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Background: Patients with severe mitral regurgitation and cardiogenic shock demonstrate a poor prognosis. Mitral transcatheter edge-to-edge repair could alter patient management., Methods and Results: We systematically reviewed PubMed/Medline, Scopus, and Cochrane Library until January 2023, including studies assessing transcatheter edge-to-edge repair in patients with severe mitral regurgitation and cardiogenic shock. Studies with <5 patients were excluded. The primary outcome was device success and all-cause death, while secondary outcomes included myocardial infarction, stroke, and heart failure hospitalization rates at 30-day and intermediate-term follow-up. A fixed-effects meta-analysis was used to estimate pooled rates. Risk of bias was assessed with the Newcastle-Ottawa Scale. A total of 24 studies and 5428 patients were included, with a mean age of 71.2±3.3 years and a high mean Society of Thoracic Surgery score (15.2±8.9). Device success was achieved in 86% (95% CI, 85%-87%) and mitral regurgitation ≤2+ in 89% (95% CI: 88%-90%). The 30-day all-cause mortality rate was 14% (95% CI, 13%-15%). Stroke, myocardial infarction, and heart failure hospitalization rates were 2% (95% CI, 1%-2%), 15% (95% CI, 13%-18%), and 9% (95% CI, 8%-10%), respectively. Patients with acute myocardial infarction had similar device success (81% [95% CI, 74%-87%]), a 30-day mortality rate of 20% (95% CI, 16%-25%), and intermediate-term mortality rate of 14% (95% CI, 9%-19%). In non-myocardial infarction populations, the 30-day mortality rate was 13% (95% CI, 13%-14%), and the intermediate-term mortality rate was 35% (95% CI, 34%-36%)., Conclusions: In patients with mitral regurgitation and cardiogenic shock, transcatheter edge-to-edge repair is associated with favorable 30-day and intermediate-term outcomes. Limitations, including the observational design of included studies and considerable heterogeneity, necessitate further research in this setting.

Aim: Asymptomatic atrial fibrillation (AF) is frequent and associated with disease progression. This meta-analysis aimed to estimate the prevalence of asymptomatic AF and identify risk factors associated with asymptomatic status., Methods: MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until January 8, 2025. Double-independent study selection, data extraction and quality assessments were performed. Random-effects meta-analysis was used. Estimates are presented with the asymptomatic individuals in the nominator and the symptomatic patients in the denominator. The assessment of the prevalence of asymptomatic AF and the identification of risk factors associated with the asymptomatic status comprised the main endpoints., Results: Thirty-seven studies (224273 participants) were included. The prevalence of asymptomatic AF was 27% (95% confidence interval {CI}=[22%,33%]; I2=100%). Risk factors positively associated with the asymptomatic status were male sex (odds ratio {OR}=1.67, 95%CI=[1.48,1.89], p<0.001, I2=85%), diabetes mellitus (OR=1.19, 95%CI=[1.07,1.33], p=0.002, I2=87%), chronic kidney disease (OR=1.21, 95%CI=[1.08,1.36], p<0.001, I2=80%) and stroke/transient ischemic attack (OR=1.43, 95%CI=[1.18,1.73], p<0.001, I2=95%), while heart failure was negatively associated with asymptomatic AF (OR=0.71, 95%CI=[0.54,0.94], p=0.017, I2=97%). Asymptomatic status was also positively associated with permanent AF (OR=2.13, 95%CI=[1.28,3.55]; p=0.004; I2=98%) and negatively associated with catheter ablation (OR=0.63, 95%CI=[0.44,0.91]; p=0.012; I2=95%), beta-blockers (OR=0.90, 95%CI=[0.82,0.98]; p=0.018; I2=68%) and antiarrhythmics (OR=0.53, 95%CI=[0.35,0.79]; p=0.002; I2=95%)., Conclusions: Asymptomatic AF was estimated around 27%, with large variability depending on the prevalence of risk factors associated with asymptomatic status. Asymptomatic individuals had distinct characteristics compared to symptomatic patients, regardless of symptoms' assessment methods and rhythm/rate control interventions. Our results could inform AF screening practices to target asymptomatic individuals., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Coronary atherosclerosis, marked by lipid deposition and inflammation, drives cardiovascular morbidity. Traditional treatments focus on lipid reduction, yet newer therapies target plaque composition, aiming to enhance stability and prevent coronary events., Areas Covered: A comprehensive literature search was conducted across PubMed, Embase, and Scopus till January 2025 to identify studies on coronary plaque modification. This review highlights current and emerging therapies for coronary plaque modification. Key pharmacologic agents include Proprotein convertase subtilisin/kexin type 9 inhibitors for lipid management, colchicine for inflammation control, and Glucagon-like peptide-1 receptor agonists, and Sodium-glucose cotransporter-2 inhibitors for metabolic benefits. Clinical trials indicate these agents' roles in reducing plaque volume and vulnerability. Advances in imaging and biomarkers, such as lipoprotein(a) and inflammatory markers, enable refined monitoring of plaque changes over time., Expert Opinion: Future management of atherosclerosis may involve personalized strategies, integrating AI-driven predictive tools and biomarkers to assess individual plaque characteristics and optimize therapy. Continued exploration of targeted anti-inflammatory therapies and novel biomarkers like Lp(a) could enhance outcomes, offering a more precise approach to reducing cardiovascular risk and stabilizing high-risk plaques.

Aims: Electron microscopy reveals microstructural alterations in cardiomyocyte nuclei and myofilaments in non-ischaemic cardiomyopathy (NICM), particularly in dilated cardiomyopathy (DCM). Nevertheless, the correlation between such observations and clinical outcomes, including prognosis and left ventricular reverse remodelling (LVRR), remains unclear. This study aimed to examine the association between electron microscopic findings and outcomes in patients with NICM., Methods: In this multicentre, prospective, observational study, 170 patients with NICM with reduced ejection fraction (EF) < 40%, scheduled for diagnostic endomyocardial biopsy and optimization of medical therapies, were enrolled. Electron microscopic findings of cardiomyocytes such as discontinuous or continuous nuclear envelopes and injured or preserved myofilaments were evaluated. Data on cardiac events (cardiac death or left ventricular assist device implantation) and LVRR, defined as achieving an EF > 35% with a 10% unit absolute increase, were collected 1 year post-biopsy., Results: A total of 148 patients were finally analysed. Discontinuous nuclear envelopes and myofilament injuries were observed in 17 (11%) and 46 (31%) patients with NICM, respectively. The incidence of cardiac events at 1 year did not differ between groups with discontinuous and continuous nuclear envelopes [12% vs. 6%, odds ratio (OR): 2.05, 95% confidential interval (CI): 0.40-10.6, P = 0.391], whereas the LVRR rate was significantly lower in the discontinuous group than in the continuous group (24% vs. 52%, OR: 0.29, 95% CI: 0.08-0.92, P = 0.036). The incidences of cardiac events and LVRR at 1 year differed between the injured and preserved myofilament groups (15% vs. 3%, OR: 6.64, 95% CI: 1.32-33.5, P = 0.022; 15% vs. 64%, OR: 0.10, 95% CI: 0.04-0.25, P < 0.001, respectively). These associations between electron microscopic findings and clinical outcomes persisted, even in patients who were finally diagnosed with DCM., Conclusions: Discontinuous nuclear envelopes were associated with a reduced LVRR rate, whereas injured myofilaments were correlated with higher 1 year cardiac events and a decreased LVRR. Evaluation of electron microscopic images in diagnostic endomyocardial biopsy can facilitate risk stratification of NICM or DCM with reduced EF., (© 2025 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Intracardiac echocardiography (ICE) appears to be a potential alternative for percutaneous left atrial appendage occlusion (LAAO) to transesophageal echocardiography (TEE). Thus, a meta-analysis was performed comparing ICE vs. TEE for LAAO guidance., Methods: A comprehensive literature search was performed using MEDLINE, Scopus and Web of Science electronic databases from their inception to November 2023., Results: 18 studies (124,230 patients) were included. Technical success was higher in ICE- compared to TEE-guidance (OR: 1.36, 95% CI 1.14 to 1.63, p = 0.006) and fewer devices employed (SMD: -0.22, 95% CI -0.43 to -0.01, p = 0.04, I2 = 62%). ICE guidance related with more pericardial effusion/tamponade and iatrogenic residual shunts (logRR: 0.62, 95% CI 0.36 to 0.89, p < 0.001 and RR: 1.53, 95% CI 1.12 to 2.09, p = 0.02, I2 = 1%, respectively). More vascular complications were noted in ICE group (logRR: 0.45, 95% CI 0.11 to 0.78, p = 0.009)., Conclusion: ICE-guided imaging is an effective alternative to TEE in LAAO, as it shows better efficacy than TEE, considering technical success. However, the higher rates of adverse events should be carefully considered., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: None., (© 2025. The Author(s).)

