Metabolic and Hormonal Determinants of Glomerular Filtration Rate and Renal Hemodynamics in Severely Obese Individuals.

OBJECTIVE: Renal function is often compromised in severe obesity. A true measurement of glomerular filtration rate (GFR) is unusual, and how estimation formulae (EstForm) perform in such individuals is unclear. We characterized renal function and hemodynamics in severely obese individuals, assessing the reliability of EstForm. METHODS: We measured GFR (mGFR) by iohexol plasma clearance, renal plasma flow (RPF) by 123I-ortho-iodo-hippurate, basal and stimulated vascular renal indices, endothelium-dependent and -independent vasodilation using flow-mediated dilation (FMD) as well as metabolic and hormonal profile in morbid, otherwise healthy, obese subjects. RESULTS: Compared with mGFR, the better performing EstForm was CKD-EPI (5.3 ml/min/1.73 m2 bias by Bland-Altman analysis). mGFR was directly related with RPF, total and incremental glucose AUC, and inversely with PTH and h8 cortisol. Patients with mGFR below the median shown significantly higher PTH and lower vitamin D3. Basal or dynamic renal resistive index, FMD, pulse wave velocity were not related with mGFR. In an adjusted regression model, renal diameter and plasma flow remained related with mGFR (R2 = 0.67), accounting for 15% and 21% of mGFR variance, respectively. CONCLUSIONS: CKD-EPI formula should be preferred in morbid obesity; glucose increments during oral glucose tolerance test correlate with hyperfiltration; RPF and diameter are independent determinants of mGFR; slightly high PTH values, frequent in obesity, might influence mGFR

Low Occurrence of Infections and Death in a Real-World Cohort of Patients with Cardiac Implantable Electronic Devices

Background. The incidence of infections and death in patients implanted with cardiac implantable electronic devices (CIEDs) is not fully known yet. Aim. To describe the incidence of CIED-related infection and death, and their potential predictors in a contemporary cohort of CIED patients. Methods. All consecutive patients implanted with a CIED at our institution were prospectively enrolled. Follow-up visits were performed 2 weeks after CIED implantation for all patients, and then every 6 months for implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT) patients and every 12 months for pacemaker (PM) patients. The adjudication of CIED-related infections was performed by two independent investigators and potential disagreement was resolved by a senior investigator. Results. Between September 2016 and August 2020, a total of 838 patients were enrolled (34.6% female; median age 77 (69.6–83.6); median PADIT score 2 (2–4)). PMs were implanted in 569 (68%) patients and ICD/CRT in 269 (32%) patients. All patients had pre-implant antibiotic prophylaxis and 5.5% had an antibiotic-eluting envelope. Follow-up data were available for 832 (99.2%) patients. After a median follow-up of 42.3 (30.2–56.4) months, five (0.6%) patients had a CIED-related infection and 212 (25.5%) patients died. Using multivariate Cox regression analysis, end-stage chronic kidney disease (CKD) requiring dialysis and therapy with corticosteroids was independently associated with a higher risk of infection (hazard ratio (HR): 14.20; 95% confidence interval (CI) 1.48–136.62 and HR: 14.71; 95% CI 1.53–141.53, respectively). Age (HR: 1.07; 95% CI 1.05–1.09), end-stage CKD requiring dialysis (HR: 6.13; 95% CI 3.38–11.13) and history of atrial fibrillation (HR: 1.47; 95% CI 1.12–1.94) were independently associated with all-cause death. Conclusions. In a contemporary cohort of CIED patients, mortality was substantially high and associated with clinical factors depicting a population at risk. On the other hand, the incidence of CIED-related infections was low

Percutaneous pericardiocentesis for pericardial effusion: predictors of mortality and outcomes

