Comprehensive Management With the ABC (Atrial Fibrillation Better Care) Pathway in Clinically Complex Patients With Atrial Fibrillation: A Post Hoc Ancillary Analysis From the AFFIRM Trial

Background For patients with atrial fibrillation, a comprehensive care approach based on the Atrial fibrillation Better Care (ABC) pathway can reduce the occurrence of adverse outcomes. The aim of this paper was to investigate if an approach based on the ABC pathway is associated with a reduced risk of adverse events in "clinically complex" atrial fibrillation patients, including those with multiple comorbidities, polypharmacy, and prior hospitalizations. Methods and Results We performed a post hoc analysis of the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. The principal outcome was the composite of all-cause hospitalization and all-cause death. An integrated care approach (ABC group) was used in 3.8% of the multimorbidity group, 4.0% of the polypharmacy group, and 4.8%, of the hospitalized groups. In all "clinically complex" groups, the cumulative risk of the composite outcome was significantly lower in patients managed consistent with the ABC pathway versus non-ABC pathway-adherent (all P<0.05). Cox regression analysis showed a reduction of composite outcomes in ABC pathway-adherent versus non-ABC pathway-adherent for multimorbidity (hazard ratio [HR], 0.61, 95% CI, 0.44-0.85), polypharmacy (HR, 0.68, 95% CI, 0.47-1.00), and hospitalization (HR, 0.59, 95% CI, 0.42-0.85) groups. Secondary analyses showed that the higher number of ABC criteria fulfilled the larger associated reduction in relative risk, even for secondary outcomes considered. Conclusions Use of an ABC consistent pathway is associated with fewer major adverse events in patients with atrial fibrillation who have multiple comorbidities, use of polypharmacy, and prior hospitalization

Improved Outcomes by Integrated Care of Anticoagulated Patients with Atrial Fibrillation using the simple ABC (Atrial Fibrillation Better Care) Pathway

BACKGROUND: Integrated care for the clinical management of atrial fibrillation patients is advocated as a holistic way to improve outcomes; the simple Atrial fibrillation Better Care (ABC) pathway has been proposed. The ABC pathway streamlines care as follows: 'A' Avoid stroke; 'B' Better symptom management; 'C' Cardiovascular and Comorbidity optimization. METHODS: We performed a post hoc analysis of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial. An 'integrated care' approach was defined according to the ABC pathway. Patients fulfilling all criteria were categorized as the 'ABC' group; those not fulfilling all criteria were the 'non-ABC' group. Trial-adjudicated all-cause death, composite outcome of stroke/major bleeding/cardiovascular death, and first hospitalization were the main study outcomes. RESULTS: Among the 4060 patients in the original cohort, 3169 (78%) had available data to compare integrated care (ABC; n\u202f=\u202f222; 7%) vs non-ABC (n\u202f=\u202f2947; 93%) management. Over a median follow-up of 3.7 (interquartile range, 2.8-4.6) years, atrial fibrillation patients managed with integrated care (ABC group) had lower rates for all study outcomes (all P &lt; .001) compared with the non-ABC group. A Cox multivariable regression analysis showed that atrial fibrillation patients managed in the ABC group had a significantly lower risk of all-cause death (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17-0.75), composite outcome (HR, 0.35; 95% CI, 0.18-0.68), and first hospitalization (HR, 0.65; 95% CI, 0.53-0.80). CONCLUSIONS: The simple ABC pathway allows the streamlining of integrated care for atrial fibrillation patients in a holistic manner and is associated with a lower risk of adverse outcomes (including mortality, stroke/major bleeding/cardiovascular death, and hospitalization)

Inelastic response spectra for an integrated displacement and energy-based seismic design (DEBD) of structures

