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Despite enormous developments in medicine, infective endocarditis (IE) remains an ongoing issue for physicians due to increased morbidity and persistently high mortality. Our goal was to assess clinical outcomes in patients with IE and identify determinants of in-hospital mortality. Material and methods: The analysis was retrospective, single-centered, and comprised 270 patients diagnosed with IE from 2005 to 2021 (median age 65 (51-74), male 177 (65.6%). Native IE (NVIE) was observed in 180 (66.7%), prosthetic IE (PVIE) in 88 (33.6%), and cardiac device-related IE (CDRIE) in 2 (0.7%), with non-survivors having much higher rates. Healthcare-associated IE (HAIE) was 72 (26.7%), Staphylococci were the most prevalent pathogen, and the proportion of Gram-negative bacteria (GNB) non-HACEK was significantly greater in non-survivors than survivors (11 (15%) vs. 9 (4.5%), p = 0.004). Overall, 54 (20%) patients underwent early surgery, with a significant difference between dead and alive patients (3 (4.5%) vs. 51 (25.1%, p = 0.000). The overall in-hospital mortality rate was 24.8% (67). Logistic regression was conducted on the total sample ( n = 270) for the period 2005-2021, as well as the sub-periods 2005-2015 ( n = 119) and 2016-2021 ( n = 151), to identify any differences in the trend of IE. For the overall group, the presence of septic shock (OR-83.1; 95% CI (17.0-405.2), p = 0.000) and acute heart failure (OR-24.6; 95% CI (9.2-65.0), p = 0.000) increased the risk of mortality. Early surgery (OR-0.03, 95% CI (0.01-0.16), p = 0.000) and a low Charlson comorbidity index (OR-0.85, 95% CI (0.74-0.98, p = 0.026) also lower this risk. Between 2005 and 2015, the presence of septic shock (OR 76.5, 95% CI 7.11-823.4, p = 0.000), acute heart failure (OR-11.5, 95% CI 2.9-46.3, p = 0.001), and chronic heart failure (OR-1.3, 95% CI 1.1-1.8, p = 0.022) enhanced the likelihood of a fatal outcome. Low Charlson index comorbidity (CCI) lowered the risk (OR-0.7, 95% CI 0.5-0.95, p = 0.026). For the period 2016-2021, the variable with the major influence for the model is the failure to perform early surgery in indicated patients (OR-240, 95% CI 23.2-2483, p = 0.000) followed by a complication of acute heart failure (OR-72.2, 95% CI 7.5-693.6. p = 0.000), septic shock (OR-17.4, 95% CI 2.0-150.8, p = 0.010), previous stroke (OR-9.2, 95% CI 1.4-59.4, p = 0.020) and low ejection fraction (OR-1.1, 95% CI 1.0-1.2, p = 0.004). Conclusions: Knowing the predictors of mortality would change the therapeutic approach to be more aggressive, improving the short- and long-term prognosis of IE patients.