Background and Aims: While glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively reduce body weight, their impact on lean mass remains uncertain. This meta-analysis evaluated the effects of GLP-1RAs and GLP-1/GIP receptor dual agonists (GLP-1/GIP-RAs) on body composition, focusing on total weight, fat mass, and lean mass in adults with diabetes and/or overweight/obesity., Methods: A systematic search of Medline, Embase, and the Cochrane Library was conducted through November 12, 2024. Data were analyzed using random-effects pairwise and network meta-analyses to compare interventions with placebo or active comparators., Results: Twenty-two randomized controlled trials (2258 participants) were included. GLP-1RAs significantly reduced total body weight (MD -3.55 kg, 95 %-CI [-4.81, -2.29]), fat mass (MD -2.95 kg, 95 %-CI [-4.11, -1.79]), and lean mass (MD -0.86 kg, 95 %-CI [-1.30, -0.42]), with lean mass loss comprising approximately 25 % of the total weight loss. However, the relative lean mass, defined as percentage change from baseline, was unaffected. Liraglutide, at 3.0 mg weekly or 1.8 mg daily, was the only GLP-1RA to achieve significant weight reduction without significantly reducing lean mass. Tirzepatide (15 mg weekly) and semaglutide (2.4 mg weekly) were the most effective for weight and fat mass reduction but were among the least effective in preserving lean mass., Conclusions: Potent GLP-1 RAs, such as tirzepatide and semaglutide, demonstrate greater overall weight loss but are associated with a significant reduction in lean mass., Competing Interests: Declaration of competing interest CSM reports grants through his institution from Merck, Esperion, Abbott, Massachusetts Life Sciences Center and Boehringer Ingelheim, has received personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Olympus, Genfit, Lumos, Novo Nordisk, Amgen, Corcept, Intercept, 89 Bio, Madrigal, Aligos, Esperion and Regeneron, reports educational activity meals through his institution or national conferences from Esperion, Merck, Boehringer Ingelheim and travel support and fees from UpToDate, TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None is related to this paper. CSM recused himself from handling this paper. The rest authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Vasdeki, Dimitra, Georgios Tsamos, Kleoniki I. Athanasiadou, Vasiliki Michou, Evangelos Botsarakos, Michael Doumas, Kalliopi Kotsa, and Theocharis Koufakis. Above the clouds with diabetes: from pathophysiological considerations to practical recommendations for safe flights. High Alt Med Biol. 26:87-98, 2025. Background: The prevalence of diabetes mellitus has been following an increasing trend in the last decades, leading to a growing number of travelers with diabetes seeking pretravel advice from medical professionals. Methods: This narrative review summarizes the existing evidence on the intriguing association between diabetes and air travel, analyzes safety and certification protocols, and provides practical recommendations for the management of diabetes during flights. Results: During air travel, individuals with diabetes face challenges arising from inappropriate dietary options, restricted access to medications and healthcare services, disruption of medication dosing intervals, and exposure to hypobaric conditions in the airplane cabin. In addition, people with diabetes, especially those treated with insulin, have traditionally been considered ineligible to become professional pilots. However, this approach gradually changes and numerous countries are now implementing strict protocols to determine the eligibility of pilots with diabetes to operate flights. Conclusions: Given the increasing use of technology and new drugs in daily clinical practice, there is a need for further research in the field to shed light on existing knowledge gaps and ensure safe flights for people with diabetes.

Heart failure (HF) is a major clinical challenge characterized by significant morbidity and mortality. Electrical conduction abnormalities play a critical role in HF pathophysiology and progression, often leading to suboptimal outcomes with conventional pacing techniques. Con-duction system pacing (CSP), encompassing His bundle pacing and left bundle branch area pacing, has emerged as a novel approach. Despite data come from observational studies, recent guidelines recommend that a specific population may benefit from CSP. However, significant practical considerations and challenges need to be clarified before CSP can be routinely implemented in clinical practice. The reliance on observational studies means that long-term clinical outcomes for HF patients remain uncertain until data from randomized controlled trials (RCTs) become available. Current CSP practices face challenges with lead implantation, mechanical stress on leads, and the need for more advanced tools and artificial intelligence integration to improve procedure efficacy and safety. Future large-scale RCTs are essential to identify optimal candidates and address these technical challenges, potentially leading to a paradigm shift in HF management., Competing Interests: Declarations. Ethical approval: Ethical approval is not applicable as the current paper is review. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Liver-related complications are frequent in patients with metabolic diseases, with limited treatment options currently available. This systematic review and meta-analysis aimed to assess the effect of fibroblast growth factor-21 (FGF21) analogues on hepatic steatosis, inflammation and fibrosis in patients with metabolic diseases., Methods: We conducted a systematic literature search in Pubmed, Scopus and Web of Science for randomised controlled trials (RCTs) assessing the effect of FGF21 analogues on hepatic steatosis evaluated by hepatic fat fraction (HFF), inflammation and fibrosis compared to placebo. Adverse events (AEs) were also recorded., Results: Treatment with FGF21 analogues was associated with metabolic-associated steatohepatitis (MASH) resolution without fibrosis worsening (5 studies, risk ratio [RR] 4.40, 95% confidence interval [CI]: 2.41, 8.03, p < 0.001) and fibrosis improvement by 1 grade without MASH worsening (6 studies, RR 1.79, 95% CI: 1.24, 2.59, p = 0.002). FGF21 analogues significantly lowered HFF compared to placebo (6 studies, SMD -1.08, 95% CI: -1.28, -0.88, p < 0.001), while patients receiving FGF21 analogues were more likely to exhibit a reduction in HFF by 30% (10 studies, RR 4.08, 95% CI: 3.08, 5.40, p < 0.001) or 50% (6 studies, RR 10.43, 95% CI: 5.47, 19.87, p < 0.001). HFF normalisation (≤ 5%) was more frequently achieved with FGF21 analogues (6 studies, RR 14.58, 95% CI: 4.70, 45.18, p < 0.001). The results remained robust after sensitivity analyses. Serious AE and AE leading to drug discontinuation were similar in patients receiving FGF21 analogues or placebo., Conclusions: FGF21 analogues can reduce hepatic steatosis, inflammation and fibrosis in patients with metabolic diseases, representing a possible treatment option for steatotic liver disease., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The purpose of this systematic review and meta-analysis is to investigate the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with arterial stiffness and enlighten on potential cardiometabolic co-factors., Methods: A literature search in PubMed/Medline, Embase, Scopus, and Web of Science databases was conducted. All the observational studies comparing arterial stiffness indices between adults with Non-alcoholic Fatty Liver Disease (NAFLD), Metabolic Dysfunction Associated-Fatty Liver Disease (MAFLD), or MASLD and apparently healthy individuals with normal liver function were included. Pulse wave velocity (PWV) and augmentation index (AIx) were mainly used as arterial stiffness indices., Results: Fourty one unique studies were included in the systematic review, with 27 deemed eligible for meta-analysis. Patients with MASLD had increased carotid-femoral PWV (14 studies, Mean difference (MD): 0.96 m/s, 95% confidence interval (CI) 0.65-1.27, p  < 0.001) compared with healthy individuals. This finding was independent from body mass index, triglycerides, high-density lipoprotein, systolic blood pressure, and fasting plasma glucose. Moreover, patients with MASLD had higher brachial-ankle PWV (13 studies, MD: 78.14 cm/s, 95% CI 60.37-95.90, p  < 0.001) and AIx (7 studies, MD: 3.85%, 95% CI 0.87-6.82, p  = 0.0195) compared with controls., Conclusions: MASLD is correlated with increased arterial stiffness. This relation is unaffected by common cardiometabolic risk factors., Registration: PROSPERO (ID: CRD42023468258).

Infective endocarditis (IE) is an increasingly prevalent condition with relatively high mortality, whose epidemiology has become more complex with an aging population, an increased number of comorbidities, and an increasing incidence of health-care associated IE. Epidemiological data on the causative microorganisms of IE, prevalence of involvement of the different cardiac valves, and IE-associated mortality are clinically relevant. Eligible studies were identified through a systematic search of PubMed/MEDLINE database from 2010 to 2020, and a random effects model meta-analysis was conducted. 133 studies comprising 132,584 patients from six continents were included in this systematic review. The most common causative agents were Staphylococci species in 36% of cases, followed by Streptococci species (26%) and Enterococci species (10%). Out of studies that provided further speciation, the predominant species was Staphylococcus aureus with an incidence of 29%, followed by Viridans group Streptococcus (12%). The short-term mortality rate (defined as in-hospital or 30-day mortality) was 17%. The highest mortality was reported in studies from Latin America with a mean mortality rate of 33% and the lowest mortality was reported in studies from Oceania at 13%. The aortic valve was the most commonly affected valve (46%), followed closely by the mitral valve (43%). The prevalence of tricuspid valve IE was 7% and multivalvular IE occurred in 14% of cases. Our study highlights a shift in epidemiological profile of IE over the last decade with S. aureus identified as the most common causative microorganism of IE. PROTOCOL REGISTRATION: PROSPERO CRD42024602342., 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 © 2025. Published by Elsevier Inc.)

