Semmelweis University Research Articles

Hypersensitivity reactions amongst Hungarian Patients with Hereditary Angioedema due to C1-Inhibitor Deficiency

BackgroundIn hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE), bradykinin-mediated submucosal and/or subcutaneous angioedema dominates the clinical picture. The deficiency of C1-inhibitor can lead to the over-activation of the complement system. Complement plays an important role in all types of hypersensitivity reactions. On the other hand, during the degranulation of mast cells, heparin is also released amongst other substances. Heparin can activate the plasma kinin-kallikrein system, leading to bradykinin generation. These observations suggest a possible connection between C1-INH-HAE and mast cell-mediated hypersensitivity reactions. ObjectiveTo assess the occurrence of hypersensitivity reactions in the Hungarian C1-INH-HAE population. MethodsPatients filled out a questionnaire of 112 questions, either online or on paper. The questions were about hypersensitivity and C1-INH-HAE symptoms, the relation between these 2, general health, and demographic data. The study protocol was approved by the institutional review board of Semmelweis University, Budapest, and informed consent was obtained from the participants. ResultsOne hundred and six patients (64 female, 42 male, median age 46 years) responded, with 63.2% having hypersensitivity. Hypersensitivity was provoked by pollen in 25.5% of patients, by contact sensitivity in 22.6%, by food in 21.7%, by insect sting in 19.8%, by pet in 15.1%, by drug in 14.2%, by dust mite in 5.7%, and by mold in 1.9%. In 11 patients, hypersensitivity symptoms appeared after the diagnosis of C1-INH-HAE. Six hypersensitive patients experienced improvement in their symptoms; 42 remained the same, but none experienced worsening after the diagnosis of C1-INH-HAE. In 7.8% of the hypersensitive patients, a C1-INH-HAE attack worsened the hypersensitivity symptoms, while 15.7% of the hypersensitive patients experienced a C1-INH-HAE attack provoked by contact with the provoking factor. ConclusionWhile 63.2% of our C1-INH-HAE patients have reported hypersensitivity symptoms, Eurostat's latest data puts the prevalence of self-reported allergies in Hungary at 19.3%. Since in our experience most Hungarian patients report hypersensitivity reactions as allergies, this may support a possible connection between the 2 diseases, but further molecular studies are needed.

The impact of the coronavirus pandemic on the mental health of critical care workers

The coronavirus pandemic has focused attention on the importance of critical care and highlighted the shortage of critical care specialists. Due to increasing workloads and high mortality rates, healthcare professionals were exposed to higher levels of physical and psychological stress during the pandemic than before. Our study investigated the effects of the coronavirus outbreak on the emotional, mental and moral stress of intensive care professionals. Our workgroup performed paper-based surveys among caregivers in the Department of Anaesthesiology and Intensive Therapy at Semmelweis University. The first survey was conducted at the start of the pandemic in 2020, the second survey was conducted after the third wave in 2021. We applied validated questionnaires (Professional Quality of Life, Demoralization Scale, Perceived Stress Scale, Impact of Event Scale, and Posttraumatic Growth Inventory), collected demographic data and information on lifestyle, recreation, dietary habits, and accepting psychological support. The number and demographic characteristics of the participants in the two studies are different, reflecting the changes in the workforce during the pandemic. Our results revealed no differences between the working and socio-demographic groups before the outbreak, however, one year later, nurses scored significantly higher on all negative psychological scales compared to other groups. Only a minority of the respondents had sought psychological support (9.5-12.7%), although more than a third of respondents reported the need for psychological support. Employees in new work positions showed significantly increased posttraumatic growth (2.91 ± 0.82 vs. 2.20 ± 1.06, p = 0.016). These findings demonstrate that nurses are the most strained workgroup during an uncertain and stressful period. The available mental support alone is not enough to help caregivers. Further steps are needed to improve the mental health of critical care workers. Orv Hetil. 2023; 164(42): 1646-1655.

Dermoscopic Patterns of Genodermatoses: A Comprehensive Analysis.

