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Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

Background: Adverse patient safety events (AEs) can negatively impact on healthcare workers (HCWs) by causing emotional distress and affecting professional ability. The challenge of healthcare organizations is to support HCWs involved in AEs. This study aims to investigate the second victim phenomenon in a large Italian Academic Hospital (AH). Methods: A cross sectional survey was conducted from June to November 2019 involving all HCWs working at the AH of Udine. HCWs’ demographic characteristics and answers to the Second Victim Experience and Support Tool, Italian version (IT-SVEST; 29 items representing 7 dimensions and 2 outcome variables; Likert-scale: 1-5) were collected. Higher scores indicated a greater negative impact of the AEs and a perceived inadequacy of support resources. Median (M) and interquartile range (IQR) were assessed for each item. The agreement (AGR) (respondents with a mean score ≥4) was assessed for each dimension. Relationship between items score and demographic aspects was analyzed with non-parametric tests. Results: A total of 349 HCWs joined the survey. Women were 79.4% and mean age was 39.4±10.7 years. 58.7% of respondents referred to be involved in a AEs. Lots of HCWs expressed feelings of psychological distress (AGR=26.9%) and less experienced HCWs were more affected by feelings of shame than senior ones (M = 4, IQR=1.5 vs M = 3, IQR=2; p < 0.01). Physical distress (AGR=10.9%) and professional self-efficacy (AGR=11.8%) did not had a great impact on HCWs, but younger (M = 3, IQR=2 vs M = 2, IQR=2; p < 0.01) and female (M = 3, IQR=2 vs M = 2, IQR=2; p < 0.01) HCWs were more inclined to question their skills. Support services offered by Hospital organization may be improved (AGR 8,9%). Conclusions: Psychological impact of the AEs is relevant in our cohort and less experienced and female HCWs resulted more inclined to doubt their professional abilities when involved. Improvements in support resources should be desirable to create a safer working environment. Key messages: HCWs’ psychological dimension and perceived professional self-esteem can be negatively affected by adverse events, especially for less experienced and female professionals. Healthcare organizations need to develop and to implement a second victim support program designed to provide emotional, psychological and professional support for HCWs. [ABSTRACT FROM AUTHOR]

Background: The potential impact of demanding working conditions and career opportunities on the mental health of academic professionals has recently arisen some concerns, possibly resulting in psychological distress. This study aims to assess the prevalence of depression and anxiety within Udine University, comparing academic and administrative staff. Methods: A cross-sectional survey involving regular (RP) and short-term academic professionals (STP), and administrative staff (AS) was carried out between June and December 2020 throughout the administration of an online anonymous survey. Prevalence of depressive and anxiety symptoms was assessed using PHQ-9 and GAD-7 tools. Demographic information about age, gender, marital status and seniority was collected. Relationship between mental health outcomes and professional role was analysed using nonparametric tests and ordinal logistic regression. Results: All 5 university departments participated for a total of 366 people, being 109 of them STP, 146 RP and 111 AS. 55,7% of them were female, with a mean age of 47,9 years. Compared to administrative and regular staff, short-term professionals have a higher prevalence (95%CI) of both depressive (39,4% (30,8 - 48,8) vs 14,4% (9,6 - 21,0) vs 27,0% (19,6 - 35,9); p < 0,001) and anxiety symptoms (STP: 33,0% (24,9 - 42,3); RP: 15,1% (10,2 - 21,8); AS: 22,5% (15,8 - 31,1); p < 0.005). Multivariate models suggest an increased risk of depression OR 1.61 (0.98- 2.64) and anxiety OR 2.08 (1.27-3.41) for female. Conclusions: The higher prevalence of depressive and anxiety symptoms among STP could represent the effect on younger academics’ mental health of the career uncertainty and challenging arena. The difference between AS and STP in psychological distress could be explained by the different job security status. More support should be given by universities to young academics for their both effective and healthy contribution to the progress of research. Key messages: The high level of external pressure, referred as ‘‘publish or perish’’, can play an important role in determining academics’ mental health. Investment to provide coping tools for young academics could be strategical for researchers’ empowerment. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasound (US)-guided axillary vein puncture is a safe and effective approach for cardiac implantable electronic device (CIED) implantation, and it is highly recommended by the current consensus document. However, only reports on small populations are available in the current literature regarding the comparison of this technique with other traditional approaches (subclavian vein blind puncture and cephalic vein surgical cutdown)., Purpose: We aimed to assess the effectiveness and safety of US- guided axillary vein puncture using a microintroducer kit for CIED implantation as compared to the aforementioned traditional approaches., Methods: All consecutive patients with an indication to CIED implantation were prospectively enrolled in our observational study from March 2021 to July 2023. Patients were divided into three groups based on venous access route, according to the operator's preference: cephalic vein surgical cutdown (G1), US-guided axillary vein puncture (G2), and subclavian vein blind puncture (G3). Clinical and procedural characteristics, success and complication rates were considered for analysis., Results: A total of 1000 patients (65.2% male, mean age 75.5 ± 10.8 years) were enrolled. Cephalic vein surgical cutdown was chosen in 172 (G1, 17.2%), US-guided axillary access in 433 patients (G2, 43.3%), and subclavian vein in 395 (G3, 39.5%). Success rate was 77.6% in G1, 96.3% in G2, and 97.2% in G3 (G2 vs. G3, p = 0.5; G1 vs. G2, p < 0.0001; G1 vs. G2. vs. G3, p < 0.0001). Compared to subclavian and cephalic groups, in the US-guided axillary group, a successful access was obtained with a reduced mean number of puncture attempts (G2 vs. G3: 1.3 ± 0.9 vs. 1.8 ± 1, p < 0.0001) and needed reduced times to get access (G2 vs. G3: 15 s [10-30 s] vs. 40 [20-65 s]; p < 0.0001, G1 vs. G2: 210 s [180-247 s] vs. 15 s [10-30 s]; p < 0.0001) and to reach the superior vena cava, without differences in total procedural times (72.9 ± 30.4 vs. 75.7 ± 34.8 min, p = 0.24). Bailout fluoroscopy times [1 (0-8) s vs. 20 (10-58) s, p < 0.0001] and usage of vein angiography (11.9% vs. 51.3%, p < 0.0001) were lower in G2 as compared to G3. Complication rate did not differ among the three study groups (early complications: 2.9% in G1, 2.5% in G2, and 2.5% in G3, p = 0.96; late complications: 2.9% in G1, 1.6% in G2, and 0.8% in G3, p = 0.15)., Conclusions: US-guided axillary vein puncture for CIED implantation using a microintroducer kit is a safe technique with a very high success rate. Compared to other traditional approaches, it allows to get access with a lower number of puncture attempts and with reduced times, without prolonging the total procedural time. Moreover, x-ray use and need for contrast medium are very rare in US-guided axillary approach. Hence, it should be considered the strategy of choice for most patients undergoing CIED implantation., (© 2024 The Author(s). Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterised by joint destruction and extra-articular manifestations. Different cells and soluble components of the innate as well as adaptive immune system actively contribute to the amplification and perpetuation of the inflammatory processes and structural changes. To date, the knowledge on the mechanisms involved in RA pathogenesis is increasingly precise, mainly due to the recent data obtained from studies on genetics and molecular and cellular biology. In this review article we summarised the new insights into RA pathogenesis from original research articles published in the last year.

