Hippokration General Hospital, Thessaloniki

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.

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.

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 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.

Background/Objectives: B-thalassemia is a genetic disorder that leads to reduced or absent β-globin chains, often resulting in endocrine abnormalities due to iron overload, chronic anemia, and hypoxia. This study investigates the prevalence and risk factors for glucose metabolism disturbances in transfusion-dependent β-thalassemia (TDT) patients, focusing on pancreatic iron overload and its association with other iron biomarkers. Methods: We studied two groups of TDT patients (2018–2022) at Hippokration General Hospital: Group 1 (no glucose metabolism impairment, n = 46) and Group 2 (with impaired glucose tolerance or diabetes mellitus, n = 18). Patients were assessed for factors contributing to glucose disturbances, and laboratory data were analyzed. Type 2 diabetes was diagnosed per American Diabetes Association criteria, and impaired glucose tolerance was defined by OGTT results. A multivariate logistic regression identified potential independent risk factors. In a subset of patients on iron chelation therapy, we examined the relationship between pancreatic, liver, and heart iron overload (T2* MRI) and glucose/ferritin levels. Results: Age and elevated serum GGT levels were significantly associated with impaired glucose metabolism (p = 0.02). Beta-blocker use was correlated with glucose disturbances (p = 0.02), but multivariate analysis revealed no significant independent risk factors. A significant relationship was found between pancreatic and heart iron overload (r = 0.45, p = 0.04). Conclusions: Elevated GGT levels suggest that oxidative stress and liver dysfunction play a key role in glucose metabolism disturbances. Pancreatic MRI T2* may help predict heart iron overload. Further research is needed to identify reliable biomarkers for glucose regulation in TDT.

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.

Background: Antimicrobial resistance (AMR) is recognized as one of the most important global public health threats. There is an urgent need to reduce the spread of these multidrug-resistant bacteria (MDR-B), particularly in extremely vulnerable patients. The aim of this study was to investigate whether targeted gene amplification performed directly on clinical samples can be used simultaneously with a bundle of enhanced infection control measures in a Pediatric Intensive Care Unit (PICU) endemic to MDR-B. Methods: This study had three phases: (1) the baseline phase was performed prior to intervention when first screening and sample collection were performed; (2) the intervention phase was performed when various enhanced infection control measures (EICM) were applied; and (3) the maintenance phase occurred when EICMs were combined with the implementation of targeted molecular surveillance. The presence of four carbapenemase genes, blaKPC, blaOXA-48-like, blaVIM, and blaNDM, as well as the β-lactamase genes blaTEM and blaSHV, was evaluated by PCR after DNA isolation directly from stool samples. The results were compared to culture-based phenotypic analysis. Results and Conclusions: The implementation of EICM appeared to reduce the resistance burden in this sample endemic to an MDR-B clinical setting. The direct implementation of a targeted and customized rapid molecular detection assay to clinical samples seems to be an effective clinical tool for the evaluation of EICM measures.

Introduction Physical inactivity is common in chronic kidney disease (CKD) patients; several patient- and disease-related factors are linked to a sedentary lifestyle, but social and environmental influences remain unexplored. This study evaluates the level of physical activity in patients with CKD and investigates the associations with caregivers' physical activity levels, characteristics of the residential environment, and objective measures of exercise capacity. Methods Eighty CKD patients (20 per CKD stage 2-4) were included; patients and their carers filled out the International Physical Activity Questionnaire (IPAQ), questionnaires about residential environment and past exercise habits. The CKD patients also performed a 30-sec sit-to-stand-test (30-STS) as a measure of exercise capacity. Results According to the IPAQ-score, CKD patients were largely inactive (only 10% reported health-enhancing activity levels); no differences were found between CKD stages. The 30-STS was also impaired, and the number of repetitions significantly decreased with advancing CKD stages (14.2±2.9 vs. 12.6±5.4 vs. 10.4±3.3 vs. 10.5±3.5; p=0.008). Carers were also highly inactive but still had higher physical activity compared to patients (moderate intensity metabolic equivalents (METS) p=0.03, vigorous intensity METS p=0.053); no correlation between carers' and patients' physical activity was noted (p=0.702). Patients' physical activity was associated with residential factors: living in a detached house compared to an apartment (p=0.013 for moderate intensity and p=0.017 for vigorous METS), having a garden (p=0.019 for moderate intensity and p=0.022 for vigorous METS) and accessing house by stairs (p=0.037 for vigorous METS), were associated with higher physical activity. Conclusions Physical activity was significantly reduced in CKD patients, irrespectively disease stage. Carers were also highly inactive, but no association was found between the patients' and carers' daily activities. Residential characteristics were the only factors found to be associated to patients' physical activity levels. Personalized, supportive interventions are required, taking into account the patients' social support and microenvironment, in order to increase the physical activity level in this population.