(1) Background: Genodermatoses are a clinically and genetically heterogenous group of inherited skin disorders. Diagnosing inherited skin diseases is a challenging task due to their rarity and diversity. Dermoscopy is a non-invasive, easily accessible, and rapid tool used in dermatology not only for diagnostic processes but also for monitoring therapeutic responses. Standardized terminologies have been published for its proper use, reproducibility, and comparability of dermoscopic terms. (2) Methods: Here, we aimed to investigate dermoscopic features in various genodermatoses by conducting a systematic review and comparing its results to our own findings, data of patients diagnosed with genodermatoses at the Department of Dermatology, Venereology and Dermatooncology, Semmelweis University. (3) Results: Our systematic search provided a total of 471 articles, of which 83 reported both descriptive and metaphoric dermoscopic terminologies of 14 genodermatoses. The literature data were then compared to the data of 119 patients with 14 genodermatoses diagnosed in our department. (4) Conclusion: Dermoscopy is a valuable tool in the diagnosis of genodermatoses, especially when symptoms are mild. To enable the use of dermoscopy as an auxiliary diagnostic method, existing standardized terminologies should be extended to more genodermatoses.

The effect of COVID-19 vaccination status on all-cause mortality in patients hospitalised with COVID-19 in Hungary during the delta wave of the pandemic.

The high mortality of patients with coronavirus disease 2019 (COVID-19) is effectively reduced by vaccination. However, the effect of vaccination on mortality among hospitalised patients is under-researched. Thus, we investigated the effect of a full primary or an additional booster vaccination on in-hospital mortality among patients hospitalised with COVID-19 during the delta wave of the pandemic. This retrospective cohort included all patients (n = 430) admitted with COVID-19 at Semmelweis University Department of Medicine and Oncology in 01/OCT/2021-15/DEC/2021. Logistic regression models were built with COVID-19-associated in-hospital/30day-mortality as outcome with hierarchical entry of predictors of vaccination, vaccination status, measures of disease severity, and chronic comorbidities. Deceased COVID-19 patients were older and presented more frequently with cardiac complications, chronic kidney disease, and active malignancy, as well as higher levels of inflammatory markers, serum creatinine, and lower albumin compared to surviving patients (all p < 0.05). However, the rates of vaccination were similar (52-55%) in both groups. Based on the fully adjusted model, there was a linear decrease of mortality from no/incomplete vaccination (ref) through full primary (OR 0.69, 95% CI: 0.39-1.23) to booster vaccination (OR 0.31, 95% CI 0.13-0.72, p = 0.006). Although unadjusted mortality was similar among vaccinated and unvaccinated patients, this was explained by differences in comorbidities and disease severity. In adjusted models, a full primary and especially a booster vaccination improved survival of patients hospitalised with COVID-19 during the delta wave of the pandemic. Our findings may improve the quality of patient provider discussions at the time of admission.

P04.10.A ASSESSMENT OF VDR STATUS BY IMMUNOHISTOCHEMISTRY IN CHILDHOOD MALIGNANCIES - VDR EXPRESSION PATTERN OF CNS TUMORS

Abstract BACKGROUND Childhood cancers, including CNS tumors, the second most prevalent entities after hematological malignancies cannot generally be prevented or identified through screening, the disease is often diagnosed at advanced stages, and this obviously affects patient outcomes negatively. There is an urgent need for identifying prognostic and therapeutic biomarkers. Our previous work has shown a correlation between lower vitamin D levels in children with cancer and adverse prognosis. VDR expression in childhood solid tumors has been linked to tumor characteristics and patient survival only in few studies, moreover literature found that VDR plays a role in the development of the central nervous system. METHODS For this study, 177 children with solid tumors were selected whose biopsies and tumor tissue formalin-fixed, paraffin-embedded tissue blocks were available for immunohistochemical (IHC) analysis at Semmelweis University, Budapest (Hungary). To investigate the association between the presence of VDR in the tumor tissue and outcome, tumor samples and the survival dataset of 110 children were available. RESULTS We found that minor VDR expression was associated with a significantly less favorable prognosis (p = 0.0061) in the examined childhood solid tumors. The rate of VDR expression differed significantly between tumor types (p &amp;lt;0.0001). In case of CNS tumors pathological observations on VDR expression characteristics partly not correlated with previous literature. In some ependymoma samples an utterly novel VDR pattern was observed. CONCLUSION In conclusion, VDR expression measured by IHC staining is inversely associated with aggressive characteristics in different childhood cancers. The downregulation of VDR expression in more aggressive childhood cancers suggests that functional vitamin D activity may slow or block cancer progression. The presence of VDR may have prognostic and therapeutic implications for CNS malignancies. Knowledge of the VDR status in childhood solid tumors provides clinicians with a valuable biomarker and based on this, additional therapy (vitamin D, and analogs) to use alongside conventional first-line oncotherapy.