Objectives: To review randomised controlled trials (RCT) investigating colchicine (COL) for cardiovascular (CV) prevention in patients at high to very high CV risk aiming to extract data that could be useful in rheumatology practice., Methods: A systematic search of multiple databases according to the PICO framework was performed from inception to April 3, 2023. Three researchers independently screened abstracts/titles and reviewed full texts reviewed. Data extraction was performed using a pilot-tested data extraction form., Results: A total of 14,096 references were retrieved by the search and 30 articles, describing 28 RCTs, were included in the review (Total number of patients 16,795, of which 8,463 randomised to COL; dose 0.5-2 mg/day, treatment duration 1day-29 months). Only one of the 28 RCTs provided clear information on whether patients with rheumatic diseases (more specifically gout) were enrolled in the study cohorts and previous use of COL was an exclusion criterion only in 14 (50 %) RCTs. Previous therapy with glucocorticoids and/or non-steroidal anti-inflammatory drugs and/or immune suppressive therapies was an exclusion criterion only in 9 (32 %) RCTs., Conclusion: Our results highlight the need to redefine the eligibility criteria as well as the reporting of results in future RCTs in order to minimise bias or previous exposure to COL and also obtain data that could be useful in rheumatology practice., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Increasing work-related stress in academia can have an impact on physical and mental health. The aim of this study was to analyse the coping strategies of staff employed at the University of Udine and to verify whether sociodemographic data, professional position, and the presence of anxiety or depression symptoms are related to the use of different coping strategies., Methods: We conducted a cross-sectional study between June and December 2020 using the Brief COPE questionnaire. We correlated coping strategies with professional position, sociodemographic data, and the presence of anxiety or depressive symptoms measured with the Patient Health Questionnaire-9 and the General Anxiety Disorder-7., Results: A total of 366 people participated in the study, including 109 junior academics, 146 senior academics, and 111 administrative staff (response rate 23.6%). The three most frequently used coping strategies in terms of approach coping style were planning (6.77 ± 1.41), active coping (6.58 ± 1.45) and acceptance (6.23 ± 1.44). Women were more likely than men to report using approach and avoidant coping strategies (p < 0.001). Positive reframing and religion were most commonly used by administrative staff (p < 0.05), in contrast to junior academics, who were more likely to use substances and self-blame (p < 0.05). Anxiety was found to correlate with self-blame (OR 1.94) as a coping strategy, while depression was associated with venting (OR 2.83), self-blame (OR 3.27), and humor (OR 3.02)., Conclusion: Identifying profiles of coping strategies can help higher education institutions to implement support strategies for the academic community, ultimately promoting healthier lives and more effective teaching and research. Our study has shown that women and junior academics among staff at the Udine University would benefit from a tailored health promotion intervention that encourages the use of approach coping styles to reduce their risk of developing anxiety and depressive symptoms., (© 2024. The Author(s).)