Background: Arboviruses have expanded into new regions in Europe, yet data indicate gaps in disease notifications and a risk of further spread. We aimed to report on prevalence, clinical management, and outcomes of endemic arbovirus infections in southeast Europe., Methods: In this prospective observational study (MERMAIDS-ARBO), we enrolled adults (age ≥18 years) hospitalised with an arbovirus-compatible disease syndrome within 21 days of symptom onset across 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (May 1-Oct 31, during 2016-19). We obtained data from case report forms completed by site investigators on admission and discharge. Participants were excluded if they had non-infectious CNS disorders, symptoms of another confirmed cause, an identified focal source of infection, or symptoms caused by recurrence of a pre-existing condition. The primary outcome was the proportion of participants with confirmed or probable acute infections with West Nile virus (WNV), tick-borne encephalitis virus (TBEV), Crimean-Congo haemorrhagic fever virus (CCHFV), or Toscana virus (TOSV), per reference laboratory criteria. Secondary outcomes were the proportions of patients treated with antivirals, antibiotics, or corticosteroids; the proportion of patients requiring intensive care; hospital length of stay; and mortality., Findings: Of 2896 adults screened for eligibility, 929 were recruited and 913 met protocol-defined eligibility criteria (median age 43·1 years [IQR 29·5-59·7]; 550 [60%] men, 361 [40%] women, and two [<1%] with missing data). 530 (58%) participants presented with suspected meningitis, encephalitis, or both, and 318 (35%) with fever plus myalgia, fever plus arthralgia, or both. 820 (90%) reported no international travel within 21 days before symptom onset. 727 (80%) were administered antibiotics, 379 (42%) corticosteroids, and 222 (24%) antivirals. The median length of hospital stay was 9 days (IQR 6-14), and 113 (12%) required intensive care. Of 847 participants with a reference laboratory sample who met full eligibility criteria for analysis, 110 (13%) were diagnosed with 114 confirmed or probable acute arbovirus infections (four had coinfections or cross-reactivity): one (<1%) with CCHFV, 16 (2%) with TBEV, 44 (5%) with TOSV, and 53 (6%) with WNV. There was one death (<1%) of an individual with WNV. Of the 110 participants, 49 (45%) had a local clinician-attributed arbovirus discharge diagnosis., Interpretation: Our data highlight the need to strengthen arbovirus surveillance systems for the early detection of emerging and re-emerging outbreaks, including investments to increase awareness of arbovirus infections among clinicians, to improve access to specialist diagnostics, and to develop effective and accessible vaccines and treatments to protect populations and health systems in southeast Europe., Funding: European Commission and Versatile Emerging infectious disease Observatory., Translations: For the Greek, Albanian, Romanian, Bosnian, Serbian, and Croatian translation of the summary see Supplementary Materials section., Competing Interests: Declaration of interests LT has received consulting fees from the Medicines and Healthcare products Regulatory Agency, as well as AstraZeneca and Synairgen (paid to their institution); speakers fees from Eisai; and support for conference attendance from AstraZeneca. VBr has received speakers fees and support for conference attendance from, and participated on a data and safety monitoring board for, SC Pfizer Romania. VK declares having received support for conference attendance from MSD, Pfizer, and Menarini, and having participated on a data and safety monitoring board for MSD and Menarini. AMV declares having received consulting fees from Medichub Media; having received lecture fees from Ewopharma Romania, Gilead Sciences, Zentiva, and Alfasigma Romania; having received conference attendance support from Pfizer Romania, MSD Romania, and Ewopharma Romania; having participated in a data and safety monitoring board for MSD Romania; and being President of Asociatia Medicilor Infectionisti Mures. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Arboviruses are increasingly affecting Europe, partly due to the effects of climate change. This increase in range and impact emphasises the need to improve preparedness for emerging arboviral infections that often co-circulate and might have overlapping clinical syndromes. We aimed to strengthen surveillance networks for four clinically relevant arboviruses in southeast Europe., Methods: This study reports an in-depth analysis of the MERMAIDS-ARBO prospective observational study in adults (ie, aged ≥18 years) hospitalised with an arbovirus-compatible disease syndrome in 21 hospitals in seven countries in southeast Europe over four arbovirus seasons (May 1-Oct 31, 2016-19) to obtain arbovirus prevalence outcomes. The main objectives of the MERMAIDS-ARBO study, describing the clinical management and outcomes of four arboviruses endemic to southeast Europe, including Crimean-Congo haemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), Toscana virus, and West Nile virus (WNV), are reported elsewhere. In this analysis, given the challenges associated with arbovirus diagnostics, we developed a diagnostic algorithm accounting for serology outcomes and sample timing to study arbovirus prevalence in southeast Europe. Serum samples were collected on days 0, 7, 28, and 60 after hospital admission and tested for anti-CCHFV IgG and IgM antibodies with ELISAs (confirmed with an indirect immunofluorescence test) and for IgG and IgM antibodies specific to TBEV, Toscana virus, and WNV with custom-printed protein microarrays (confirmed with virus neutralisation tests). All acute-phase samples were tested by PCR for all four viruses. Descriptive analyses were performed for virus-reactive cases by geography and year, and possible factors (eg, age, sex, and insect bites) associated with virus reactivity were assessed., Findings: Of 2896 individuals screened, 913 were eligible for inclusion, of whom 863 (514 men, 332 women, and 17 unknown) had samples sent to the study reference laboratories and were included in molecular and serological analyses. Some individuals had insufficient clinical data to be included in the clinical analysis, but met the eligibility criteria for and were included here. Serum sampling was incomplete (eg, samples missing from one or more timepoints or no data on time since symptom onset) for 602 (70%) patients, and the timing of collection was often heterogeneous after symptom onset up to 40 days (average median delay of 5-6 days across all timepoints), affecting the ability to diagnose arbovirus infection by serology. By use of an interpretation table incorporating timing and completeness of sampling, one (<1%) participant had a confirmed recent infection with CCHFV, ten (1%) with TBEV, 40 (5%) with Toscana virus, and 52 (6%) with WNV. Most acute confirmed infections of Toscana virus were found in Albania (25 [63%] of 40), whereas WNV was primarily identified in Romania (36 [69%] of 52). Albania also had the highest overall Toscana virus seropositivity (168 [60%] of 282), mainly explained by patients confirmed to be exposed or previously exposed (104 [62%] of 168). Patients without antibodies to WNV or Toscana virus were significantly younger than patients with antibodies (mean difference -8·48 years [95% CI -12·31 to -4·64] for WNV, and -6·97 years [-9·59 to -4·35] for Toscana virus). We found higher odds of Toscana virus reactivity in men (odds ratio 1·56 [95% CI 1·15 to 2·11]; p=0·0055), WNV reactivity with mosquito bites versus no mosquito bites (2·47 [1·54 to 3·97]; p=0·0002), and TBEV reactivity with tick bites versus no tick bites (2·21 [1·19 to 4·11]; p=0·018)., Interpretation: This study shows that despite incomplete and heterogeneous data, differential diagnosis of suspected arbovirus infections is possible, and the diagnostic interpretation algorithm we propose could potentially be used to strengthen routine diagnostics in clinical settings in areas at risk for arboviral diseases. Our data highlight potential hotspots for arbovirus surveillance and risk factors associated with these particular arbovirus infections., Funding: European Commission and Versatile Emerging infectious disease Observatory., Translations: For the Greek, Albanian, Romanian, Bosnian, Serbian, and Croatian translation of the summary see Supplementary Materials section., Competing Interests: Declaration of interests LT has received consulting fees from the UK Medicines and Healthcare products Regulatory Agency, as well as AstraZeneca and Synairgen (paid to their institution); speaker's fees from Eisai; and support for conference attendance from AstraZeneca. VBr has received speaker's fees and support for conference attendance from SC Pfizer Romania, and participated on a data and safety monitoring board for SC Pfizer Romania. VK declares having received support for conference attendance from MSD, Pfizer, and Menarini, and having participated on a data and safety monitoring board for MSD and Menarini. AMV declares having received consulting fees from MedicHub Media; having received lecture fees from Ewopharma Romania, Gilead Sciences, Zentiva, and Alfasigma Romania; having received conference attendance support from Pfizer Romania, MSD Romania, and Ewopharma Romania; having participated on a data and safety monitoring board for MSD Romania; and being President of Asociatia Medicilor Infectionisti Mures. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Pulmonary arterial hypertension (PAH) is a severe complication among adult patients with congenital heart disease (ACHD). This study presents real-world data on risk stratification, pharmacotherapy and survival rates in PAH-ACHD., Methods: Data from PAH-ACHD patients were analyzed using The Hellenic Pulmonary Hypertension Registry (HOPE), spanning eight specialized centers between 2015 and 2023. Patients were categorized into low, intermediate, and high-risk groups using the ESC/ERS three-strata model to assess 1-year mortality risk., Results: A total of 93 PAH-ACHD patients were included (median age 38.5 years, 60.2 % women). Most patients had an atrial septal defect (37.6 %) or a ventricular septal defect (35.5 %), with 11.8 % presenting with complex ACHD. Eisenmenger syndrome was present in 35.5 % of patients. The proportion of low-risk patients nearly doubled from first to last assessment (24.7 % vs. 40.9 %, p = 0.001). Initially, 52.7 % of patients were on PAH monotherapy, with a subsequent shift towards combination therapy (73.1 %) during follow-up. Over a median follow-up of 5.9 years, 29 patients (31.1 %) died, with 1- and 5-year survival rates of 95.5 % and 81.9 %, respectively. Compared to the high-risk group, low- and intermediate-risk patients exhibited a 70 % and 50 % lower hazard of death, respectively. The lowest survival rates were observed in patients with Eisenmenger physiology., Conclusion: Survival prospects were favorable for the non-high risk patients in this nationwide cohort of PAH-ACHD patients. The observed shift towards combination therapy use may have contributed to the improvement in 1-year ESC mortality risk, underscoring the importance of timely combination therapy with PAH drugs., Competing Interests: Declaration of competing interest Dr. A. Arvanitaki has received travel grants from MSD. Dr. Eftychia Demerouti received honorarium and consultation fees from Actelion Pharmaceuticals-Janssen Hellas, MSD Merck Hellas, Elpen and Galenica. Dr. A. Frogoudaki has received travel grants from Boehringer, ELPEN, Genesis Pharma and Pfizer. Dr. I. Tsangaris has received fees for lectures and/or consultations from Actelion, Bayer, ELPEN, GSK, Janssen, MSD, Pfizer and United Therapeutics. Dr. K. Naka reports lecture fees from Amgen, Astra, Bayer, BMS, Boehringer Ingelheim, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier. Athanasios Manginas reports consultation fees from Astra Zeneca, Bayer, Elpen, Janssen, MSD and Novartis. Dr. Giannakoulas has received fees for lectures and/or consultations from Actelion/Janssen, Bayer, Boehringer Ingelheim, ELPEN Pharmaceuticals, Ferrer/Galenica, GlaxoSmithKline, Gossamer-Bio, Merck Sharp and Dohme, Pfizer, Lilly, and United Therapeutics. The rest of the authors report no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Appropriate management of older people with hypertension is essential to reduce the burden of hypertensive heart disease and further cardiovascular sequelae but there may be challenges given the presence of concurrent senescent changes, comorbidities and impairment in functionality. It is recommended that frailty level and functional status are assessed periodically to understand patient needs and to guide treatment decisions. Office blood pressure should be measured with an appropriate cuff as per standard guidelines. There should be a high index of suspicion for orthostatic hypotension and white coat/masked hypertension, both common in older individuals. Cardiac imaging often identifies age-related changes that may not result from hypertension alone, including smaller ventricular volumes, a sigmoid septum and non-ischaemic fibrosis. Diastolic dysfunction is common and other pathologies, including cardiac amyloidosis, may need to be considered in the presence of red flags. Screening for atrial fibrillation during blood pressure evaluation is advised. Decisions for blood pressure management should follow current recommendations and take into consideration the patient's age and tolerance. There is limited evidence regarding heart failure management in older patients, however, disease-modifying therapy as per guidelines should be pursued. Sufficient outcome data are lacking for this patient group and a multidisciplinary approach is often needed to design optimal therapy., Competing Interests: Conflict of Interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background and Aims: Adequate lipid control has emerged as a key factor in the prevention and management of chronic kidney disease (CKD). Remnant cholesterol (RC), a lipoprotein with an established association with cardiovascular risk, has been investigated in the context of CKD. Given the conflicting results from recent studies, we performed this meta-analysis to summarize the existing evidence on the association between RC and CKD., Methods: Medline, Cochrane Library and Scopus were searched until 16 September 2024. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses. We set as primary end-point of interest the association between RC and CKD., Results: Twelve studies (4 139 674 participants) were included. Participants with RC values in the highest quantile had significantly greater odds of CKD compared to those in the lowest quantile (Odds Ratio [OR] = 1.46, 95% confidence interval [CI] = 1.26-1.68). In a sensitivity analysis confined to subjects with type 2 diabetes (T2D), those in the higher RC quantile also exhibited significantly increased odds of CKD compared to those in the lowest quantile (OR = 1.46, 95% CI = 1.20-1.78). A significant inverse association was observed between RC and estimated glomerular filtration rate (Mean Difference [MD] = -1.43 mL/min/1.73 m 2 for each 1 mmol/L increase in RC, 95% CI = [-2.67, -0.19]). Additionally, individuals with T2D-related CKD had a 24% increased risk of progression to end-stage renal disease for each 1 standard deviation increase in RC (Hazard Ratio [HR] = 1.24, 95% CI = 1.04-1.47)., Conclusions: RC is directly associated with higher risk for CKD. Beyond traditional lipid markers, greater emphasis should be placed on RC levels in individuals with or at risk for CKD., (© 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