"Hidden treasures" of Semmelweis University's buildings 2

"Hidden treasures" of Semmelweis University's buildings 2

Topological data analysis to identify cardiac resynchronization therapy patients exhibiting benefit from an implantable cardioverter-defibrillator

BackgroundCurrent guidelines recommend considering multiple factors while deciding between cardiac resynchronization therapy with a defibrillator (CRT-D) or a pacemaker (CRT-P). Nevertheless, it is still challenging to pinpoint those candidates who will benefit from choosing a CRT-D device in terms of survival.ObjectiveWe aimed to use topological data analysis (TDA) to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P.MethodsWe included 2603 patients who underwent CRT-D (54%) or CRT-P (46%) implantation at Semmelweis University between 2000 and 2018. The primary endpoint was all-cause mortality. We applied TDA to create a patient similarity network using 25 clinical features. Then, we identified multiple phenogroups in the generated network and compared the groups’ clinical characteristics and survival.ResultsFive- and 10-year mortality were 43 (40–46)% and 71 (67–74)% in patients with CRT-D and 48 (45–50)% and 71 (68–74)% in those with CRT-P, respectively. TDA created a circular network in which we could delineate five phenogroups showing distinct patterns of clinical characteristics and outcomes. Three phenogroups (1, 2, and 3) included almost exclusively patients with non-ischemic etiology, whereas the other two phenogroups (4 and 5) predominantly comprised ischemic patients. Interestingly, only in phenogroups 2 and 5 were CRT-D associated with better survival than CRT-P (adjusted hazard ratio 0.61 [0.47–0.80], p < 0.001 and adjusted hazard ratio 0.84 [0.71–0.99], p = 0.033, respectively).ConclusionsBy simultaneously evaluating various clinical features, TDA may identify patients with either ischemic or non-ischemic etiology who will most likely benefit from the implantation of a CRT-D instead of a CRT-P.Graphical abstractTopological data analysis to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P. AF atrial fibrillation, CRT cardiac resynchronization therapy, CRT-D cardiac resynchronization therapy defibrillator, CRT-P cardiac resynchronization therapy pacemaker, DM diabetes mellitus, HTN hypertension, LBBB left bundle branch block, LVEF left ventricular ejection fraction, MDS multidimensional scaling, MRA mineralocorticoid receptor antagonist, NYHA New York Heart Association

Management of Odontogenic Sinusitis: Results with Single-Step FESS and Dentoalveolar Surgery.

Odontogenic sinusitis (OS) is a well-known and important border of specialties in otorhinolaryngology and dentoalveolar surgery. Odontogenic sinusitis can develop due to iatrogenic harm or odontogenic infection. The gold standard diagnostic method is clinical and radiological-CBCT (cone beam computed tomography)-examination. The treatment of this condition requires collaboration between ENT and dentoalveolar surgery specialists and can be non-surgical or surgical based on staging. This paper aims to share the results of our clinical study whereby complex therapy was administered by a dentoalveolar surgeon and an otorhinolaryngologist in cooperation. We conducted a retrospective study comprising 111 OS patients who underwent complex therapy between 2016 and 2023 at Semmelweis University, Budapest, Hungary. All patients were treated with concurrent FESS (functional endoscopic sinus surgery) and dentoalveolar surgery. Follow-up was based on symptoms, clinical examination and CBCT imaging. Of the 111 patients, 107 were successfully treated with concurrent FESS and dentoalveolar surgery, and only 4 had further symptoms following the complex therapy and needed retreatment. The complex, single-session therapy involving FESS and oral surgery is an effective treatment method, which is less invasive and associated with fewer complications compared to previous interventions, such as the Luc-Caldwell procedure.

Patient delay and its clinical significance among head and neck cancer patients in Hungary.

Introduction: Head and neck cancers represent a major health problem in Hungary. With their high incidence and mortality rates, Hungary is one of the world leaders in these indicators. The length of patient delay, defined as time from onset of symptoms to first medical consultation, is unknown in Hungarian patients with head and neck cancer. We aimed to use a representative sample of the Hungarian head and neck cancer patient population to determine patient delay according to disease localization and stage and to identify correlations with other clinical parameters. Methods: In our retrospective study, we reviewed patient documentation. For the inclusion, the patients had to be diagnosed with malignant tumors of the oral cavity, oropharynx, hypopharynx or larynx at the Department Head and Neck Surgery of Semmelweis University between 2012 and 2017. Results: We identified 236 patients who met the inclusion criteria. The median delay was 9.5weeks (range 0-209weeks) and the mean delay of patients was 17.57weeks (SD 23.67). There was a significant difference in patient delay data by location. Among glottic cancers, the most common diagnosis was an early stage (67%), compared with other localizations, including most commonly the oropharynx (81%) and hypopharynx (80%), where a locoregionally advanced stage was more frequent. Discussion: Compared to data from different countries, the delay of Hungarian patients with head and neck cancer is significantly longer, which may contribute to the high mortality in Hungary. Screening and patient education in high-risk groups could contribute to earlier diagnosis and thus improve prognosis.