The strong genetic association between HLA-B*27 and spondyloarthritis (SpA) accounts for about 90% of the susceptibility to axial SpA (axSpA), and the presence of HLA-B*27 is helpful in classifying patients according to the Assessment of SpondyloArthritis International Society (ASAS) classification criteria. However, over the years, other HLA-B alleles have been associated with an increased risk of developing SpA; on this basis, the aim of our study was to describe the demographic, clinical, and radiological characteristics of a cohort of SpA patients who were negative for HLA-B*27. We identified 85 patients with a clinical diagnosis of SpA displaying HLA-B alleles other than HLA-B*27; HLA-B*51 emerged as the most prevalent allele (N = 33, 39%), regardless of the fulfilment of either the axial or the peripheral ASAS criteria. The second most prevalent allele in the full cohort (N = 16, 19%) and in the patients fulfilling either the axial or the peripheral criteria was HLA-B*35. The third most prevalent allele in the full cohort was HLA-B*18 (N = 12, 15%), which was also the second most prevalent allele in the patients fulfilling neither of the two sets of criteria. Overall, the clinical picture was similar across the subgroups fulfilling the different sets of ASAS criteria; however, the patients not fulfilling any ASAS criteria had a higher likelihood of having arthritis compared to the patients fulfilling the axial criteria, whereas the Bath Ankylosing Spondylitis Functional Index was significantly higher in those patients fulfilling the axial criteria compared to those who did not fulfill any criteria. Our results indicate that other HLA alleles, beyond HLA-B*27, could be useful in facilitating SpA diagnosis, particularly in patients with a clinical picture which is consistent with SpA but does not fulfill the ASAS classification criteria.

Background: Bempedoic acid (BA) is a small-molecule first-in-class of inhibitor of ATP citrate lyase that significantly lowers low-density lipoproteins cholesterol (LDL-c) in statin-intolerant and inadequate responders. Increased serum uric acid (SUA) levels and gout incidence have been described in BA-treated patients. The aim of this systematic review was to investigate the safety of BA regarding SUA levels and gout in randomised controlled trials (RCTs)., Methods: A search on 7 databases was performed from inception to May 4, 2023. RCTs of BA monotherapy or combination with other lipid-lowering treatment (LLT) in patients with increased LDL-c were included. Dual data extraction was performed with disagreements resolved through consensus. Due to the methodological purpose of this review risk-of-bias assessment of studies was not performed., Results: 6 Phase 3 RCTs ( N  = 17,975 patients of which 9,635 received BA) 9 Phase 2 RCTs ( N  = 362 patients of which 170 received BA) and an open-label extension of a Phase 3 RCT were included. Gout and/or hyperuricemia were not mentioned as exclusion criteria, previous/current use of urate-lowering therapies (ULT) and/or colchicine and/or dietary patterns were not reported. Phase 3 RCTs: 2 studies specified the number of patients experiencing hyperuricemia over the study period (BA: 4.9%-11%; placebo: 1.9%-5.6%) and the effect size was significant only in 1 study (OR = 2.0, 95% CI 1.8-2.3). Four RCTs reported a higher incidence of gout in the BA arm however, when we calculated the effect size, it was small and often not significant. Two studies reported 0 cases of gout. The paucity of information about SUA levels at baseline and/or at the end of follow-up do not allow us to quantify the effect sizes for BA-induced SUA elevation. Data on gout from Phase 2 RCTs is scant., Conclusions: Data from phase 2 and 3 RCTs do not allow for confirming a clear association between BA and gout. It is conceivable that a careful assessment of SUA levels/history of gout at baseline and the concomitant use of urate-lowering agents may be instrumental to minimise the risk of new-onset gout/gout flares in patients treated with BA., 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., (© 2023 Alunno, Carubbi, Campanozzi, Bellisario, Schoones, Mariani, Di Ruscio, Altieri and Ferri.)