Pericardial effusion can dangerously precipitate patient’s hemodynamic stability and requires prompt intervention in case of tamponade. We investigated potential predictors of in-hospital mortality, a composite outcome of in-hospital mortality, pericardiocentesis-related complications, and the need for emergency cardiac surgery and all-cause mortality in patients undergoing percutaneous pericardiocentesis. This is an observational, retrospective, single-center study on patients undergoing percutaneous pericardiocentesis (2010–2019). We enrolled 81 consecutive patients. Median age was 71.4 years (interquartile range [IQR] 58.1–78.1 years) and 51 (63%) were male. Most of the pericardiocentesis were performed in an urgency setting (76.5%) for cardiac tamponade (77.8%). The most common etiology was idiopathic (33.3%) followed by neoplastic (22.2%). In-hospital mortality was 14.8% while mortality during follow-up (mean 17.1 months) was 44.4%. Only hemodynamic instability (i.e., cardiogenic shock, hypotension refractory to fluid challenge therapy and inotropes) was associated with in-hospital mortality at the univariate analysis (odds ratio [OR] 7.2; 95% confidence interval [CI] 1.76–29.4). Non-neoplastic/non-idiopathic etiology and hemodynamic instability were associated with the composite outcome of in-hospital mortality, need for emergency cardiac surgery, or pericardiocentesis-related complications (OR 5.75, 95% CI 1.65–20.01, and OR 5.81, 95% CI 2.11–15.97, respectively). Multivariate Cox regression analysis adjusted for possible confounding variables (age, coronary artery disease, and hemodynamic instability) showed that neoplastic etiology was independently associated with medium-term mortality (hazard ratio [HR] 4.05, 95% CI 1.45–11.36). In a real-world population treated with pericardiocentesis for pericardial effusion, in-hospital adverse outcomes and medium-term mortality are consistent, in particular for patients presenting with hemodynamic instability or neoplastic pericardial effusion

(Non)local Hamiltonian and symplectic structures, recursions, and hierarchies: a new approach and applications to the N=1 supersymmetric KdV equation

Using methods of math.DG/0304245 and [I.S.Krasil'shchik and P.H.M.Kersten, Symmetries and recursion operators for classical and supersymmetric differential equations, Kluwer, 2000], we accomplish an extensive study of the N=1 supersymmetric Korteweg-de Vries equation. The results include: a description of local and nonlocal Hamiltonian and symplectic structures, five hierarchies of symmetries, the corresponding hierarchies of conservation laws, recursion operators for symmetries and generating functions of conservation laws. We stress that the main point of the paper is not just the results on super-KdV equation itself, but merely exposition of the efficiency of the geometrical approach and of the computational algorithms based on it.Comment: 16 pages, AMS-LaTeX, Xy-pic, dvi-file to be processed by dvips. v2: nonessential improvements of exposition, title change

The impact of particle radiotherapy on the functioning of cardiac implantable electronic devices: a systematic review of in vitro and in vivo studies according to PICO criteria

The number of oncological patients who may benefit from proton beam radiotherapy (PBT) or carbon ion radiotherapy (CIRT), overall referred to as particle radiotherapy (RT), is expected to strongly increase in the next future, as well as the number of cardiological patients requiring cardiac implantable electronic devices (CIEDs). The management of patients with a CIED requiring particle RT deserves peculiar attention compared to those undergoing conventional photon beam RT, mostly due to the potential generation of secondary neutrons by particle beams interactions. Current consensus documents recommend managing these patients as being at intermediate/high risk of RT-induced device malfunctioning regardless of the dose on the CIED and the beam delivery method used, despite the last one significantly affects secondary neutrons generation (very limited neutrons production with active scanning as opposed to the passive scattering technique). The key issues for the current review were expressed in four questions according to the Population, Intervention, Control, Outcome criteria. Three in vitro and five in vivo studies were included. Based on the available data, PBT and CIRT with active scanning have a limited potential to interfere with CIED that has only emerged from in vitro study so far, while a significant potential for neutron-related, not severe, CIED malfunctions (resets) was consistently reported in both clinical and in vitro studies with passive scattering

High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma: an Intergruppo Italiano Linfomi randomized trial

Background and Objectives. Poor prognosis diffuse large cell lymphoma (DLCL) responds poorly to standard chemotherapy. Randomized studies comparing high-dose chemotherapy with autologous stem-cell transplantation (ASCT) against standard chemotherapy have produced conflicting results. Dose-dense chemotherapy with granulocyte colony-stimulating factor (G-CSF) support seems to hold promise. The purpose of this multicenter, randomized trial was to compare failure-free and overall survival in patients with poor prognosis DLCL treated with high-dose sequential (HDS) chemotherapy followed by ASCT or an outpatient dose-dense chemotherapy regimen (MegaCEOP). Design and Methods. Between 1996 and 2001, 130 DLCL patients, aged <= 60 years, with intermediate-high or high-risk disease, according to the International Prognostic Index score, and/or bone marrow involvement were enrolled. Sixty were randomized to HDS chemotherapy plus high-dose mitoxantrone and melphalan with ASCT (arm A) and 66 to the MegaCEOP regimen (6-8 courses of an escalated dose of cyclophosphamide and epirubicin plus vincristine and prednisone with G-CSF every 2-weeks) (arm B); 4 patients were considered ineligible. Results. The complete remission rate was 59% in arm A and 70% in arm B (p=0.18). After a median follow-up of 78 months, the 6-year failure-free survival was 45% in arm A and 48% in arm B (hazard ratio=1.15, 95% confidence intervals =0.72-1.84, p=0.56). The 5-year overall survival was 49% in arm A and 63% in arm B (hazard ratio=1.67, 95% confidence interval=0.98-2.85, p=0.06). Two cases of secondary acute myeloid leukemia were observed after treatment in group A. Interpretations and Conclusions. HDS and ASCT as initial therapy for patients with poor-prognosis DLCL does not provide a benefit over that of outpatient dose-dense MegaCEOP chemotherapy