The most common gastrointestinal alterations in patients with post-COVID syndrome

Post-COVID syndrome may affect the gastrointestinal tract. However, risk factors of post-COVID syndrome are still unknown. We aimed to identify the most common gastrointestinal symptoms, abnormal laboratory findings and risk factors relevant to post-COVID syndrome. In this retrospective study, we included 79 patients admitted to Semmelweis University Department of Surgery, Transplantation and Gastroenterology between October 2020 and September 2022. We investigated clinical data, laboratory findings and determined the major risk factors. Most of the patients were women (46/79), their mean age was 47.6 years and patients were overweight (BMI: 26.3 kg/m2). The most common comorbidities were cardiovascular diseases (21/79), hypertension (20/79), diabetes (11/79) and malignant diseases (9/79). Typical indications for gastroscopy were dyspepsia (16/79) and epigastric pain (10/79). The most common indications for colonoscopy were diarrhea (29/79) and weight loss (28/79). Among abnormal laboratory findings, liver enzymes levels (GOT: 83.5 U/L, GPT: 85 U/L, GGT: 70 U/L) and ferritin (351.5 ng/mL) were higher in post-COVID patients. Typical conditions diagnosed by gastroscopy, colonoscopy and abdominal ultrasound were gastroesophageal reflux disease (11/26), irritable bowel syndrome (2/19) and diffuse hepatic lesions, respectively. The number of unvaccinated patients was higher compared to those receiving any COVID-19 vaccines (58% vs. 29%). Of the vaccinated patients, 12 patients received mRNA vaccines (10 Pfizer-BioNTech, 2 Moderna) and 6 patients received viral vector vaccines (2 AstraZeneca, 4 Sputnik V). We identified female gender, obesity, cardiovascular diseases, cancer, hypertension and diabetes as major risk factors of post-COVID syndrome. Vaccinated status may prevent post-COVID gastrointestinal symptoms. Orv Hetil. 2023; 164(31): 1206-1212.

Thyroid disturbances after COVID-19 and the effect of vaccination in children: a prospective tri-center registry analysis

Rapidly evolving clinical data suggest that the novel coronavirus (SARS-CoV-2) and vaccination against COVID-19 might be associated with thyroid disturbances. However, studies remain limited among the pediatric population. Our aim was to assess the prevalence and permanence of thyroid autoimmunity (TA) and dysfunction in children after an acute infection and its potential association with vaccination. A prospective, multicenter registry analysis was performed among 458 children (mean age: 12.4 ± 3,8 years, 45.4% male) with preceding COVID-19. Patient inclusion lasted from 24th March, 2021 to 23rd March, 2022 at three pediatric outpatient facilities at Semmelweis University, Budapest. Primary outcomes were the rate of thyroid disturbances assessed by laboratory parameters (thyroid function tests, antithyroglobulin [ATG] and anti-thyroid peroxidase [ATPO] antibodies) and thyroid ultrasound. TA rate among vaccinated and unvaccinated children was determined. Children with newly diagnosed thyroid alterations were followed up for 12.7 ± 4.3 months. Six children had previous thyroid disease. Out of 452 children, 30 cases (6.6%) of newly diagnosed TA (six of them had abnormal thyroid-stimulating hormone [TSH] levels) and eight cases (1.8%) of isolated TSH elevation were observed. Ultrasound-proven autoimmune thyroiditis (AIT) was 4.0%. No association was found between COVID-19 vaccination and thyroid autoimmunity (χ2(1,N = 452) = 0.138, p = 0.815). Among children with TA, 73.3% had long-lasting alterations. Conclusion: Vaccination had no effect on the prevalence of TA. Until further controlled studies state otherwise, children with preceding COVID-19 might benefit from thyroid screening.What is Known:• Numerous case reports implicate that coronavirus disease-2019 (COVID-19) and vaccination against SARS-CoV-2 can be responsible for thyroid disturbances.• Thyroid alterations discovered during acute COVID-19 tend to cease by time and only incidental thyroid autoimmunity (TA) is diagnosed after COVID-19. In adults, no increase in vaccine-related hyper- or hypothyroidism was found.What is New:• TA rate after COVID-19 vaccination among children was not increased. TA had no role in long COVID syndrome.• We discovered a considerable rate of TA (6.6%) and ultrasound-proven autoimmune thyroiditis (AIT) (4.0%) after SARS-CoV-2 infection, and the majority of these alterations remained positive after 6 months.