The term spondyloarthritis (SpA) encompasses a group of interrelated disorders characterised by the involvement of the musculoskeletal system as well as extra-articular manifestations like acute anterior uveitis, psoriasis and inflammatory bowel diseases (IBD). Likewise, IBD may present with various extra-intestinal manifestations among which those involving the musculoskeletal system, namely peripheral and axial SpA are the most common. The identification of patients with both SpA and IBD is of paramount importance in clinical practice since the coexistence of these two entities has been associated with great disability and decreased quality of life. In order to achieve an early diagnosis of IBD-SpA it is instrumental that rheumatologists seek for gastrointestinal symptoms in SpA patients and likewise that gastroenterologists seek for inflammatory musculoskeletal symptoms in patients with IBD. This narrative review aims at critically appraising the available evidence about SpA occurring in IBD patients versus IBD occurring in patients with SpA and at highlighting similarities and differences between the two scenarios., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: Transvenous lead extraction (TLE) has become a pivotal part of a comprehensive lead management strategy, dealing with a continuously increasing demand. Nonetheless, the literature about the long-term impact of TLE on survivals is still lacking. Given these knowledge gaps, the aim of our study was to analyse very long-term mortality in patients undergoing TLE in public health perspective., Methods: This prospective, single-centre, observational study enrolled consecutive patients with cardiac implantable electronic device (CIED) who underwent TLE, from January 2005 to January 2021. The main goal was to establish the independent predictors of very long-term mortality after TLE. We also aimed at assessing procedural and hospitalization-related costs., Results: We enrolled 435 patients (mean age 70 ± 12 years, with mean lead dwelling time 6.8 ± 16.7 years), with prevalent infective indication to TLE (92%). Initial success of TLE was achieved in 98% of population. After a median follow-up of 4.5 years (range: 1 month-15.5 years), 150 of the 435 enrolled patients (34%) died. At multivariate analysis, death was predicted by: age (≥77 years, OR: 2.55, CI: 1.8-3.6, p < 0.001), chronic kidney disease (CKD) defined as severe reduction of estimated glomerular filtration rate (eGFR <30 mL/min/1.73 m 2 , OR: 1.75, CI: 1.24-2.4, p = 0.001) and systolic dysfunction assessed before TLE defined as left ventricular ejection fraction (LVEF) <40%, OR: 1.78, CI 1.26-2.5, p = 0.001. Mean extraction cost was €5011 per patient without reimplantation and €6336 per patient with reimplantation respectively., Conclusions: Our study identified three predictors of long-term mortality in a high-risk cohort of patients with a cardiac device infection, undergoing successful TLE. The future development of a mortality risk score before might impact on public health strategy., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response., Objectives: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19., Methods: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline., Results: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%)., Conclusions: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)., Competing Interests: Funding Support and Author Disclosures This research was supported by the Collegium Medicum of Nicolaus Copernicus University (grant ID ZES.WL.2.2021). Dr Navarese has received speaker and consultancy fees from Amgen, Sanofi-Regeneron, Bayer; and has received grants from Abbott, outside the submitted work. Dr Gurbel has received grants and personal fees from Bayer HealthCare LLC, Otitopic Inc, Amgen, Janssen, U.S. WorldMeds LLC, Instrumentation Laboratory, Haemonetics, Medicure Inc, Idorsia Pharmaceuticals, Hikari Dx, and Novartis; has received personal fees from UpToDate, outside the submitted work; has a patent issued (Detection of Restenosis Risk in Patients and Assessment of Cardiac Health and Thrombotic Risk in a Patient); and is an expert witness in litigation involving clopidogrel. Dr Gorog has received institutional research grants from Bayer and Bristol Myers Squibb; and has received speaker fees from AstraZeneca, Bayer, and Boehringer Ingelheim. Dr Andreotti has received lecture/consultancy fees from Amgen, Bayer, BMS/Pfizer, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: SARS-CoV-2 spreads primarily through respiratory droplets of symptomatic individuals. With respect to asymptomatic individuals, there are conflicting results in the literature and a lack of studies specifically examining transmission in healthcare settings., Methods: The aim of this retrospective study, conducted in a northeastern Italian region, was to estimate the contagiousness of asymptomatic healthcare workers (HCWs) who tested positive for SARS-CoV-2. Asymptomatic HCWs who tested positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (rRT-PCR) at a regular screening nasopharyngeal or oropharyngeal swab between 1 February 2020 and 15 September 2020 were considered index cases. Contacts who were at high risk of infection and had follow-up swabs were included. Contacts were considered infected if they had a positive follow-up swab and/or symptoms associated with COVID-19 confirmed by a positive test within 14 days of exposure. Information was taken from records previously collected to identify contacts. Infectivity was estimated using the attack rate (AR) with a 95% confidence interval (95% CI)., Results: Thirty-eight asymptomatic HCWs who were positive at the screening swab and 778 contacts were identified. Contacts included 63.8% of colleagues, 25.6% of patients, 7.7% of family members and 3.0% of other contacts. Seven contacts tested positive for SARS-CoV-2 (AR: 0.91%, 95% CI: 0.89-0.93). Five of them were family members (AR: 8.3%), one was a colleague (0.2%) and one was a contact of other type (4.2%)., Conclusions: Viral spread by asymptomatic HCWs was less than in other settings. Identification of risk factors for transmission and reliable indicators of infectivity would be important to prioritize preventive measures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Coronary microvascular dysfunction (CMD) may cause symptoms of myocardial ischemia (microvascular angina [MVA]), but recent studies suggested that it might also contribute to the syndrome of heart failure with preserved ejection fraction (HFpEF). In this study we assessed the relation of CMD with findings of HFpEF in MVA patients., Methods: We enrolled 36 consecutive patients with MVA, in whom we assessed: 1) coronary blood flow (CBF) response to adenosine and cold pressor test (CPT) by color-Doppler echocardiography of the left anterior descending coronary artery; 2) complete echocardiographic examination; 3) N-terminal-pro-B-natriuretic peptide (NT-proBNP); 4) grade of dyspnea by the modified Medical Research Scale., Results: Among patients, 15 had definite HFpEF findings (group 1), 12 had equivocal HFpEF findings (group 2) and 9 had no evidence of HFpEF findings (group 3). Group 1 patients were older, had more cardiovascular risk factors and higher NT-proBNP levels (P=0.018), and showed a higher prevalence of diastolic dysfunction. Left ventricle dimensions and systolic function, however, did not differ among groups. Dyspnea was also not significantly different among groups (P=0.19). CBF to adenosine was 1.85±0.47, 1.78±0.40 1.49±0.32 in group 1, 2 and 3, respectively (P=0.13). Similarly, CBF response to CPT was 1.57±0.4, 1.49±0.2 and 1.45±0.3 in the 3 groups, respectively (P=0.74). Both CBF response to adenosine and CPT showed no relation with the severity of dyspnea symptoms., Conclusions: Our data suggest that in patients with MVA there is no relation between the grade of impairment of coronary microvascular dilatation and findings of HFpEF.

