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This is the second of a series of papers dedicated to the EASY-NET research programme (NET-2016-02364191). The rationale, structure and methodologies are described in the previous contribution. Scientific literature demonstrated that Audit & Feedback (A&F) is an effective strategy for continuous quality improvement and its effectiveness varies considerably according to factors that are currently little known. Some recent publication pointed out, with the contribution of an international group of experts, 15 suggestions to optimize A&F and developed a tool to evaluate their application. This tool, called REFLECT-52, includes 52 items related to the 15 suggestions and organized into four categories relating to the "Nature of the desired action", to the "Nature of the data available for feedback", to the "Feedback Display" and to the "Intervention delivery". Then, the aim of this work was to evaluate the level of adherence of A&F interventions tested in EASY-NET to suggestions from the literature by using a slightly adapted version of the REFLECT-52 tool, in its original language. In EASY-NET, 14 A&F interventions with different characteristics and in different clinical and organizational contexts were tested in seven Italian regions, each of these was evaluated by the respective research groups. Overall, the level of adherence was high in three of the four categories analysed, with some difficulties reported regarding the nature of the data available for feedback. In fact, contrary to what the literature suggests, it was not possible to send repeated feedback for some interventions and, in some cases, the data available for feedback presented a delay longer than one year. In summary, this analysis has confirmed a high level of compliance of the interventions tested with the suggestions from the literature, but it has also allowed researchers to identify critical aspects that need to be addressed for the future development of these strategies.

Fluid retention is a major determinant of symptoms in patients with heart failure (HF), and it is closely associated with prognosis. Hence, congestion represents a critical therapeutic target in this clinical setting. The first therapeutic strategy in HF patients with fluid overload is optimization of diuretic intervention to maximize water and sodium excretion. When diuretic therapy fails to relieve congestion, renal replacement therapy represents the only alternative option for fluid removal, as well as a way to restore diuretic responsiveness. On this background, the pathophysiology of fluid balance in HF is complex, with heart, kidney, and lung being deeply involved in volume regulation and management. Therefore, the interplay between these organs should be appreciated and considered when fluid overload in HF patients is targeted., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: ADP-induced platelet activation leads to cell surface expression of several proteins, including TF (tissue factor). The role of ADP receptors in platelet TF modulation is still unknown. We aimed to assess the (1) involvement of P2Y 1 and P2Y 12 receptors in ADP-induced TF exposure; (2) modulation of TF pos -platelets in anti-P2Y 12 -treated patients with coronary artery disease. Based on the obtained results, we revisited the intracellular localization of TF in platelets., Methods: The effects of P2Y 1 or P2Y 12 antagonists on ADP-induced TF expression and activity were analyzed in vitro by flow cytometry and thrombin generation assay in blood from healthy subjects, P2Y 12 -/- , and patients with gray platelet syndrome. Ex vivo, P2Y 12 inhibition of TF expression by clopidogrel/prasugrel/ticagrelor, assessed by VASP (vasodilator-stimulated phosphoprotein) platelet reactivity index, was investigated in coronary artery disease (n=238). Inhibition of open canalicular system externalization and electron microscopy (TEM) were used for TF localization., Results: In blood from healthy subjects, stimulated in vitro by ADP, the percentage of TF pos -platelets (17.3±5.5%) was significantly reduced in a concentration-dependent manner by P2Y 12 inhibition only (-81.7±9.5% with 100 nM AR-C69931MX). In coronary artery disease, inhibition of P2Y 12 is paralleled by reduction of ADP-induced platelet TF expression (VASP platelet reactivity index: 17.9±11%, 20.9±11.3%, 40.3±13%; TF pos -platelets: 10.5±4.8%, 9.8±5.9%, 13.6±6.3%, in prasugrel/ticagrelor/clopidogrel-treated patients, respectively). Despite this, 15% of clopidogrel good responders had a level of TF pos -platelets similar to the poor-responder group. Indeed, a stronger P2Y 12 inhibition (130-fold) is required to inhibit TF than VASP. Thus, a VASP platelet reactivity index <20% (as in prasugrel/ticagrelor-treated patients) identifies patients with TF pos -platelets <20% (92% sensitivity). Finally, colchicine impaired in vitro ADP-induced TF expression but not α-granule release, suggesting that TF is open canalicular system stored as confirmed by TEM and platelet analysis of patients with gray platelet syndrome., Conclusions: Data show that TF expression is regulated by P2Y 12 and not P2Y 1 ; P2Y 12 antagonists downregulate the percentage of TF pos -platelets. In clopidogrel good-responder patients, assessment of TF pos -platelets highlights those with residual platelet reactivity. TF is stored in open canalicular system, and its membrane exposure upon activation is prevented by colchicine., Competing Interests: Disclosures M. Camera, M. Brambilla, and P. Canzano are inventors of a patent application covering the work described in the study. The other authors report no conflicts.

Circulating small extracellular vesicles (sEVs) contribute to inflammation, coagulation and vascular injury, and have great potential as diagnostic markers of disease. The ability of sEVs to reflect myocardial damage assessed by Cardiac Magnetic Resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) is unknown. To fill this gap, plasma sEVs were isolated from 42 STEMI patients treated by primary percutaneous coronary intervention (pPCI) and evaluated by CMR between days 3 and 6. Nanoparticle tracking analysis showed that sEVs were greater in patients with anterior STEMI ( p = 0.0001), with the culprit lesion located in LAD ( p = 0.045), and in those who underwent late revascularization ( p = 0.038). A smaller sEV size was observed in patients with a low myocardial salvage index (MSI, p = 0.014). Patients with microvascular obstruction (MVO) had smaller sEVs ( p < 0.002) and lower expression of the platelet marker CD41-CD61 ( p = 0.039). sEV size and CD41-CD61 expression were independent predictors of MVO/MSI (OR [95% CI]: 0.93 [0.87-0.98] and 0.04 [0-0.61], respectively). In conclusion, we provide evidence that the CD41-CD61 expression in sEVs reflects the CMR-assessed ischemic damage after STEMI. This finding paves the way for the development of a new strategy for the timely identification of high-risk patients and their treatment optimization.

