Hygeia Hospital

Abstract BACKGROUND Positron emission tomography (PET) is increasingly used in patients with brain tumors, yet its adoption varies across institutions. METHODS To assess the current landscape, a cross-sectional survey was conducted among European Organization for Research and Treatment of Cancer (EORTC) – Brain Tumour Group (BTG) sites between June 2024 and August 2024. RESULTS Out of the 312 sites invited, 103 replies from 20 countries in the Europe/Middle East region were received. PET availability was reported by 96/103 (93.2%) sites, of whom 74 reported PET use in patients with brain tumors. Most frequently, PET was performed in glioma (69/74, 93.2%), followed by brain metastasis (58/74, 78.4%), meningioma (52/74, 70.3%), and CNS lymphoma (46/74, 62.2%). Amino acid PET was used at 62/71 centers (87.3%), mainly in glioma (58/59, 98.3%) and for differentiation of tumor progression from treatment-related changes (58/59, 98.3%), differential diagnosis (54/59, 91.5%), and hotspot delineation (47/59, 79.7%). Somatostatin receptor (SSTR) PET was performed at 50/68 sites (73.5%), predominantly in meningioma (48/49, 98.0%), and for patient selection before radioligand therapy (41/49, 83.7%) as well as for target volume definition in radiotherapy (33/49, 67.3%) and differential diagnosis (27/49, 55.1%). PET was covered by statutory health insurance at 46/59 (78.0%) centers for amino acid PET and 33/49 (67.3%) for SSTR PET according to self-reported information. Main reasons for not performing PET in clinical routine included limited availability of tracers (14/29, 48.3%), high cost (11/29, 37.9%), and PET considered unnecessary by referring physicians (8/29, 27.6%). CONCLUSION PET is widely used among EORTC-BTG sites, although implementation varies and is influenced by factors such as tracer availability, cost, and institutional perceptions. While further data from broader surveys including non-academic institutions is needed, the findings support the implementation of PET as clinical trial endpoint.

Abstract Background/Introduction Paravalvular leak is a complication of valve replacement with 1% to 3% of patients developing symptoms including heart failure or hemolysis. Purpose This study aims to evaluate the long-term outcomes in whom the primary indication for paravalvular leak closure was hemolysis. Methods We included patients from five Greek hospitals between February 2013 and March 2024. The primary endpoint was the assessment of short and long-term changes in hemolysis parameters, including lactate dehydrogenase, hemoglobin, and indirect bilirubin at 1, 6, 12, and 24 months post-procedure versus baseline values. Secondary endpoints included clinical success, defined as improved hemolysis with transfusion-free status for at least 6 months and survival analysis during the follow-up. Results The study included 42 patients who underwent transcatheter closure of paravalvular leak for hemolytic anemia, with a 15±9 month follow up. Mean age was 69.7±10.3 years and 69% were male. For the primary endpoint, the mean pre-procedural lactate dehydrogenase was 1196±592 IU/L. Although reductions at 1 month (891±1051 IU/L, p=0.221), 6 months (504±378 IU/L, p=0.060), and 12 months (569±312 IU/L, p=0.085) were not statistically significant, a remarkable decrease was observed at 24 months (479±364 IU/L, p=0.040). Hemoglobin levels did not significantly change from pre-procedural values (9.91±1.7 g/dl) at 1 month (10.85±4.3 g/dl, p=0.196), 6 months (10.98±1.91 g/dl, p=0.051), 12 months (10.98±2.19 g/dl, p=0.097) and 24 months (13.09±5.7 g/dl, p=0.065). Indirect bilirubin, with a baseline of 2.4±2.19 mg/dl, showed significant reductions at all time points: 1 month (1.50±1.9 mg/dl, p<0.001), 6 months (0.66±0.44 mg/dl, p=0.003) and 12 months (0.76±0.42 mg/dl, p=0.005). A more than 50% reduction in lactate dehydrogenase was achieved by 44.4% of patients at 1 month, 61.5% at 6 months, 66.7% at 12 months, and 81.3% at 24 months. Similarly, >50% reduction in indirect bilirubin was observed in 58.3% at 1 month, 62.5% at 6 months, and 80% at 12 months. For the secondary endpoints, the need for transfusions significantly decreased from 63.4% pre-procedure to 14.7% at 6 months (p<0.001). Clinical success was achieved in 85.3% of patients. The technical success was 88.1%. The rates of remaining moderate paravalvular leak were 88.1% pre procedurally versus 7.1% at discharge, p<0.001. During the follow-up period of 15±9 months, the survival rate was 66.7%, with 14 patient deaths. Conclusions Transcatheter paravalvular leak closure significantly reduced hemolysis indices (lactate dehydrogenase, indirect bilirubin) with sustained benefits over 24 months. While hemoglobin showed a non-significant increase, transfusion requirements markedly decreased, with most patients remaining transfusion-free for at least 6 months. Overall, transcatheter paravalvular leak closure appears to be an effective option for selected patients.