Permanent pacemaker implantation (PPI) represents a frequent complication after transcatheter aortic valve implantation (TAVI) due to atrio-ventricular (AV) node injury. Predictors of early AV function recovery were investigated. We analyzed 50 consecutive patients (82 ± 6 years, 58% males, EuroSCORE: 7.8 ± 3.3%, STS mortality score: 5 ± 2.8%). Pacemaker interrogations within 4−6 weeks from PPI were performed to collect data on AV conduction. The most common indication of PPI was persistent third-degree (44%)/high-degree (20%) AV block/atrial fibrillation (AF) with slow ventricular conduction (16%) after TAVI. At follow-up, 13 patients (26%) recovered AV conduction (i.e., sinus rhythm with stable 1:1 AV conduction/AF with a mean ventricular response >50 bpm, associated with a long-term ventricular pacing percentage < 5%). At multivariate analysis, complete atrio-ventricular block independently predicted pacemaker dependency at follow-up (p = 0.019). Patients with persistent AV dysfunction showed a significant AV conduction time prolongation after TAVI (PR interval from 207 ± 50 to 230 ± 51, p = 0.02; QRS interval from 124 ± 23 to 147 ± 16, p < 0.01) compared to patients with recovery, in whom AV conduction parameters remained unchanged. Several patients receiving PPI after TAVI have recovery of AV conduction within a few weeks. Longer observation periods prior to PPI might be justified, and algorithms to minimize ventricular pacing should be utilized whenever possible.

Background: Coronary microvascular dysfunction can be responsible for both stable angina and acute coronary syndrome (ACS). There are scarce data, however, about comparisons of clinical characteristics and outcomes of these 2 groups of patients., Materials and Methods: We studied 47 consecutive patients who underwent coronary angiography for angina syndromes and showed no obstructive stenosis. Patients were divided in 2 groups, according to their clinical presentation, i.e., stable angina ( n = 21) or non-ST segment elevation ACS (NSTE-ACS; n = 26). An intracoronary acetylcholine (Ach) test was performed in 12 and 17 patients of the 2 groups, respectively. Angina status, assessed by Seattle Angina Questionnaire (SAQ), and clinical events were assessed after 1, 6, and 30 months. An exercise stress test was performed 1 month after discharge., Results: Clinical characteristics and exercise test results of the 2 groups were largely similar. Ach testing induced epicardial or microvascular spasm in 6 (50.0%) and 10 (58.8%) stable and NSTE-ACS patients, respectively ( p = 0.72). Stable patients reported higher rates of angina, compared to NSTE-ACS patients, both at 1 ( p = 0.04) and 30 months (81 vs. 50%, p = 0.036) of follow-up. SAQ scores were also lower in stable vs. NSTE-ACS patients. Ach testing results showed no association with clinical outcomes., Conclusion: Clinical characteristics and exercise and Ach testing results are similar in angina patients with no-obstructive coronary artery disease with a stable or NSTE-ACS presentation. Stable patients show a worse symptomatic outcome irrespective of Ach test results., 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 Cambise, Telesca, Tremamunno, Felici, De Vita, Filice, Ingrasciotta, Ruscio, Crea and Lanza.)

Background: Atrioventricular (AV) conduction disturbances requiring permanent pacemaker implantation (PPI) are a common complication after transcatheter aortic valve implantation (TAVI). However, a significant proportion of patients might recover AV conduction at follow-up., Objectives: The aim of our study was to evaluate the recovery of AV conduction by determination through Wenckebach point in patients with PPI and therefore identify patients who could benefit from device reprogramming to avoid unnecessary RV pacing., Methods: We enrolled 43 patients that underwent PM implantation after TAVI at our Department from January 2018 to January 2021. PM interrogation was performed at follow-up and patients with native spontaneous rhythm were further assessed for AV conduction through WP determination., Results: A total of 43 patients requiring a PM represented the final study population, divided in patients with severely impaired AV conduction (no spontaneous valid rhythm or WP < 100; 26) and patients with valid AV conduction (WP ≥ 100; 17). In the first group patients had a significantly higher number of intraprocedural atrioventricular block (AVB) (20 vs. 1, p < 0.005), showed a significant higher implantation depth in LVOT (7.7 ± 2.2 vs. 4.4 ± 1.1, p < 0.05) and lower ΔMSID (-0.28 ± 3 vs. -3.94 ± 2, p < 0.05)., Conclusion: AV conduction may recover in a significant proportion of patients. In our study, valve implantation depth in the LVOT and intraprocedural AV block are associated with severely impaired AV conduction. Regular PM interrogation and reprogramming are required to avoid unnecessary permanent right ventricular stimulation in patients with AV conduction recovery., 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 Pelargonio, Scacciavillani, Donisi, Narducci, Aurigemma, Pinnacchio, Bencardino, Perna, Spera, Comerci, Ruscio, Romagnoli, Crea, Burzotta and Trani.)