M-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study

Background In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. Objective The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. Methods A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. Results This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients’ acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients’ satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. Conclusions The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS. Trial Registration ClinicalTrials.gov NCT03064776; https://clinicaltrials.gov/ct2/show/record/NCT03064776 International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2017-021346

P-167 Bacterial contamination of embryo culture medium in conventional in vitro fertilisation versus ICSI

Abstract Study question Our aim is presenting a clinical case of pregnancy using intracytoplasmatic sperm injection with bacterial contamination of embryo culture after failed conventional in vitro fertilisation. Summary answer Intracytoplasmatic sperm injection (ICSI) can be an effective and safe method to prevent embryo culture infection in case of microbial contamination of semen. What is known already Contamination of embryo culture is rare, but can be detrimental. The most common sources are semen and follicular fluid. We currently have no standard protocols for monitoring biological fluids. Semen often contains bacteria even if hygiene rules for collection are followed. Most studies found no significant difference in the effectiveness of in vitro fertilisation treatment in the presence or absence of bacteriospermia. This can be explained by sperm preparation techniques, antibiotic content of culture media and use of ICSI. Most centres advise against contaminated embryo transfers, but some achieved pregnancy after removing the zona pellucida or using ICSI. Study design, size, duration This is a case report of two consecutive in vitro fertilisation - ICSI cycles at the Division of Assisted Reproduction, Department of Obstetrics and Gynecology, Semmelweis University, Budapest in 2022. Participants/materials, setting, methods First we performed conventional in vitro fertilisation in a couple with secondary infertility because of oligoasthenozoospermia. For the second time we suggested ICSI due to bacterial growth observed in the embryo culture medium. Microbiological analyses were carried out. We video-recorded the cytoplasmic infection of one oocyte following ICSI with time-lapse microscopy. Main results and the role of chance After conventional in vitro fertilisation we observed a proliferation of rods in the embryo culture medium. The control culture medium was sterile. The semen and infected embryo culture medium contained Escherichia coli and Staphylococcus hominis. The oocytes did not fertilize and degenerated. The husband was asymptomatic and did not have alteration in physical examination therefore he was not treated with antibiotics. In next cycle we performed ICSI. 2 of 14 oocytes fertilized normally and developed into high-quality blastocysts. One embryo was transferred resulting in live birth and one embryo was cryopreserved. We video-documented proliferation of bacteria in one fertilised oocyte but not in the others. Infected oocyte was removed from culture and its culture medium showed Escherichia coli and Cutibacterium acnes. Fungal culture and sexually transmitted diseases were negative. The semen only contained Escherichia coli. The cervix culture was negative. Escherichia coli was resistant to gentamicin contained in culture medium. Limitations, reasons for caution We only had one case of bacterial contamination in 30 years and therefore can not conclude to the routine use of ICSI if microbial infections of biological fluids are present. Wider implications of the findings ICSI can be offered to patients with bacterial contamination of semen and can help reducing the risk of infection of embryo culture. We can prevent the disadvantages of excessive antibiotic treatments. New guidelines are needed how to handle bacterial contamination of embryo culture media. Trial registration number not applicable

