Patients on mechanical ventilation may receive intravenous fluids via restrictive or liberal fluid management. A clear and objective differentiation between restrictive and liberal fluid management strategies is lacking in the literature. The liberal approach has been described as involving fluid rates ranging from 1.2 to 12 times higher than the restrictive approach. A restrictive fluid management may lead to hypoperfusion and distal organ damage, and a liberal fluid strategy may result in endothelial shear stress and glycocalyx damage, cardiovascular complications, lung edema, and distal organ dysfunction. The association between fluid and mechanical ventilation strategies and how they interact toward ventilator-induced lung injury (VILI) could potentiate the damage. For instance, the combination of a liberal fluids and pressure-support ventilation, but not pressure control ventilation, may lead to further lung damage in experimental models of acute lung injury. Moreover, under liberal fluid management, the application of high positive end-expiratory pressure (PEEP) or an abrupt decrease in PEEP yielded higher endothelial cell damage in the lungs. Nevertheless, the translational aspects of these findings are scarce. The aim of this narrative review is to provide better understanding of the interaction between different fluid and ventilation strategies and how these interactions may affect lung and distal organs. The weaning phase of mechanical ventilation and the deresuscitation phase are not explored in this review.The online version contains supplementary material available at 10.1186/s40635-023-00526-2. Ventilatory management may be affected by restrictive and liberal fluid strategies due to physiological interaction between heart–lung, possibly yielding to distal organ damage in critical ill patients. Pre-clinical studies evaluated the effects of different fluid strategies on ventilator-induced lung injury during assisted ventilation, at different PEEP levels, as well as after an abrupt decrease in PEEP.The online version contains supplementary material available at 10.1186/s40635-023-00526-2. Dosis sola facit venenum”, all things are poison and it is the dose that makes something poisonous. Optimizing tissue perfusion and oxygen delivery while preventing fluid overload is a challenge in critically ill patients. Restrictive fluid management ), a more negative inspiratory Ppl may increase transvascular filtration pressure. In the presence of extremely negative Ppl, due to intense inspiratory effort against obstructed airways, a sudden increase in pulmonary transvascular filtration pressure and lung edema may occur [Ppl, resulting from spontaneous breathing (or assisted ventilation), and hypervolemia  increases Ph, thus increasing the risk of edema, which can be even worse in the presence of increased vascular permeability [Pulmonary transvascular filtration pressure is defined as the difference between vascular hydrostatic pressure  and UK guidelines for the management of ARDS—support restrictive fluid therapies , 58. Evip < 0.05) [Organ damage may also be caused by insufficient fluid therapy. For example, an excessively restrictive approach can lead to renal hypoperfusion and further functional impairment , 34, 64.Even in specific syndromes, such as ARDS, it seems that distinct phenotypes (hyper- or hypoinflammatory) may respond differently to restrictive or liberal approaches, as demonstrated in the cohort in the Fluids and Catheters Treatment Trial . In thisOver the last decades, attempts to improve outcomes by fluid balance have ranged from dehydration and negative fluid balance to normovolemia and even moderate hypervolemia as primary therapeutic goals . The 201pendelluft, defined in this study as the percentage of the Vt that moves during inspiration from the non-dependent to the dependent lung region) could be a leading mechanism for VILI and P-SILI. The authors showed that regional pendelluft during BiPAP may reflect local swings in Ppl during spontaneous breathing and be associated with an increase in specific inflammatory biomarkers in patients with ARDS. On the other hand, muscle paralysis and controlled ventilation were shown to be safer than spontaneous breathing in severe acute lung injury in an animal model [Some studies have suggested that assisted spontaneous breathing modes such as PSV could be associated with a reduction in VILI and length of stay in the ICU, and an increase in ventilator-free days in experimental and clinical studies –75. Althal model .Vt and moderate-to-high PEEP after recruitment maneuver) is associated with a lower incidence of acute kidney injury [2/FiO2 ratio due to changes in hemodynamics—namely a reduction in cardiac output and a proportional reduction in venous admixture.Protective controlled ventilation  [PSV is a frequently used mode of assisted ventilation in patients who are breathing spontaneously. Intense inspiratory efforts during assisted ventilation could lead to hemodynamic impairment , 21, 70,Vt. In this context, both pressure control ventilation (PCV) and volume control ventilation (VCV) with the same tidal volume resulted in comparable cardiac output during MV. However, PCV may result in higher cardiac outputs when lower Vt are used [Vt is positively and linearly correlated with Ppl. Vascular filtration pressure for an intrathoracic vessel is the difference between hydrostatic vascular pressure and Ppl, and researchers have shown that superior vena cava transmural pressure decreased during inspiration in VCV, whereas right atrium transmural pressure did not [The effects of controlled ventilation on cardiac output and tissue perfusion partially depend on are used , 87, 88.are used . In an aare used , 90; secare used ; in this did not . This reIt has been shown that PSV in combination with a restrictive fluid strategy resulted in less lung epithelial damage in a model of acute lung injury. One likely explanation is that damage to tight junctions, which was identified by a decrease in occludin expression, was observed in animals during PSV combined only with a liberal fluid strategy but not with a restrictive fluid approach. The interaction between the mode of MV and the fluid strategy may have a mechanistic relationship . In addiThe choice of PEEP levels should also take into account the volume status. It has been shown in clinical studies that a high PEEP level can decrease kidney function despite the fluid strategy because it can increase peak inspiratory pressures . The comThe clinical evidence is scarce and mainly limited to a few experimental studies, therefore the effects of interaction between MV and fluid management on organ damage are still poorly understood. Thus, it would be reckless to address clinical recommendations based on it. Nevertheless, some possible clinical implications from these experimental studies should be pointed out. First, whenever restrictive or liberal fluids are strongly recommended, caution should be taken when choosing the ventilatory strategy. Especially in the early phase of resuscitation, when large amounts of fluids are warranted, assisted ventilation and intense inspiratory efforts may cause higher transvascular filtration pressures, vascular edema, and epithelial cell damage, especially with concurrent lung and endothelial damage. Experimental data show that despite protective ventilation, high and rapid intravenous fluid boluses can be associated with worsened lung injury and respiratory function . In thisThe understanding of physiological heart–lung interaction is fundamental to optimize fluid strategies and mechanical ventilation setting. Accepted definitions of restrictive or liberal fluid strategies do not exist. Both restrictive and liberal fluid strategies may lead to hypoperfusion and edema of distal organs, respectively. Assisted ventilation may cause self-inflicted lung injury associated with liberal fluid strategies, while controlled ventilation may impair hemodynamics, and thus distal organ damage with restrictive fluid strategies, especially when high PEEP levels are used. Gradual transitioning of ventilatory patterns is suggested to promote lung protection due to the impact on vascular compartment. Optimization of the type and mechanical ventilation setting should consider careful titration of fluid strategies in critically ill patients.Additional file 1: Table S1. Restrictive and liberal fluid strategies in experimental and clinical studies.