Newborn screening is a public health measure to diagnose rare diseases at birth, thereby minimising negative effects of late treatment. Genomic technologies promise an unprecedented expansion of screened diseases at low cost and with transformative potential for newborn screening programmes. However, barriers to the public funding of genomic newborn screening are poorly understood, particularly in light of the heterogenous European newborn screening landscape. This study therefore aims to understand whether international newborn screening experts share a common understanding of the barriers to fund genomic newborn screening. For this purpose, we convened 21 European newborn screening experts across a range of professions and national backgrounds in a Delphi study. Stable consensus, determined via the Wilcoxon matched-pairs signed-ranks test, was found via three consecutive survey rounds for all presented barriers. Experts generally judged the scenario of genomic newborn screening being available to every newborn in seven years to be unlikely, identifying treatability and the absence of counselling and a skilled workforce as the most significant barriers to public funding. We identify value re-definition for rare disease treatments, centralisation of genomic expertise, and international research consortia as avenues for pan-European actions which build on the consensus achieved by our Delphi panel., Competing Interests: Declaration of competing interest Anne-Sophie Chalandon and Alicia Granados are employed by Sanofi S.A. The views presented here are those of the authors and not necessarily those of Sanofi S.A., its directors, officers, or staff. Julian Nam is employed by F. Hoffmann-La Roche Ltd. The views presented here are those of the authors and not necessarily those of F. Hoffmann-La Roche Ltd., its directors, officers, or staff. Andreas Clemens is employed by Novartis AG. The views presented here are those of the authors and not necessarily those of Novartis AG, its directors, officers, or staff. All other authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: This study aimed to assess the risk management of drug safety in an operating theater setting within a hospital-based treatment facility., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Infective endocarditis (IE) remains a difficult disease to diagnose and treat, with a persistently high mortality rate. There is a lack of recent data on IE in Bulgaria over the last decades., Methods: This study is retrospective, single-centered, and includes 270 patients diagnosed with IE for the period 2005-2021. We compared two periods, 2005-2015 (n = 119) and 2016-2021 (n = 151), to find the characteristics changes., Results: The study included 177 (65.5%) male patients. In the second period, there is a significant increase in age from 62 (44-73) to 67 (53-75), ( p = 0.023); in the Charlson comorbidities index (CCI) from 3 (1-4) to 4 (2-6), ( p = 0.000); in cases with chronic kidney diseases (CKDs) from 15 (12.6%) to 55 (36.9%), ( p = 0.001); coronary arterial diseases (CADs) from 20 (16.85%) to 44 (29.1%), ( p = 0.018); and atrial fibrillation (AF) from 13 (10.9%) to 36 (23.8%), ( p = 0.006). Ejection fraction decreased significantly in the second period from 63 (56-70) to 59 (51-66), ( p = 0.000). Almost half of the patients 123 (45.6%) had no known predisposing cardiac condition, and 125 (46.3%) had an unknown port of entry. IE was community-acquired in 174 (64.4%), healthcare-associated in 72 (26.7%), and injection-drug-use-related IE in 24 (8.9%). The study population included 183 (67.8%) native valve IE, 85 (31.5%) prosthetic IE, and 2 (0.74%) intracardiac-device-related IE. The hemocultures were positive in 159 (59.6%), and the most frequent pathogenic agent was staphylococci-89 (33.3%) ( Staphylococcus aureus -44 (16.5%) and coagulase negative staphylococci-45 (16.8%)). Only 54 (20%) of patients underwent early surgery. The all-cause 30-day mortality rate was 67 (24.8%). There is no significant difference between the two periods in terms of the characteristics listed above., Conclusions: The profile of IE in Bulgaria has changed with increasing age and comorbidity, changing predisposing cardiac conditions, and entry door. The most common pathogen was the Staphylococcus spp. The 30-day mortality rate remains high.

Introduction: Dental personnel are potentially exposed to pathogenic microorganisms, as well as to possible sources of infection. The same is true for dental students, for whom it is crucial to acquire knowledge on infection control and appropriate dental techniques during their training., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Infective endocarditis (IE) continues to be a disease with high mortality despite medical advances., Objective: The objective of this study was to investigate the characteristics and prognosis of IE according to the affected valves., Materials and Methods: This study was retrospective and single-centered, and it included 270 patients with a diagnosis of IE, for the period 2005-2021, who received treatment at the University Hospital "St. Georgi" in Plovdiv, Bulgaria., Results: Single-valve IE (SIE) was found in 82.6% (n-223), multivalvular IE (MIE) in 16.66% (n = 45) and device IE (CDRIE) in 0.74% (n = 2) of patients. The most commonly affected valve was the aortic valve, in 44.8% (n = 121). The predominant multivalvular involvement was aortic-mitral valves (AV-MV) (13.7%, n = 37). The patients with tricuspid valve (TV) IE were significantly younger, at 39 (30) years, and were more frequently male (80.8%). Mortality was higher in MIE than in SIE (31.1% vs. 23.8%) and was the highest in multivalve aortic-tricuspid (AV-TV) IE (75%). Early surgery was performed most in AV-MV IE, in 29.7% (n = 11). The Charlson comorbidity index (CCI) was significantly higher in MV 4 (4) and AV 3 (3) vs. TV IE 1 (5) ( p = 0.048 and p = 0.011, respectively). Septic shock occurred most frequently in AV-TV involvement (75%; p = 0.0001). The most common causative agents were of the Staphylococcus group. Staphylococcus aureus more often affected TV alone (46.2%, n = 124) vs. AV (9.9%, n = 14; p = 0.0001) and vs. MV (22.6%, n = 17; p = 0.022); Staphylococcus coagulase-negative (CNG) was the prevalent cause of MV IE (22.7%, n = 17) vs. AV-MV (2.7%, n = 1; p = 0.007). Streptococci were represented in a low percentage and only in left-sided IE, more frequently in AV-MV (18.9%, n = 7) vs. AV (6.6%, n = 8; p = 0.025)., Conclusions: The aortic valve is the most frequently affected valve, as single-valve IE or as multivalve AV-MV, with the predominant causative agents being of the Staphylococcus group. AV-TV IE has the worst prognosis, with the most common complication of septic shock and the highest in-hospital mortality.