Bone Tissue Engineering (BTE) is a field of regenerative medicine continuously improving, thanks to the development of new biomaterials used as grafts or scaffolds for repairing bone defects. In recent years, chitosan, a natural biopolymer extracted mainly from crustacean shells, has demonstrated unique and desirable characteristics for BTE applications, such as: biocompatibility, biodegradability, and osteoconductive behavior. Additionally, the presence of numerous active amine groups in its chemical structure allows it to be easily modified. Data suggest that chitosan scaffolds are highly biomimetic, and show an interesting bioactivity, and antibacterial behavior. We have demonstrated, in a critical overview, how chitosan-based scaffolds may hold great interest for BTE applications in medical and dental applications. Future research should be focused on the use of chitosan-scaffolds combined with other biomaterials or bioactive molecules, to increase their overall regenerative potential, also in critical-sized defects. In conclusion, chitosan can be considered a promising biomaterial in BTE and clinical dentistry., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Older patients are less likely to receive percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) compared to younger patients. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003-2018 by using the administrative Lombardy Health Database (Italy)., Methods: We considered all patients aged ≥75 years hospitalized with AMI (either STEMI or NSTEMI) from 2003 to 2018 in Lombardy. Patients were grouped according to whether they were treated or not with PCI during the index hospitalization. The primary outcome was in-hospital mortality. The secondary endpoints were 1-year mortality and 1-year re-hospitalization for acute heart failure (AHF) or AMI., Results: 116,063 patients aged ≥75 years (mean age 83 ± 6; 48% males; 46% STEMI) were hospitalized with a primary diagnosis of AMI. Thirty-seven percent of them ( n = 42,912) underwent PCI. The in-hospital mortality rate was significantly lower in PCI-treated patients (6% vs. 15%; p < 0.0001). One-year mortality and 1-year re-hospitalization for AHF/AMI were less frequent in PCI-treated patients (16% vs. 41% and 15% vs. 21%, respectively; p < 0.0001). The adjusted risks of the study endpoints were lower in PCI-treated patients: OR 0.37 (95% CI 0.36-0.39) for in-hospital mortality; HR 0.37 (95% CI 0.36-0.38) for 1-year mortality; HR 0.74 (95% CI 0.71-0.77) for 1-year re-hospitalization for AHF/AMI. Similar results were found in STEMI and NSTEMI patients considered separately., Conclusions: Our real-world data showed that in patients with AMI ≥ 75 years of age, PCI use is associated with lower in-hospital and 1-year mortality.

Background: Patients on chronic dialysis are less likely to be treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Therefore, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue., Methods: We analyzed data of patients on chronic dialysis hospitalized with AMI from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they underwent or not PCI during index hospitalization. The primary outcome was in-hospital mortality, 1-year mortality was the secondary endpoint., Results: During the study period, 265,048 patients were hospitalized with AMI. Of them, 3206 (1.2%) were on chronic dialysis (age 71 ± 11; 72% males). Among dialysis patients, 44% underwent PCI, while 54% underwent PCI among non-dialysis patients ( p < 0.0001). Dialysis was an independent predictor of treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%, significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; p < 0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; p < 0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients undergoing PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality., Conclusions: This study showed that in AMI patients on chronic dialysis, PCI is associated with a significant in-hospital and 1-year survival benefit. Yet, they underwent PCI less frequently than patients with preserved renal function., Competing Interests: The authors declare no conflict of interest. Simonetta Genovesi is serving as Guest Editor of this journal. We declare that Simonetta Genovesi had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Gary David Lopaschuk., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Zirconia and polyetheretherketone (PEEK) are two biomaterials widely investigated as substitute for metals in oral prosthetic rehabilitation. To achieve a proper biomechanical behavior, the prosthetic biomaterials must ensure a good resistance to loads, as this is a crucial characteristic enabling their use in dental applications. The aim of this study was to investigate differences in the fracture resistance of different biomaterials in an experimental environment: fixed partial dentures (FPDs) screwed in a prototype of biomimetic mandible. 10 Samples of FPDs were allocated in 2 groups (A and B): Group A (n=5) involved FPDs in zirconia-ceramic, and Group B (n=5) involved FPDs in PEEK-composite. The samples were loaded by means of a three-point bending mechanical test, and the load to fracture has been evaluated generating a point-by-point graphics (speed/load and time/deformation). The samples were further analyzed by micro-computed tomography (micro-CT) and described under experimental loading conditions. Zirconia-ceramic FDPs were the samples reporting the worst results, showing a lower value of vertical displacement with respect to PEEK-based samples. The micro-CT results have further confirmed the preliminary results previously described. This in vitro study aims to give analytic data on the reliability of PEEK as a reliable and strong biomaterial for prosthetic treatments., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Oral malignant melanoma (OMM) has a prevalence less than 1% of all melanomas and it commonly develops on the oral mucosa following a slow and unspecific transformation of unstable melanocytic lesions, often resulting in a diagnostic delay. The marker PReferentially Expressed Antigen in MElanoma (PRAME) seems to be a valid tool to investigate the biological and histological nature of cutaneous melanocytic lesions, but to date its use to characterize pigmented lesions in the oral cavity is largely unexplored. The aim of this study was to create preliminary knowledge on the PRAME expression in OMM, and to compare its expression respect to other dysplastic pigmented lesions of the oral cavity. Interestingly, PRAME has been demonstrated to be reliable in the clinical conditions investigated in our pilot study; in fact, it has clearly differentiated the cases of Melanoma, which showed diffuse and intense positivity (score 6+/7+) to PRAME, from the other melanocytic nevi, which resulted to be mainly negative to PRAME. This means a better differential diagnosis, a reliable early diagnosis and a proper clinical/surgical management of the oncological lesions. In conclusion, PRAME can be a valid qualitative marker for differential diagnosis, not only in cutaneous melanomas, but also in malignant melanoma of the entire head and neck area., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated cardiovascular and renal protection. Whether their benefits occur also during hospitalization for acute myocardial infarction (AMI) in patients with diabetes mellitus (DM) is not known. We evaluated in-hospital outcomes of patients hospitalized with AMI according to their chronic use of GLP-1 RA and/or SGLT-2i., Methods: Using the health administrative databases of Lombardy, patients hospitalized with AMI from 2010 to 2019 were included. They were stratified according to DM status, then grouped into three cohorts using a propensity score matching: non-DM patients; DM patients treated with GLP-1 RA and/or SGLT-2i; DM patients not treated with GLP-1 RA/SGLT-2i. The primary endpoint of the study was the composite of in-hospital mortality, acute heart failure, and acute kidney injury requiring renal replacement therapy., Results: We identified 146,798 patients hospitalized with AMI (mean age 71 ± 13 years, 34% females, 47% STEMI; 26% with DM). After matching, 3,090 AMI patients (1030 in each group) were included in the analysis. Overall, the primary endpoint rate was 16% (n = 502) and progressively increased from non-DM patients to DM patients treated with and without GLP-1 RA/SGLT-2i (13%, 16%, and 20%, respectively; P < 0.0001). Compared with non-DM patients, DM patients with GLP-1 RA/SGLT-2i had a 30% higher risk of the primary endpoint, while those not treated with GLP-1 RA/SGLT-2i had a 60% higher risk (P < 0.0001)., Conclusion: Chronic therapy with GLP-1 RA and/or SGLT-2i has a favorable impact on the clinical outcome of DM patients hospitalized with AMI., (© 2023. The Author(s).)