C. difficile toxin production or toxin gene presence. In two phase 3 trials with varied diagnostic testing methods, dosing with fecal microbiota spores, live-brpk  was associated with low rCDI rate ≤8 wks . In ECOSPOR IV, recurrence rates with FMS ≤8 wks were similar by diagnostic method . We evaluated (post hoc) if pt microbiome profiles differed by diagnostic method at study entry.rCDI is characterized by diarrhea reemergence after symptom resolution on standard-of-care antibiotics and positive test for a) ECOSPOR III, a placebo-controlled trial in pts with ≥2 prior rCDI episodes and diagnosis by toxin EIA (TOX+) and b) ECOSPOR IV, an open-label trial in pts with ≥1 prior rCDI and diagnosis by TOX+ with/without PCR or PCR+. Pts had ≥3 unformed stools/day for 2 consecutive days and symptom resolution on antibiotics before enrolling. Samples were analyzed for alpha diversity and engraftment of dose species not present at baseline using whole metagenomic sequencing. Concentrations of primary bile acids (1°BA), which cause C. difficile spore germination, were measured by targeted LC–MS panel. Statistical analyses in FMS-treated pts compared Shannon diversity, engraftment, and 1°BA concentration changes from paired baseline–Week 1 samples between subgroups.Baseline (pre-dose) stool samples were obtained from pts in P>0.05); engraftment magnitude after FMS was comparable across trials (P>0.05) . Baseline 1°BA concentrations were comparable across trials (P>0.05) and subgroups (P>0.05) and decreased by Week 1 after FMS in TOX+ (P< 0.001) and PCR+ (P< 0.001) subgroups .Baseline Shannon diversity was similarly low across TOX+ and PCR+ subgroups (Regardless of diagnostic method, microbiota diversity appeared similarly disrupted at baseline and improved rapidly by 1 wk after FMS. Engraftment magnitude and 1°BA concentration changes appeared similar across diagnostic subgroups. These data further support the low recurrence rates shown in trials of FMS.Anne J. Gonzales-Luna, PharmD, BCIDP, Cidara Therapeutics: Grant/Research Support|Ferring Pharmaceuticals: Personal Fees|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support Kevin Litcofsky, PhD, Seres Therapeutics: inventor on patents assigned to Seres Therapeutics|Seres Therapeutics: Employment|Seres Therapeutics: Stocks/Bonds Tim Straub, MS, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Dina Hot, PhD, Aimmune Therapeutics: Employee Barbara McGovern, MD, Seres Therapeutics: Stocks/Bonds Brooke Hasson, PhD, Sage Therapeutics: Stocks/Bonds|Seres Therapeutics: Stocks/Bonds Matthew Sims, MD, PhD, Adaptive Phage Therapeutics: Grant/Research Support|Applied Biocode: Advisor/Consultant|Biotest AG: Grant/Research Support|ContraFect: Grant/Research Support|Finch: Grant/Research Support|Janssen: Grant/Research Support|Leonard-Meron Biosciences: Grant/Research Support|Merck and Co: Grant/Research Support|Novozyme: Grant/Research Support|OpGen: Advisor/Consultant|OpGen: Grant/Research Support|Pfizer: Grant/Research Support|Prenosis: Advisor/Consultant|Prenosis: Grant/Research Support|QIAGEN: Grant/Research Support|Seres: Grant/Research Support|Summit Therapeutics: Grant/Research Support Christopher Ford, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Matthew Henn, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds


Candida infections in acute care hospitals, it is critical to understand the epidemiology of healthcare-associated acquisition of these fungal pathogens. Electronic health record (EHR) data is an underutilized resource in identifying potential transmission in this setting.Given increasing resistance and incidence of Candida glabrata ( >48 hrs after admission) between 1/1/2018 and 2/29/2020. Patient location in the hospital and documented contacts between patients and healthcare personnel (HCP) were extracted from the hospital EHR system. Documented contact by a HCP with 2 different patients within 6 hours was considered a potential connection between patients. Prior room occupancy within 7 days was considered potential environmental source. Similarity of C. glabrata infection was determined by isolate antifungal susceptibility profiling where minimum inhibitory concentration (MIC) to fluconazole and micafungin had to be within one doubling dilution difference.Retrospective analysis of potential source of hospital-onset infections (HOI) with C. glabrata infections were identified, of which 104, were considered HOIs. Of the 104 HOIs, 16 (15%) were associated with HCP connections, though 3 (3%) were also associated with prior room occupants. Four of the isolates matched exactly, while 7 had the same patterns of resistance and the MICs of fluconazole were within a single doubling dilution while micafungin was the same. One of the latter isolates was resistant to fluconazole. The mean time between HCP-associated infections was 11 days and the mean number of connections was 25.A total of 156 Time-line of Candida glabrata infections and HCP-associated connectionsTop panel and lower panel are part of the same timeline but split into two panels for visualization. Dots denote collection date of C. glabrata isolates. Larger grey dots are isolates from potential source patients  while black larger dots are the target patients. In two cases there was suspected onward transmission from a secondary infection, denoted by the larger blue dots. Arrows denote the associated transmission. Highlighted dots denote community vs. hospital-onset primary infections.C. glabrata leading to HOI is a rare event; however, HCP-mediated transmission was the main source of identified potential transmission events rather than direct environmental contamination. While antimicrobial stewardship, early identification, and prevention interventions should continue to be prioritized in Candida prevention programs, EHR data can be helpful in identifying potential transmission events. Further studies are needed to evaluate C. glabrata colonization pathways, as well as other Candida spp., such as C. auris, which may have different transmission characteristics.Transmission of Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant Sean Zhang, MD, PhD, Applied BioCode: Grant/Research Support|IMMY Diagnostics: Grant/Research Support|KARIUS: Advisor/Consultant|Pearl Diagnostics: Grant/Research Support|Scanogen: Grant/Research Support|T2 biosystems: Advisor/Consultant|Vela Diagnostics: Grant/Research Support


The COVID-19 pandemic has disrupted mental healthcare delivery in many countries. The restricted access to psychiatric services and double disasters (pandemic and earthquakes) coincided in Croatia, potentially placing people with severe mental illness (SMI) in a very vulnerable position.The aim of this study was to examine the changes in substance use in people with SMI in the first and the second COVID-19 wave and co-occurring earthquakes. The secondary aim was to explore whether the type of treatment  vs. treatment as usual) influenced those changes.This study was nested within the RECOVER-E project . The study involved 90 participants with SMI assessed at two time points: in May/June 2020 (during the first COVID-19 wave and after Zagreb earthquake) and in December 2020/January 2021 (during the second COVID-19 wave and after Petrinja earthquake). The changes in the use of psychoactive substances  were assessed using self-reported survey.The increase in tobacco smoking behavior and the use of sedatives was observed in both COVID-19 waves in people with SMI. No increase was reported in cannabis and other drugs use, while less than 5% of participants reported increase in alcohol consumption. Not receiving CMHT service predicted the increase in sedative use.Ensuring accessible mental health care provided by CMHT is recommended for counteracting the negative effect of external stressors (such as pandemic and co-occurring earthquakes) on the increased substance use among people with SMI.S. Levaj Grant / Research support from: Project RECOVER-E - European Union’s Horizon 2020 research and innovation programme; Grant Agreement No 779362., S. Medved Grant / Research support from: Project RECOVER-E - European Union’s Horizon 2020 research and innovation programme; Grant Agreement No 779362., J. Gerlach: None Declared, L. Shields-Zeeman Grant / Research support from: Project RECOVER-E - European Union’s Horizon 2020 research and innovation programme; Grant Agreement No 779362., F. Bolinski Grant / Research support from: Project RECOVER-E - European Union’s Horizon 2020 research and innovation programme; Grant Agreement No 779362., Z. Bradaš Grant / Research support from: Project RECOVER-E - European Union’s Horizon 2020 research and innovation programme; Grant Agreement No 779362., Z. Madžarac Grant / Research support from: Project RECOVER-E - European Union’s Horizon 2020 research and innovation programme; Grant Agreement No 779362., I. Rojnić Palavra: None Declared, M. Rojnić Kuzman Grant / Research support from: Project RECOVER-E - European Union’s Horizon 2020 research and innovation programme; Grant Agreement No 779362.


Herpes zoster (HZ) is characterized by a painful dermatomal rash and is associated with increased healthcare costs. Research quantifying work productivity loss and activity impairment associated with HZ is limited and outdated. This study aimed to describe severity of HZ related pain, health related quality of life, activity impairment, and work productivity among employed adults diagnosed with HZ in the Department of Veterans Affairs (VA) Health System.th Revision (ICD-10) HZ diagnosis were invited to complete an online survey. Respondents were indexed on their HZ diagnosis and included if aged 18-70 years, reported working for pay at index, and had 6 months of baseline continuous enrollment. Respondents were excluded if they had a baseline HZ vaccine, did not complete the survey within 30 days after index, or reported not having HZ or experiencing a rash > 14 days prior to index. Questions used to assess outcomes were based on validated survey instruments (Table 1). Work productivity was described among respondents employed at survey completion. Data were collected from 05/04/2021 to 07/07/2022. Descriptive statistics were used to summarize survey responses.This cross-sectional study utilized a self-reported survey among adults in the VA health system. Eligibility was assessed biweekly from electronic health record data, and adults with an incident International Classification of Diseases, 10Among 231 respondents completing the survey, mean (standard deviation [SD]) age was 49 (10) years and 79% were male. Overall, 70% reported experiencing pain in the last 7 days. Mean (SD)  “average-pain” severity and EQ-5D-3L scores were 4.0 (2.8)  and 0.69 (0.22) , respectively. Mean (SD) activity impairment was 42% (33%). Mean (SD) absenteeism, presenteeism, and overall work impairment were 17% (27%), 35% (30%), and 43% (35%) out of 202, 192, and 202 respondents, respectively.Burden associated with HZ is substantial, with a significant proportion experiencing pain, activity impairment, and work productivity loss. These results provide updated context on the impact of HZ in this population of employed adults in the VA health system.Funding: GlaxoSmithKline Biologicals SA (GSK study identifiers: 208907/HO-16-16967).Shaloo Gupta, MS; ORCID: 0000-0002-2535-2892, Cerner Enviza: Salary|GSK: Funding to employer to conduct and support this study Nai-Chung N. Chang, PhD; ORCID: 0000-0002-4541-8967, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Kantar Health: Grant/Research Support|Myriad Genetic Laboratories, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support Nikita Stempniewicz, MSc, GSK: Salary|GSK: Ownership Interest Chenchu Bhavani K. Tirupati, MS, MBA, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Kantar Health: Grant/Research Support|Myriad Genetic Laboratories, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support Gregorio Coronado, MBA, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Kantar Health: Grant/Research Support|Myriad Genetic Laboratories, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support Julie A. Lynch, PhD, RN, MBA; ORCID: 0000-0003-0108-2127, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support Cosmina Hogea, PhD; ORCID: 0000-0002-0686-2395, Gilead Sciences: Ownership Interest|GSK: Salary at the time of the submitted work|GSK: Ownership Interest Emily Mulvihill, MBA; ORCID: 0000-0002-1430-8837, Cerner Enviza: Salary|GSK: Funding to employer to conduct and support this study Scott L. DuVall, PhD, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support