P-148 The importance of filopodia during early human embryonic development

Abstract Study question The aim of this study was to examine the relation between the presence of filopodia and the embryo viability in human in vitro fertilised embryos. Summary answer The presence of filopodia related to a faster blastocyst development, a better blastocyst quality and higher morphokinetic scores which indicates a higher embryo viability. What is known already Filopodia are involved in numerous cellular processes, for example cell migration, neuronal extension growth and during embryonic development. There is no uniform name to describe these cytoplasmic string structures in the literature. Beside the frequent presence in different cell functions, we have limited information about its function in human embryos. In the early 2000s, the occurrence of filopodia or cytoplasmic strings at the blastocyst stage was classified as a negative sign of embryo viability, but more recently, it has been described as a positive feature, however, the importance and clinical significance of this structure is still controversial. Study design, size, duration Evaluation of the morphokinetic data on the development of 208 embryos from 78 IVF cycles. Examination was carried out at the Division of Assisted Reproduction, Department of Obstetrics and Gynaecology, Semmelweis University, Budapest between December 2020 and March 2021. Participants/materials, setting, methods Embryos from both conventional IVF (cIVF) and intracytoplasmic sperm injection (ICSI) treatments were analysed and evaluated. The dynamics of embryo development, embryo morphology and morphokinetic scores generated by time-lapse system was compared between the embryos with filopodia (FP+) and embryos without filopodia- (FP-) groups. Main results and the role of chance 81.2% of the embryos had filopodia in blastocyst stage. Embryos created by cIVF had 77%, while embryos fertilised by ICSI had 86% of filopodia presence (p = 0.08). FP+ embryos developed in a greater number into a higher quality blastocyst (52.1% vs 20.5%, p = 0,02), their KIDScore was higher (6.1 ± 2.1 vs 4,7 ± 2,07, p &amp;lt; 0.001) and they showed a tendency of higher implantation rate (39.7% vs 14.3% p = 0.16) than the FP- group. The dynamic of the early embryo development was similar between the two groups, however, FP+ embryos reached blastocyst stage significantly earlier (tB: 103.9 hours vs. tB: 107.6 hours; p = 0.007). Based on our results, there was a higher number of embryos with filopodia than without, and the presence of it is not related to the fertilisation method. These embryos developed faster into a blastocyst stage, their morphokinetic parameters were better. KIDScore and iDAScore embryo evaluation systems also recommend in a greater number the FP+ blastocysts for ET. We could also observe vesicle like transport along the filopodia, which leads us to believe that there might be a molecular communication between the differentiating cell populations. Limitations, reasons for caution Due to the low number of cases, the higher implantation rate is not significant. Wider implications of the findings The examination of this feature improves our knowledge of the early embryonic development and may help us to make decisions about the embryos with higher implantation potential. Trial registration number Not applicable

Photon counting detector CT can identify mild coronary artery in-stent restenosis more reliably

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Cardiovascular Imaging Research Group, Medical Imaging Centre, Semmelweis University. Introduction The improved spatial resolution of photon-counting detector CT (PCD-CT) allows better image quality and less artefacts even in high-density structures, such as coronary artery stents. Purpose Our aim was to compare the prevalence of coronary artery in-stent restenosis using conventional CT and PCD-CT. Methods Our retrospective study included consecutive patients with coronary artery stents who underwent coronary CT angiography (CCTA) either with PCD-CT between January and December 2022 or with a 280-slice conventional CT scanner in 2019. The following categories were used: none, not severe, severe in-stent restenosis and stents with non-diagnostic image quality. Results Altogether 253 patients were included in our study (215 patients who underwent CCTA with a conventional CT and 38 patients who had PCD-CT examination). The mean age was 62.7±10.8 years and 46.8% were women. In-stent restenosis was detected significantly more frequently in case of PCD-CT examination, as compared to conventional CCTA (47.7% and 27.4%, respectively; p = 0.023). Among the 15 patients who underwent ultra-high resolution PCD-CT examination, only one (6.7%) had a non-diagnostic image quality for the assessment of in-stent restenosis, while 34 cases (15.8%) were non-diagnostic in the conventional CCTA group. Conclusions The better image quality provided by PCD-CT notably helps the evaluation of in-stent restenosis and can therefore contribute to the identification of mild in-stent restenosis. Moreover, the number of non-diagnostic CCTA scans can be decreased by using ultra-high resolution technique.

