk of in-hospital mortality.

Influence of involvement of anterior leaflet versus posterior leaflet on residual regurgitation as assessed by transesophageal echocardiography in patients undergoing valve repair for mitral regurgitation due to mitral valve prolapse.

BACKGROUND: Repair of anterior leaflet prolapse is technically more challenging and this might influence outcomes as compared to the repair of posterior leaflet prolapse in patients undergoing surgical correction of mitral regurgitation. We investigated the association of anterior leaflet prolapse with minor residual mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) who underwent valve repair. METHODS: Eligible for this study were consecutive patients with severe MR due to MVP, who underwent mitral valve repair with residual MR by postpump transesophageal echocardiography

Predictive value of less than moderate residual mitral regurgitation as assessed by transesophageal echocardiography for the short-term outcomes of patients with mitral regurgitation treated with mitral valve repair.

BACKGROUND: Traditionally, in patients with mitral regurgitation (MR) a successful mitral valve repair is considered when residual MR by post-pump transesophageal echocardiography (TEE) is less than moderate or absent. Little is known about the prognostic value of less than moderate (mild or mild-to-moderate) residual MR for the early outcome of patients treated with mitral valve repair. METHODS: Eligible for this study were patients undergoing isolated mitral valve repair. Patients with moderate or severe residual MR after valve repair were excluded. The primary endpoint of the study was the composite of death or need of reintervention. RESULTS: A total of 98 patients (54 with no residual MR-Group 1, and 44 with less than moderate residual MR-Group 2) were analyzed. Of these, 72% presented with New York Heart Association (NYHA) 3/4, and 38% were women. The primary endpoint of the study occurred in 3 (5.5%) patients in Group 1 and 6 (13.6%) patients in Group 2 MR (P = 0.31). There was a trend toward a higher incidence of use of inotropic drugs post-interventional (P = 0.12), and a longer hospital stay among patients with less than moderate residual MR (P = 0.18). CONCLUSION: In our study population, patients with less than moderate residual MR had a trend toward a higher risk of early adverse outcomes as compared with patients with no residual MR by post-pump TEE. Studies with a larger patient population and longer follow-up data may be useful to better define the clinical significance of residual mild MR after mitral vale repair.

Characterization of columnar inertial modes in rapidly rotating spheres and spheroids.

We consider fluid-filled spheres and spheroidal containers of eccentricity ϵ in rapid rotation, as a proxy for the interior dynamics of stars and planets. The fluid motion is assumed to be quasi-geostrophic (QG): horizontal motions are invariant parallel to the rotation axis z, a characteristic which is handled by use of a stream function formulation which additionally enforces mass conservation and non-penetration at the boundary. By linearizing about a quiescent background state, we investigate a variety of methods to study the QG inviscid inertial wave modes which are compared with fully three-dimensional (3D) calculations. We consider the recently proposed weak formulation of the inviscid system valid in spheroids of arbitrary eccentricity, to which we present novel closed-form polynomial solutions. Our modal solutions accurately represent, in both spatial structure and frequency, the most z-invariant of the inertial wave modes in a spheroid, and constitute a simple basis set for the analysis of rotationally dominated fluids. We further show that these new solutions are more accurate than those of the classical axial-vorticity equation, which is independent of ϵ and thus fails to properly encode the container geometry. We also consider the effects of viscosity for the cases of both no-slip and stress-free boundary conditions for a spherical container. Calculations performed under the columnar approximation are compared with 3D solutions and excellent agreement has been found despite fundamental differences in the two formulations.

Transapical transcatheter mitral valve-in-valve implantation versus minimally invasive surgery for failed mitral bioprostheses.

OBJECTIVES: The aim of this study was to compare early outcomes and survival of patients undergoing minimally invasive mitral valve replacement through a right anterior minithoracotomy (MIMVR) versus patients undergoing transcatheter transapical mitral valve-in-valve (M-VIV) implantation for a failed mitral bioprostheses. METHODS: From 2005 to 2015, 61 patients with a failed mitral bioprosthesis underwent either MIMVR ( n = 40 patients, 65.6%) or M-VIV implantation ( n = 21, 34.4%) at our institution. The groups were compared in terms of early outcomes and survival rates. Treatment selection bias was controlled by a propensity score and was included along with the comparison variable in the multivariable analyses of outcome. RESULTS: Patients with M-VIV implantation were older ( P = 0.03), had more pulmonary hypertension ( P = 0.02) and a higher EuroSCORE ( P = 0.001). In-hospital mortality was 7.5% ( n = 3) in the MIMVR group and 4.7% ( n = 1) in the M-VIV group [odds ratio (OR) = 2.46; P = 0.512]. Incidence of stroke was 12.5% ( n = 5) in the MIMVR group vs 4.7% ( n = 1) in the M-VIV group (OR = 0.887; P = 0.935). No significant differences were noted in postprocedural complications, even after adjusting the results for the propensity score. M-VIV patients had shorter stays in the intensive care unit and in the hospital ( P = 0.02). In the M-VIV group, 28% ( n = 7) had less than mild paravalvular leakage, whereas no patients had mild paravalvular leakage in the MIMVR group ( P < 0.001). Finally, the 2-year survival rates were 86 ± 1% vs 87 ± 1% in patients undergoing MIMVR compared with those undergoing M-VIV implantation, respectively ( P = 0.1). CONCLUSIONS: In selected patients, M-VIV can be performed safely with results comparable with those of surgical therapy.