Based on ideas due to Scovel–Weinstein, I present a general framework for constructing fluid moment closures of the Vlasov–Poisson system that exactly preserve that system’s Hamiltonian structure. Notably, the technique applies in any space dimension and produces closures involving arbitrarily-large finite collections of moments. After selecting a desired collection of moments, the Poisson bracket for the closure is uniquely determined. Therefore data-driven fluid closures can be constructed by adjusting the closure Hamiltonian for compatibility with kinetic simulations. N space dimensions is the Vlasov–Poisson system,e, mass m, position f and V has been suppressed. This single-component model generalizes simply to allow for multiple plasma species. The Vlasov–Poisson system can be derived as a formal closure of the BBGKY hierarchy1 using Bogoliubov’s hypothesis3 expressing all many-body correlations as functionals of f.The simplest non-dissipative kinetic model for a single-component plasma in k fluid moment k fluid moment couples to the degree-k fluid moments becomes a function of only those first k fluid moments. Thus, it becomes feasible to solve a finite collection of hydrodynamic equations to find time evolution of the first k fluid moments. Of course, there is no guarantee that moment evolution determined by a fluid closure bears any relation to moment evolution determined by the parent kinetic model, unless the fluid closure is chosen wisely.Kinetic plasma models, like the Vlasov–Poisson system, are formally equivalent to infinite hierarchies of hydrodynamic equations for the fluid moments. The degree-7 and intuitive guesswork. More recently, advances in machine learning9 have accelerated the development of data-driven fluid closures, as well as other data-driven reduced-order models10. But fluid closures built using black-box neural networks are known to deliver poor results when employed over large simulation time intervals. There is therefore a growing effort to incorporate inductive bias into data-driven fluid closures, with the hope of improving long-term predictions. For example, Huang et al.12 and Porteous et al.13 developed variable-moment neural-network-based fluid closures that automatically enforce hyperbolicity of the ensuing moment evolution equations.Traditional methods for developing fluid closures involve some combination of asymptotic expansions14, or a library of candidate terms16, offers a novel path toward data-driven closure modeling for non-dissipative kinetic plasmas. As presented here, the framework applies specifically to fluid closures of the Vlasov–Poisson system in N space dimensions. However, similar ideas apply to other non-dissipative kinetic plasma models, such as the Vlasov–Maxwell system19.This Article presents a framework for building variable-moment fluid closures that automatically enjoy an important structural property inherent to non-dissipative kinetic plasma models: Hamiltonian structure. The framework involves two essential components. (1) Specification of a Poisson bracket for the first 20 structure of collisional kinetic theory. Notably, metriplectic dynamical systems always decompose as the sum of a Hamiltonian part and a dissipative part; the framework developed here applies to the Hamiltonian part.The framework still applies in the presence of dissipation caused by particle collisions since a dissipative fluid closure should respect the metriplecticinfinite hierarchy of fluid moments for the Vlasov–Poisson system was first identified by Gibbons21. However, finding true Poisson brackets for finite, but arbitrarily large collections of fluid moments for the Vlasov–Poisson system represents an outstanding theoretical challenge. The Poisson bracket for the closure framework presented here provides the first complete solution. In the context of slab drift kinetic models, Tassi24 previously found Hamiltonian fluid moment closures with any number of fluid moments. But the methods underlying this result fail to extend to other dissipation-free kinetic models in any obvious manner. In the Vlasov–Poisson context, Holm and Tronci25 found Hamiltonian fluid moment closures that include arbitrarily-large collections of fluid moments that do not include the density moment. Otherwise, the best available partial solutions for Vlasov–Poisson work in one space dimension The Hamiltonian structure underlying the 26 studied Jacobi closures for drift kinetics that include two moments. Chandre and Shadwick27 found a Jacobi closure that accommodates all fluid moments with degree 28 of Perin et al.29 that also found Hamiltonian closures with 30 through a Jacobi-closure derivation of the earliest Hamiltonian fluid model due to Morrison and Greene. Jacobi closures involving moments with degree 31 dramatically highlighted this last point by revealing an earlier fluid moment model32 as a false-positive; a claimed Hamiltonian fluid closure including moments with degree At a schematic level, derivations of Jacobi closures work by first substituting an unknown closure relation into the Poisson bracket for the parent kinetic model, and then finding conditions the closure relation needs to satisfy in order for the closure bracket to satisfy the Jacobi identity. These conditions take the form of nonlinear partial differential equations (PDEs) that, in general, do not admit solutions or cannot be solved in closed form. However, there are notable exceptions. Tassif, evolution equations for the parameters are derived that ensure a time-evolving parametric f solves the kinetic equation exactly. This procedure only works for very special parametric f. For example, a distribution function of the form n is a positive function and 33 initiated a program aimed at finding moment closures with arbitrarily high-degree moments by re-parameterizing a multiple waterbag exact reduction.  Simple explicit formulas express the fluid moments of multiple waterbags as polynomials in waterbag parameters. Whenever these polynomial relationships can be inverted to give waterbag parameters in terms of fluid moments a Hamiltonian moment closure results. However, due to the general insolubility of large-degree polynomial equations, the inversion has only been demonstrated for a single waterbag. Like Jacobi closures, Hamiltonian closures based on exact reductions have yet to accommodate fluid moments of arbitrarily large degree.Derivations of Hamiltonian moment closures based on exact reductions work like the classical variation of parameters method. After postulating a parametric form for the distribution function f is given byn denotes the density, the gradient of the scalar function k centered fluid moment. "f therefore accommodate arbitrarily high-degree moments by increasing the integer N, sets them apart from all previous Hamiltonian fluid closures that currently appear in the literature.The Hamiltonian moment closures presented here fall into the exact reduction category. The relevant parametric form for A priori, the theory developed here implies there will not be any departure from evolution predicted by the reduced moment equations and evolution predicted by the unreduced Vlasov–Poisson system provided the initial distribution function is of the form specified in  Such distributions, which are relevant to self-consistent beam dynamics in particle accelerators, also give rise to a moment closure problem, where the moments are redefined as the phase space integralsDemonstrating that  compriseC(V) contains smooth functions on V with mild growth  at infinity. The dual space V. The duality pairing between dv denotes the Lebesgue measure on The following notation is used in what follows without further comment. If contactomorphism groupG. This Section aims to provide a self-contained introduction to G and its properties with greatest relevance to fluid moments. For this Section and "37 by Abraham and Marsden. Marsden and Weinstein18 were first to recognize that G is the Lie group that integrates the Lie algebra underlying the Vlasov equation. Subsequently, Gay-Balmaz and Tronci38 used structural properties of contactomorphisms to show that the integrable Bloch-Iserles system is geodesic flow on a subgroup of G. Gay-Balmaz and Tronci40 also provide additional exposition concerning the contactomorphism group as part of their ongoing efforts in quantum-classical hybrid modeling.A complete understanding of the Hamiltonian moment closures described in this Article requires familiarity with some of the rich structure of the N-dimensional vector space representing the configuration space for an N-degree of freedom Hamiltonian system with basis Q is endowed with any particular inner-product structure. The corresponding momentum phase space is Q. The dual basis on canonical 1-formP is defined by canonical symplectic form is the 2-form contactomorphismLet B, known as the group of fiber translations. Note that if B to the Abelian group of smooth functions on configuration space is a group isomorphism.The contactomorphisms zero section in phase space. The submanifold Z contains the static system states. The contactomorphisms S will be referred to as the group of isostatic contactomorphisms. The isostatic contactomorphisms complement the fiber translations in the following sense.Let b and a unique isostatic contactomorphism s such that The product mappingG. In particular, given The proof proceeds by constructing the inverse of Z is a graph over Q. Let Q. Given P. There is therefore a function S. Moreover, the fiber translation g. In fact, Observe that the zero section Q in P as Z, and set Z, i.e. s is a contactomorphism, q. Eliminate the ambiguity in the definition of g and The following argument shows that for each infinitesmial contactomorphisms comprises pairs X is a vector field on P, P, and G and Lie bracket on The Lie algebra infinitesimal fiber translations comprises pairs B is Abelian. When identifying viap-independent functions. Denote the image Lie subalgebra of isostatic infinitesimal contactomorphisms comprises pairs X is tangent to Z and C(P), namely The Lie subalgebra mentclass2pt{minimC(P), G on G on The dual space C(P) of phase space functions under the standard  Poisson bracket. The problem of finding reduced models, in particular reduced fluid models, for Vlasov–Poisson may therefore be approached