Abstract Background The Greek National Network of Precision Medicine in Cardiology consists of a consortium of public sector hospitals, forensic services and genetic testing institutes. Aim This network aims to prevent sudden death in young people and study hereditary cardiovascular diseases in Greece. Method Two large national registries have been established, one for patients with hereditary heart diseases and one for sudden deaths in young people. A National Registration Platform has been created. Those registries lead to the evaluation of families with hereditary diseases or with sudden death in young people and to the identification of people within the families who suffer from hereditary cardiovascular disease (CV) and are not aware of it. At the same time, it identifies areas of the country with clusters of inherited CV diseases. Results Within the framework of the network, as a pilot project, we present the results of our own hospital which has tested 2.500 patients with inherited heart diseases and has performed 316 genetic tests on patients diagnosed with hereditary disease. Of the 316 patients, 42 tested positive for pathogenic (P) genetic variation, 74 positive for a likely pathogenic (LP) variant, and 72 for variant of unknown significance. The percentage of genes with the detected variants is shown in Figure 1. Out of the 116 families with P/LP variants, 88 families had at least the proband tested at our center and an average of 2.5 family members were also screened. From 233 screened relatives of probands with P/LP variants, 149 (64%) were found positive for the proband's variant. Clinical evaluation revealed typical or subclinical disease in 35% of the relatives, while 29% of them were phenotype negative. At the same time, areas with a founder effect phenomenon were identified in the country, specifically in Crete [hypertrophic cardiomyopathy (HCM) and ATTR inherited amyloidosis], Attica (HCM), Central Greece (PLN cardiomyopathy) and the Cyclades (Naxos disease-JUP cardiomyopathy). Also nests of rare hereditary diseases such as Cohen disease in Fourni of Ikaria and Wilson disease in Kalymnos, as well as areas of the Peloponnese and the island of Ios with neuromuscular diseases that also have cardiovascular involvement. Conclusion Greece, due to its islands and isolated areas, is a natural park of rare cardiovascular diseases. The Greek National Network of Precision Medicine in Cardiology constitutes an added value for the country's health services by identifying areas that need special interventions as well as populations that we have not been able to identify until now.Genetic profile of patients

To evaluate the association between modelled substitution of total, red, and white meat with dairy subtypes (low-fat, full-fat, and fermented) and the 20-year cumulative incidence of type 2 diabetes (T2D), among apparently healthy adults. The present analysis included data from 2000 individuals free of atherosclerotic cardiovascular disease and T2D at baseline (age 43 ± 13 years; 51% women), participating in the ATTICA cohort study (2002-2022). Food intake was assessed using a validated semi-quantitative food-frequency questionnaire. The 20-year cumulative incidence of T2D was 26.3% (95%CI [24.4, 28.3%]). Participants who developed T2D during follow-up reported significantly higher red meat consumption compared to those who did not (5.0 vs. 4.5 times/week; P = 0.016). Modelled substitution of one daily serving of total meat per 1000 kcal with full-fat dairy, in fully adjusted models, suggested a trend (at P < 0.10) of lowering 20-year T2D risk (OR 0.38, 95%CI [0.14, 1.05]); similarly, substitution of one daily serving/1000 kcal of total meat with fermented dairy showed a trend of lowering T2D risk (OR 0.39, 95%CI [0.15, 1.07]). Substituting red meat with full-fat dairy was not associated with T2D risk (OR per one daily serving/1000 kcal = 0.37, 95%CI [0.11, 1.19]); similarly, substitutions with low-fat, fermented dairy or white meat showed not significant associations with T2D risk. Substituting total and red/processed meat with full-fat or fermented dairy products in modeled analyses indicated potentially favorable, though largely non-significant, associations with long-term risk of T2D.

KPC-producing Gram-negative pathogens have disseminated worldwide and cause infections of various organs and systems. Given the limited therapeutic options for such infections, trimethoprim-sulfamethoxazole may be a consideration. We evaluated the available in vitro and clinical data on trimethoprim-sulfamethoxazole for treating patients with infections caused by KPC-producing pathogens. Five resources (Embase, Google Scholar, Scopus, PubMed, and Web of Science) were used for identifying relevant studies. In total, 12 in vitro studies were included. These studies demonstrated that the susceptibility of KPC-producing pathogens to trimethoprim-sulfamethoxazole ranged from 7 to 100% (> 70% in 7/12 studies), and the minimum inhibitory concentration (MIC) ranged from ≤ 0.25 (in 2 studies) to > 32 (in 2 studies) mg/L. Additionally, a prospective cohort study evaluated 14 patients who received trimethoprim-sulfamethoxazole to treat infections caused by KPC-producing bacteria. Of those, 13 out of 14 (93%) patients achieved a clinical cure. Clinical published data assessing trimethoprim-sulfamethoxazole's effectiveness for treating infections due to KPC-producing Gram-negative pathogens are limited. While data from in vitro studies suggest the consideration of trimethoprim-sulfamethoxazole when pathogens are susceptible, more clinical evidence is needed to use the drug safely in this population.