Objective: Second victims are defined as healthcare workers involved in an unanticipated adverse patient event, who experienced professional and psychological distress. The Second Victim Experience and Support Tool (SVEST) is a survey developed and validated in the United States, which describes the experience of second victims. This study aims to perform the cross-cultural adaptation of the SVEST and to evaluate its psychometric characteristics in the Italian context., Methods: Translation and cross-cultural adaptation process was performed according to the World Health Organization guidelines. Then, 349 healthcare workers, including nurses, doctors, residents, and technicians, involved in direct patient care-a potential second victim-completed the Italian version of SVEST in a validation survey at the Academic Hospital of Udine. The SVEST consists of 29 items, divided into 7 dimensions, 2 outcome variables, and 7 support options. The Italian version was assessed for internal consistency through Cronbach α, for content validity with content validity index for scales and for item and for construct validity with Confirmatory Factor Analysis., Results: The internal consistency of the instrument was adequate in its overall evaluation with Cronbach α value of 0.88 (95% confidence interval = 0.86). The content validity index for scales was 0.94 and that for item was 0.70. The confirmatory factor analysis results showed a good model fit for the 9-factor structure (χ2 = 676.18, df = 327, P < 0.001). Root mean squared error of approximation, Akaike information criterion, and comparative fix index Tucker-Lewis index values also suggested a good fit to the data., Conclusions: The Italian version of the SVEST can be used to evaluate second victim experiences, demonstrating adequate validity, reliability, and good psychometric properties., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Diabetes mellitus (DM) is a risk factor for left ventricle (LV) diastolic dysfunction. Aim of this study was to investigate whether endothelial and/or autonomic dysfunction are associated with LV diastolic dysfunction in DM patients., Methods: We studied 84 non-insulin-dependent type 2 DM (T2DM) patients with no heart disease by assessing: 1) LV diastolic function by echocardiography; 2) peripheral vasodilator function, by measuring flow-mediated dilation (FMD) and nitrate-mediate dilation (NMD); 3) heart rate variability (HRV) on 24-h Holter electrocardiographic monitoring., Results: Twenty-five patients (29.8%) had normal LV diastolic function, while 47 (55.9%) and 12 (14.3%) showed a mild and moderate/severe diastolic dysfunction, respectively. FMD in these 3 groups was 5.25 ± 2.0, 4.95 ± 1.6 and 4.43 ± 1.8% (p = 0.42), whereas NMD was 10.8 ± 2.3, 8.98 ± 3.0 and 8.82 ± 3.2%, respectively (p = 0.02). HRV variables did not differ among groups. However, the triangular index tended to be lower in patients with moderate/severe diastolic dysfunction (p = 0.09) and a significant correlation was found between the E/e' ratio and both the triangular index (r = -0.26; p = 0.022) and LF amplitude (r = -0.29; p = 0.011)., Conclusions: In T2DM patients an impairment of endothelium-independent, but not endothelium-dependent, dilatation seems associated with LV diastolic dysfunction. The possible role of cardiac autonomic dysfunction in diastolic dysfunction deserves investigation in larger populations of patients., (© 2021 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Medical students and residents play an important role in patient care and ward activities, thus they should follow hospital procedures and ensure best practices and patient safety. A survey concerning staff on training was conducted to assess the perceived quality of healthcare from healthcare workers (HCWs), residents, medical students and patients in Udine Academic Hospital, Italy. Between December, 2018 and March, 2019, a 5-point Likert-scale questionnaire was administered in 21 units, covering four thematic areas: patients and medical staff satisfaction with the quality of care provided by residents and students, patient privacy, clinical risk management, patient perception of staff on training. Data analysis included descriptive analysis and ordered logistic regressions. A total of 596/1,863 questionnaires were collected from: HCWs (165/772), residents (110/355), students (121/389), and patients (200/347). Residents were rated high both by patients (median = 5, IQR = 4-5, OR 0.49, 95%CI 0.26-0.93) and HCWs (median = 4, IQR = 3-5, OR 0.14, 95%CI 0.08-0.26), with a lower score for medical students on the same topic, both by patients (median = 4, IQR = 3-5, OR 2.94, 95%CI 1.49-5.78) and HCWs (median = 3, IQR = 2-3, OR 0.41, 95%CI 0.25-0.67). Therefore, the role of staff on training in quality and safety of healthcare deserves integrated regular evaluation, since direct interaction with patients contributes to patients' perception of healthcare., Competing Interests: The authors have declared that no competing interests exist.

Transvenous lead extraction (TLE) has seen a rapid expansion in the past 20 years. The procedure has changed from early techniques involving simple manual traction that frequently proved themselves ineffective for chronically implanted leads, and carried significant periprocedural risks including death, to the availability of a wide range of more efficacious techniques and tools, providing the skilled extractor with a well-equipped armamentarium. The reduction in morbidity and mortality associated with these new extraction techniques has widened indications to TLE from prevalent use in life-threatening situations, such as infection and sepsis, to a more widespread use even in noninfectious situations such as malfunctioning leads. Powered sheaths have been a remarkable step forward in this improvement in TLE procedures and recent registries at high-volume centers report high success rates with exceedingly low complication rates. This review is aimed at describing technical features of powered sheaths as well as reported performance during TLE procedures., (© 2021 Wiley Periodicals LLC.)