This is the first contribution of a series of interventions describing the EASY-NET research program (Bando Ricerca Finalizzata 2016, funds 2014-2015; NET-2016-02364191). Here, the objective is to illustrate the background and the research question, the structure and organization, the methodologies and the expected results of the programme. The main theme is audit&feedback (A&F), a proven and widespread technique for improving the quality of health care. EASY-NET, funded by the Italian Ministry of Health and by the governments of the participating Italian Regions, starts its research activities in 2019 with the aim of evaluating the effectiveness of A&F in improving care for different clinical conditions in various organizational and legislative contexts. The research network involves seven Italian Regions, each conducting specific research activities described by as many work packages (WP): Lazio (the leading Region, coordinator of the research activities), Friuli Venezia Giulia, Piedmont, Lombardy, Emilia-Romagna, Calabria, and Sicily. The involved clinical areas include the management of chronic diseases, emergency care for acute conditions, surgery in the oncological area, the treatment of heart disease, obstetrics, and the use of caesarean section and post-acute rehabilitation. The involved settings concern the community, the hospital, the emergency room, and the rehabilitation facilities. Different experimental or quasi-experimental study designs are applied in each WP to achieve specific objectives of the specific clinical and organizational context. In all WPs, the process and outcome indicators are calculated on the basis of the Health Information Systems (HIS) and, in some cases, they are integrated with measures obtained from ad hoc data collections. The programme aims to contribute to the scientific evidence on A&F also exploring the obstacles and favourable factors for its effectiveness and to promote its implementation in the health service, with the ultimate aim of improving the access to healthcare and the health outcomes for citizens.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents about 6-8% of patients presenting with myocardial infarction (MI), and it is associated with a significant risk of mortality, rehospitalisation, and angina burden, with high associated socioeconomic costs. It is important to note that multiple mechanisms may be responsible for MINOCA. However, to date, there are few prospective clinical trials on MINOCA and the treatment of these patients is still not defined, most likely because of the multiple underlying pathogenic mechanisms. The PROMISE trial is a randomised, multicentre, prospective, superiority, phase IV trial that will include 180 MINOCA patients randomised 1:1 to a "precision-medicine approach", consisting of a comprehensive diagnostic workup and pharmacological treatment specific for the underlying cause, versus a "standard of care" approach, consisting of routine diagnostic workup and standard medical treatment for acute coronary syndrome. The aim of this study is to evaluate if the "precision-medicine approach" will improve the angina status, evaluated using the Seattle Angina Questionnaire summary score, at 12 months (primary endpoint). Secondary endpoints include the rate of major adverse cardiovascular events at 12-month follow-up, the related primary and secondary healthcare costs, and the ability of cardiac magnetic resonance to evaluate the different mechanisms of MINOCA. Of importance, the results derived from this trial may pave the way for a new pathophysiology-driven approach with cause-target therapies personalised for the mechanisms of MINOCA (ClinicalTrials.gov: NCT05122780).

The current overview aimed to summarise the findings provided by systematic reviews (SRs) on the effect of surgical procedures in the acceleration of tooth movement and to assess the methodological quality of the included SRs. Three electronic databases have been explored. SRs addressing the effects of surgical procedures on the acceleration of tooth movement were included. The methodological quality of the included SRs was assessed using the updated version of "A Measurement Tool to Assess Systematic Review" (AMSTAR-2). Twenty-eight (28) SRs were included. The methodological quality of the included reviews ranged between critically low (6 studies) and high (12 studies). The most common critical weakness in the included reviews was the absence of clearly a-prior established review methods and any significant deviations from the protocol. The most studied surgical procedure was corticotomy, followed by micro-osteoperforation, piezocision and periodontally accelerated osteogenic orthodontics. The majority of the included SRs supported short-term favourable effects of corticotomy on treatment time and tooth movement rate, in the short-term. However, the authors of the included SRs reported that results were based on weak quality evidence. Conflicting results arise from the existent SRs with regards to the effectiveness of piezocision and micro-osteoperforation. Few SRs summarised complications and side effects of surgical techniques, supporting absence of loss of tooth vitality, periodontal problems, or severe root resorption. The current overview of SRs highlighted the need of high quality SRs comparing different surgical approaches for tooth movement acceleration though network meta-analysis, in order to determine the most efficient instrument for orthodontic movement acceleration., (© 2022 The Authors.)

Background: Diabetes mellitus (DM) is associated with an increased mortality risk in patients hospitalized with acute myocardial infarction (AMI); however, no studies have investigated the impact of the duration of DM on in-hospital mortality. In this study, we evaluated in-hospital mortality in AMI patients according to DM status and its duration., Methods: Using health administrative databases of Lombardy, DM patients≥50 years hospitalized with AMI from 2010 to 2019 were included in the analysis and were stratified according to the duration of DM: &lt;5, 5-10, and &gt; 10 years. The primary endpoint was mortality during AMI hospitalization and the secondary endpoint was 1-year mortality in comparison with No-DM patients. Logistic and Cox regressions analyses were used to estimate odds ratios (ORs, CI 95%) and hazard ratios (HRs, CI 95%) for the outcomes, according to DM status and duration and AMI type (STEMI and NSTEMI)., Results: Our study cohort comprised 29,566 and 109,247 DM and No-DM patients, respectively. Adjusted ORs and HRs showed a significantly higher risk of in-hospital mortality (OR 1.50, 95% CI 1.43-1.58) and 1-year mortality (HR 1.51, 95% CI 1.46-1.55) in DM patients in comparison with those without. These risks increased progressively with the duration of DM, with the highest risk observed in patients with DM duration ≥ 10 years (OR 1.59, 95% CI 1.50-1.69 for in-hospital mortality and HR 1.59, 95% CI 1.53-1.64 for 1-year mortality). These findings were similar in STEMI and in NSTEMI patients., Conclusions: Our study demonstrates that the duration of DM parallels mortality risk in patients hospitalized with AMI, highlighting that DM duration should be considered as an important early prognostic risk factor in patients with AMI., (© 2022. The Author(s).)

Aims: COVID-19 has dramatically impacted the healthcare system. Evidence from previous studies suggests a decline in in-hospital admissions for acute myocardial infarction (AMI) during the pandemic. However, the effect of the pandemic on mechanical complications (MC) in acute ST-segment elevation myocardial infarction (STEMI) has not been comprehensively investigated. Therefore, we evaluated the impact of the pandemic on MC and in-hospital outcomes in STEMI during the second wave, in which there was a huge SARS-CoV-2 diffusion in Italy., Methods and Results: Based on a single center cohort of AMI patients admitted with STEMI between February 1, 2019, and February 28, 2021, we compared the characteristics and outcomes of STEMI patients treated during the pandemic vs. those treated before the pandemic. In total, 479 STEMI patients were included, of which 64.5% were during the pandemic. Relative to before the pandemic, primary percutaneous coronary intervention (PCI) declined (87.7 vs. 94.7%, p = 0.014) during the pandemic. Compared to those admitted before the pandemic (10/2019 to 2/2020), STEMI patients admitted during the second wave (10/2020 to 2/2021) presented with a symptom onset-to-door time greater than 24 h (26.1 vs. 10.3%, p = 0.009) and a reduction of primary PCI (85.2 vs. 97.1%, p = 0.009). MC occurred more often in patients admitted during the second wave of the pandemic than in those admitted before the pandemic (7.0 vs. 0.0%, p = 0.032). In-hospital mortality increased during the second wave (10.6 vs. 2.9%, p = 0.058)., Conclusion: Although the experience gained during the first wave and a more advanced hub-and-spoke system for cardiovascular emergencies persists, late hospitalizations and a high incidence of mechanical complications in STEMI were observed even in the second wave., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Penso, Frappampina, Cosentino, Tamborini, Celeste, Ianniruberto, Ravagnani, Troiano, Marenzi and Pepi.)