It is estimated that the number of patients with a cardiac implantable electronic device (CIED) in Greece exceeds 120,000, and this population is expected to further rise by 5% annually. The importance of adequate monitoring and follow-up management of these devices is well-recognized. However, the increasing complexity and growing number of CIEDs makes their management a demanding medical service. Traditionally, interrogation and programming of CIEDS is performed using a portable programmer by qualified personnel, requiring patient physical presence. During the last decade, remote monitoring (RM) of CIEDs tends to become more and more popular given the advantages and improved outcomes in many groups of patients. Currently, RM represents the standard of care for CIED follow-up, and it is recommended by major cardiology societies worldwide, including the European Society of Cardiology. The objective of this statement is to summarize the current management of patients with CIED in Greece and the available evidence about clinical efficacy and safety of RM of CIEDs, present the most recent guideline recommendations, and, finally, propose actions to move toward the widespread adoption of RM of CIEDs in Greece., (Copyright © 2025 Hellenic Society of Cardiology. Publishing services by Elsevier Inc. All rights reserved.)

Background: A positive family history is considered the strongest recognizable risk factor for developing inflammatory bowel diseases (IBD) and is present in 8-12% of cases., Aims: To determine the prevalence of familial IBD and also to compare the clinical characteristics and extraintestinal manifestations between familial and sporadic cases., Methods: We conducted a cross-sectional study based on retrospectively-prospectively collected data from a cohort of IBD patients followed in daily clinical practice. Patients with biopsy-confirmed familial and sporadic IBD aged 16-90 years old were included in the study. A comprehensive questionnaire was used to collect data on each site visit. Logistic regression analysis and chi-squared test were used., Results: In total, 265 patients with IBD were included. 12.1% had a first-degree relative with IBD present (16.4% in Crohn's disease and 5.7% in the ulcerative colitis group, P < 0.05). Familial IBD patients were mainly females, were more frequently diagnosed with Crohn's disease and had a higher risk for hospitalization due to an IBD flare (P < 0.05), to undergo a surgical procedure (P < 0.001), to require treatment with biologic agents (P < 0.05), to develop perianal disease (P < 0.05), and extraintestinal manifestations (P < 0.05), mainly spine joint complications, erythema nodosum, and anterior uveitis., Conclusion: In this study, a positive family history of IBD was present in 16.4% of Crohn's disease and 5.7% of ulcerative colitis patients and was associated with a greater risk for hospitalization, surgical procedures, occurrence of perianal disease, need for treatment with biologic agents, and development of extraintestinal manifestations., Competing Interests: Declarations. Conflict of interest: No potential conflicts of interest. STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items., (© 2025. The Author(s).)