Background: Patient registries and databases are essential tools for advancing clinical research in the area of rare diseases, as well as for enhancing patient care and healthcare planning. The primary aim of this study is a landscape analysis of available European data sources amenable to machine learning (ML) and their usability for Rare Diseases screening, in terms of findable, accessible, interoperable, reusable(FAIR), legal, and business considerations. Second, recommendations will be proposed to provide a better understanding of the health data ecosystem., Methods: In the period of March 2022 to December 2022, a cross-sectional study using a semi-structured questionnaire was conducted among potential respondents, identified as main contact person of a health-related databases. The design of the self-completed questionnaire survey instrument was based on information drawn from relevant scientific publications, quantitative and qualitative research, and scoping review on challenges in mapping European rare disease (RD) databases. To determine database characteristics associated with the adherence to the FAIR principles, legal and business aspects of database management Bayesian models were fitted., Results: In total, 330 unique replies were processed and analyzed, reflecting the same number of distinct databases (no duplicates included). In terms of geographical scope, we observed 24.2% (n = 80) national, 10.0% (n = 33) regional, 8.8% (n = 29) European, and 5.5% (n = 18) international registries coordinated in Europe. Over 80.0% (n = 269) of the databases were still active, with approximately 60.0% (n = 191) established after the year 2000 and 71.0% last collected new data in 2022. Regarding their geographical scope, European registries were associated with the highest overall FAIR adherence, while registries with regional and "other" geographical scope were ranked at the bottom of the list with the lowest proportion. Responders' willingness to share data as a contribution to the goals of the Screen4Care project was evaluated at the end of the survey. This question was completed by 108 respondents; however, only 18 of them (16.7%) expressed a direct willingness to contribute to the project by sharing their databases. Among them, an equal split between pro-bono and paid services was observed., Conclusions: The most important results of our study demonstrate not enough sufficient FAIR principles adherence and low willingness of the EU health databases to share patient information, combined with some legislation incapacities, resulting in barriers to the secondary use of data., (© 2024. The Author(s).)

Deep periorbital burns are an important issue mainly due to the presence of the eyes in the region, and the crucial importance of preservation of vision. There is no consensus regarding their treatment. A retrospective analysis of the treatment and outcome of 446 patients with deep burns of the periorbital region admitted to the Department of Burns and Plastic Surgery of St George's University Hospital in Plovdiv, Bulgaria over 10 years was conducted. The study covers 446 patients, 162 female (36.5%) and 284 male (63.5%) aged from 5 months to 92 years. Deep periorbital burns accounted for 74.8% of hospitalized deep facial burns. Most frequent burn agents were hot liquids and flames. The mean total body surface area affected was 19.6% (min 0.5%, max 80.0%). Concomitant ocular pathology was diagnosed in 14% (n=63) of the patients. An early, staged and precise surgical approach was preferred, aimed at fast wound closure without sacrificing survived tissues. Follow up time ranged from 3 months to 5 years, median 37 months. Late ocular sequelae occurred in 7.4% (n=33) of the patients. There was no incidence of secondary corneal perforation or definitive loss of vision. Timely and adequate treatment during the acute period can minimize initial damage and late sequelae. Favor is given to the early, balanced surgical approach aimed at rapid wound closure between day 2 and 10 post burn. Preservation of vision is a determining factor for the significance of trauma and the effectiveness of treatment., (© 2024 Euro-Mediterranean Council for Burns and Fire Disasters.)