Background: Prior statin therapy has a cardioprotective effect in patients undergoing elective or urgent percutaneous coronary intervention (PCI). However, data on patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI are still controversial. We retrospectively evaluated the effect of prior statin therapy on in-hospital clinical outcomes in consecutive STEMI patients undergoing primary PCI. Methods: A total of 1790 patients (mean age 67 ± 11 years, 1354 men) were included. At admission, all patients were interrogated about prior (>6 months) statin therapy. The primary endpoint of the study was the composite of in-hospital mortality, acute pulmonary edema, and cardiogenic shock in patients with or without prior statin therapy. Results: A total of 427 patients (24%) were on prior statin therapy. The incidence of the primary endpoint was similar in patients with or without prior statin therapy (15% vs. 16%; p = 0.38). However, at multivariate analysis, prior statin therapy was associated with a lower risk of the primary endpoint, after adjustment for major prognostic predictors (odds ratio 0.61 [95% CI 0.39−0.96]; p = 0.03). Conclusions: This study demonstrated that prior statin therapy is associated with a better in-hospital clinical outcome in patients with STEMI undergoing primary PCI compared to those without prior statin therapy.

Background: The symptomatology in Burning Mouth Syndrome (BMS) is complex and it should be considered in accordance with a biopsychosocial model., Objectives: To evaluate the multidimensional aspects of pain with a complete battery of tests and to analyse its relationship with potential predictors such as mood disorders, sleep and quality of life., Methods: Forty patients with BMS versus an equal number of age and sex-matched healthy controls were enrolled. The VAS, SF-MPQ, BPI, PD-Q, BDI-II, STAI, PSQI, ESS, SF-36 and OHIP-14 were administered., Results: The scores of the VAS, SF-MPQ, BPI, PD-Q, BDI-II, STAI, PSQI, SF-36 and OHIP-14 were statistically significantly higher in the BMS patients than the controls (p < .001**). A strongly linear correlation between pain (VAS, SF-MPQ, BPI and PD-Q) and disease onset (STAI, BDI-II, PSQI and sub-items of SF-36 and OHIP-14) was found. In the multiple regression analysis, the contributions of the BDI-II and OHIP-14 were found to be statistically significant with the SF-MPQ, PD-Q and BPI in terms of severity and interference, while the contributions of the STAI and sleep were found to be statistically significant with the SF-MPQ and BPI in terms of severity and interference, respectively., Conclusions: Pain tests are differently correlated with mood and quality of life. Therefore, a complete analysis of the patient requires several tools to better understand the multidimensional aspects of pain in BMS., (© 2022 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

The coronavirus disease (COVID)-19 pandemic continues to have an impact on health care. A potential new wave can be foreseen concerning the impact of the pandemic on medical research and literature. We focused our attention on journals belonging to "Medicine, General and Internal" Clarivate™ category and "Q1" journal impact factor quartile. We found that since January 2020, 9621 papers regarding COVID-19 have been published in these journals. This occurred at the expense of non-COVID-19-related scientific papers as most journals did not increase the total number of their published articles. Thus, our analysis may outlook a new potential scientific wave related to COVID-19, in addition to the clinical ones, possibly delaying the improvement in the quality of care for other diseases in the next years., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: An adequate blood supply plays a leading role in the healing process of the post-extractive socket; its coagulation leads to fibrin clot formation, which acts as a physical barrier able to prevent postoperative bleeding and microbial infection. The purpose of this study was to evaluate the effectiveness of antiaggregant drugs in healing post-extraction sockets compared to natural wound healing. Methods: This was a single-center prospective clinical trial. Extraction sockets allocated in healthy patients and in patients assuming antiplatelet drugs were considered. Thirty consecutive patients under (treated with/in treatment with) oral antiplatelet treatment were enrolled in the test group. In order to provide a control group, 30 consecutive patients meeting all the exclusion and inclusion criteria were enrolled. The extraction of the mono-radicular tooth was atraumatically performed without gingivoplasty or osteotomy procedures that could influence the healing process. Photographs were obtained before and immediately after surgery and at 3-, 7-, 14- and 28-days follow-up. Results: All patients assumed the prescribed therapy and their post-operative recovery was uneventful without any kind of post-extractive complications. The results of inter-group comparison show that on the third and seventh days of follow-up, the antiplatelet group expressed a statistically significant higher level of healing compared to the control group (p < 0.05), while no statistically significant differences were recorded at 14- and 28-days follow-up. Conclusions: Patients treated with antiplatelet agents seemed to show that this therapy can positively affect the healing process after tooth extractions.

Background: COVID-19 had an adverse impact on the management and outcome of acute coronary syndromes (ACS), but most available data refer to March-April 2020., Aim: This study aims to investigate the clinical characteristics, time of treatment, and clinical outcome of patients at hospitals serving as macro-hubs during the second pandemic wave of SARS-CoV-2 (November 2020-January 2021)., Methods and Results: Nine out of thirteen "macro-hubs" agreed to participate in the registry with a total of 941 patients included. The median age was 67 years (IQR 58-77) and ST-elevation myocardial infarction (STEMI) was the clinical presentation in 54% of cases. Almost all patients (97%) underwent coronary angiography, with more than 60% of patients transported to a macro-hub by the Emergency Medical Service (EMS). In the whole population of STEMI patients, the median time from symptom onset to First Medical Contact (FMC) was 64 min (IQR 30-180). The median time from FMC to CathLab was 69 min (IQR 39-105). A total of 59 patients (6.3%) presented a concomitant confirmed SARS-CoV-2 infection, and pneumonia was present in 42.4% of these cases. No significant differences were found between STEMI patients with and without SARS-CoV-2 infection in treatment time intervals. Patients with concomitant SARS-CoV-2 infection had a significantly higher in-hospital mortality compared to those without (16.9% vs. 3.6%, P < 0.0001). However, post-discharge mortality was similar to 6-month mortality (4.2% vs. 4.1%, P = 0.98). In the multivariate analysis, SARS-CoV-2 infection did not show an independent association with in-hospital mortality, whereas pneumonia had higher mortality (OR 5.65, P = 0.05)., Conclusion: During the second wave of SARS-CoV-2 infection, almost all patients with ACS received coronary angiography for STEMI with an acceptable time delay. Patients with concomitant infection presented a lower in-hospital survival with no difference in post-discharge mortality; infection by itself was not an independent predictor of mortality but pneumonia was., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferlini, Castini, Ferrante, Marenzi, Montorfano, Savonitto, D’Urbano, Lettieri, Cuccia, Marino, Visconti and Carugo.)

Aims: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19., Methods and Results: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19., Conclusion: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities., (This article has been co-published with permission in the European Heart Journal and Cardiovascular Research. © The European Society of Cardiology 2021. All rights reserved. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

Purpose: The present systematic review and meta-analysis aimed to investigate the available evidence in the literature to answer the following focused question: In partially edentulous arches with reduced bone width, do implants placed after horizontal bone augmentation exhibit differences in survival and success rate compared to narrow-diameter implants placed in native bone?, Materials and Methods: A population, intervention, comparison and outcome question was defined and an electronic search was conducted using the MEDLINE (via PubMed) and Cochrane Oral Health Group databases to identify all studies analysing the use of standard-diameter implants inserted in regenerated bone or narrow-diameter implants for the rehabilitation of partially or completely edentulous atrophic maxillae and mandibles. Inclusion criteria and quality assessments were established, and studies were selected on this basis., Results: Twenty-four studies met the inclusion criteria and were analysed cumulatively. A comparative meta-analysis was not possible due to the lack of studies directly comparing the two rehabilitation methods in question. A cumulative implant survival rate of 97.80% (1246/1274; pooled proportion 0.984, 95% confidence interval 0.977-0.991) was reported for the narrow implants placed in atrophic ridges, while similar results were obtained for the standard-diameter implants placed in regenerated bone, with a cumulative implant survival rate of 97.94% (1332/1360; pooled proportion 0.983, 95% confidence interval 0.976-0.990)., Conclusions: The present systematic review found high and comparable survival rates between narrow- and standard-diameter implants placed in regenerated bone; however, well-designed randomised controlled trials are required to support the hypothesis that both treatment strategies are successful in comparable circumstances.