The severe socio-economic impact of recent earthquakes has further highlighted the crucial need for a paradigm shift in performance-based design criteria and objectives towards a low-damage design philosophy, in order to reduce losses in terms of human lives, repair/reconstruction costs, and recovery time (deaths, dollars and downtime). Currently, displacement-based parameters are typically adopted to design/assess the seismic performance of the structures, by limiting the maximum displacement or the maximum interstorey drift ratio (IDR) reached by the structure under different earthquake intensities. However and arguably, displacement-based quantities are characterized by inherent weaknesses, since, for instance, they are not cumulated parameters, thus not able to capture directly the effects of multiple cycles, deterioration and damage cumulation. Therefore, in the last decades, energy-based approaches were investigated and developed in order to establish alternative engineering demand parameters for the assessment of post-event damage through a dynamic energy balance. Towards the main goal of developing an integrated Displacement and Energy-Based Design/assessment procedure (DEBD) for actual use in practice, this research work proposes an innovative approach based on the use of inelastic spectra correlating the energy components with the corresponding maximum displacement response parameters of the structure. In practical terms, the proposal is to further integrate and develop the well-known Direct Displacement-Based Design, by directly adopting the hysteretic energy as an additional design parameter. The energy inelastic spectra are developed through an extensive parametric analysis of Single-Degree-of-Freedom (SDoF) systems, with different nonlinear hysteretic models. In such an approach, the maximum seismic energy demand imparted to a structure can be directly predicted and controlled, whilst distinguishing the various components of the energy balance, including the hysteretic one. The effects of near-field and far-field earthquakes are also investigated. Results show that in the first case the seismic demand is concentrated in the peak of a few large cycles that absorb the demand energy induced by the high component in peak ground velocity in the second case the higher equivalent number of plastic cycles tends to become critical for structures with inadequate structural details and prone to suffer by cumulative cycles and overall plastic fatigue mechanisms

All-Optical Reconfiguration of Ultrafast Dichroism in Gold Metasurfaces

Optical metasurfaces have come into the spotlight as a promising platform for light manipulation at the nanoscale, including ultrafast all-optical control via excitation with femtosecond laser pulses. Recently, dichroic metasurfaces have been exploited to modulate the polarization state of light with unprecedented speed. This work theoretically predicts and experimentally demonstrates by pump–probe spectroscopy the capability to reconfigure the ultrafast dichroic signal of a gold metasurface by simply acting on the polarization of the pump pulse, which is shown to reshape the spatio-temporal distribution of the optical perturbation. The photoinduced anisotropic response, driven by out-of-equilibrium carriers and extinguished in a sub-picosecond temporal window, is readily controlled in intensity by tuning the polarization direction of the excitation up to a full sign reversal. Hence, nonlinear metasurfaces are here demonstrated to offer the flexibility to tailor their ultrafast optical response in a fully all-optically reconfigurable platform

Prevalence of New-Onset Atrial Fibrillation and Associated Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis

Background: New-onset atrial fibrillation (NOAF) is a common complication in patients with sepsis, although its prevalence and impact on outcomes are still unclear. We aim to provide a systematic review and meta-analysis on the prevalence of NOAF in patients with sepsis, and its impact on in-hospital mortality and intensive care unit (ICU) mortality. Methods: PubMed and EMBASE were systematically searched on 26 December 2021. Studies reporting on the prevalence of NOAF and/or its impact on in-hospital mortality or ICU mortality in patients with sepsis or septic shock were included. The pooled prevalence and 95% confidence intervals (CI) were calculated, as well as the risk ratios (RR), 95%CI and 95% prediction intervals (PI) for outcomes. Subgroup analyses and meta-regressions were performed to account for heterogeneity. Results: Among 4988 records retrieved from the literature search, 22 articles were included. Across 207,847 patients with sepsis, NOAF was found in 13.5% (95%CI: 8.9–20.1%), with high heterogeneity between studies; significant subgroup differences were observed, according to the geographical location, study design and sample size of the included studies. A multivariable meta-regression model showed that sample size and geographical location account for most of the heterogeneity. NOAF patients showed an increased risk of both in-hospital mortality (RR: 1.69, 95%CI: 1.47–1.96, 95%PI: 1.15–2.50) and ICU mortality (RR: 2.12, 95%CI: 1.86–2.43, 95%PI: 1.71–2.63), with moderate to no heterogeneity between the included studies. Conclusions: NOAF is a common complication during sepsis, being present in one out of seven individuals. Patients with NOAF are at a higher risk of adverse events during sepsis, and may need specific therapeutical interventions