at the level of the algebra C(P). Adopting this point of view requires addressing how the Lie algebra C(P) might be “reduced.” For the purposes of this Article, any reduction should somehow encode the objects dual to the first h that are polynomial in momentum p with degree at most The  Hamiltonian structure underlying the Vlasov–Poisson system is dual to the Lie algebra C(P) include proper Lie subalgebras: subspaces of C(P) that close under Poisson bracket. For example, the phase space functions that only depend on the configuration variable q  comprise an Abelian Lie subalgebra dual to the space of density moments. More generally, the momentum polynomials with degree at most 1 close under Poisson bracket becauseC(P) provides insufficient flexibility to accommodate fluid moments with degree between 0 and Plausible reductions of large ideals C(P) such that the quotient space arbitrary functions in C(P) must be contained in C(P). Unfortunately, as for subalgebra reduction, quotient algebra reduction cannot accommodate the fluid moments with degree between 0 and can successfully encode moments with degree between 1 and Quotient algebra reduction offers a more nuanced alternative to subalgebra reduction. Instead of attempting to encapsulate moments in a small subalgebra, quotient algebra reduction aims to find entclass1pt{minima35 by Scovel and Weinstein devises an alternative Lie-theoretic reduction strategy that hybridizes subalgebra reduction and quotient algebra reduction. Developed originally for application to phase space moments, Scovel–Weinstein theory adapts to the fluid moment context in straightforward fashion. In fact, their methods apply any time a Lie group G admits a decomposition by Lie subgroups G is the contactomorphism group, B is the group of fiber translations, and S is the group of isostatic contactomorphisms. Each of these groups is described with some detail in "The paperG is a Lie group that admits a decomposition by Lie subgroups Scovel–Weinstein mapG on B. This extra variable b is the price paid for “untangling” the Lie–Poisson structure on e in the group B. The mapping e to b.Suppose that f is advected by canonical transformations that prescribe the motion of individual particles in phase space. These canonical transformations naturally reside with the contactomorphism group G. The Scovel–Weinstein map This advection interpretation warrants further elaboration. Along a solution of the Vlasov–Poisson system, the distribution function quotient algebravia the quotient algebra construction. The reduced Scovel–Weinstein mapNow suppose that the Lie subalgebra This Section uses Poisson-geometric and Lie-theoretic methods to identify a Poisson bracket on a space that encodes density, fluid momentum, pressure, and higher fluid moments up to some truncation order kfluid momentk tensor field on configuration space 41 instead of ordinary tensors, but here these two kinds of objects are identified using the standard flat metric on configuration space.) If f. This is true, for example, when the moment generating function associated with the sequence fluid moment vector with degree between i. Denote the set of all such fluid moment vectors k fluid moments, and thatA degree-f at q. The precise goal of this Section is constructing a Poisson bracket on the spacecentered moments.Although specifying moments of each degree fluid comomentk tensor field on configuration space Q. If Q , every degree-k fluid comoment may be expressed using index notation asfluid comoment vector with degree between i. The vector space of all fluid comoment vectors with degree between n and The Poisson bracket on Fluid comoment vectors with degree between 1 and Let 42 between symmetric contravariant tensors, modulo degree not closed under the Schouten concomitant. Instead, these tensors possess a quotient Lie algebra structure. A similar quotient algebra structure was first noticed by Channell36 in the context of phase space moments. Partially motivated by Channell’s observations, Holm and Tronci25 found the Lie–Poisson bracket associated with  adm adm18) ak growth rate e. Regularizing short-scale Coulomb interactions therefore represents an alternative cure for the ill-posedness problem that avoids center manifolds.Ill-posedness of the V in the kinetic equation , bu, bu\docu57. Those reduced-order models assume the reduced, data-driven dependent variables admit constant symplectic or Poisson structures, or else rely on transformations to such variables. In contrast, the method presented here assumes the reduced dependent variables admit the non-constant Poisson structure provided by Scovel–Weinstein theory. In addition, the reduced dependent variables used here may either be simply related to physical quantities of interest, namely the fluid moments, or allowed to have a more flexible interpretation determined implicitly during training.The theory developed so far leads to a framework for constructing data-driven fluid closures of the Vlasov–Poisson system with Hamiltonian structure. This framework assumes availability of a legacy simulation code for the Vlasov–Poisson system; either particle-in-cell (PIC) codes or continuum codes will suffice. The framework presented here should be contrasted with the structure-preserving reduced-order modeling techniques developed by Hesthaven, Pagliantini, and Ripamontimodel35, who introduced the notion of a model for phase space moments. If it is deemed desireable for the variables f associated with W that parameterizes the energy must be adjusted to an optimal value Developing a closure that includes fluid moments up to degree-k candidate moment is given byW. (2) Reconstruct the distribution function f. Then compute the corresponding “ground-truth” evolved moment vector k ground-truth evolved moment is given byW are chosen in order to maximize agreement between moment evolution predicted by the Vlasov–Poisson system and moment evolution predicted by the Hamiltonian hydrodynamic model for the field Finding the optimal parameter value k candidate evolved momentW-dependence of the loss S(W) can be made more explicit. For example, when S(W) with Through application of the binomial formula for the degree-This Article has described a new method for developing fluid moment closures of the Vlasov–Poisson system with Hamiltonian structure. These closures apply in any number of space dimensions, and allow for collections of fluid moments with degree between 0 and 13 indicate that it is possible to construct such closures while strictly enforcing hyperbolicity. The results presented in the present Article therefore suggest investigation of the following intriguing question. Is it possible to develop expressive variable-moment data-driven fluid closures that strictly enforce both hyperbolicity and Hamiltonian structure? Within the closure framework presented here, such a constraint would limit the allowable forms of the closure Hamiltonian Variable-moment data-driven fluid closures garner increasing attention in the machine learning community. Recent resultsThe fluid closures presented here always include all fluid moments up to and including some maximum degree 18. Forthcoming publications will reveal that the Lie-theoretic methods used here transfer to the electromagnetic problem in a mathematically and physically appealing fashion. Other interesting applications of Scovel–Weinstein theory to fluid and phase space moments should be explored as well. For example, while the Lie algebra decomposition This Article has treated the electrostatic limit of collisionless plasma kinetic theory. Variable-moment fluid closures with Hamiltonian structure would also be interesting to develop for the electromagnetic problem, as embodied by the Vlasov–Maxwell system58. Finding the Casimirs would also be a necessary step when including dissipation in the fluid closures presented here using a metriplectic20 bracket.Each of the fluid closures developed here is associated with a certain direct-sum Poisson bracket 24 has found variable-moment fluid closures for slab drift-kinetic systems. But the methods used by Tassi to find closures are seemingly unrelated to the Lie-theoretic methods of Scovel–Weinstein. Is it possible to find Tassi’s drift kinetic closures using Scovel–Weinstein theory35 as was done for the closures presented here? An affirmative result might suggest a path toward variable-moment gyrofluid closures for more intricate gyroaveraged kinetic theories such as full-f gyrokinetics61. In a similar vein, it would be interesting to determine whether the closures presented here can be understood as limits of the multiple waterbag reductions described by Perin et al.33.As mentioned in the introduction, Tassi35 in the context of beam dynamics apply to a wider class of dissipation-free statistical closure problems than originally envisioned. There are many possible extensions. For example, consider the problem of solving the functional Vlasov equation for a variational weakly-nonlinear wave equation with random initial data. The algebra of functionals on the field-theoretic phase space enjoys a canonical Poisson bracket. By decomposing this algebra into affine functionals and functionals that vanish together with their first functional derivatives for the vacuum state, Scovel–Weinstein theory may be applied. The result will be Hamiltonian evolution equations for a finite collection of field correlation functions. These non-dissipative correlation dynamics do not seem to have been studied previously. In fact any dynamical system with an underlying Lie–Poisson Hamiltonian structure stands to benefit from the Scovel–Weinstein reduction method. Interestingly, combining Scovel–Weinstein with an analogue of phase space moments for the ideal compressible Euler equations appears to produce an extended theory of smoothed-particle hydrodynamics62.More broadly, this Article suggests that the methods developed by Scovel–Weinstein