Objective: The aim of this study was to assess the impact of lockdown due to the coronavirus COVID-19 pandemic on the periodontal status of patients with periodontitis in supportive periodontal therapy., Method and Materials: A retrospective analysis of patients affected by periodontitis stage III-IV-grade A, B, and C, who had their supportive periodontal therapy to September 2020, after a period of 6 months from the planned maintenance recall (March 2020) was performed. Clinical parameters full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), and probing depth (PD) were evaluated. Patients were assigned to three groups: A (nonsmokers); B (< 10 cigarettes/day); and C (> 10 cigarettes/day). Statistical analysis was used to compare intra-group and inter-group differences., Results: In total, 55 subjects with the mean age of 47.7 ± 7.0 years were enrolled. The number of participants in group A and group B decreased, respectively, from 25 (45.5%) to 20 (36.4%) and from 17 (30.9%) to 13 (23.6%). The C group increased from 13 (23.6%) to 22 (40.0%). A statistically significant increase in mean FMPS was recorded in group A (from 22.5 ± 3.5 to 30.0 ± 28.3; P < .0001); group B (from 22.5 ± 12.7 to 42.5 ± 3.5; P < .0001); and group C (from 22.5 ± 25.5 to 42.5 ± 10.6; P < .0001). A statistically significant increase in mean FMBS was recorded in group A (from 15.0 ± 7.1 to 25.0 ± 21.2; P < .0001); group B (from 15.0 ± 0.0 to 37.5 ± 3.5; P < .001); and group C (from 12.5 ± 3.5 to 30.0 ± 7.1; P < .0001). A statistically significant increase in mean PD was recorded in group A (from 4.48 ± 0.5 to 5.25 ± 1.2; P < .001); in group B (from 4.71 ± 0.7 to 5.38 ± 1.31; P < .0001); and group C (from 6.00 ± 0.0 to 7.09 ± 1.1; P < .0001)., Conclusions: Within the limitations of this study the results showed that the pandemic period resulted in an increase in probing depth for the patients in regular SPT, possibly due to increased tobacco consumption.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly become a worldwide pandemic. On top of respiratory complications, COVID-19 is associated with major direct and indirect cardiovascular consequences, with the latter probably being even more relevant, especially in the setting of time-dependent cardiovascular emergencies. A growing amount of data suggests a dramatic decline in hospital admissions for acute myocardial infarction (AMI) worldwide during the COVID-19 pandemic, mostly since patients did not activate emergency medical systems because hospitals were perceived as dangerous places regarding the infection risk. Moreover, during the COVID-19 pandemic, patients with AMI had a significantly higher in-hospital mortality compared to those admitted before COVID-19, potentially due to late arrival to the hospital. Finally, no consensus has been reached regarding the most adequate healthcare management pathway for AMI and shared guidance on how to handle patients with AMI during the pandemic is still needed. In this review, we will provide an update on epidemiology, clinical characteristics, and outcomes of patients with AMI during the COVID-19 pandemic, with a special focus on its collateral cardiac impact., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Toscano, Cosentino, Campodonico, Bartorelli and Marenzi.)

Background: Acute kidney injury (AKI) is a well-known complication of ST-elevation acute myocardial infarction (STEMI) with an adverse impact on prognosis. Since AKI develops more frequently in elderly patients, we hypothesized that its higher incidence in older STEMI patients might explain their increased in-hospital mortality. We assessed the relationship between AKI and in-hospital mortality in patients with STEMI of different age groups., Methods: We retrospectively evaluated 5136 STEMI patients treated with primary percutaneous coronary intervention (pPCI). We defined AKI as ≥0.5 mg/dl creatinine increase in the first 72 h. Patients were grouped according to age (<75 [n = 4040] or ≥ 75 [n = 1096] years). The primary endpoint was in-hospital mortality., Results: The incidence of AKI was 7%. It was 4.6% in patients <75 years and 15.1% in those ≥75 years (P < 0.0001). The overall in-hospital mortality was 4%. It was 2.6% and 8.5% in patients younger and older than 75 years, respectively (P < 0.0001). It was higher in AKI than in non-AKI patients, both in the overall population (27% vs. 2%) and in the two age groups (25% vs. 2% and 29% vs. 5% in younger and older patients, respectively; P < 0.0001). The adjusted odds ratio of in-hospital mortality associated with AKI progressively decreased in parallel with increasing age decades (from 24.7 [95% CI 11.2-54.1] in patients <65 years to 3.9 [95% CI 1.6-9.7] in those >85 years)., Conclusions: In STEMI patients treated with pPCI, AKI incidence and in-hospital mortality steadily increase with age. However, the prognostic impact of AKI is progressively reduced as age increases., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Considerations about implant surface wear and metal particles released during implant placement have been reported. However, little is known about implant surface macro- and microstructural components, which can influence these events. The aim of this research was to investigate accurately the surface morphology and chemical composition of commercially available dental implants, by means of multivariate and multidimensional statistical analysis, in order to predict their effect on wear onset and particle release during implant placement., Methods: The implant surface characterization (roughness, texture) was carried out through Confocal Microscopy and SEM-EDS analysis; the quantitative surface quality variables (amplitude and hybrid roughness parameters) were statistically analyzed through post hoc Bonferroni's test for pair comparisons., Results: The parameters used by discriminant analysis evidenced several differences in terms of implant surface roughness between the examined fixtures. In relation to the observed surface quality, some of the investigated implants showed the presence of residuals due to the industrial surface treatments., Conclusions: Many structural components of the dental implant surface can influence the wear onset and particles released during the implant placement.

Vitamin D deficiency is a prevalent condition, occurring in about 30-50% of the population, observed across all ethnicities and among all age groups. Besides the established role of vitamin D in calcium homeostasis, its deficiency is emerging as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and major CVDs, such as coronary artery disease, heart failure, and atrial fibrillation. Moreover, in all these clinical settings, vitamin deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial. In this review, we aimed to summarize the currently available evidence supporting the link between vitamin D deficiency and major CVDs in terms of its prevalence, clinical relevance, prognostic impact, and potential therapeutic implications.