Background: A sizeable number of patients with a diagnosis of non-ST segment elevation acute coronary syndrome show non-obstructive coronary artery disease. In this study we assessed whether differences in vascular and cardiac autonomic function exist between non-ST segment elevation acute coronary syndrome patients with obstructive or non-obstructive coronary artery disease., Methods and Results: Systemic endothelium-dependent and independent vascular dilator function (assessed by flow-mediated dilation and nitrate-mediated dilation of the brachial artery, respectively) and cardiac autonomic function (assessed by time-domain and frequency-domain heart rate variability parameters) were assessed on admission in 120 patients with a diagnosis of non-ST segment elevation acute coronary syndrome. Patients were divided into two groups according to coronary angiography findings: (a) 59 (49.2%) with obstructive coronary artery disease (≥50% stenosis in any epicardial arteries); (b) 61 (50.8%) with non-obstructive coronary artery disease. No significant differences between the two groups were found in both flow-mediated dilation (5.03 ± 2.6 vs. 5.40 ± 2.5%, respectively; P  = 0.37) and nitrate-mediated dilatation (6.79 ± 2.8 vs. 7.30 ± 3.4%, respectively; P  = 0.37). No significant differences were also observed between the two groups both in time-domain and frequency-domain heart rate variability variables, although the triangular index tended to be lower in obstructive coronary artery disease patients (30.2 ± 9.5 vs. 33.9 ± 11.6, respectively; P  = 0.058). Neither vascular nor heart rate variability variables predicted the recurrence of angina, requiring emergency room admission or re-hospitalisation, during 11.3 months of follow-up., Conclusions: Among patients admitted with a diagnosis of non-ST segment elevation acute coronary syndrome we found no significant differences in systemic vascular dilator function and cardiac autonomic function between those with obstructive coronary artery disease and those with non-obstructive coronary artery disease., (© The European Society of Cardiology 2020.)

Sustainable Development Goals (SDGs) and 2030 Agenda represent global development programs. Education can widen the acknowledgement of their relevance and their applications. This survey aims to assess awareness, knowledge and attitudes towards SDGs and sustainability among first-year students in nine Italian Universities. A Likert scale-based online questionnaire of 70 items was compiled by students from March to July 2019. It examined knowledge and expectations referred to sustainable development concepts, indicators and documents/models accounting for sociodemographic variables. Statistical analyses performed were Chi-square test, Fisher's Exact test, Kendall's W correlation coefficient, univariate and multivariate analysis. The questionnaire was completed by 1676 students. A low percentage referred a good knowledge of SDGs and 2030 Agenda, most of them had never attended related educational activities previously. Better knowledge of SDGs and 2030 Agenda was observed in case of previous specific educational activities ( p < 0.001). The expectation towards university guaranteeing an education on SDGs was high, both for personal wisdom and for usefulness in future professional context. A significant difference ( p < 0.001) in such expectations was found, as healthcare students were less interested than colleagues of other areas. The results showed low knowledge but interest towards sustainable development. A scheduled implementation of academic initiatives should be considered.

Background: Emergency Department (ED) crowding reduces staff satisfaction and healthcare quality and safety, which in turn increase costs. Despite a number of proposed solutions, ED length of stay (LOS) - a main cause of overcrowding - remains a major issue worldwide. This retrospective cohort study was aimed at evaluating the effectiveness on ED LOS of a procedure called "Diagnostic Anticipation" (DA), which consisted in anticipating the ordering of blood tests by nurses, at triage, following a diagnostic algorithm approved by physicians., Methods: In the second half of 2019, the ED of the University Hospital of Ferrara, Italy, adopted the DA protocol on alternate weeks for all patients with chest pain, abdominal pain, and non-traumatic bleeding. A retrospective cohort study on DA impact was conducted. Using ED electronic data, LOS independent predictors (age, sex, NEDOCS and Priority Color Code, imaging tests, specialistic consultations, hospital admission) were evaluated through multiple regression., Results: During the weeks when DA was adopted, as compared to control weeks, the mean LOS was shorter by 18.2 min for chest pain, but longer by 15.7 min for abdominal pain, and 33.3 for non-traumatic bleeding. At multivariate analysis, adjusting for age, gender, triage priority, specialist consultations, imaging test, hospitalization and ED crowding, the difference in visit time was significant for chest pain only (p < 0.001)., Conclusions: The impact of DA varied by patients' condition, being significant for chest pain only. Further research is needed before the implementation, estimating the potential proportion of inappropriate blood tests and ED crowding status.