BackgroundThe cornerstone of surgical education and practice is the surgical journal, but the ability to disperse the vital information within their pages had previously been limited. The use of Twitter by surgical journals has increased in recent years and has allowed these journals to reach a wider audience than they previously could. In this article, we discuss the role Twitter engagement has on a journal’s impact factor, visibility, and prestige.MethodsThe authors compiled a list of journals using the SciMago Journal and Country rank platform. Included journals’ Twitter profiles were then assessed using Twitonomy, an online platform that collects and processes data regarding individual Twitter profiles. Statistical analysis was conducted to determine the relationship between Twitter use and SCImago Journal Rank (SJR).ResultsSimple linear regression and multiple linear regression models determined that the only variables that had a statistically significant impact on all journals were the age of the Twitter account (p=0.003) and the percentage of retweets (p=0.001). When it comes to specialty-specific journals, further analysis showed that the only significant factor regarding its impact on SJR was the percentage of retweets (p=0.007).ConclusionsSurgical journals' regular use of Twitter is important in the dissemination of important information to a wide audience. This article shows that the most important variable to determine the impact and visibility of a surgical journal is the percentage of retweets. Further research should be performed to better understand how to use Twitter and other social media platforms to reach a larger audience. Since their advent, surgical journals have been a powerhouse of medical information. However, the manner in which surgical journals are advertised and obtained by the user has inevitably changed alongside the evolution of technology. From a historical perspective, awareness of the journals and their literature content depended on two things: 1) journal access and (2) the user’s knowledge regarding the journal’s platform to extract required information [ journal Traditionally, the merit and impact of a journal or article are determined based on bibliometrics . BibliomTo date, Twitter remains unparalleled as a leader in the transmission of evidence-based information to members of the medical community . SurgicaDespite the popularity and ubiquitous nature of Twitter, a limited number of studies examine how Twitter usage may affect the impact of the journals' scientific influence as measured by the SCImago Journal Rank (SJR) . The SJRUtilizing the SCImago Journal and Country Rank platform, a search was conducted on May 15, 2022, to identify relevant surgical journals in the following specialties: plastic surgery, cardiac surgery, orthopedic surgery, and neurosurgery. To ensure all relevant journals were accounted for, we utilized the following MeSH terms: "plastic surgery," "plastic and reconstructive surgery" and "aesthetic surgery," "thoracic" and "cardiac surgery" and "cardiovascular surgery," "orthopaedic" and "orthopedic," and "neurosurgery." The aforementioned MeSH terms were utilized in conjunction with the journal category filter tool provided by the SCImago platform to further validate our screening process. Journals were excluded on the basis of either non-English language or lack of presence on Twitter. Furthermore, journals with Twitter accounts associated with multiple specialties were excluded as well. Of the 86 journals found, 54 were included based on our inclusion criteria. For journals with dedicated Twitter profiles, the change in SJR between the year the Twitter account was established and 2021 was recorded. Whether or not journals experienced an increase in SJR since joining Twitter was investigated.Assessment of the journal's Twitter involvement was assessed utilizing the Twitonomy software, an online platform that allows users to collate and process data related to individual user profiles. Utilization of this software was found in a study that performed a similar analysis solely in the field of orthopedics . ThroughStatistical analysis was conducted using Student’s t-test (one-sample), analysis of variance (ANOVA), and Pearson correlations. All statistical analysis was performed using R Software version 4.1.3 (2022-03-10). Prior to any analysis, all values were normalized so that they could more accurately be compared despite spanning over different ranges. This analysis was performed at two levels: first, by looking at associations between Twitter presence and SJR ranking across specialties and then by looking at these associations on a specialty-by-specialty basis.To explore and understand the relationship between Twitter presence and SJR ranking, several statistical methods were employed to assess the statistical importance of our variables of interest. These included simple linear regression models, multiple linear regression models, and the ANOVA procedure.This analysis was performed at two levels: first, by looking at associations between Twitter presence and SJR ranking across specialties; second, by looking at these associations on a specialty-by-specialty basis. The analysis that includes all specialties is outlined in the Global Analysis section, and the specialty-by-specialty analysis is outlined in the Analysis by Specialty section.Global analysisSingle Variable Linear RegressionsIn this analysis, each of the variables mentioned above was used singly as a predictor to model the SJR score via a simple linear regression. The global analysis results are visualized in Figure Table As shown in Table Multiple Linear RegressionBased on the results from the global analysis in Table As shown in the regression model in Table Analysis by specialtyDifferences in Means Between SpecialtiesIn order to determine if there was a significant difference in SJR scores when taking the journal specialty into consideration, an ANOVA test was performed. Implementation of the ANOVA test allowed us to determine whether there is a significant difference in the mean of the SJR when the independent variables are taken into account, individually and collectively. This type of analysis is beneficial when the effects of categorical variables are being investigated, as is the case with the journal specialty variable. The results of the ANOVA test are shown in Table Using the Bonferroni correction for multiple tests of significance, we evaluated the effect of these variables at the α = 0.05/9 = 0.006 significance level. A significant p-value for this analysis indicates that the SJR changes with the independent variable under consideration when all other variables are controlled for. In this analysis, only the percentage of retweets emerges as significant. This is consistent with the results of the former analysis shown in Table Intriguingly, it also appears that the number of followers and journal specialty may also be significant. This is indicated by their relatively low p-value when considered individually and significant interaction terms. The effects of these variables in relation to the SJR of a journal are the subject of the subsequent analysis.The results of the previous ANOVA analysis Table  underscoThe results of this study suggest that there is a relationship between a journal’s Twitter activity and its SJR score. This is consistent with previous studies that have also found an association between Twitter activity and SJR, specifically with the number of followers ,11,14-16Specific to our analysis, the percentage of retweets emerged as having the most significant relationship with SJR out of all the variables assessed. The percentage of retweets was consistently associated with a statistically significant p-value, either through single linear regressions or multiple linear regression. Intriguingly, the percentage of retweets remained significant even when the journal specialty was controlled for, which could mean that this relationship remains constant across different medical specialties. Future studies into the relationship between Twitter activity and journal impact should look more into the effect that the percentage of retweets has on predicting a journal’s impact.Previous studies have investigated the impact that other social media, such as Facebook or Instagram, have on a journal’s impact -21. All Some limitations of this study include the sample size of journals under consideration. This study only analyzed 58 journals, of which only 54 had Twitter metrics available. Furthermore, our study only looked at journals from four different medical specialties. This limits the statistical power of the effects noted in our investigation. Future studies can benefit from investigating whether this effect remains consistent when considered over a larger number of journals and across multiple different specialties. Lastly, the granularity of the data was also a limiting factor. Our data only included Twitter data as of May 15, 2022. Future studies can look into dynamic relationships between Twitter activity and SJR scores and how the relationship between these variables changes over time.In recent years, surgical specialties have increased utilization of Twitter as it relates to their impact on the medical community. Overall, in our study, a significant relationship was observed between the journal’s SJR and Twitter activity along with the respective surgical specialty. At every stage of analysis, the percentage of retweets was found to have the greatest significance of all variables analyzed in this study. Given the exponential use of social media and its growing presence in the field of medicine, it is imperative that further research is conducted to understand the interconnectedness of social media and journal impact factors. Furthermore, understanding the link between social media presence and its effects on capturing the intended audience will allow new scientific developments to reach greater distances that will inevitably impact the care delivered to patients around the globe.


To evaluate the reliability of automated fluid detection in identifying retinal fluid activity in OCT scans of patients treated with anti-VEGF therapy for neovascular age-related macular degeneration by correlating human expert and automated measurements with central retinal subfield thickness (CSFT) and fluid volume values.We utilized an automated deep learning approach to quantify macular fluid in SD-OCT volumes  from patients of HAWK and HARRIER Studies. Three-dimensional volumes for IRF and SRF were measured at baseline and under therapy in the central millimeter and compared to fluid gradings, CSFT and foveal centerpoint thickness (CPT) values measured by the Vienna Reading Center.41.906 SD-OCT volume scans were included into the analysis. Concordance between human expert grading and automated algorithm performance reached AUC values of 0.93/0.85 for IRF and 0.87 for SRF in HARRIER/HAWK in the central millimeter. IRF volumes showed a moderate correlation with CSFT at baseline  and weaker correlation under therapy . SRF and CSFT correlations were low at baseline  and under therapy . The residual standard error  and marginal residual standard deviations  of fluid volume were high compared to the range of CSFT values.Deep learning-based segmentation of retinal fluid performs reliably on OCT images. CSFT values are weak indicators for fluid activity in nAMD. Automated quantification of fluid types, highlight the potential of deep learning-based approaches to objectively monitor anti-VEGF therapy. Age-related macular degeneration (AMD) accounts for 7% of global blindness and is one of the leading causes of irreversible vision loss in developed countries , 2. On aNeovascular AMD is characterized by abnormal angiogenesis originating either from the choroid or, less frequently, from the retinal circulation . These aDeep learning-based algorithms have been proposed for the classification of intraretinal (IRF) and subretinal fluid (SRF) on a pixel by pixel basis and their accuracy will further improve in the near future. The focus of this study was to provide evidence that the performance of such an automated deep learning algorithm can be considered consistent with or even superior to the ground truth represented by measurements made by a certified reading centre in the relevant aspects of anti-VEGF monitoring: identifying retinal fluid presence or absence, evaluating fluid resolution under therapy fluid and correlating measured fluid volumes with the traditionally used marker CSFT in a large number of OCT scans of patients treated with an approved therapy for neovascular AMD (nAMD). Furthermore, we evaluated and compared thickness measurements from the automated layer boundary identification algorithm with centre point thickness (CPT) and CSFT measurements by the Vienna Reading Center representing the current gold standard measurements.This retrospective study was conducted in accordance with the