Epigenetics encompasses heritable and stable changes in gene expression caused by external chromosomal modifications, without altering the underlying DNA sequence. Epigenetic modifications, established during early development and maintained through successive cell divisions, play a critical role in regulating gene expression. Post-translational modifications (PTMs) are a key aspect of epigenetics and are essential for modulating protein functionality, as well as regulatory cellular processes, including proliferation, differentiation, metabolic pathways, and tumorigenic events. Among these, the small ubiquitin-related modifier (SUMOylation) system is a reversible PTM mechanism that alters target protein interaction surfaces through covalent binding to lysine residues, thereby influencing protein structure and function. Acute myeloid leukemia (AML) is a highly aggressive malignancy characterized by the clonal expansion of primitive hematopoietic stem cells of the myeloid lineage in the bone marrow. Despite recent advancements in therapeutic strategies and an improved understanding of leukemogenic pathways, patient outcomes remain poor, particularly in elderly populations. Consequently, efforts have focused on developing novel agents, including co-targeting specific mutations or integrating targeted therapies into combinatorial chemotherapeutic regimens. Emerging evidence suggests that SUMOylation plays a significant role in AML pathogenesis and treatment response, representing a promising therapeutic target for advanced disease cases. This review provides a brief analysis of the functional role of the SUMOylation system in AML and highlights its potential as a therapeutic target. We also discuss current knowledge gaps and propose directions for future research to advance precision medicine approaches for AML treatment.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix., Competing Interests: Declaration of interests OAC declares grants from the German Federal Ministry of Education and Research (BMBF), Cidara, the German Center for Infection Research (DZIF), EU Directorate-General Research and Innovation, F2G, Gilead, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; consulting fees from AbbVie, AiCuris, Basilea, Biocon, Cidara, Seqirus, Gilead, GSK, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partner, MSGERC, Mundipharma, Noxxon, Octapharma, Pardes, Partner Therapeutics, Pfizer, PSI, Scynexis, and Seres; honoraria from Abbott, AbbVie, Akademie für Infektionsmedizin, Al-Jazeera Pharmaceuticals–Hikma, amedes, AstraZeneca, Deutscher Ärzteverlag, Gilead, GSK, Grupo Biotoscana–United Medical–Knight, Ipsen Pharma, Medscape–WebMD, MedUpdate, MSD, Moderna, Mundipharma, Noscendo, Paul-Martini-Stiftung, Pfizer, Sandoz, Seqirus, Shionogi, streamedup!, Touch Independent, and Vitis; payment for expert testimony from Cidara; and board participation from Boston Strategic Partners, Cidara, IQVIA, Janssen, MedPace, PSI, Pulmocide, Shionogi, The Prime Meridian Group, and Vedanta Biosciences. RS declares grants from DZIF and Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen; honoraria from Pfizer, Akademie für Infektionsmedizin, and Hikma; travel support from the European Confederation of Medical Mycology (ECMM), Pfizer, and Page Medical; and has board membership for Young ECMM. MB declares honoraria and board participation from Angelini, Cidara, Gilead, Menarini, MSD, Pfizer, Shionogi, and Mundipharma. SC-AC reports an untied educational grant from F2G, and travel support from the Asia Fungal Working Group and the International Society for Human & Animal Mycology (ISHAM). AHG declares a research grant paid to his institution from Gilead Sciences; consulting fees from Basilea, Pfizer, and Mundipharma; and honoraria from Gilead, MSD, Mundipharma, Basilea, and Pfizer. OK declares research grants from the EU, German Research Foundation (DFG), BMBF, and BMG; consulting fees paid to his institution from Mundipharma; honoraria paid to his institution from Gilead, Pfizer, and Fujifilm Wako; receipt of microbiology media for evaluation from Mast Diagnostika; and reports receipt of chemical substances (antifungal drugs) for susceptibility testing. CL-F declares grants paid to her institution from Gilead Sciences and Astellas Pharma; consulting fees from Merck Sharp and Dohme; honoraria from Gilead Sciences, Merck Sharp and Dohme, Pfizer, BioMerieux, F2G, Immy, and Shionogi; travel support from Gilead; and advisory board fees from Mundipharma. LO-Z declares grants paid to his institution from Scynexis, Pulmocide, Pfizer, Basilea, Eurofins Viracor, and T2 Biosystems; honoraria from Pfizer, Gilead, F2G, GSK, Melinta, Eurofins Viracor, and Knight–Biotoscana. RR-R declares support for this work by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre grant (NIHR203308). LPW declares a grant paid to his institution from F2G; consulting fees from Mundipharma, Pfizer, F2G, and Gilead; honoraria from Gilead, Mundipharma, and Pfizer; travel support from Mundipharma and Gilead; board participation from F2G, Mundipharma, Gilead, and Pfizer; and receipt of equipment from Launch Diagnostics for his institution. AA-I declares consulting fees from WHO; payments for educational talks from Gilead, Pfizer, and Mundipharma; travel support from Gilead; and has unpaid roles as President of the Asociación Española de Micología and as a member on the scientific advisory board of the Joint Programming Initiative on Antimicrobial Resistance. MCA declares research grants and contract work paid to her institution from Cidara–Mundipharma, F2G–Shionogi, and Scynexis; and speaker honoraria from Gilead and F2G–Shionogi. RB-A declares participation for the MSD advisory board and GSK advisory board. AJB declares grant funding paid to his institution from the Foundation for Innovative New Diagnostics and the Global Antibiotic Research and Development Partnership. JG declares grants paid to his institution from Fondo de Investigación Sanitaria, Gilead, Cidara, F2G, Scynexis, and Mundipharma; honoraria from Gilead, Pfizer, MSD, and Mundipharma; and travel support from Gilead and Scynexis. FH declares travel support from ISHAM; has unpaid roles as Treasurer for the Netherlands Society for Medical Mycology, Vice-President of ISHAM, and chair of the Division of Microbial Genomics of the Royal Netherlands Society for Microbiology; reports receipt of reduced price or free diagnostic reagents and kits to run validation tests from CHROMagar, Bruker MDx, Pathonostics, OLM Diagnostics, and Altona Diagnostics. MH declares grants from Astellas, Scynexis, Gilead, IMMY, MSD, Pfizer, Euroimmun, Mundipharma, Melinta, and Pulmocide; and research funding from Gilead Sciences, Astellas, Mundipharma, Euroimmun, MSD, GSK, Basilea, Pulmocide, Scynexis, AiCuris, Melinta, Partner, F2G, Shionogi, Stendahl, and Pfizer. SH declares grants paid to his institution from Merck, Pfizer, Cidara, Avir Pharma, Sunovion, F2G, and Pulmocide; and consulting fees from TFF and Takeda. SSK declares speaker honoraria from Pfizer, MSD, Basilea, Gilead, and Hikma; payments for advisory board member meetings from Menari and MSD; and has roles as President-elect of the International Society of Antimicrobial Chemotherapy and President of the Lebanese Society for Infectious Diseases and Clinical Microbiology. PK declares grants paid to his institution from BMBF, the B-FAST (Bundesweites Forschungsnetz Angewandte Surveillance und Testung), NAPKON (Nationales Pandemie Kohorten Netz, German National Pandemic Cohort Network), NUM (Netzwerk Universitätsmedizin, Network of University Medicine), and the State of North Rine-Westphalia, Germany; consulting fees from Ambu, Gilead Sciences, Munipharma, Noxxon, and Pfizer; honoraria from Akademie für Infektionsmedizin, Ambu, Astellas Pharma, BioRad Laboratories, Datamed, ECMM, Gilead Sciences, GPR Academy Ruesselsheim, HELIOS Kliniken, Jazz Pharmaceuticals Germany, medupdate, MedMedia, MSD, Pfizer, Scilink Comunicación Científica, streamedup!, University Hospital and LMU Munich, and Vitis; a German patent application (DE 10 2021 113 007.7) has been filed by the University of Cologne (Cologne, Germany), listing PK as one of three inventors; board participation from Ambu, Gilead Sciences, Pfizer Pharma, Mundipharma, and Noxxon; honoraria for reviews and royalties from book authorships from Elsevier; and an unpaid role of Editor for Mycoses (Wiley) and Annals of Medicine (Taylor & Francis online). TL declares consulting fees from Gilead, Merck/MSD, Roche, Recordati, Mundipharma, and Pharming; and honoraria from Merck/MSD, AstraZeneca, Pfizer, Mundipharma, Gilead, Sanofi Pasteur, and Recordati. REL declares royalties from UptoDate; consulting fees from Basilea, F2G, and Gilead; and honoraria from Basilea, Gilead, Avir, and Pfizer. MHN declares consulting fees from Basilea; and was one of the authors of the Infectious Diseases Society of America (IDSA) guideline for aspergillosis. DS declares lecture fees from Pfizer and Hikma. TT declares honoraria from Asahikasei Pharma Japan, Pfizer Japan, MSD Japan, and Sumitomo Pharma Japan. DCV declares a grant from the senior clinician and senior scientist research scholar programme of the Fonds de Recherche du Québec–Santé; grants paid to his institution for clinical trial support from Cidara therapeutics, Janssen Pharmaceuticals, and Moderna; further grants paid to his institution from the Public Health Agency of Canada (COVID Immunity Task Force: DISCoVER project, UNCoVER project, and VISID project), the Jeffrey Modell Foundation, and the Canadian Institutes of Health Research; consulting fees from AstraZeneca, CSL Behring, Merck Canada, Moderna, Novartis Canada, Qu Biologics, and Shire (Takeda); honoraria from CSL Behring; travel support from the Association of Medical Microbiology and Infectious Disease (AMMI) Canada; has a patent pending (Electronic Filing System ID: 40101099); has unpaid roles as Chair of the AMMI Canada Guidelines Committee, member of the Clinical Immunology Society Education Committee and Continuing Education Committee, patient advocate of the Medical Committees of the Association des patients immunodéficients du Québec and the Canadian Immunodeficiency Patient Organization, patient advocate as medical advisor to the Regroupement Trisomie 21 and the Leukemia & Lymphoma Society of Canada; and reports receipt of equipment to his institution from the McGill University Health Centre Foundation and the Montreal General Hospital Foundation. JA declares research grants from Pfizer, Gilead, and Knight; and honoraria from Knight and Gilead. FC declares honoraria from Pfizer, Knight, and Sandoz; travel support from Pfizer and Mundipharma; and board participation from Pfizer and Sandoz. LYAC declares honoraria from Pfizer paid to her institution, and board participation from CIDARA Therapeutics (paid to her institution). ALC declares a grant from Knight–United Medical; honoraria from Mundipharma, Sandoz, and Knight–United Medical; travel support from Mundipharma and Knight–United Medical; and advisory board membership from Mundipharma and Sandoz. ACo declares fees for lectures from Gilead, Pfizer, and Mundipharma; and advisory board fees from Gilead, MSD, Mundipharma, and Pfizer. DECL declares a Biotechnology and Biological Sciences Research Council–US National Science Foundation project grant (BB/W002760/1) held by Elizabeth Ballou; honoraria from Gilead; and travel support from a project grant (BB/W002760/1). LD declares payment for lectures from Pfizer. SG declares a grant from the NIHR Manchester Biomedical Research Centre Dowager Countess Eleanor Peel Trust. RK declares a grant from Pfizer for support of investigator-initiated research; and payments for lectures from Pfizer, Mundipharma, and Gilead. KL declares a grant from TECOmedical paid to her institution; consulting fees from Mundipharma paid to her institution; payments for lectures and presentations from Gilead and Pfizer, paid to herself, and Mundipharma and FUJIFILM Wako Chemicals Europe, paid to her institution; travel support from Gilead, Pfizer, and AstraZeneca; and payment for board participation from Pfizer paid to her institution. MSL declares funding from the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. MKM declares consulting fees from GenMark Diagnostics, NED Biosystems, and Vericel; honoraria from Thermofisher Scientific; payment for expert testimony; a patent for neutrophil therapeutic; and board participation from Karius. JM declares grants from Gilead, Mundipharma, and VIRCELL; and honoraria and travel grants from Gilead, all paid to his institution. SCM declares grants from DZIF and the University of Cologne (Cologne, Germany); consulting fees from Octapharma; honoraria from Pfizer; and board participation from Octapharma. MMi declares a grant from Gilead paid to her institution; honoraria from AstraZeneca, Gilead, Janssen, Mundipharma, and Pfizer; and board participation from Allovir, Moderna, Mundipharma, and Shionogi. PM declares consulting fees and honoraria from Menarin, Pfizer, MSD, Viatris, and Mundipharma. VO declares role and stock options from Volumeer. PP declares grants from F2G, Melinta, Scynexis, and Astellas; and board participation from F2G, Basilea, Scynexis, Melinta, and ISHA Pharmaceuticals. TFP declares grants from Cidara, F2G, and Scynexis paid to his institution; board participation from Gilead, Scynexis, and Basilea; and roles as Treasurer (past) of the Immunocompromised Host Society, Treasurer (past) and IDSA liaison (current) of the Texas Infectious Diseases Society, and member of the board of directors of the Mycoses Study Group Education and Research Consortium. PP-A declares grants paid to his institution from Instituto de Salud Carlos III and Gilead; honoraria from Gilead, Pfizer, and MSD; and board participation from Gilead. ER declares research grants from Merck, AbbVie, Shionogi, Cidara Therapeutics, Melinta, and Pfizer paid to his institution; payments as scientific advisor and member of the speaker bureau from Gilead, Merck, Shionogi, Mundipharma, and Pfizer, paid to his institution. CR declares grants and research support paid to his institution from Chimerix, Cidara, and Scynexis; consulting fees from Avir Pharma, Merck Canada, and Pfizer Canada; and honoraria from Avir Pharma, Merck Canada, and Sunovion Pharmaceuticals Canada. TR declares speaker fees from Hikma, and lecture fees from Akademie für Infektionsmedizin. RSa declares honoraria from Pfizer. JS-G declares honoraria from Gilead, Menarini, and Pfizer; travel support from AstraZeneca; and board participation from Pfizer. JSi declares honoraria and travel support from Pfizer, MSD, and Gilead. RSo declares honoraria for lectures from Pfizer, MSD, Mylan, Cipla, and Glenmark; and advisory board fees from Pfizer, MSD, Mylan, Cipla, Glenmark, and Hoffmann la Roche. AS declares grants from Astellas and Mayne, and consulting fees from GSK. JStei declares a grant from Pfizer, and honoraria from Pfizer and Gilead. JStem declares grants paid to his institution from the German Federal Ministry of Education and Research, the Medical Faculty of the University of Cologne (Cologne, Germany), Basilea Pharmaceuticals, and Noscendo; consulting fees from Gilead, Micron Research, and Alvea; and honoraria from AbbVie, Gilead, Hikma, and Pfizer. AFT declares grants from the UK–Ireland Fellowship, Gilead Sciences, and Associates of Cape Cod (Fungitell). GRT declares grants and consulting fees from Astellas, Basilea, Cidara, F2G, Mundipharma and Melinta; and board participation from Pfizer. NW declares grants from bioMerieux, Bruker, F2G, Mycovia, Sfunga, and Scynexis; honoraria from the American Society for Microbiology and the American College of Veterinary Internal Medicine; travel support from the Clinical and Laboratory Standards Institute, Page Medical, and the American College of Veterinary Internal Medicine; has roles within the Clinical and Laboratory Standards Institute, the American Society for Microbiology, and the British Society for Antimicrobial Chemotherapy; and reports receipt of drugs (drug powder) from Scynexis, Basilea, Cidara, F2G, and Mycovia. BWi declares a grant from Schülke & Mayr paid to her institution; and honoraria from Mundipharma, bioMérieux, BD, CapeCod, and Schülke & Mayr. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Current guidelines and consensus statements advise caution in using direct oral anticoagulants (DOACs) for morbidly obese patients with body mass index (BMI) >40 kg/m2, indicating warfarin as the most studied treatment., Methods: We systematically searched databases from their inception to January 4, 2024, to identify studies that evaluated the effectiveness and safety of DOACs compared to warfarin in patients with BMI >40 kg/m2 and atrial fibrillation (AF) or venous thromboembolism (VTE). The outcomes of allcause mortality, major and minor bleeding, stroke/systematic embolism (SE), VTE, and their composite endpoint were analyzed using a random-effects model., Results: This meta-analysis included 24 studies and 119,960 morbidly obese patients with AF or VTE on oral anticoagulation therapy: 51,363 on DOACs (43%) vs. (57%) 68,597 on warfarin. DOAC use was significantly associated with lower all-cause mortality and major bleeding risk compared to warfarin. Although the risk of composite endpoint, stroke/SE, and VTE was lower in the DOAC group, no statistically significant difference was observed, indicating no superiority of warfarin compared to DOAC use. The risk of minor bleeding events, hemorrhagic stroke, and ischemic stroke was lower in the DOAC compared to the warfarin group. The same trend favoring DOACs over warfarin in all assessed endpoints was observed in the subgroup analysis based on anticoagulation indication (AF or VTE)., Conclusion: Our findings have documented a potentially more effective and safer profile of DOACs compared to warfarin in morbidly obese patients regardless of the indication for anticoagulation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Transfusion-dependent thalassemia (TDT) is a type of protein aggregation disease. Its clinical heterogeneity imposes challenges in effective management. Red blood cell (RBC) variables may be clinically relevant as mechanistic parts or tellers of TDT pathophysiology. This is a cross-sectional study of RBC and plasma physiology in adult TDT subjects versus healthy control. TDT plasma was characterized by increased protein carbonylation, antioxidants, and larger than normal extracellular vesicles. RBCs were osmotically resistant but prone to oxidative hemolysis. They overexposed phosphatidylserine and exhibited pathologically low proteasome proteolytic activity (PPA), that correlated with metabolic markers of the disease. RBC ultrastructure was distorted, with splenectomy-related membrane pits of 300-800 nm. Plasma metabolomics revealed differences in heme metabolism, redox potential, short-chain fatty acids, and NO bioavailability, but also in catecholamine pathways. According to coefficient of variation assessment, hemolysis, iron homeostasis, PPA and phosphatidylserine exposure were highly variable among patients, as opposed to RBC fragility, and plasma antioxidants, amino acids, and catecholamines. Sex-based differences were detected in hemolysis, redox and energy variables, while splenectomy-related differences referred to thrombotic risk, RBC morphology, and plasma metabolites with neuroendocrine activity. Hepcidin varied according to oxidative hemolysis and metabolic markers of bacterial activity. Subjects with higher (>10 g/dL) pretransfusion Hb levels presented mildly distorted profiles and lower membrane-associated PPA, while classification by severity of mutations revealed different levels of hemostasis, inflammation, plasma epinephrine, hexosamines, and methyltransferase activity markers. The currently reported heterogeneity of cellular and biochemical features probably contributes to the wide phenotypic diversity of TDT at clinical level., (Copyright © 2025 American Society of Hematology.)