Trait mental fatigue (MF) and cognitive dysfunction significantly impair the quality of life in people with multiple sclerosis (PwMS), particularly impacting information processing speed (IPS) and verbal learning-memory (VL/M). We assessed 66 PwMS and 38 healthy controls (HC) via the oral form of the Symbol Digit Modalities Test (SDMT-Of) for IPS, the Greek Verbal Learning Test (GVLT) for VL/M, and the cognitive subscale of the Modified Fatigue Impact Scale (MFIS-c) for MF. This aimed at investigating the mediating role of MF in the relationship between IPS and VL/M in PwMS. PwMS performed significantly worse than HC across all domains. Mediation analysis, controlling for age, sex, education, disease duration, and MS-type, revealed a significant effect of IPS on VL/M in PwMS. This effect became non-significant once MF was introduced, whereas the indirect effect of IPS on VL/M through MF remained significant. No significant mediation effects were observed in HC, even after controlling for age, sex, and education, underscoring the unique impact of MF on MS. This study highlights the mediating role of trait MF in cognitive deficits among PwMS, suggesting that interventions targeting MF could enhance cognitive performance. The study is registered with ClinicalTrials.gov Identifier NCT04806568 (https://www.clinicaltrials.gov/study/NCT04806568).

Background Formation of galactose-deficient IgA1 (Gd-IgA1) immunoglobulin is the initial step in the immunological cascade leading to IgA nephropathy (IgAN). Targeted-release budesonide (TRB), an evidence-based regimen without major side-effects, has recently been approved for IgAN treatment; herein we present our preliminary real-world data regarding prompt response to TRB. Methods Patients with primary IgAN who remained with Uprot >1 g/24 h despite conventional treatment for 6 months were started on TRB, and re-evaluated at 3 (T3) and 6 (T6) months. Reduction of proteinuria by ≥30%, at T3 and T6 was regarded as very early (VER) and early response (ER), respectively. Kidney biopsies were evaluated according to Oxford classification (MEST-C) score. Results Thirty-seven IgAN patients, male/female 26/11, mean ± standard deviation age 50.38 ± 14.32 years and mean time since diagnosis 45.65 ± 56.67 months, were included. Seventeen (45.94%) patients demonstrated VER, increasing to 29 (78.3%) as ER (P = .004). Patients who demonstrated VER had a shorter time interval since diagnosis compared with non-VER, 29.41 ± 6.96 vs 65.37 ± 17.64 months (P = .05), and preserved estimated glomerular filtration rate at diagnosis and T0, while time since diagnosis was the main factor associated with ER, 38.36 ± 19.6 vs 78.67 ± 18.64 months, in ER and non-ER respectively (P = .05). Patients with M0, E0, S0 and T0 had no significant changes during T0–T6, while patients with M1, E1, S1 and even T1 had significantly reduced proteinuria (P = .006, P = .0011, P < .0001 and P < .0001, respectively). Conclusions Almost half of the patients showed proteinuria reduction after TRB treatment at 3 months, and the proportion increased significantly at 6 months. Patients likely to have a prompt proteinuria reduction were relatively close to diagnosis, retained kidney function and had active lesions in kidney biopsy.

Background: A personalized, non-invasive assessment approach for evaluating the risk of obstructive coronary artery disease (CAD) is crucial for patients with an intermediate or low clinical likelihood of CAD before undergoing invasive coronary angiography (ICA). This method allows clinicians to effectively rule out the presence of obstructive CAD without the need for ICA or to determine if a referral for ICA is warranted. Emerging lipidomics biomarkers may be valuable in this process. However, technological challenges in detecting structurally similar lipids and the requirement for advanced computational tools have so far impeded the clinical application of lipidomics research. Hypothesis: Our study aims to develop an innovative non-invasive diagnostic test utilizing novel lipidomics biomarkers, potentially revolutionizing current risk classification schemes for CAD. Methods: In this post-hoc analysis of the CorLipid trial (NCT04580173), we employed extreme gradient boosting (XGBoost) machine learning to assess the predictive power of a lipidomics panel for obstructive CAD risk. Liquid chromatography-mass spectrometry analyzed lipid profiles from 146 individuals undergoing ICA. SYNTAX Score (SS) was used to define obstructive CAD as SS>0 versus non-obstructive CAD (SS=0). Results: Of the 146 participants (25% female, mean age: 61 ±11 years old), 55% had obstructive CAD (SS>0). Lipidome changes [phosphatidylinositols, (lyso-)phosphatidylethanolamine, (lyso-)phosphatidylcholine, triglycerides, diglycerides, and sphingomyelins] were investigated to identify lipids potentially associated with the phenotype and complexity of CAD. Using this information, 290 quantified serum lipid species were utilized to develop an XGBoost algorithm with 17 serum biomarkers ( consisting of sphingolipids, glycerophospholipids, triacylglycerols, galectin-3, glucose, low-density lipoprotein, and lactate dehydrogenase) with very good discriminative ability [ROC AUC: 0.875 (95%CI: 0.867-0.883)], excellent sensitivity (100%) but moderate specificity (62.1%) for the prediction of obstructive CAD. Conclusions: These findings indicate that a deep-learning-based non-invasive diagnostic test, using lipidomics serum biomarkers, could reliably rule-out obstructive CAD without necessitating ICA. To enhance generalizability, these results should be validated in larger and similar cohorts. Further research, particularly leveraging machine learning, is promising for refining risk stratification.