Background: Due to its common association with chronic pain experience, cognitive impairment (CI) has never been evaluated in patients with burning mouth syndrome (BMS). The purpose of this study is to assess the prevalence of CI in patients with BMS and to evaluate its relationship with potential predictors such as pain, mood disorders, blood biomarkers, and white matter changes (WMCs). Methods: A case-control study was conducted by enrolling 40 patients with BMS and an equal number of healthy controls matched for age, gender, and education. Neurocognitive assessment [Mini Mental State Examination (MMSE), Digit Cancellation Test (DCT), the Forward and Backward Digit Span task (FDS and BDS), Corsi Block-Tapping Test (CB-TT), Rey Auditory Verbal Learning Test (RAVLT), Copying Geometric Drawings (CGD), Frontal Assessment Battery (FAB), and Trail Making A and B (TMT-A and TMT-B)], psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and 36-Item Short Form Health Survey (SF-36)], and pain assessment [Visual Analogic Scale (VAS), Total Pain Rating index (T-PRI), Brief Pain Inventory (BPI), and Pain DETECT Questionnaire (PD-Q)] were performed. In addition, blood biomarkers and MRI of the brain were recorded for the detection of Age-Related WMCs (ARWMCs). Descriptive statistics, the Mann-Whitney U -test, the Pearson Chi-Squared test and Spearman's correlation analysis were used. Results: Patients with BMS had impairments in most cognitive domains compared with controls ( p < 0.001 ** ) except in RAVLT and CGD. The HAM-D, HAM-A, PSQI, ESS, SF-36, VAS, T-PRI, BPI and PD-Q scores were statistically different between BMS patients and controls ( p < 0.001 ** ) the WMCs frequency and ARWMC scores in the right temporal (RT) and left temporal (LT) lobe were higher in patients with BMS ( p = 0.023 * ). Conclusions: Meanwhile, BMS is associated with a higher decline in cognitive functions, particularly attention, working memory, and executive functions, but other functions such as praxis-constructive skills and verbal memory are preserved. The early identification of CI and associated factors may help clinicians to identify patients at risk of developing time-based neurodegenerative disorders, such as Alzheimer's disease (AD) and vascular dementia (VD), for planning the early, comprehensive, and multidisciplinary assessment and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Canfora, Calabria, Cuocolo, Ugga, Buono, Marenzi, Gasparro, Pecoraro, Aria, D'Aniello, Mignogna and Adamo.)

Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, glycemia is a very stable parameter, while in poorly controlled DM patients, it oscillates greatly throughout the day and between days. Clinically, GV could be measured by different parameters, but there are no guidelines on standardized assessment. Nonetheless, DM patients with high GV experience worse cardiovascular disease outcomes. In vitro and in vivo studies showed that high GV causes several detrimental effects, such as increased oxidative stress, inflammation, and apoptosis linked to endothelial dysfunction. However, the evidence that treating GV is beneficial is still scanty. Clinical trials aiming to improve the diagnostic and prognostic accuracy of GV measurements correlated with cardiovascular outcomes are needed. The present review aims to evaluate the clinical link between high GV and cardiovascular diseases, taking into account the underlined biological mechanisms. A clear view of this challenge may be useful to standardize the clinical evaluation and to better identify treatments and strategies to counteract this DM aspect.

Background: Reliable preprocedural risk scores for the prediction of Contrast-Induced Acute Kidney Injury (CI-AKI) following Percutaneous Coronary Intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI) are lacking. Aim of this study was to derive and validate a preprocedural Risk Score in this setting., Methods: Two prospectively enrolled patient cohorts were used for derivation and validation (n = 3,736). CI-AKI was defined as creatinine increase ≥0.5 mg/dl <72 h postpPCI. Odds ratios from multivariable logistic regression model were converted to an integer, whose sum represented the Risk Score., Results: Independent CI-AKI predictors were: diabetes, Killip class II-III (2 points each), age > 75 years, anterior MI (3 points), Killip class IV (4 points), estimated GFR < 60 ml/min/1.73m 2 (5 points). The Risk Score c-statistic was 0.84 in both cohorts. Compared with patients with Risk Score ≤ 4, the relative risks of CI-AKI among patients scoring 5-9 were 6.2 (derivation cohort) and 7.1 (validation cohort); among patients scoring ≥10, 19.8, and 21.4, respectively., Conclusions: Among STEMI patients, a simple preprocedural Risk Score accurately and reproducibly predicted the risk of CI-AKI, identifying ¼ of patients with a seven-fold risk and 1/10 of patients with a 20-fold risk. This knowledge may help tailored strategies, including delaying revascularization of nonculprit vessels in patients at high risk of CI-AKI., (© 2020 Wiley Periodicals LLC.)

Dental anxiety is a crucial problem for dentistry because it may represent a significant risk to oral health. Different factors, whether non-cognitive (e.g., traumatic dental events) or cognitive (e.g., the patient's subjective perceptions), may cause dental anxiety. However, previous studies have assessed these factors as independent predictors of dental anxiety, without providing any exploration of potential mediational pathways. The current study assessed the role of certain cognitive dimensions (i.e., the dentist's perceived professionalism and communicational attitudes, and the patient's perceived lack of control) as mediators between traumatic dental events and dental anxiety. The sample comprised 253 patients who had accessed a public university hospital dental surgery. The mediation analysis used a structural equation modeling. Traumatic dental events were positively associated with dental anxiety but, among the cognitive factors, only lack of control was. Furthermore, lack of control mediated the relationship between traumatic dental events and dental anxiety, although this mediation was only partial. This study sheds light on the mechanisms through which non-cognitive and cognitive factors may affect dental anxiety. The clinical implications for dental practice, in terms of improving the psychological well-being of patients, are discussed., (© 2021 The Authors. European Journal of Oral Sciences published by John Wiley & Sons Ltd on behalf of Scandinavian Division of the International Association for Dental Research.)

The identification of new biomarkers allowing an early and more accurate characterization of patients with ST-segment elevation myocardial infarction (STEMI) is still needed, and exosomes represent an attractive diagnostic tool in this context. However, the characterization of their protein cargo in relation to cardiovascular clinical manifestation is still lacking. To this end, 35 STEMI patients (17 experiencing resuscitated out-of-hospital cardiac arrest (OHCA-STEMI) and 18 uncomplicated) and 32 patients with chronic coronary syndrome (CCS) were enrolled. Plasma exosomes were characterized by the nanoparticle tracking analysis and Western blotting. Exosomes from STEMI patients displayed a higher concentration and size and a greater expression of platelet (GPIIb) and vascular endothelial (VE-cadherin) markers, but a similar amount of cardiac troponin compared to CCS. In addition, a difference in exosome expression of acute-phase proteins (ceruloplasmin, transthyretin and fibronectin) between STEMI and CCS patients was found. GPIIb and brain-associated marker PLP1 accurately discriminated between OHCA and uncomplicated STEMI. In conclusion, the exosome profile of STEMI patients has peculiar features that differentiate it from that of CCS patients, reflecting the pathophysiological mechanisms involved in STEMI. Additionally, the exosome expression of brain- and platelet-specific markers might allow the identification of patients experiencing ischemic brain injury in STEMI.