Purpose: Secondary hyperparathyroidism is one of the most common complications of chronic kidney disease. The optimal treatment for chronic kidney disease nowadays is kidney transplant. Nonetheless, hyperparathyroidism does not always resolve after transplantation leading to tertiary hyperparathyroidism. The management of tertiary hyperparathyroidism can be either medical (calcimimetics) or surgical (parathyroidectomy). The aim of this study is to compare the medical and surgical treatment in terms of control of hyperparathyroidism and long-term implications on kidney graft function., Methods: We carried out a systematic review and meta-analysis of relevant studies up to March 2024 on MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Scopus databases. We compared the parathyroid hormone, calcium, creatinine and estimated glomerular filtration rate between the groups of patients that were treated with parathyroidectomy and those that were treated with calcimimetcs. Subsequently, we performed a trial sequential analysis to corroborate our findings., Results: Four studies were included in the final analysis with a total number of 247 patients. Parathyroidectomy resulted in a greater decrease in parathyroid hormone and calcium levels (WMD 149.37, CI 95% 126.81-171.93, p < 0.0001 and WMD 0.7, CI 95% 0.45-0.96, p < 0.0001 respectively) but there was no difference between the surgical and medical management groups in the creatinine and eGFR levels (CI 95%, -0.62-0.17, p = 0.27 and CI 95%, -8.06 - 20.54 p = 0.39). The trial sequential analysis corroborated these findings., Conclusion: Parathyroidectomy is more effective in controlling hyperparathyroidism in kidney transplant recipients, as it leads to a greater decrease in parathyroid hormone and calcium levels. However, there is no difference in the long-term function of the kidney graft, as the creatinine and estimated glomerular filtration values were similar in the surgical and medical management groups., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2025. Crown.)