Declaration of Helsinki and the International Conference of Harmonization of Good Clinical Practice guidelines. We included SD-OCT data of 44,903 SD-OCT volume scans from 2771 patients with nAMD enrolled in the prospective double-masked, multicentre, active-controlled, randomized clinical trials HAWK . The sponsor of each respective trial provided the data, but the analyses, content and conclusions presented here are solely the responsibility of the authors.Treatment and imaging protocol for the studies have been presented previously . In thesThese were then analysed using a previously published  deep leaTo measure retinal thickness, we employed the Iowa Reference Algorithms  to automatically delineate inner limiting membrane (ILM) and outer RPE boundaries of the retina. Bruch’s membrane (BM) was automatically delineated using an in-house designed convolutional neural network trained to segment a smooth BM boundary on retinal OCT scans . We defiTo evaluate central retinal thickness in its entirety, we compared both CPT and CSFT measurements collected by the Vienna Reading Center (both ILM to RPE inner surface and ILM to Bruchs’ membrane (BM)) with measurements made by the algorithm. This analysis was done in a subsection of patients using 50 baseline and 50 follow-up visits of different, randomly chosen eyes with OCT-device distribution being proportional to their prevalence in the respective studies . Due to the low number of Topcon scans, these were excluded in this analysis.If not indicated otherwise, all measurements were analysed separately at baseline and follow-up visits. For the fluid volumes and CSFT values, the median, and interquartile range are reported. Spearman’s correlation coefficient (ρ) was used to examine the associations between fluid volumes and CSFT as well as CSFT with expert grading. We utilized Cohen’s terminology to describe the magnitude of correlation (ρ): 0.20 ≤ ρ < 0.5 small; 0.50 ≤ ρ < 0.7 moderate; ρ ≥ 0.70 large .Additionally, linear regressions for CSFT and SRF height explained by fluid volume were performed to determinate the residual standard deviations at baseline. For the follow-up visit measurements, the linear mixed models for CSFT explained by fluid volume with random effects were used to report the marginal residual standard deviations.Statistical analyses were performed in R version 4.1.0.Figure We analysed 17,161 OCT scans from monthly visits over two years in HARRIER and 23,986 OCT monthly scans in HAWK. In the central millimetre, the concordance for the detection of fluid between expert grading and algorithmic reading reached a value of 0.93 for IRF and 0.87 for SRF in HARRIER, see Fig. The quantified monitoring of fluid volumes over time allows an objective overview about fluid resolution patterns and disease activity Fig. . IRF volWe analysed 734 baseline visits in HARRIER and macular IRF volume showed a moderate correlation with CSFT at 1 mm: ρ = 0.510, 3 mm: ρ = 0.507 and 6 mm: ρ = 0.508. The association of SRF with CSFT at baseline was very weak for 1 mm: ρ = 0.091, 3 mm: ρ = 0.089 and 6 mm: ρ = 0.146.16,427 follow-up visits were analysed to highlight the value of CSFT measurements as treatment guidance during monitoring. The correlation of IRF and CSFT was weak under therapy; 1 mm: ρ = 0.250 | 3 mm: ρ = 0.289 | 6 mm: ρ = 0.278. Association of SRF with CSFT improved only marginally; 1 mm: ρ = 0.305 | 3 mm: ρ = 0.363 | 6 mm: ρ = 0.361 Fig. .Fig. 4a The residual standard error at baseline  and the marginal residual standard deviations at follow-up  of fluid volume were high compared to the range of CSFT values, reflecting the inaccuracy of CSFT to determine fluid volumes and their fluctuation.We analysed 1065 baseline visits from the HAWK trial. Consistently, IRF volumes showed only a moderate association with CSFT at baseline for 1 mm: ρ = 0.481, 3 mm: ρ = 0.459 and 6 mm: ρ = 0.447. The correlation of SRF and CSFT was weak at baseline for 1 mm: ρ = 0.094, 3 mm: ρ = 0.119 and 6 mm: ρ = 0.199. When analysing the 22,921 follow-up visits in HAWK, IRF had an even weaker correlation with CSFT under therapy than at baseline for 1 mm: ρ = 0.241, 3 mm: ρ = 0.271 and 6 mm: ρ = 0.251. The low association of SRF with CSFT did not increase much under therapy for 1 mm: ρ = 0.255, 3 mm: ρ = 0.305 and 6 mm: ρ = 0.302 Fig. .The residual standard error, i.e. the variability of individual fluid volumes at baseline  and the marginal residual standard errors at follow-up  of fluid volume were high compared to the range of CSFT values.The correlations of CSFT measured using automated algorithms were high with all thickness values measured by the Vienna Reading Center. (i.e. CSFT and CPT measured both from ILM to BM and ILM to RPE). However, the correlation was more robust for CSFT values from ILM to RPE  compared to the enlarged CSFT definition where RPE detachments are included .When treating patients with anti-VEGF drugs, the goal is to optimize therapeutic benefit while minimizing treatment burden. With the change from early fixed monthly treatment regimens to flexible, i.e. monitoring-driven pro re nata (PRN) and treat-and-extend strategies, rewards such as patient compliance, reduced cost and fewer injection related complications are a huge benefit , 18, 19.The task of our study was to comprehensively assess fluid management by comparing the accuracy and outcomes of human and automated procedures including the related parameters, semi quantitative 1D CSFT versus pixel-based 3D volumes, in a phase of transition of available procedures. Our results show that deep learning-based image evaluation is able to bridge the current gap using automated algorithms convincingly with AUC values for the detection of IRF reaching as high as 0.933 in the central millimetre, where IRF is most relevant and 0.916 for SRF in the central 6 mm, where SRF is predominantly located. This was true for all of the OCT devices used in both studies even though the algorithm was not validated on Topcon devices. In terms of detecting the presence of IRF and SRF in OCT scans, the computerized analysis achieved accuracies in the range of inter-observer agreement between certified reading experts reported in the literature . Such huThe diagnostic tasks in nAMD care include a comprehensive evaluation of disease activity at first presentation, i.e. baseline, and a time-sensitive and precise long-term monitoring of recurrence and therapeutic response thereafter. When assessing fluid volumes and CSFT at baseline, we observed only moderate to small correlations despite substantial amounts of retinal fluid present in the untreated macula. It has already been shown that the large quantities of SRF are not limited to the foveal region, but are mostly located around the central IRF. Distinct SRF pooling is therefore primarily unlikely to be represented by the one-dimensional marker that is CSFT . Apart fIn terms of fluid/function correlation, it has already been shown that the presence of IRF and SRF has different ramifications for the retina. While SRF seems to be correlated with a better visual outcome at baseline visits and seems to have a better tolerance towards infrequent treatment regimens , IRF is Limitations of the study are its retrospective nature, yet, no prospective trials using automated fluid volume quantification have been conducted so far as the deep learning tools are just becoming available. It will be most revealing to understand the impact of a volume-driven in contrast to a conventional CSFT-triggered regimen on retreatment frequency and particularly visual outcome. The population size and image quantity with more than 40.000 scan volumes in our study is large enough to provide relevant results including those retrieved from statistical deviations, although these data should be used for further evaluation instead of final conclusions at this stage. A further limitation is that the algorithm was developed and validated using Spectralis, Cirrus and Biotigen systems but not on Topcon devices. However, Topcon scans contributed less than 5% of data and reported performance AUC values are similar between devices, meaning that the model seems to generalize well.Our study demonstrates that the identification of fluid volumes and central retinal thickness values from automated deep learning-based segmentation of retinal OCT scans reached high concordance with expert grading. AI tools can perform at the level of certified reading professionals and even beyond human inter-reader variability, safe time to achieve precision results and provide objectivity in monitoring patients not only in clinical trials, but particularly real-world practice. Furthermore, automated quantification of nAMD features across the entire macula, beyond retinal thickness measurements, illustrates the potential of such approaches to realistically analyse disease activity and therapeutic response in order to optimally support robust treatment decision in nAMD patients in clinical routine. Automated and accurate quantification of the fluid response should improve the therapeutic management of nAMD by avoiding subjective variability between clinicians/investigators, establishing a reliable structure/function correlation and lead to the development of advanced management protocols. Prospective clinical studies will have to be performed to provide future evidence of such a point-of-care concept. In the future, these tools will be important guides for treatment decisions on intervals, substances and monitoring needs and should supplement or replace retinal thickness measurements allowing to deliver the diagnostic benefit of high-resolution three-dimensional imaging as a therapeutic benefit to our patients.Many recent trials for regulatory approval of novel substances introducing longer-acting compounds base retreatment intervals on CSFT.Retinal thickness and fluid amounts provide different information, and treatment decisions regarding fluid should not be based on thickness only. Retinal thickness does not provide reliable information on fluid volume and vice versa. Deep learning-based image evaluation is able to bridge this gap using automated algorithms convincingly.Supplemental Materials