Prevalence and Impact of Atrial Fibrillation in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

Background: In patients with COVID-19, cardiovascular complications are common and associated with poor prognosis. Among these, an association between atrial fibrillation (AF) and COVID-19 has been described; however, the extent of this relationship is unclear. The aim of this study is to investigate the epidemiology of AF in COVID-19 patients and its impact on all-cause mortality. Methods: A systematic review and meta-analysis were performed and reported according to PRISMA guidelines, and a protocol for this study was registered on PROSPERO (CRD42021227950). PubMed and EMBASE were systematically searched for relevant studies. A random-effects model was used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). Results: Overall, 31 studies were included in the analysis, with a total number of 187,716 COVID-19 patients. The prevalence of AF was found to be as high as 8% of patients with COVID-19 (95% CI: 6.3–10.2%, 95% prediction intervals (PI): 2.0–27.1%), with a high degree of heterogeneity between studies; a multiple meta-regression model including geographical location, age, hypertension, and diabetes showed that these factors accounted for more than a third of the heterogeneity. AF COVID-19 patients were less likely to be female but more likely older, hypertensive, and with a critical status than those without AF. Patients with AF showed a significant increase in the risk of all-cause mortality (OR: 3.97, 95% CI: 2.76–5.71), with a high degree of heterogeneity. A sensitivity analysis focusing on new-onset AF showed the consistency of these results. Conclusions: Among COVID-19 patients, AF is found in 8% of patients. AF COVID-19 patients are older, more hypertensive, and more likely to have a critical status. In COVID-19 patients, AF is associated with a 4-fold higher risk of death. Further studies are needed to define the best treatment strategies to improve the prognosis of AF COVID-19 patients

Expression of angiogenesis related factors in glioblastoma and peritumor tissue

Glioblastoma (GBM) is a lethal brain glial tumor characterized by extensive angiogenesis that is mostly triggered by tumor hypoxia. We previous reported that in GBM and in peritumor areas, endothelial cells expressed CD105, which probably marks newly formed vessels with a quite similar morphology. In this study, with the aim of better understanding the involvement of angiogenesis in tumor progression, we analyzed, by immunohistochemistry, the expression of Hypoxia-inducible factor (HIF) 1α and 2α, VEGF and its receptors (VEGFR-1 and -2) in GBM and in peritumor tissue. Twenty two patients were enrolled in this study. Tissue specimens were derived from enhanced lesion (first area) and white matter at a distance ≤1 mm from the tumor edge (second area). Immunoreactivity for all markers was detected not only in the tumor but also in the peritumor tissue and it was present in neoplastic cells, in endothelium and in apparently normal glial cells. HIF1α and 2α expression was mainly confined in the nuclei. VEGF, localized in the cytoplasm, showed diffuse expression with an intense staining in GBM. VEGFR-1 and 2 immupositivity was localized especially to the cell membrane and also to the cytoplasm, as expected. All molecule staining was evident in a heterogeneous manner and there was no significant difference in the expression marker levels between the first and second area also in relation to the presence or absence of tumor cells in the second area. No significant correlation was found between the above molecule expression and survival time. In conclusion, we demonstrated that HIF1α, HIF2α, VEGF and VEGFR-1 and -2 are present in peritumor area, probably reflecting perturbations of oxygenation emanating from the tumor microenvironment. Since, unfortunately, the response to anti-VEGF therapy is transient and the majority of patients eventually relapse, the gain of a deeper knowledge of the above molecule role, in the peritumor tissue, may lead to consider them as the target for new treatment regimens to counteract angiogenesis. Supported by FIRB “Accordi di Programma” 201