Cardiac resynchronization therapy (CRT) is a cornerstone in the treatment of dyssynchronous heart failure with reduced ejection fraction. However, the phenomenon of non-response has plagued CRT since its initial application. Notwithstanding issues such as failure to capture the left ventricle, lower-than-required pacing delivery percent, and failure to optimize atrioventricular and interventricular delays, there are patients who fail to exhibit an adequate response to CRT in its classical biventricular pacing (BiVP) form. Several modalities have been proposed as a means to remedy this issue, including pacing the conduction system itself-His or left bundle branch pacing, allowing for intrinsic conduction in some myocardial segments, pacing the left ventricle from multiple points in the coronary sinus (multipoint pacing), or even combining the above (e.g., His/left bundle pacing and BiVP leading to His/left bundle-optimized CRT). In the present review, we present recent evidence for the advantages and disadvantages of each modality and attempt to formulate a pathophysiology and simulation-based strategy to determine the best way forward for delivering CRT in non-responders to BiVP.

Introduction: The epidemiology of candidemia has shifted in the past few decades; drug-resistant non-albicans Candida species have become more prevalent worldwide. The aim of this retrospective study was to determine the epidemiology of Candida species isolated from hospitalized neonates, children and adults, and to investigate a potential changing susceptibility pattern in a large general tertiary hospital., Methods: All unique Candida strains isolated from candidemia cases between 1 January 2020 and 15 October 2024 were identified, and their susceptibility profile was characterized. The distribution pattern in different ward types (medical, surgical, pediatric and ICU) was recorded. Cumulative annual susceptibility profiles were compared., Results: Candidemia incidence increased during the COVID-19 pandemic, from 0.63/1000 patient-days in 2020 to 0.96/1000 patient-days in 2022, and has since slightly decreased (0.83 and 0.89 in 2023 and 2024, respectively). Candidemia-associated mortality was high (>50%) in 2020 and peaked during the pandemic. During the study period, Candida parapsilosis remained the most frequent Candida spp. However, since the first isolation of Candida auris from the bloodstream in late 2022, and despite intense infection control measures taken, its frequency sharply climbed to the second position after only C. parapsilosis in the first 10 months of 2024 (33.6% vs. 25.2% for C. parapsilosis and 21.0% for C. albicans ). While C. albicans has remained highly susceptible to fluconazole (1% resistance rate), C. parapsilosis manifested significant resistance to fluconazole during 2022-2024 (52%). C. auris was universally resistant to azoles and one isolate also resistant to echinocandins., Conclusions: A high prevalence of azole resistance of C. parapsilosis, the most frequently isolated Candida species, persists, and a significant rise of C. auris was recorded in nosocomial bloodstream infections with severe implications on public health.

Background/Objectives : Diagnosis-related group (DRG)-based financing, a subcategory of case-based payment models, has been established as the primary reimbursement scheme in most high-income countries. Almost 40 years thereafter, the impact of the reform on gynecologic oncology funding and recompensation has not been clearly elucidated. This systematic review aims to address the scarce bibliographic data, consolidate the information regarding DRG-based systems in gynecologic oncology, evaluate the advantages and challenges of its implementation worldwide, and examine alternative and complementary recompensation schemes in this context. Methods : A stringent and comprehensive literature review of original articles using online databases (Google Scholar and Pubmed) yielded 173 potential results. Results : These were further assessed for relevance and eligibility and, finally, an in-depth investigation of 15 articles was conducted. We concluded that, despite the fact that DRG-based financing may be beneficial in most healthcare scenarios, the reimbursement scheme is challenged in the context of gynecologic oncology. Conclusions : An innovative approach comprising a combination of the values of case-based and value-based payment models would extend healthcare services beyond acute treatments and propose new perspectives in holistic healthcare provision in a financially sustainable environment.

Objective: To investigate whether T-bet+ B cells, as well as age-associated B cells/ABCs (CD19+CD21-CD11c+T-bet+) and double-negative B cells/DN (CD19+IgD-CD27- CXCR5-T-bet+), serve as prognostic and/or therapeutic tools for systemic lupus erythematosus (SLE) in humans., Methods: Flow cytometry was used for enumerating T-bet+ B cells and ABCs/DN subsets, found in the peripheral blood of 10 healthy donors and 22 active SLE patients. Whole blood assay cultures, combined with in vitro pharmacological treatments, were performed to evaluate the effects of hydroxychloroquine, anifrolumab and fasudil (a ROCK kinase inhibitor) on T-bet+ B cells' percentage. Moreover, previously published single-cell RNA sequencing (scRNA-seq) data were used in a meta-analysis to allow characterization of genes and pathways associated with the biology of T-bet in B cells., Results: T-bet+ B cells displayed an expansion in SLE patients [1.47 (1.9 - 0.7) vs 10.85 (37.4 - 3.6)]. Similarly, both ABCs and DN were found to be expanded. Interestingly, percentages of T-bet+ B cells positively correlated with patients' SLEDAI scores (rs=0.55, p=0.007). Cell culture experiments conducted, revealed that all three agents tested can deplete T-bet+ B cells (without affecting the cell viability of lymphocytes, T cells and B cells). According to bioinformatics analyses, T-bet is highly expressed in two B cell clusters with pathogenic characteristics for SLE (designated as atypical memory B cells and activated naïve B cells). These clusters can be targeted for therapeutic interventions., Conclusions: T-bet+ B cells can serve as a putative prognostic biomarker of lupus severity. Circumstantial data suggest that these cells may promote disease pathogenesis and may represent a novel therapeutic target., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Immunology.)

Childhood obesity is a well-known risk factor for primary hypertension (HTN), especially during puberty. Validated automated oscillometric devices based on universal protocols using proper cuffs according to arm sizes must be selected for blood pressure (BP) measurement in clinical practice. Recent recommendations have addressed the importance of accurate BP measurement in patients with obesity. The American Heart Association (AHA) suggests using a cone-shaped cuff, while the European Society of Hypertension (ESH) emphasizes the significance of cuff characteristics based on arm size. The applicability of cone-shaped cuffs over cylindrical cuffs has been studied in adults with obesity. Most studies focused on the upper arm's shape and provided evidence that the use of cylindrical cuffs may overestimate BP in individuals with obesity, while the conical cuff was proposed as a proper alternative. However, current validation studies for BP measurement devices have not included the arm's size as a recruiting criterion, which may compromise the accuracy of devices in individuals with obesity. This review discusses the role of arm characteristics in cuff selection and the potential role of conical cuffs as an alternative to commonly used cylindrical ones in BP measurement in pediatric patients with obesity., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This study evaluates the health-related quality of life (HRQoL) among patients with hemophilia A currently undergoing prophylactic treatment at the Hemophilia Center of Northern Greece. Using the Haem-A-QoL questionnaire, we assessed various HRQoL dimensions in a cohort of 29 adult male patients, analyzing the impact of age, disease severity, and treatment regimens. The results revealed that younger patients (18-30 years old) exhibited significantly better overall HRQoL scores (total score of 25.36) compared to older age groups (37.81 for the 31-45 group and 43.71 in the 45+ group), particularly in the physical health (29.16 vs. 48.43 vs. 58.57) and mental well-being domains (25 vs. 37.11 vs. 41.07). Interestingly, moderate hemophilia patients reported lower HRQoL (42.31) than those with severe form (34.85), suggesting unique challenges in managing their condition. The 'Sports/Free Time' domain had the highest scores (65.81), indicating significant limitations in physical activities in the everyday lives of affected individuals. However, better outcomes were observed in the mental dimension (36.09), work/study (34.88), family planning (10.68), and relationships aspects (16.67), where our cohort reported very low scores compared to similar studies, indicating a significantly better quality of life in these domains. These findings highlight the importance of personalized psychosocial support and targeted interventions to address the specific needs of hemophilia patients, particularly in enhancing physical activity opportunities and managing the psychological burden of moderate hemophilia. The study contributes valuable insights into the HRQoL of hemophilia patients and underscores the necessity for tailored approaches to improve patient outcomes across all dimensions of life.