This article examines the effects of magnetohydrodynamics and heat absorption on an incompressible Jeffrey fluid’ time-dependent free convection flow over an infinite, vertically heated plate with homogeneous heat flux. The constitutive equation for heat flow utilizes the Prabhakar-like fractional derivative. The Laplace transform technique obtains the precise solution for the momentum and thermal profiles. The typical case and well-known outcomes from the literature are retrieved as restraining cases. The graphical analysis of the impact of the flow and fractionalized parameters on the thermal and momentum profiles is presented. Additionally, a comparison is made between the ordinary model and the Prabhakar-like fractional model, which shows that the latter better captures the retention of the physical features of the problem. It is concluded that the Prabhakar-like fractional model is better suited for describing the memory effect of the thermal and momentum fields. Mansour3 analyzed the radiative influence of the fluid flow past a sheet. The consequences of natural convective movement on a vertically extended plate under continuous suction were examined by Soundalgekar4. Ishak6 examines how a boundary layer's nonlinear thermal flow affects a horizontal plate. Raptis and Singh7 go on to study the freely convective transferring of fluid through an hastening surface. Singh and Kumar8 investigated the effect of induced heat transfer on flow in a vertical plate at such a high velocity, taking into account the effect of the magnetic field. Cheng9 provides a precise solution to a heat exchange problem involving natural convective from a surface in a flow-permeable medium. Kumari and Pop10 define free convection's boundary layer as a homogenous heat flow in a porous medium.15 and the references therein provide some more recent work on this study.It is common knowledge that various researchers and scientists are keen to study an unsteady viscous fluid’s natural convection due to its various applications, significant properties, and modern technologies. Natural convection properties are illustrated in a wide range of manufacturing sectors because they play a significant contribution in manufacturing; for instance, in nuclear reactors, building ventilation, clay coatings, polymer processing, geothermal systems, waste liquids, food processing industries, greases, nuclear reactors, dehydration, and other emulsions that continue to capture their interest. Several researchers have investigated the volatility of convective flow through a moving vertical plate under variable boundaries16. Seth et al.17 examined the significance of chemical reactivity with a radiative heat source on magnetohydrodynamic flow over a sponge medium with time exponential acceleration. Rehman et al.18 explored the MHD micropolar liquid flowing over the curve surface. Fetecau et al.19 studied the MHD convective flow in a porous material across an infinitely vertically oscillating plate with constant heat flux in incompressible viscous fluids. Many further evaluations of magnetohydrodynamic mixed convective flow under various physical constraints were established. The recent correct solutions for such flows by Vieru20, Toki21 and Rajesh22 are only a few examples. The restricted solutions of MHD via a horizontal oscillating surface with heat flow in a permeable material were found by Samiulhaq et al.23 using integral transforms.The word magnetohydrodynamic (MHD) is contained in the word magneto-meaning magnetic, hydro-means water and liquid and dynamic raising to the movement. MHD influences selenology development by influencing magnetic flux appearance, burning, and magnetic field generation concentration. This is important in chemical engineering, meteorology, electronics, metallurgy and meteorology25. The blood circulation model has effectively employed Jeffrey fluid models because of its viscoelastic behavior, which plays a significant and useful role in biological and fluid mechanics. Newtonian and Maxwell fluids are connected to Jeffrey’s fluid as an exception. A curved elastic surface that produced the MHD of Jeffrey nanomaterial fluid was inspected by Saif et al.26 to see if it would move. Khan et al.27 examined the time dependence of the natural convection flow of a Jeffrey-type fluid over a long oscillating wall, along with the effects of velocity and temperature. Yasmeen et al.28 investigated a quantitative and qualitative method to examine the Jeffrey fluid’s peristaltic flow and Hartmann boundary condition. Sunitha29 investigated the double diffusion of a Jeffrey fluid containing gold nano-particles via an asymmetric tube. Dalir30 numerically studied the convection flow of a Jeffrey fluid with entropy generation across a stretched sheet. Nadeem et al.31 studied stagnation point flow for unsteady oscillations in the Jeffrey fluid. Aziz et al.32 discussed the effect of velocity on the unstable MHD mixed convective motion of Jeffrey-based fluid through an indefinitely ramped, closed vertical wall. The flow of Jeffrey material toward a nonlinear stretching surface with variable surface thickness is studied by Hayat et al.33 regarding its magnetohydrodynamic at a stagnation point.36 examined the effects of nanoparticles on the nonlinear Jeffery stream problem using Jeffrey liquids' responses to changing viscosity in an MHD.Non-Newtonian fluids have recently gained popularity in research because standard Newtonian fluids cannot adequately explain the flow features of various fluids used in engineering and industrial tenders38. Mittag–Leffler has three parametric functions: the properties of the Prabhakar function discussed by Gara and Garrappa39 and investigated thermal transport using Prabhakar memory. Giusti and Colombaro40 studied a linear visco-elastic model using the Prabhakar fractional operator. Rehman et al.41 studied the generalized Mittag–Leffler function from the exact solution of a free convective flow of Prabhakar fractional Maxwell fluid under Newtonian heating. The majority of works43, and44 are concerned with flow issues involving diverse fluids, fractional operators and heat transport occurrences.Fractional calculus (FC), one of the developments of classical calculus, was given by Leibniz in 1695. In recent years, the FC theory has played an important role in fluid mechanics, biology, mechatronics, electrochemistry, physics, engineering, entropy, rheology and mechanics. Fractional calculus can describe particular engineering processes and physical models more clearly and effectively. Fractional derivatives are Grünwald-Letnikov derivatives, Caputo derivatives, Atangana-Baleanu derivatives, Hadamard derivatives, Caputo-Fabrizio derivatives, Leibnitz derivatives, Liouville and Riemann–Liouville derivatives, Reisz derivatives in various mathematical operatorsThe present work investigates a Prabhakar-like fractional Jeffrey-type fluid that moves across an infinite vertical surface with uniform heat flux. The purpose of this novel mathematical fractional model is to consider generalized effects and propose the Prabhakar method with generalizations of Fourier’s law. The constitutive equations employed the Prabhakar derivative to account for the generalized memory effects. In the end, an appraisal between the fractional Jeffrey fluid, fractional viscous fluid, and ordinary Jeffrey fluid, ordinary viscous fluid is also given. It can be seen that fractional Jeffrey fluid and fractional viscous fluid move more slowly than ordinary Jeffrey fluid and ordinary viscous fluid. Further, the physical effects of various fractional and fluid parameters have been analyzed graphically by Mathcad software. Prabhakar operators with coefficients may be beneficial in choosing a mathematical model that can account for both experimental and hypothetical data.The analysis involves studying the unsteady, incompressible, electrically conducting free convective flow of a Jaffrey fluid over an endless vertical plate, where the plate is oriented vertically along the x-axis, and the y-axis is perpendicular to it as shown in Fig. 46.Momentum EquationEnergy balance equationFourier’s Law of thermal fluxAssuming the conventional Boussineq's approximation and the conditions mentioned above, the governing equations for the fluid velocity and thermal transport are given byThe relevant initial/ boundary conditionPresenting the dimensionless parameters as follows:By substituting into Eqs. –6), the, the6), 40:In this study, the momentum and energy equations were solved using a reliable fractional mathematical model known as the regularized Prabhakar fractional derivative, which can be mathematically expressed asLetCharacterized the Prabhakar integral, andThe Laplace transformation of the regularized Prabhakar fractional derivative operator If we set 2, (13)2, and (16) and using condition (11)2, we attain the transmuted problem:Applying the Laplace transform to Eqs. , (12)2, Using Eq.  in Eq. , we get2Solving differential Eq.  subject After using the exponential function series formula, kk!, Eq.  takes thBy applying the inverse Laplace transform to Eq. , the solIn this distinct case, when 47, Eqs. (Taking nto Eqs.  and 25)\document47, Eqs.  and 26)\document1,  and using condition 1, 1, 12)1, 1, 1, and (2ondition 1, we acqSolving differential Eq.  subject To calculate the inverse Laplace transform, Eq.  can be wThe inverse Laplace transform of Eq.  can be aIn the specific scenario where n in Eq. , can be To calculate the inverse Laplace transform of Eq. , equatioIf from Eq.  as folloBy employing equation  from theWhen from Eq.  as folloThe inverse Laplace transform of Eq.  is;37\do50 have utilized the Gaver–Stehfest algorithm methods52 to solve fractional differential equations as an effective approach for numerical Laplace methods. The Gaver-Stehfest algorithm52 can be expressed mathematically as follows:When dealing with complex transform fields, obtaining the inverse transform sequentially for practical or physical applications is not always feasible. Therefore, several numerical methods, such as the inverse Laplace transform, have been employed to obtain the required result. Some recent studies53 as an alternative approximation for the solution of the temperature and velocity fields. Mathematically, Tzou's technique can be stated as follows.The bracket function This research focuses on the study of free convection of unsteady flows of an incompressible MHD Jaffrey-type fluid over an boundless movable upright flat plate with uniform heat flux. The study uses Prabhakar fractional derivative in the constitutive equations to consider generalized memory effects. The Laplace transform technique derives dimensionless temperature and velocity fields regarding exponential functions. The solutions of the conventional model are also obtained as a special case corresponding to the integer order derivative. Numerical results are gained using Mathcad software, and the outcomes are presented in graphical form in Figs. All parameters and profiles used in this study are dimensionless. The effects of fractional parameters, Isuch as entclass1pt{minimaFigures entclass1pt{minimaOn the other hand, Fig. Furthermore, Fig. Finally, Fig. Figure To validate our gotten results for temperature and velocity outlines, Fig. The reliability of various numerical inversion methods for the Laplace transform is demonstrated in Table Figure The velocity profile of fractional Jeffrey fluid increases by increasing the values of fractional parameters It can be observed that when With larger values of Grashof numbers It is investigated whether the velocity field is elevated as time values increase.Enhancing the Jeffrey parameter It can be seen that fractional Jeffrey fluid and fractional viscous fluid move more slowly than ordinary Jeffrey fluid and ordinary viscous fluid.Our required solutions are equivalent due to inversion procedures, namely Stehfest's and Tzou.In this article, we have considered the free convection of unsteady flows of an incompressible MHD Jaffrey-type fluid flows over an boundless movable vertical flat plate with uniform heat flux. The time-fractional Prabhakar derivative is used in the constitutive equation to generalize the memory effect. The Laplace transform procedure is used to attain the precise solution for both momentum and thermal profiles. A comparison of fractional viscous fluid and fractional Jeffrey fluid, as well as an ordinary viscous fluid and an ordinary Jeffrey fluid, is also given by using. Using the Prabhakar operators with certain fractional coefficient values could be a good way to choose a mathematical model that fits both experimental and theoretical data. The following are some important conclusions:Supplementary Information.