Background: Current knowledge regarding the relationship between aortic valve sclerosis (AVSc), cardiovascular risk factors, and mortality in patients with known coronary artery disease (CAD) is still unclear. The present study aimed at investigating the prevalence of AVSc as well as its association with long-term all-cause mortality in high-risk CAD patients that has never been explored in large cohorts thus far. Methods and Results: In this retrospective and observational cohort study we enrolled high-risk CAD patients, hospitalized at Centro Cardiologico Monzino (CCM), Milan, Italy, between January 2006 and December 2016. The morphology and function of the aortic valve were assessed from the recorded echocardiographic images to evaluate the presence of AVSc, defined as a non-uniform thickening of the aortic leaflets with no consequences on hemodynamics. Data on 5-year all-cause mortality was retrieved from a Regional database. Of the 5,489 patients initially screened, 4,938 (mean age 67 ± 11 years, 3,954 [80%] men) were enrolled in the study. In the overall population, AVSc was detected in 2,138 (43%) patients. Multivariable LASSO regression revealed that age, female gender, diabetes mellitus, previous MI, and left ventricular ejection fraction were independently associated with AVSc. All-cause mortality (adjusted hazard ratio: 1.29, 95%CI: 1.05-1.58) was significantly higher in AVSc than in non-AVSc patients. Conclusions: AVSc is frequently detected in high-risk CAD patients and is associated with long-term mortality. Our findings corroborate the hypothesis that AVSc is an underestimated marker of systemic cardiovascular risk. Thus, AVSc detection may be used to improve long-term risk stratification of high-risk CAD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Myasoedova, Genovese, Cavallotti, Bonomi, Chiesa, Campodonico, Rondinelli, Cosentino, Baldassarre, Veglia, Pepi, Alamanni, Colombo, Marenzi and Poggio.)

Coronary artery disease (CAD) patients are at high ischemic risk, and new biomarkers reflecting atherosclerotic disease severity and coronary plaque vulnerability are required. The Brain-Derived Neurotrophic Factor (BDNF) affects endothelial and macrophage activation suggesting its involvement in atherosclerotic plaque behavior. To investigate whether plasma BDNF is associated with in vivo coronary plaque features, assessed by optical coherence tomography (OCT), in both acute myocardial infarction (AMI) and stable angina (SA) patients, we enrolled 55 CAD patients (31 SA and 24 AMI), and 21 healthy subjects (HS). BDNF was lower in CAD patients than in HS ( p < 0.0001), and it decreased with the presence, clinical acuity and severity of CAD. The greater BDNF levels were associated with OCT features of plaque vulnerability in overall CAD as well as in SA and AMI patients ( p < 0.03). Specifically, in SA patients, BDNF correlated positively with macrophages' infiltration within atherosclerotic plaque ( p = 0.01) and inversely with minimal lumen area ( p = 0.02). In AMI patients a negative correlation between BDNF and cap thickness was found ( p = 0.02). Despite a small study population, our data suggest a relationship between BDNF and coronary plaque vulnerability, showing that vulnerable plaque is positively associated with plasma BDNF levels, regardless of the clinical CAD manifestation.

Background: Cardiogenic shock (CS) is the leading cause of in-hospital mortality in ST-segment elevation myocardial infarction (STEMI). Only limited data are available on the long-term outcome of STEMI patients with CS undergoing contemporary treatment. We aimed to investigate long-term mortality and its predictors in STEMI patients with CS and to develop a risk score for long-term mortality prediction., Methods and Results: We retrospectively included 465 patients with STEMI complicated by CS and treated with primary angioplasty and intra-aortic balloon pump between 2005 and 2018. Long-term mortality, including both in-hospital mortality and all-cause mortality following discharge from the index hospitalization, was the primary endpoint. The long-term mortality (median follow-up 4 (2.0-5.2) years) was 60%, including in-hospital mortality (34%). At multivariate analysis, independent predictors of long-term mortality were age (HR 1.41, each 10-year increase), admission left ventricular ejection fraction (HR 1.51, each 10%-unit decrease) and creatinine (HR 1.28, each mg/dl increase), and acute kidney injury (HR 1.81). When these predictors were pooled together, the area under the curve (AUC) for long-term mortality was 0.80 (95% CI 0.75-0.84). Using the four variables, we developed a risk score with a mean (cross-validation analysis) AUC of 0.79. When the score was applied to in-hospital mortality, its AUC was 0.79, and 0.76 when the score was applied to all-cause mortality following discharge., Conclusions: In STEMI patients with CS, the risk of death is still substantial in the years following the index event. A simple clinical score at the time of the index event accurately predicts long-term mortality risk.

Background and Aims: Diabetes mellitus (DM) is a frequent comorbidity in ST-elevation-myocardial infarction (STEMI) patients and carries a higher risk of in-hospital mortality. We recently demonstrated that the higher in-hospital mortality of STEMI patients with DM, when compared to that of patients without DM, is mainly associated with their more frequent cardiac and renal dysfunction. These exploratory results prompted us to hypothesize that this higher risk in DM patients is mediated by their lower cardio-renal functional reserve., Methods and Results: We included 5152 STEMI patients treated with primary angioplasty. By using an advanced statistical methodology (path analysis), able to clarify the putative causal paths between variables of interest, we reported that the higher in-hospital mortality of STEMI patients with DM is possibly caused by its adverse impact on cardio-renal function., Conclusion: This statistical approach allows to reinforce the well-known notion that DM is associated with an increased in-hospital mortality risk in STEMI and sheds lights on the causal relationship among DM, cardio-renal dysfunction, and higher in-hospital mortality. Whether the mortality gap between DM and non-DM patients with STEMI can be reduced by pharmacological strategies combining cardio-renal protective effects is an intriguing question that deserves an answer in the future., Competing Interests: Declaration of competing interest None., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Monocyte recruitment after vascular injury and their migration through the vessel wall represent crucial events in the initiation, progression, and destabilization of atherosclerotic plaque. Circulating monocytes are exposed to stimuli that alter their physiological state, and among them, lipids play a key role. Several studies investigated the mechanisms by which lipids affect monocyte functions promoting coronary atherosclerotic plaque initiation, but information on the relationship between lipid composition and function of monocyte is scant. We aimed at studying the migration of circulating monocytes isolated from patients with acute myocardial infarction (AMI) at hospital presentation and investigating its correlation with cellular lipid profile. The migration of monocytes was tested using both fetal bovine serum (FBS) and autologous serum as chemoattractant stimuli. Monocyte lipid profile was evaluated through an untargeted lipidomics approach, using a liquid chromatography/time-of-flight mass spectrometry platform. We observed that AMI patients' monocytes showed a significant increase in FBS and autologous serum-mediated migration compared to controls. Moreover, a different monocyte lipidomic profile between the two study groups was detected. In particular, AMI patients' monocytes showed an altered composition in ceramides, with an increase in lactosylceramide and in phospholipids (ie, phosphatidylethanolamine and lisophosphatidylethanolamine). Of note, a positive correlation between lactosylceramide levels and monocyte migration was observed. Furthermore, the lactosylceramide synthase inhibition significantly reduced FBS-induced monocyte migration. Our results highlight the influence of lactosylceramide on the monocyte migration capacity, pointing out a new possible mechanism of lipids in the onset of atherothrombosis and, hence, in AMI., (© 2021 Federation of American Societies for Experimental Biology.)