Background: Current clinical decision support systems (DSS) are trained and validated on observational data from the clinic in which the DSS is going to be applied. This is problematic for treatments that have already been validated in a randomized clinical trial (RCT), but have not yet been introduced in any clinic. In this work, we report on a method for training and validating the DSS core before introduction to a clinic, using the RCT data themselves. The key challenges we address are of missingness, foremost: missing rationale when assigning a treatment to a patient (the assignment is at random), and missing verification evidence, since the effectiveness of a treatment for a patient can only be verified (ground truth) if the treatment was indeed assigned to the patient - but then the assignment was at random., Materials: We use the data of a multi-armed clinical trial that investigated the effectiveness of single treatments and combination treatments for 240+ tinnitus patients recruited and treated in 5 clinical centres., Methods: To deal with the 'missing rationale for treatment assignment' challenge, we re-model the target variable that measures the outcome of interest, in order to suppress the effect of the individual treatment, which was at random, and control on the effect of treatment in general. To deal with missing features for many patients, we use a learning core that is robust to missing features. Further, we build ensembles that parsimoniously exploit the small patient numbers we have for learning. To deal with the 'missing verification evidence' challenge, we introduce counterfactual treatment verification, a verification scheme that juxtaposes the effectiveness of the recommendations of our approach to the effectiveness of the RCT assignments in the cases of agreement/disagreement between the two., Results and Limitations: We demonstrate that our approach leverages the RCT data for learning and verification, by showing that the DSS suggests treatments that improve the outcome. The results are limited through the small number of patients per treatment; while our ensemble is designed to mitigate this effect, the predictive performance of the methods is affected by the smallness of the data., Outlook: We provide a basis for the establishment of decision supporting routines on treatments that have been tested in RCTs but have not yet been deployed clinically. Practitioners can use our approach to train and validate a DSS on new treatments by simply using the RCT data available to them. More work is needed to strengthen the robustness of the predictors. Since there are no further data available to this purpose, but those already used, the potential of synthetic data generation seems an appropriate alternative., Competing Interests: Declaration of competing interest None., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Percutaneous coronary interventions (PCI) are the mainstay of treating obstructive coronary artery disease. However, procedural planning and individualization of the procedure is necessary for different patient phenotypes to optimize outcomes. Specifically, post-PCI pharmacotherapy with antiplatelets complicates the management of patients at high bleeding risk due to comorbidities, such as atrial fibrillation. Aiming to limit post-procedural adverse events and reduce the procedure-related bleeding risk, several novel technologies and hypotheses have been tested in clinical practice. Such frontiers include limiting the duration of dual antiplatelet therapy or even prescribing single regimens, using drug-coated balloons for performing the intervention and the effect of imaging-guided PCI in optimizing stent expansion. Furthermore, specific instruction in different patient phenotypes, such as atrial fibrillation and chronic kidney disease, are emerging, as despite both pathologies being considered at high bleeding risk, one size does not fit all. Thus, our review will provide all the recent updates on the field as well as algorithms and expert opinions on how to manage this, particularly common, phenotype of patient., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Osteoporosis is a metabolic skeletal disease characterized by low bone mass and strength, and increased risk for fragility fractures. It is a major health issue in aging populations, due to fracture-associated increased disability and mortality. Antiresorptive treatments are first line choices in most of the cases., Areas Covered: Bone homeostasis is complicated, and multiple factors can compromise skeletal health. Bone turnover is a continuous process regulated by the coupled activities of bone cells that preserves skeletal strength and integrity. Imbalance between bone resorption and formation leads to bone loss and increased susceptibility to fractures. Antiresorptives prevent bone loss and reduce fracture risk, by targeting osteoclastogenesis and osteoclast function and survival. Their major drawback is the coupling of osteoclast and osteoblast activity, due to which any reduction in bone resorption is followed by suppression of bone formation., Expert Opinion: During the last couple of decades significant progress has been made in understanding of the genetic and molecular basis of osteoporosis. Critical pathways and key molecules that mediate regulation of bone resorption have been identified. These factors may underpin novel therapeutic avenues for osteoporosis, but their potential for translation into clinical applications is yet to be tested.

Purpose: Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers., Methods: After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured., Results: All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%)., Conclusion: In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: This study was performed in line with the principles of the 1964 Helsinki Declaration and its later amendments. Approval was granted by the Ethics Committee of Hippokration General Hospital. Informed consent: Informed consent was obtained from all individual participants included in this study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: A post hoc analysis used pooled STRIVE/ReSTORE trial data to determine outcomes with rezafungin versus caspofungin by Candida species and antifungal susceptibility., Methods: The efficacy and safety of once weekly rezafungin 400/200 mg versus once daily caspofungin 70/50 mg was demonstrated in the randomized, double-blind phase 2 STRIVE (NCT02734862) and phase 3 ReSTORE (NCT03667690) trials involving adults with candidaemia and/or invasive candidiasis. In this analysis, data were pooled for patients with a documented Candida infection within 96 hours of randomization who also received ≥1 dose of study drug. Treatment outcomes were evaluated by Candida species and baseline MICs. Susceptibility was determined using European Committee on Antimicrobial Susceptibility Testing E.Def 7.4 broth microdilution methodology, with Tween 20-supplemented medium for rezafungin., Results: A total of 294 patients were included (rezafungin: N = 139, caspofungin: N = 155). Susceptibility testing at baseline identified three rezafungin non-susceptible isolates. Day 14 global cure rates were numerically similar between groups for C. albicans (rezafungin: 61.0% [36/59], caspofungin: 65.2% [45/69]) and C. tropicalis (rezafungin: 70.4% [19/27], caspofungin: 63.6% [14/22]), but higher with rezafungin than caspofungin for C. glabrata (rezafungin: 71.1% [27/38], caspofungin: 60.0% [21/35]) and C. parapsilosis (rezafungin: 78.6% [11/44], caspofungin: 55.6% [15/27]). Day 30 all-cause mortality rates were numerically similar between groups for C. albicans (rezafungin: 22.0% [13/59], caspofungin: 18.8% [13/69]) and C. glabrata (rezafungin: 15.8% [6/38], caspofungin: 11.4% [4/35]), but higher with caspofungin than rezafungin for C. tropicalis (rezafungin: 18.5% [5/27], caspofungin: 31.8% [2/22]) and C. parapsilosis (rezafungin: 7.1% [1/14], caspofungin: 29.6% [8/27]). Day 5/14 mycological eradication rates were numerically similar between treatments for C. albicans and C. parapsilosis, but higher with rezafungin for C. glabrata and C. tropicalis. Outcomes by Candida species were not associated with treatment-specific MICs., Discussion: Rezafungin appears to be an effective treatment for candidaemia/invasive candidiasis irrespective of baseline Candida species., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: High triglyceride (TG) levels are associated with increased atherosclerotic cardiovascular disease (ASCVD) risk in the general population. Yet, the role of TG in familial hypercholesterolemia (FH) remains understudied. This research aims to evaluate the link between TG levels and ASCVD prevalence in adult patients with FH., Methods: This cross-sectional analysis, derived from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH), involves categorizing patients into tertiles based on their TG concentrations., Results: In our study of 1772 adults with heterozygous FH (HeFH), aged 51 ± 15 years at registration and diagnosed at 44 ± 16 years, TG concentrations in the 1st (80 mg/dL), 2nd (124 mg/dL), and 3rd (200 mg/dL) tertiles revealed varying ASCVD prevalence (18.0%, 28.5% and 28.5%, respectively). Adjusted for ASCVD risk factors, TGs ≥116 mg/dL were linked to higher ASCVD risk than levels <116 mg/dL (OR: 1.37, 95% CI 1.05-1.80, P = .02)., Conclusions: A notable association with ASCVD is evident in FH patients, even at relatively low TG levels, starting from 116 mg/dL (1.31 mmol/L)., Competing Interests: Declaration of competing interest PA, CVR, GL, AG, EK, KP, VK, ID, VG, GA, EP, GP, CA, CB and CK have no relevant conflict of interest to report. LR has received research grants and honoraria from Amgen, Sanofi-Aventis, Viatris, Novartis, Vianex and Servier. IS has given talks, received honoraria, and participated in clinical trials sponsored by MSD, Amgen, Sanofi. GK has given talks, attended conferences and participated in trials sponsored by Amgen, Angelini, MSD, Lilly, Vianex and Sanofi and has also accepted travel support to conferences from Amgen, Sanofi and MSD. KT has participated in educational, research and advisory activities sponsored by Amgen, Angelini, Astra-Zeneca, Bayer, Boehringer-Ingelheim, Elpen, Lilly, MSD, Mylan, Novo Nordisk, Sanofi and Vianex. ES has participated in educational and advisory activities sponsored by AstraZeneca, Medtronic, MSD, Sanofi and Servier. VK has given talks and attended conferences sponsored by AstraZeneca, MSD, Sanofi-Aventis, and Vianex. MD has participated in educational, research and advisory activities sponsored by Menarini, Elpen, AstraZeneca, MSD, Bayer, Sanofi, Novartis, and Servier. VL has given lectures, attended conferences and participated in trials sponsored by Novo Nordisk, Sanofi-Aventis, Novartis, AstraZeneca, Boehringer-Ingelheim, MSD, GSK, Vianex, Elli Lilly, Elpen, Mylan and Aegereon. EZ has received honoraria for lectures from Amgen. Sanofi, MSD, and Astra Zeneca. HM participated in educational, research and consulting activities supported by healthcare companies, including Amgen, AstraZeneca, Elpen, Genesis Pharma, Novartis, Pfizer, Sanofi, Viatris, Vianex. AB has received honoraria from Vianex, Amarin and Sanofi. EL has participated in educational, research and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer-Ingelheim, Novartis, Novo Nordisk, Valeant and Servier., (Copyright © 2024 National Lipid Association. Published by Elsevier Inc. All rights reserved.)