Adherence to the Atrial Fibrillation Better Care (ABC) pathway and the risk of major outcomes in patients with atrial fibrillation:A post-hoc analysis from the prospective GLORIA-AF Registry

BackgroundThe 'Atrial fibrillation Better Care' (ABC) pathway has been proposed to streamline a more holistic or integrated care approach to atrial fibrillation (AF) management. We aimed to analyse the impact of adherence to the ABC pathway on the risk of major adverse outcomes in a contemporary prospective global cohort of patients with AF.MethodsPatients enrolled Phase II and III of the GLORIA-AF Registry with complete data on ABC pathway adherence and follow-up were included in this post-hoc analysis between November 2011 and December 2014 for Phase II, and between January 2014 and December 2016 for Phase III. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Multivariable Cox-regression and delay of event (DoE) analyses were used to evaluate the association between adherence to the ABC pathway and the risk of outcomes.FindingsWe included 24,608 patients in this analysis (mean age: 70.2 (10.3) years, 10,938 (44.4%) females). Adherence to the ABC pathway was associated with a significant risk reduction for the primary outcome, with greatest magnitude observed for full ABC pathway adherence (adjusted Hazard Ratio [aHR] 0.54, 95% Confidence Interval [CI]: 0.44-0.67, p InterpretationAdherence to the ABC pathway in patients with AF was associated with a reduced risk of major adverse events, including mortality, thromboembolism and MACE. This underlines the importance of using the ABC pathway in the clinical care of patients with AF.FundingThis study was funded by Boehringer Ingelheim

Relevance of tumour surrounding area in chemoresistance of glioblastoma (GBM)

The mechanisms responsible for resistance to damage in normal cells might determine chemoresistance in both tumor cells and cancer stem cells (CSC). Relapse due to chemoresistant residual disease is a major cause of death in GBM. Increasing body of evidence indicates that not only tumor area (TT), but also tissue surrounding the tumor border (pTT) of GBM contains tumor cells and CSC, which could contribute to the disease progression. Therefore, the need to have a deeper insight in this area through identification of the characteristics that confer chemoresistance. In this study, the expression of molecules involved in chemoresistance was investigated in samples derived from TT and from pTT at &lt;1 cm from the tumor border, in 40 patients with GBM. The expression of O6-methylguanine-DNA methyltransferase (MGMT), a suicidal DNA repair protein; Breast Cancer Resistance Protein (BCRP1), a drug efflux transporter, and A2B5 (c-series gangliosides) has been determined by immunohistochemistry. The percentage of MGMT positive cells was higher (p&lt;0.0001, paired Student’s t test) in pTT (median: 53.5, range: 0.6-92.4) with respect to TT (median: 3.3, range: 0.0-70.7). The same trend was observed in BCRP1 expression (p&lt;0.02; pTT, median: 27.6, range: 1.0-95.6; TT, median: 10.1, range: 0.2-72.1). No difference was found between pTT and TT in A2B5 expression (p=0.69, pTT, median: 29.8, range: 0.0-98.4; TT, median: 26.0, range: 0.0-96.8). Patients were then divided into two groups according to presence (group A) or absence (group B) of tumor cells in pTT. The trend previous observed in MGMT expression was maintained in both groups, while only in group A a statistically significant difference in BCRP1 expression was observed. Our results confirm that the tissue surrounding GBM is not a normal tissue, and that it represents a frontline of tumor invasion, particularly for the presence of some molecules involved in chemoresistance, which could explain the disease recurrence after the conventional treatment of GBM. Experiments about the expression of above mentioned molecules in CSC from pTT and TT are in progress. Supported by FIRB, ACCORDI DI PROGRAMMA 201