Analysis methods for in-beam PET images in proton therapy treatment verification: a comparison based on Monte Carlo simulations

Background and purpose: In-beam Positron Emission Tomography (PET) is one of the modalities that can be used for in-vivo non-invasive treatment monitoring in proton therapy. PET distributions obtained during various treatment sessions can be compared in order to identify regions that have anatomical changes. The purpose of this work is to test and compare different analysis methods in the context of inter-fractional PET image comparison for proton treatment verification. Methods: For our study we used the FLUKA Monte Carlo code and artificially generated CT scans to simulate in-beam PET distributions at different stages during proton therapy treatment. We compared the Beam-Eye-View method, the Most-Likely-Shift method, the Voxel-Based-Morphology method and the gamma evaluation method to compare PET images at the start of treatment, and after a few weeks of treatment. The results were compared to the CT scan. Results and conclusions: Three-dimensional methods like VBM and gamma are preferred above two-dimensional methods like MLS and BEV if much statistics is available, since the these methods allow to identify the regions with anomalous activity. The VBM approach has as disadvantage that a larger number of MC simulations is needed. The gamma analysis has the disadvantage that no clinical indication exist on tolerance criteria. In terms of calculation time, the BEV and MLS method are preferred. We recommend to use the four methods together, in order to best identify the location and cause of the activity changes.Comment: 9 pages, 5 figure

A cloud based tool for knowledge exchange on local scale flood risk

There is an emerging and urgent need for new approaches for the management of environmental challenges such as flood hazard in the broad context of sustainability. This requires a new way of working which bridges disciplines and organisations, and that breaks down science-culture boundaries. With this, there is growing recognition that the appropriate involvement of local communities in catchment management decisions can result in multiple benefits. However, new tools are required to connect organisations and communities. The growth of cloud based technologies offers a novel way to facilitate this process of exchange of information in environmental science and management; however, stakeholders need to be engaged with as part of the development process from the beginning rather than being presented with a final product at the end. Here we present the development of a pilot Local Environmental Virtual Observatory Flooding Tool. The aim was to develop a cloud based learning platform for stakeholders, bringing together fragmented data, models and visualisation tools that will enable these stakeholders to make scientifically informed environmental management decisions at the local scale. It has been developed by engaging with different stakeholder groups in three catchment case studies in the UK and a panel of national experts in relevant topic areas. However, these case study catchments are typical of many northern latitude catchments. The tool was designed to communicate flood risk in locally impacted communities whilst engaging with landowners/farmers about the risk of runoff from the farmed landscape. It has been developed iteratively to reflect the needs, interests and capabilities of a wide range of stakeholders. The pilot tool combines cloud based services, local catchment datasets, a hydrological model and bespoke visualisation tools to explore real time hydrometric data and the impact of flood risk caused by future land use changes. The novel aspects of the pilot tool are; the co-evolution of tools on a cloud based platform with stakeholders, policy and scientists; encouraging different science disciplines to work together; a wealth of information that is accessible and understandable to a range of stakeholders; and provides a framework for how to approach the development of such a cloud based tool in the future. Above all, stakeholders saw the tool and the potential of cloud technologies as an effective means to taking a whole systems approach to solving environmental issues. This sense of community ownership is essential in order to facilitate future appropriate and acceptable land use management decisions to be codeveloped by local catchment communities. The development processes and the resulting pilot tool could be applied to local catchments globally to facilitate bottom up catchment management approaches

Singular solutions of fully nonlinear elliptic equations and applications

We study the properties of solutions of fully nonlinear, positively homogeneous elliptic equations near boundary points of Lipschitz domains at which the solution may be singular. We show that these equations have two positive solutions in each cone of $\mathbb{R}^n$, and the solutions are unique in an appropriate sense. We introduce a new method for analyzing the behavior of solutions near certain Lipschitz boundary points, which permits us to classify isolated boundary singularities of solutions which are bounded from either above or below. We also obtain a sharp Phragm\'en-Lindel\"of result as well as a principle of positive singularities in certain Lipschitz domains.Comment: 41 pages, 2 figure