Quality of sleep (QoS) and mood may impair oral cancer survivors' wellbeing, however few evidences are currently available. Therefore, we aimed to assess the prevalence of sleep disorders, anxiety and depression among five-year oral cancer survivors (OC survivors). 50 OC survivors were compared with 50 healthy subjects matched for age and sex. The Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Hamilton Rating Scales for Depression and Anxiety (HAM-D, HAM-A), the Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI) were administered. The global score of the PSQI, ESS, HAM-A, HAM-D, NRS, T-PRI, was statistically higher in the OC survivors than the controls ( p -value: <0.001). QoS of OC survivors was significantly impaired, especially with regard to some PSQI sub-items as the subjective sleep quality, sleep latency and daytime dysfunction ( p -value: 0.001, 0.029, 0.004). Moreover, poor QoS was negatively correlated with years of education ( p -value: 0.042 *) and positively correlated with alcohol consumption ( p -value: 0.049 *) and with the use of systemic medications ( p -value: 0.044 *). Sleep disorders and mood disorders are common comorbidities in OC survivors; therefore, early assessment and management before, during and after treatment should be performed in order to improve the quality of life of OC survivors.

The primary cause of tooth loss in the industrialized world is periodontitis, a bacterial anaerobic infection whose pathogenesis is characterized by composite immune response. At present, the diagnose of periodontitis is made by a complete status check of the patient's periodontal health; full-mouth plaque score, full-mouth bleeding score, probing depth, clinical attachment level, bleeding on probing, recessions, mobility, and migration are evaluated in order to provides a clear picture of the periodontal conditions of a single patient. Chair-side diagnostic tests based on whole saliva could be routinely used by periodontists for a very early diagnosis of periodontitis, monitoring, prognosis, and management of periodontal patients by biomarker detection, whose diagnostic validity is related to sensitivity and specificity. Recent paper reviews and meta-analyses have focused on five promising host derived biomarkers as candidate for early diagnosis of periodontitis: MMP-8 (Metalloproteinase-8), MIP-1α (Macrophage inflammatory protein-1 alpha), IL-1 β (Interleukin-1 beta), IL-6 (Interleukin-6), and HB (Hemoglobin), and their combinations. Chair-side Lab-on-a-chip (LOC) technology may soon become an important part of efforts to detect such biomarkers in saliva medium to improve worldwide periodontal health in developed nations as well as in underserved communities and poor countries. Their applications in preventive and predictive medicine is now fundamental, and is aimed at the early detection of risk factors or the presence or evolution of the disease, and in personalized medicine, which aims to identify tailor-made treatments for individual patients. The aim of the present paper is to be informative about host derived periodontal biomarkers and, in particular, we intend to report information about the most important immune response derived biomarkers and Hemoglobin as candidates to be routinely utilized in order to obtain a chair-side early diagnosis of periodontal disease.

Background: Macrophages play a key role in coronary plaque destabilization. In-vitro human monocyte-derived macrophages (MDMs) are used to study macrophages infiltrating tissue. Optical coherence tomography (OCT) provides an in-vivo insight of the coronary arteries. We compared the MDMs morpho-phenotype and culprit plaque features at OCT in acute coronary syndrome (ACS) patients according to the underlying plaque pathobiology., Methods: Sixty-six patients undergoing coronary angiography and pre-angioplasty OCT of the culprit vessel were allocated to three groups according to mechanism of ACS at OCT and C-reactive protein levels (cut-off: 2 mg/Ll): 1) plaque rupture with systemic inflammation; 2) plaque rupture without systemic inflammation, 3) plaque with intact fibrous cap. A blood sample was collected to obtain MDMs, categorized as having "round" or "spindle" morphology., Results: Thirty-two patients (48.5%) were assigned to Group 1, 10 (15.2%) to Group 2 and 24 (36.4%) to Group 3. The "round" MDMs were significantly more frequent in Group 1 (39.25 ± 4.98%) than in Group 2 (23.89 ± 3.10%) and Group 3 (23.02 ± 7.89%), p = 0.008. MDMs in Group 1 as compared to Groups 2 and 3 showed lower efferocytosis (8.74 ± 1.38 vs 9.74 ± 2.15 vs 11.41 ± 2.41; p = 0.012), higher tissue factor levels (369.84 ± 101.13 vs 301.89 ± 59.78 vs 231.74 ± 111.47; p = 0.001) and higher heme oxygenase-1 expression (678.78 ± 145.43 vs 419.12 ± 74.44 vs 409.78 ± 64.33; p = 0.008)., Conclusions: MDMs of ACS patients show morpho-phenotypic heterogeneity with prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation. Such MDMs subpopulation may take part to the cellular pathways leading to fibrous cap rupture with the subsequent thrombus formation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.

Background: Mitochondrial biomarkers have been investigated in different critical settings, including ST-elevation myocardial infarction (STEMI). Whether they provide prognostic information in STEMI, complementary to troponins, has not been fully elucidated. We prospectively explored the in-hospital and long-term prognostic implications of cytochrome c and cell-free mitochondrial DNA (mtDNA) in STEMI patients undergoing primary percutaneous coronary intervention., Methods: We measured cytochrome c and mtDNA at admission in 466 patients. Patients were grouped according to mitochondrial biomarkers detection: group 1 (-/-; no biomarker detected; n = 28); group 2 (-/+; only one biomarker detected; n = 283); group 3 (+/+; both biomarkers detected; n = 155). A composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema was the primary endpoint. Four-year all-cause mortality was the secondary endpoint., Results: Progressively lower left ventricular ejection fractions (52 ± 8%, 49 ± 8%, 47 ± 9%; p = 0.006) and higher troponin I peaks (54 ± 44, 73 ± 66, 106 ± 81 ng/mL; p = 0.001) were found across the groups. An increase in primary (4%, 14%, 19%; p = 0.03) and secondary (10%, 15%, 23%; p = 0.02) endpoint rate was observed going from group 1 to group 3. The adjusted odds ratio increment of the primary endpoint from one group to the next was 1.65 (95% CI 1.04-2.61; p = 0.03), while the adjusted hazard ratio increment of the secondary endpoint was 1.55 (95% CI 1.12-2.52; p = 0.03). The addition of study group allocation to admission troponin I reclassified 12% and 22% of patients for the primary and secondary endpoint, respectively., Conclusions: Detection of mitochondrial biomarkers is common in STEMI and seems to be associated with in-hospital and long-term outcome independently of troponin., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results

Despite the technological advancements in the last 40 years, conditions such as refractory cardiogenic shock and cardiac arrest still present a very high mortality rate in real-world clinical practice. In this light, we have reviewed the techniques, indications, contraindications, and results of the socalled Veno-Arterial Extracorporeal Circulatory Membrane Oxygenation (VA-ECMO) in the adult population to evaluate the current results of this temporary cardio-pulmonary support as salvage and/or bridge therapy in the patient suffering from refractory cardiogenic shock or cardio-circulatory arrest. The results are encouraging, especially in the setting of refractory cardiogenic shock and in-hospital cardiac arrest. Among a selected population, the prompt institution of a VA-ECMO may radically change the prognosis by sustaining vital functions while looking for the leading cause or waiting for the reversal of the temporary cardio-respiratory negative condition. The future directions aim to standardized and shared protocols, miniaturization of the machines, and possibly the institution of specialized "ECMO teams" for in and the out-of-hospital institution of the tool., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)