N-terminal fragment of B-type natriuretic peptide predicts coexisting subclinical heart and vessel disease.

BACKGROUND: Identification of preclinical cardiovascular disease represents a challenge. We evaluate N-terminal proB-type natriuretic peptides (NT-proBNP) as markers of both cardiac and vascular subclinical disease in a community-based study including asymptomatic middle- aged study participants. METHODS AND RESULTS: In total, 807 study participants without previous cardiovascular disease were recruited. They underwent thorough laboratory assessment (including NT-proBNP), ultrasound examination of heart and evaluation of coronary calcium score and carotid intima-media thickness, by computed tomography and ultrasound, respectively.Cardiac and vascular disease were defined as one among left ventricular (LV) ejection fraction less than 50% (3.1%), E/E' ratio more than 15 (9%), LV mass index more than 115 in men or more than 95 g/m in women (20%), LV end diastolic diameter more than 55 mm (2.5%), coronary calcium score more than 100 AU (13%), or carotid intima-media thickness more than 1.2 mm (21%), respectively. NT-proBNP [OR, 1.275; 95% (confidence interval) CI, 1.007-1.613, P < 0.001], 10-year Framingham risk score (FRS; OR 1.132; 95% CI, 1.058-1.212, P < 0.001) and lower creatinine clearance (OR, 0.983; 95% CI, 0.971-0.994, P < 0.001) predicted cardiac (220, 27%), whereas 10-year Framingham risk score (OR, 1.340; 95% CI, 1.245-1.674, P < 0.001) and NT-proBNP (OR, 1.501; 95% CI, 1.181-1.907, P < 0.001) predicted vascular involvement (215, 26%), at multivariate analysis. In total, 84 study participants (10.1%) had coexisting cardiac and vascular disease. NT-proBNP increased linearly from health study participants to study participants with only cardiac or vascular involvement, up to coexisting cardiovascular disease. CONCLUSION: Coexisting cardiac and vascular involvement in asymptomatic study participants is common. Along with traditional risk factors, NT-proBNP appears a valuable biomarker for global subclinical heart and vessels disease.

Low versus high dose erythropoiesis-stimulating agents in hemodialysis patients with anemia: A randomized clinical trial.

The increased risks of death and adverse events with erythropoiesis-stimulating agent (ESA) therapy targeting a higher hemoglobin level are established. It is uncertain whether the adverse effects of ESA therapy are related to dose and are mitigated when a fixed low ESA dose is used. We conducted a multicenter, prospective randomized open-label, blinded-endpoint (PROBE) trial to evaluate fixed low versus high dose ESA therapy on patient outcomes. We intended to recruit 2104 hemodialysis patients >18 years with anemia or receiving ESA treated at dialysis clinics in Italy. The intervention was fixed low (4000 IU epoetin alfa equivalent weekly) or high (18,000 IU epoetin alfa equivalent weekly) dose ESA for 12 months. Primary outcomes were serum transferrin, ferritin, albumin, C-reactive protein and ESA dose. Secondary outcomes were the composite of death or cardiovascular event, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, cardiovascular hospitalization, and quality of life. Study recruitment was terminated after inclusion of 656 participants with convergence of ESA dose between groups during follow up. Fixed low dose ESA had uncertain effects on serum ferritin (delta of delta (DD) 3.9 ng/ml, 95% CI -85.0 to 92.8), transferrin (9.2 mg/dl, -6.3 to 24.8), transferrin saturation (3.7%, -5.0 to 12.3), serum albumin (-0.03 g/dl, -0.2 to 0.1), or C-reactive protein (-0.6 mg/l, -3.3 to 2.1). In addition, fixed dose therapy had inconclusive effects on the composite endpoint of mortality and cardiovascular events (hazard ratio [HR] 0.95, 95% CI 0.66 to 1.37), death (0.98, 0.64 to 1.52), nonfatal myocardial infarction (0.52, 0.18 to 1.52), nonfatal stroke (no events), hospital admission for cardiovascular causes (0.93, 0.50 to 1.72) or health-related quality of life. A fixed low ESA dose in hemodialysis patients has uncertain effects on serum parameters, mortality, cardiovascular events, and quality of life. Hemoglobin targets may be so entrenched in nephrology practice that a trial of ESA dose is no longer possible.