#3785 PROPOSAL OF A NOVEL RISK PREDICTION SCORE FOR MAJOR ADVERSE CARDIOVASCULAR EVENTS IN LUPUS NEPHRITIS

Abstract Background and Aims Patients with systemic lupus erythematosus have an increased risk of cardiovascular diseases (CVD) vastly contributing to morbidity and mortality. Besides traditional risk factors, lupus-related factors also contribute to the overall risk. Our major objective was to identify both traditional and non-traditional factors that could aid the prediction of CVD risk and major adverse cardiovascular events (MACE) in this population. MACE was defined as the composite of nonfatal myocardial infarction, hospitalization due to heart failure, coronary revascularization, stroke, and cardiovascular death. We also aimed to create a model that could be applied after a prompt assessment of lupus nephritis patients to estimate the long-term CVD risk. Method We conducted a single-center retrospective analysis on lupus nephritis patients. Demographic variables, cardiovascular events, clinical and histological data were collected from patients who underwent kidney biopsy between 2005 and 2020 (Figure 1). Chi-square, Mann-Whitney U-test, and logistic regression analyses were performed to investigate risk factors for MACE (IBM SPSS Statistics v28). Receiver Operating Characteristic (ROC) curve was used to determine optimal cut-off values. The study was approved by the Semmelweis University Regional and Institutional Committee of Science and Research Ethics (SE RKEB 225/2018). Results 91 patients were enrolled in this period. The mean age was 37.3±12.3 years, 86% females, and the mean follow-up time was 62±48 months. Fourteen patients (15.4%) suffered at least one MACE, of which 13 (14.3%) occurred after diagnosing lupus and 8 (8.8%) after the biopsy. Two patients deceased of a cardiovascular event. Out of the traditional risk factors, increased age (35.8±11.1 vs 45.5±15.1 years, p = 0.012) entailed a higher occurrence of MACE. Complete white blood cell (3.54±0.41 vs 3.25±0.87 Giga/liter, p = 0.026) and neutrophil count (2.85±0.33 vs 3.11±0.83 Giga/liter, p = 0.001) were higher, while diastolic blood pressure was lower (89.5±10.96 vs 78.43±6.9 mmHg, p&amp;lt;0.001) at the time of the biopsy in patients with MACE complication. Age, neutrophil count, and diastolic blood pressure were proven to be independent predictors of MACE (Table 1). Based on these observations, we proposed a new model (CANDE: Cardiovascular risk –based on Age, Neutrophil count, and Diastolic blood pressure– Estimation score) that is a stronger predictor of MACE and can be used to calculate MACE risk from the time of the biopsy in lupus nephritis patients (Figure 1). The higher the score was, the more often the MACE cases were present (Table 1). ROC curve analysis demonstrated that at 0.78 cut-off value the score predicts MACE occurrence at the time of the biopsy with a sensitivity of 0.75 and a specificity of 0.61. The analyses of MACE subgroups revealed that neutrophil-lymphocyte ratio was elevated in patients who were hospitalized because of heart failure (5.66±4.61 vs 9.68±6.46, p = 0.046), while neutrophil-thrombocyte ratio was higher in patients with coronary revascularization in their medical history (0.023±0.015 vs 0.06±0.028, p = 0.02). This also indicates the importance of neutrophils in CVD risk assessment. Conclusion Age, neutrophil count, and diastolic blood pressure are demonstrated to be independent risk factors of MACE in lupus nephritis. The score calculated from these parameters (CANDE) is a stronger predictor of MACE at the time of the biopsy. A larger cohort is needed to validate these promising results.

Comprehensive frailty assessment with multidimensional frailty domains as a predictor ofmortality among vascular and cardiac surgicalpatients.

The frailty concept has become a fundamental part of daily clinical practice. In this study our purpose was to create a risk estimation method with a comprehensive aspect of patients' preoperative frailty. In our prospective, observational study, patients were enrolled between September 2014 and August 2017 in the Department of Cardiac Surgery and Department of Vascular Surgery at Semmelweis University, Budapest, Hungary. A comprehensive frailty score was built from four main domains: biological, functional-nutritional, cognitive-psychological and sociological. Each domain contained numerous indicators. In addition, the EUROSCORE for cardiac patients and the Vascular POSSUM for vascular patients were calculated and adjusted for mortality. Data from 228 participants were included for statistical analysis. A total of 161 patients underwent vascular surgery, and 67 underwent cardiac surgery. The preoperatively estimated mortality was not significantly different (median: 2.700, IQR (interquartile range): 2.000-4.900 vs. 3.000, IQR: 1.140-6.000, P = 0.266). The comprehensive frailty index was significantly different (0.400 (0.358-0.467) vs. 0.348 (0.303-0.460), P = 0.001). Indeceased patients had elevated comprehensive frailty index (0.371 (0.316-0.445) vs. 0.423 (0.365-0.500), P < 0.001). In the multivariate Cox model an increased risk for mortality in quartiles 2, 3 and 4 compared with quartile 1 as a reference was found (AHR (95% CI): 1.974 (0.982-3.969), 2.306 (1.155-4.603), and 3.058 (1.556-6.010), respectively). The comprehensive frailty index developed in this study could be an important predictor of long-term mortality after vascular or cardiac surgery. Accurate frailty estimation could make the traditional risk scoring systems more accurate and reliable.