Background: Healthcare-Associated Infections (HAIs) represent one of the leading issues to patient safety as well as a significant economic burden. Similarly, Antimicrobial Use (AMU) and Resistance (AMR) represent a growing threat to global public health and the sustainability of healthcare services., Methods: A Point Prevalence Survey (PPS) following the 2016 ECDC protocol for HAI prevalence and AMU was conducted at Ferrara University Hospital (FUH). Data were collected by a team of trained independent surveyors in 2016 and 2018. Risk factors independently associated with HAI were assessed by a multivariate logistic regression model., Results: Of the 1102 patients surveyed, 115 (10.4%) had an active HAI and 487 (44.2%) were on at least 1 systemic antimicrobial agent. Factors independently associated with increased HAI risk were a "Rapidly Fatal" McCabe score (expected fatal outcome within 1 year), presence of medical devices (PVC, CVC, indwelling urinary catheter or mechanically assisted ventilation) and a length of hospital stay of at least 1 week. The most frequent types of HAI were pneumonia, bloodstream infections, and urinary tract infections. Antimicrobial resistance to third-generation cephalosporins was observed in about 60% of Enterobacteriaceae., Conclusions: The survey reports a high prevalence of HAI and AMU in FUH. Repeated PPSs are useful to control HAIs and AMU in large acute-care hospitals, highlighting the main problematic factors and allowing planning for improvement actions.

Management of patients presenting to the Emergency Department with chest pain is continuously evolving. In the setting of acute coronary syndrome, the availability of high-sensitivity cardiac troponin assays (hs-cTn) has allowed for the development of algorithms aimed at rapidly assessing the risk of an ongoing myocardial infarction. However, concerns were raised about the massive application of such a simplified approach to heterogeneous real-world populations. As a result, there is a potential risk of underdiagnosis in several clusters of patients, including women, for whom a lower threshold for hs-cTn was suggested to be more appropriate. Implementation in clinical practice of sex-tailored cut-off values for hs-cTn represents a hot topic due to the need to reduce inequality and improve diagnostic performance in females. The aim of this review is to summarize current evidence on sex-specific cut-off values of hs-cTn and their application and usefulness in clinical practice. We also offer an extensive overview of thresholds reported in literature and of the mechanisms underlying such differences among sexes, suggesting possible explanations about debated issues., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Giulio Francesco Romiti et al.)

Statins are a main curbstone in the prevention of cardiovascular disease (CVD), pandemic in 21st century. CVD displays evident sex and gender differences, not only in clinical manifestation and outcomes but also in pharmacological treatment. Whether statin therapy should be differentially prescribed according to sex is a matter of debate. Aside a different pharmacological action, statins are not proven to be less effective in one gender comparing to the other, nor to be less safe. Nevertheless, up to date evidence shows that statins have not been adequately tested in women, especially in primary prevention trials. Since data-lacking, making a treatment decision on women is potentially harmful, although female individuals represent the majority of the population and they have a greater lifetime CVD risk. Therefore, adequately powered randomized control trials with longer follow-up are warranted to establish if a benefit on CV events and mortality prevention exists in both sexes. The aim of the present review is to summarize the sex and gender differences in statin use: it raises concerns and updates perspectives towards an evidence-based and sex-tailored prevention of CVD management., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role., Methods: Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied., Results: At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p<0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p<0.001 and from 24.3±1.1 to 31.1±1.5μM, p<0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p<0.001, and from 341±14 to 312±14 pM, p<0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001)., Conclusions: The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Evidence from studies conducted in Western countries indicates that a significant proportion of hospital beds are occupied by patients who experience a delayed hospital discharge (DHD). However, evidence about this topic is lacking in Italy, and little is known on the patients' and organisational characteristics that influence DHDs. Therefore, we carried out a survey in all the hospitals of a Northern Italian region to analyse the prevalence and the determinants of DHD., Methods: A cross-sectional study was carried out during an index period of 15 days in 256 operative units in Emilia-Romagna, a Northern Italian region with 4.4 million inhabitants, to identify patients medically fit for discharge but still hospitalised. The characteristics of these patients (n = 510) were compared with all the other patients (n = 5,815) hospitalised in the same operative units during the index period using multilevel logistic regression models., Results: The one-day prevalence of DHD was 8.1%. More than half of DHD patients (52.7%) waited to access long-term/rehabilitation units or residential care homes, 16.7% experienced a delay for family-related reasons, and 14.5% were waiting to be admitted to other rehabilitation services. Among DHD patients hospitalised in long-term/rehabilitation units, 45.3% were waiting to be transferred to residential care homes. Patients' characteristics associated with a higher likelihood of DHD in multilevel logistic regression were older age, provision of intensive care, a diagnosis of dementia, tumours or femoral/shoulder fractures, and a number of comorbidities. Patients hospitalised in long-term/rehabilitation units, as well as in orthopaedics/traumatology units, were significantly more likely to have a DHD compared with patients hospitalised in general surgery units. Moreover, compared with Local Health Authority Hospitals, being hospitalised in Hospital Trusts was associated with a higher likelihood of DHD., Conclusions: Although the prevalence of DHD in the present study is markedly lower than that reported in the literature, we submit that the DHD problem should be addressed with major organisational innovations, with a special focus on the ageing of the population and epidemiological trends. Organisational changes imply new ways of managing emerging clusters of patients whose needs are not efficiently or effectively met by traditional organisation models and services.