Introduction: Endometriosis is a benign gynecological condition that shares many characteristics with cancer cells, including immune evasion, survival, adhesion, invasion, and angiogenesis. The simultaneous investigation of tissue hypoxia, EMT, and proliferative index in endometriosis, endometrial, and ovarian carcinomas may provide new insight into the evolution and progression of gynecological neoplasms., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Acute hepatitis E virus (HEV) infection is recognized as a zoonosis in several European countries. We describe the characteristics and outcomes of locally acquired acute HEV hepatitis., Methodology: A prospective study was conducted among adult patients with acute HEV hepatitis at the University Hospital in Plovdiv, South Bulgaria between January 2020 and May 2022. An acute HEV infection case was a patient with acute hepatitis and laboratory-confirmed anti-HEV IgM antibodies and/or HEV RNA in serum. Demographic data, clinical manifestations, laboratory test results, and outcomes were recorded., Results: A total of 46 patients were selected. Median age of 65 years (interquartile range [IQR] 50.8-74.3). 28 (60.87%) were male. 22 (47.83%) had comorbidities such as diabetes (15), liver cirrhosis (3), hepatitis B virus infection (2), and malignancies (2). Of the 46, 18 (39.13%) patients were viremic and, HEV genotype 3 was detected. The median (IQR) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet, and international normalized ratio levels were 992 (495.8-1714.3) U/L, 715 (262.5-1259.3) U/L, 204 (132.3-235.5) µmol/L, 204 (132.3-235.5) ×109 L, and 1.0 (0.89-1.19), respectively. Six patients with underlying liver diseases had severe hepatitis. A young patient with osteoarthritis progressed to acute liver failure and died. The persistent HEV infection was ruled out in 2 malignant patients who tested HEV RNA negative three months after discharge., Conclusions: Acute HEV hepatitis is a diagnosis to consider after excluding other causes of acute viral hepatitis. A diagnostic workup should include timely testing for HEV to identify the most vulnerable to severe consequences., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Radka Komitova, Ani Kevorkyan, Elitsa Golkocheva-Markova, Mariya Atanasova, Vanya Rangelova, Ralitsa Raycheva, Chyidem Ismailova, Asya Stoyanova, Tencho Tenev.)

Background: The delay in diagnosis for rare disease (RD) patients is often longer than for patients with common diseases. Machine learning (ML) technologies have the potential to speed up and increase the precision of diagnosis in this population group. We aim to explore the expectations and experiences of the members of the European Reference Networks (ERNs) for RDs with those technologies and their potential for application., Methods: We used a mixed-methods approach with an online survey followed by a focus group discussion. Our study targeted primarily medical professionals but also other individuals affiliated with any of the 24 ERNs., Results: The online survey yielded 423 responses from ERN members. Participants reported a limited degree of knowledge of and experience with ML technologies. They considered improved diagnostic accuracy the most important potential benefit, closely followed by the synthesis of clinical information, and indicated the lack of training in these new technologies, which hinders adoption and implementation in routine care. Most respondents supported the option that ML should be an optional but recommended part of the diagnostic process for RDs. Most ERN members saw the use of ML limited to specialised units only in the next 5 years, where those technologies should be funded by public sources. Focus group discussions concluded that the potential of ML technologies is substantial and confirmed that the technologies will have an important impact on healthcare and RDs in particular. As ML technologies are not the core competency of health care professionals, participants deemed a close collaboration with developers necessary to ensure that results are valid and reliable. However, based on our results, we call for more research to understand other stakeholders' opinions and expectations, including the views of patient organisations., Conclusions: We found enthusiasm to implement and apply ML technologies, especially diagnostic tools in the field of RDs, despite the perceived lack of experience. Early dialogue and collaboration between health care professionals, developers, industry, policymakers, and patient associations seem to be crucial to building trust, improving performance, and ultimately increasing the willingness to accept diagnostics based on ML technologies., (© 2024. The Author(s).)

The second most prevalent healthcare-associated infection in neonatal intensive care units (NICUs) is ventilator-associated pneumonia (VAP). This review aims to update the knowledge regarding the incidence of neonatal VAP and to summarize possible strategies for prevention. The VAP incidence ranges from 1.4 to 7 episodes per 1000 ventilator days in developed countries and from 16.1 to 89 episodes per 1000 ventilator days in developing countries. This nosocomial infection is linked to higher rates of illness, death, and longer hospital stays, which imposes a substantial financial burden on both the healthcare system and families. Due to the complex nature of the pathophysiology of VAP, various approaches for its prevention in the neonatal intensive care unit have been suggested. There are two main categories of preventative measures: those that attempt to reduce infections in general (such as decontamination and hand hygiene) and those that target VAP in particular (such as VAP care bundles, head of bed elevation, and early extubation). Some of the interventions, including practicing good hand hygiene and feeding regimens, are easy to implement and have a significant impact. One of the measures that seems very promising and encompasses a lot of the preventive measures for VAP are the bundles. Some preventive measures still need to be studied.