Os limites da fração de ejeção do ventrículo esquerdo (FEVE) para a insuficiência cardíaca (IC) com FEVE levemente reduzida (ICFElr) têm sido questionados, já que evidências demonstram que alguns medicamentos utilizados para IC com FEVE <40% (ICFEr) demonstram eficácia também em populações com FEVE < 60%. Objetivo do estudo foi comparar a sobrevida total e cardiovascular de pacientes com IC com FEVE 40-59% com paciente com ICFEr e IC com FEVE ≥ 60%. Foram incluídos pacientes com IC descompensada que preencheram os critérios diagnósticos de Framingham na admissão hospitalar entre 2009 e 2011. Os pacientes foram divididos em ICFEr, IC com FEVE 40-59% e IC com FEVE ≥ 60%. O método de Kaplan-Meier foi usado para detectar a sobrevida geral e cardiovascular em 10 anos. A significância estatística foi estabelecida em p <0,05. Foram incluídos 400 pacientes, com idade média de 69 ± 14 anos. A sobrevida cardiovascular nos pacientes com IC e FEVE 40-59% não foi diferente em comparação aos pacientes com ICFEr , mas foi estatisticamente diferente em comparação aos com FEVE ≥ 60% . Não houve diferença na taxa de sobrevida de 10 anos entre diferentes grupos de FEVE. O grupo de pacientes com IC e FEVE ≥ 60% teve maior sobrevida cardiovascular que os outros grupos. No entanto, o limite superior para o fenótipo ICFEIr ainda é discutido no contexto de quais são os critérios adequados de normalidade para a FEVE.A insuficiência cardíaca (IC) é uma síndrome, cujo manejo baseia-se na classificação da fração de ejeção do ventrículo esquerdo (FEVE). As diretrizes recentesA análise pré-especificada do estudo PARAGON-HF descreve redução de desfechos clínicos em pacientes com FEVE > 45% e ≤ 57% com sacubitril-valsartan, reforçando a hipótese de que um limite superior mais alto para ICFElr poderia ser adequado para a previsão de resultados.Análises de ensaios clínicos sugerem os pacientes com ICFElr têm beneficio semelhante com os tratamentos comprovadamente eficazes para ICFEr.O objetivo do presente estudo é comparar a sobrevida total e cardiovascular de pacientes com IC com FEVE 40-59% com a da população com ICFEr e com IC com FEVE ≥ 60% em um período de 10 anos de seguimento.Estudo de seguimento de uma coorte, no qual foram incluídos pacientes com > 18 anos com diagnóstico de IC por critérios de Framingham, confirmados por ecocardiograma, no período entre janeiro de 2009 e dezembro de 2011 e acompanhados por 10 anos. A população foi dividida em três grupos de FEVE: ICFEr, IC com FEVE 40-59% e IC com FEVE ≥ 60%.Para rastrear a sobrevida do paciente, efetivou-se busca nos prontuários médicos ou por contato telefônico. Para aqueles com inconsistência dos dados, foi realizada busca no Registro Civil do Estado.Os desfechos avaliados foram: sobrevida total e a sobrevida livre de desfechos cardiovasculares  durante o tempo de acompanhamento.Hazard Ratio(HR) com seus respectivos intervalos de confiança (IC) de 95%. P <0,05 foi considerado para indicar significância estatística.Análise estatística: para comparar as características quantitativas basais, utilizou-se o teste ANOVA, e o teste de Kaplan-Meier foi realizado para avaliar a sobrevida. O teste de log-rank foi usado para determinar as diferenças nas distribuições de sobrevivência, seguido por regressão de Cox univariada e multivariada, ajustada para idade, hipertensão, diabetes mellitus, doença arterial coronariana, índice de massa corporal, doença pulmonar obstrutiva crônica e doença renal crônica. Foi obtido um valor deDa população inicial de 423 pacientes provenientes da região metropolitana de Porto Alegre, 400 foram incluídos . 60,1% apresentavam classe funcional III/IV da New York Heart Association.Dos pacientes acompanhados, 324 (81%) pacientes morreram. A taxa de sobrevida foi de 32,8% em 5 anos. Nenhuma associação estatisticamente significativa foi demonstrada entre os grupos de IC estratificados por FEVE < 40%, FEVE 40-59% e FEVE ≥ 60% e a mortalidade total .Na análise de Kaplan-Meier, observa-se que os pacientes com ICFEr tiveram uma sobrevida mediana de 4,5 anos, seguidos por IC com FEVE 40-59%  e por IC com FEVE ≥ 60% .A análise univariada e multivariada ajustada para idade, hipertensão, DM, DAC, IMC, DPOC e DRC. Em relação à sobrevida cardiovascular, o grupo ICFE 40-59% somente foi estatisticamente diferente em comparação com ICFE ≥ 60%  . A sobrevida cardiovascular foi significativamente maior no grupo FEVE ≥ 60% que nos outros grupos de FEVE, o que corrobora resultados de registros com populações semelhantes.Nossos resultados não demonstraram diferença significativa na sobrevida entre o fenótipo ICFE 40-59% e os outros grupos de FEVE. Esse resultado reproduz os de outros estudos com populações de pacientes internados por IC, os quais não demostraram a FEVE como marcador de sobrevida total.A maioria das características dos pacientes com FEVE de 40-59% teve distribuição intermediária em relação aos outros grupos, mas houve maior prevalência de DAC nos ICFEr e com FEVE 40-59% em comparação com FEVE ≥ 60% . Este fato já foi associado à menor sobrevida cardiovascular em populações com IC e disfunção sistólica. Entretanto, as diferenças observadas entre os grupos em nosso estudo são semelhantes às observadas em um recente registro europeu.A baixa taxa de prescrição das medicações modificadoras de prognóstico para IC retratam o sério problema da aplicação das diretrizes na prática clínica. que demonstrou a eficácia da empagliflozina versus placebo para redução de desfechos de morte cardiovascular e/ou hospitalização em pacientes com FEVE>40%, mas com maior tamanho de efeito no subgrupo com FEVE até 60%, ainda que o P de interação entre os grupos tenha sido não significativo. Esse resultado configura um alinhamento epidemiológico com os nossos dados e dos outros estudos já mencionados.Por fim, a plausibilidade da ideia de redimensionar o ponto de corte da FEVE da ICFElr para cima também pode ser reforçada pelos dados do recente estudo EMPEROR-PreservedOs resultados do seguimento de 10 anos da nossa coorte de pacientes com IC demonstrou que a sobrevida geral dos pacientes com FEVE 40-59% não diferiu dos dois outros grupos e, em relação à sobrevida cardiovascular, foi significativamente menor que a de pacientes com FEVE≥60%. Esses dados sugerem plausibilidade epidemiológica para a rediscussão sobre limites de FEVE para o fenótipo ICFElr. suggest the following phenotypes of HF: HF with reduced LVEF (<40%) (HFrEF), HF with mildly reduced LVEF (40-49%) (HFmrEF), HF with preserved LVEF (≥50%) (HFpEF). However, the upper limit for HFmrEF is still a matter of debate regarding the most appropriate criteria of normality for LVEF.The management of heart failure (HF) patients is based on left ventricular ejection fraction (LVEF) classification. Recent guidelinesPrespecified analysis of the PARAGON-HFstudy reveals a reduction in clinical outcomes in patients with LVEF > 45% and ≤ 57% with sacubitril/valsartan, reinforcing the hypothesis that a higher upper limit for HFmrEF could be more adequate for result prediction.Clinical studies have suggested that patients with HFmrEF have similar benefits from therapies shown to be effective for HFrEF.The aim of the present study was to compare overall and cardiovascular survival between HF patients with LVEF of 40-59% and HF patients with LVEF ≥ 60% in a 10-year follow-up period.This was a cohort study of adult patients (>18 years old) with diagnosis of HF according to the Framingham criteria, confirmed by echocardiogram between January 2009 and December 2011, who were followed for 10 years. The study population was divided into three groups – HFrEF, HF with LVEF 40-59% and HF with LVEF ≥ 60%.Patient survival was assessed by review of medical records or by telephone contact. In case of data inconsistency, a search in the civil registration system was made.The following outcomes were evaluated during the follow-up period: overall survival and survival free of cardiovascular outcomes .Comparisons of quantitative characteristics at baseline were made using the ANOVA test, and the Kaplan-Meier test was used for survival analysis. The log-rank test was used to determine differences in survival distribution, followed by univariate and multivariate Cox regression, adjusted for age, hypertension, diabetes mellitus, coronary artery disease (CAD), body mass index (BMI), chronic obstructive pulmonary disease (COPD) and chronic renal disease (CRD). Hazard ratio (HR) values and respective 95% confidence interval (CI) was determined, and a p<0.05 was defined as statistically significant.Of the initial sample of 423 patients from the metropolitan region of Porto Alegre, 400 were included ; 60.1% had New York Heart Association functional class III/IV. A total of 324 (81%) died. The five-year survival rate was 32.8%. No statistically significant association was found between the LVEF groups and overall mortality .In the Kaplan-Meier analysis, patients with HFrEF had a median survival of 4.5 years, patients with LVEF of 40-59% had a median survival of 5.7 years, and patients with LVEF ≥ 60% had a median survival of 8.8 years.Univariate and multivariate analysis adjusted for age, hypertension, DM, CAD, BMI, CPOD and CRD was performed. Regarding cardiovascular survival, statistically difference was observed between the LVEF 40-59% and LVEF ≥ 60% groups only  .Cardiovascular survival was significantly higher in the group of patients with LVEF ≥ 60% compared with the other LVEF groups, which corroborates previous studies with similar populations.Our results did not show significant differences in survival between the groups of patients categorized by LVEF. This result reproduces findings from other studies on populations of patients hospitalized for HF, which also did not describe LVEF as a marker of overall survival.Most characteristics of patients with LVEF 40-59% showed intermediate distribution as compared with the other groups. However, the prevalence of CAD in patients with HFrEF and LVEF 40-59% was higher compared with patients with LVEF ≥ 60% . This fact had already been associated with lower cardiovascular survival in populations with HF and systolic dysfunction.Nevertheless, the differences detected between the groups in our study are similar to those reported in a recent European registry.The low rate of prescription of prognostic-modifiers drugs for HF reflects a serious difficulty in applying guideline recommendations in clinical practice.that showed greater efficacy of empagliflozin over placebo in reducing the outcomes of cardiovascular death and/or hospitalization in patients with LVEF>40%. The effect was greater in the subgroup of patients with LVEF<60%, even though the interaction p between the groups was not statistically significant. This result configures an epidemiological alignment with our findings and results of previously mentioned studies.Finally, the plausibility of the idea of raising the cut-off values of LVEF in HFrEF is also supported by results of the recent EMPEROR-Preserved studyResults of the 10-year follow-up of our cohort of HF patients demonstrated that, in patients with LVEF 40-59%, the overall survival was not different from that in the other two LVEF groups, and cardiovascular survival was significantly lower than in patients with LVEF ≥60%. These data suggest epidemiological plausibility for redefinition of the LVEF cutoffs for HFmrEF.