Background: Adults with congenital heart disease (ACHD) are lifelong at high risk for premature cardiovascular events and life-threatening complications, suggestive of early or accelerated cardiovascular disease. Endothelial and microvascular dysfunction as well as arterial stiffness play a key role in the emergence and progression of cardiovascular complications. As vascular dysfunction may precede the occurrence of adverse events, early identification of endothelial damage markers in ACHD is crucial. Aim: This is the first systematic review and meta-analysis of studies investigating the endothelial and microvascular function in ACHD patients versus healthy controls. Methods: We systematically searched four major electronic databases (PubMed, CENTRAL, Scopus, Web of Science), ClinicalTrials.gov and grey literature. We included studies evaluating endothelial and microvascular function with any semi- or non-invasive method in adult patients with and without ACHD. Studies exploring arterial stiffness indices were also investigated. Results: In total, 31 studies (1118 ACHD patients, 794 controls) were included in this systematic review. Branchial arterial endothelium-dependent (assessed via flow-mediated dilatation, FMD) and -independent vasodilation (assessed via nitroglycerine-mediated dilatation, NMD) were impaired in ACHD patients versus controls (mean difference [MD] -2.5, 95% confidence intervals [CI] -3.7; -1.3 and MD -3.9, 95%CI -6.8; -1.0, respectively). Microvascular dysfunction was also evident; significantly lower reactive hyperemia index and peripheral arterial tonometry (PAT) ratio were found in ACHD patients compared with controls (MD −0.26, 95%CI −0.48; −0.04 and MD −0.26, 95%CI −0.5; −0.4, respectively). Regarding arterial stiffness, pooled analysis revealed non-significant differences in pulse wave velocity between the study groups (standardized MD 0.2, 95%CI -0.2; 0.6). However, augmentation index was significantly higher in ACHD (standardized MD 1.6, 95%CI 0.8; 2.4). Conclusions: ACHD patients have impaired endothelial and microvascular function and increased arterial stiffness, factors that may be responsible for the increased adverse cardiovascular events in this population.

Background: Percutaneous ultrasound-guided renal biopsy (PRB) is a key element for diagnosis and management of several renal pathologies. We aimed to lay out the experience of our pediatric nephrology unit performing PRBs. The rationale and findings of these biopsies, safety issues and considerations of the extracted data are going to be analyzed. Methods: A retrospective study was conducted from 2008 to 2023 based on the review of the medical records of pediatric patients who underwent PRBs. In total, 216 kidney biopsies in 206 patients were performed: 115 (53.2%) during the 2008–2015 period and 101 (46.8%) during the 2016–2023 period. Results: The most frequent clinical indication for PRBs was nephritic syndrome followed by nephrotic syndrome, observed in 84 (40.8%) and 72 (34.9%) patients, respectively. The predominant diagnosis was minimal change disease (MCD) (23.3%), followed by focal segmental glomerulosclerosis (FSGS) (15%) equal to lupus nephritis (LN) (15%), and immunoglobulin A nepropathy (10.2%). Minor complications, such as subcapsular hematomas were observed in approximately 15% of patients while no therapeutic intervention was needed. Conclusions: This report is the first review of pathohistological data covering a pediatric population over a 15-year period in Greece and one of the largest in southeastern Europe, especially in the Balkan region. The main indication for a PRB was nephritic syndrome; however, MCD was the main histological diagnosis. This study emphasis the fact that PRBs constitute a safe and reliable method of diagnostic approach to kidney diseases in childhood and offers important information on therapeutic approaches as well as the prognosis of these patients.