Abstract Background and Aims Acute kidney injury (AKI) is a possible immune related adverse event (IRAE) of immunotherapy on cancer patients. Rechallenging with immune checkpoint inhibitors (ICIs) after acute kidney injury is a complex clinical decision with potential risks and benefits. Current data on the timing and the outcomes of rechallenge following AKI are sparse, but the potential benefits of continued ICI therapy may outweigh the risks of rechallenge, especially if there are limited alternative treatment options. Method We assessed the records of all patients from January 2020 to February 2024 that were treated with ICIs, developed biopsy proven kidney injury associated with immunotherapy and then after the resolution of kidney injury they were rechallenged with ICI. Results We included 7 patients, 5 males and 2 females, with mean age at the time of kidney biopsy 66 years, and median follow up time 13 months. The most common primary malignancy was non-small cell lung carcinoma (n = 6) and there was one case of renal cell carcinoma (n = 1). Most patients (n = 6) were treated with the PD-1 inhibitor pembrolizumab, and one patient received a combination of two checkpoint inhibitors ipilimumab and nivolumab. Four patients were also treated with chemotherapy apart from ICI, and one also received targeted therapy (axitinib). Six patients were presented with AKI [AKI stage 2 KDIGO (n = 4), AKI stage 3 (n = 2)] and one patient with severe nephrotic syndrome. The median time to developing kidney injury from immunotherapy initiation was 13 months. Five patients also developed extrarenal immune related adverse events (IRAEs) during the follow-up time. Dermatitis (n = 3) and pneumonitis (n = 2) were the most common followed by hepatitis (n = 1) and colitis (n = 1). Renal biopsy showed acute interstitial nephritis (AIN) in 2 patients, acute tubular injury (ATI) in 2 patients, mixed ATI/AIN in one patient, ATI with diabetic nephropathy in one patient and membranous nephropathy (MN) with a lupus-like pattern in immunofluorescence in the patient with nephrotic syndrome. All patients received corticosteroids (prednisone 1 mg/kg) empirically. Prednisone was withdrawn in patients with ATI and DN/ATI. Immunotherapy was temporarily withheld. All patients experienced recovery of kidney function 2 months after the initiation of prednisone (among them the patient with DN/ATI who required renal replacement therapy at the time of biopsy) and the patient with nephrotic syndrome experienced partial remission of proteinuria. After rechallenging, five patients continued ICI treatment without recurrence of kidney injury until the end of follow-up time. The patient with DN/ATI developed severe pneumonitis one month after rechallenging that required reinitiation of corticosteroids and the patient with MN experienced proteinuria relapse, so immunotherapy was withdrawn in both patients. Conclusion Reintroducing immunotherapy after AKI is feasible in selected cases after timely diagnosis and therapy of renal injury, especially when there is lack of alternative oncological treatment options and it requires close collaboration among nephrologists and oncologists to continue ICI therapy while safeguarding renal health.

The care of patients with brain tumors is a complex task that requires quality standards and quality assurance indicators. In the present study, several quality indicators were evaluated in routine clinical care. The EORTC Brain Tumor Group (BTG) developed quality indicators from published guidelines and tested them in 19 BTG sites across Europe. Each site extracted data from the files of 20 randomly selected glioblastoma patients diagnosed in 2018. Associations between quality indicators, site characteristics and median overall survival (mOS) were examined. A total of 364 patient files were evaluated at 19 sites. Excellent compliance was observed in the documentation of neuropathology report with isocitrate dehydrogenase (IDH) status (92.0%), O6 -methylguanine DNA methyltransferase promoter methylation (MGMT) status (78.0%), multidisciplinary case discussion (95.3 %), extent of resection (87.1%), and radiotherapy details (96.9%) as well as consent to chemotherapy (75.5%). Performance was not as good for early postoperative MRI (67.2%), psycho-oncological care (40.5%), avoiding antineoplastic therapy in the last weeks of life (63.1%) and early referral to palliative services (23.5%). Timely start of radiotherapy (P = .0153), the presence of a radiotherapy report in the medical record (P = .0077), and patient education on oral chemotherapy (P = .0002) were positively associated with mOS, while early referral to palliative care was associated with shorter mOS (P < .0001). The quality indicators tested in this research project performed with some variability between sites. Significant associations between individual quality indicators and mOS were observed. The proposed quality indicators should be validated prospectively.