Sharing sensitive research data in the practice of personalised medicine

Fragmentation of health data and biomedical research data is a major obstacle for precision medicine based on data-driven decisions. The development of personalized medicine requires the efficient exploitation of health data resources that are extraordinary in size and complexity, but highly fragmented, as well as technologies that enable data sharing across institutions and even borders. Biobanks are both sample archives and data integration centers. The analysis of large biobank data warehouses in federated datasets promises to yield conclusions with higher statistical power. A prerequisite for data sharing is harmonization, i.e., the mapping of the unique clinical and molecular characteristics of samples into a unified data model and standard codes. These databases, which are aligned to a common schema, then make healthcare information available for privacy-preserving federated data sharing and learning. The re-evaluation of sensitive health data is inconceivable without the protection of privacy, the legal and conceptual framework for which is set out in the GDPR (General Data Protection Regulation) and the FAIR (findable, accessible, interoperable, reusable) principles. For biobanks in Europe, the BBMRI-ERIC (Biobanking and Biomolecular Research Infrastructure - European Research Infrastructure Consortium) research infrastructure develops common guidelines, which the Hungarian BBMRI Node joined in 2021. As the first step, a federation of biobanks can connect fragmented datasets, providing high-quality data sets motivated by multiple research goals. Extending the approach to real-word data could also allow for higher level evaluation of data generated in the real world of patient care, and thus take the evidence generated in clinical trials within a rigorous framework to a new level. In this publication, we present the potential of federated data sharing in the context of the Semmelweis University Biobanks joint project. Orv Hetil. 2023; 164(21): 811-819.

Parasomnia patients and risk of injury, a 16-years clinical study

PurposeWe aimed to analyze the risk of injury in different age and gender groups experiencing parasomnias. MethodsWe collected clinical data of adult parasomnia patients seen between 2007 and 2023, from the database of the Institute of Behavioral Sciences Semmelweis University in Budapest. We classified them by age (19–39 and ≥40 years) and biological sex groups. Binary logistic regression was calculated to find the association between alcohol and tobacco use and dangerous activities, using odds ratios (ORs) at 95% CIs. ResultsOut of 45 parasomnia patients (64.5% female, and 73.4% in the 19–39 years age group), 69% experienced somnambulism and 20% had nightmare disorder. Dangerous behaviors and injuries related to sleepwalking included shoulder dislocation (6.3%), injury from breaking objects (25%), and sex without consent (12.5%). In our results, alcohol use was associated with parasomnia events 21-fold in males compared to females (p<0.05). Dangerous behavior was significantly higher in males and younger, than in older adults (OR: 4.91 and 4.61, p<0.05). ConclusionParasomnias require particular care due to the risk of injury. The remarkably high odds of dangerous sleepwalking activities in males and young adults require further attention and explanation.

Tumour-stroma ratio (TSR) in breast cancer: comparison of scoring core biopsies versus resection specimens

PurposeTumour-stroma ratio (TSR) is an important prognostic and predictive factor in several tumour types. The aim of this study is to determine whether TSR evaluated in breast cancer core biopsies is representative of the whole tumour.MethodDifferent TSR scoring methods, their reproducibility, and the association of TSR with clinicopathological characteristics were investigated in 178 breast carcinoma core biopsies and corresponding resection specimens. TSR was assessed by two trained scientists on the most representative H&E-stained digitised slides. Patients were treated primarily with surgery between 2010 and 2021 at Semmelweis University, Budapest.ResultsNinety-one percent of the tumours were hormone receptor (HR)-positive (luminal-like). Interobserver agreement was highest using 100 × magnification (κcore = 0.906, κresection specimen = 0.882). The agreement between TSR of core biopsies and resection specimens of the same patients was moderate (κ = 0.514). Differences between the two types of samples were most frequent in cases with TSR scores close to the 50% cut-off point. TSR was strongly correlated with age at diagnosis, pT category, histological type, histological grade, and surrogate molecular subtype. A tendency was identified for more recurrences among stroma-high (SH) tumours (p = 0.07). Significant correlation was detected between the TSR and tumour recurrence in grade 1 HR-positive breast cancer cases (p = 0.03).ConclusionsTSR is easy to determine and reproducible on both core biopsies and in resection specimens and is associated with several clinicopathological characteristics of breast cancer. TSR scored on core biopsies is moderately representative for the whole tumour.