Vilnius University Hospital Santaros Klinikos Research Articles

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Gastric Cancer Peritoneal Metastases: Results from the Lithuanian PIPAC Program.

Peritoneal metastases (PM) of gastric cancer (GC) are considered a terminal condition, with reported median survival ranging from 2 to 9 months. Standard treatment typically involves systemic chemotherapy alone or combined with targeted therapy or immunotherapy, though efficacy is limited. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged as a novel technique for treating GC PM, although it remains an experimental treatment under investigation. This study aimed to summarize the outcomes of GC PM treatment with PIPAC from the Lithuanian PIPAC program. All patients who underwent PIPAC for GC PM at Vilnius University Hospital Santaros Klinikos between 2015 and 2022 were included in this retrospective study. The safety of PIPAC was assessed by postoperative complications according to the Clavien-Dindo classification. Efficacy was evaluated based on the peritoneal carcinomatosis index (PCI), ascites dynamics throughout the treatment, and long-term outcomes. In total, 32 patients underwent 71 PIPAC procedures. Intraoperative and postoperative morbidity related to PIPAC occurred after three (4.2%) procedures. Following PIPAC, there was a tendency towards a decrease in median PCI from 10 (Q1 3; Q3 13) to 7 (Q1 2; Q3 12), p = 0.75, and a decrease in median ascites volume from 1300 mL (Q1 500; Q3 3600) at the first PIPAC to 700 mL (Q1 250; Q3 4750) at the last PIPAC, p = 0.56; however, these differences were not statistically significant. The median overall survival after PM diagnosis was 12.5 months (95% CI 10-17), and the median survival after the first PIPAC procedure was 5 months (95% CI 4-10). PIPAC is a safe and feasible treatment option for GC PM; however, well-designed prospective studies are needed to fully assess its efficacy.

Evaluation of the performance of digital x-ray systems in pelvis radiography

The aim of this study was to investigate the performance of eight digital radiography systems and to optimise the dose-image quality relationship for digital pelvis radiography. The study involved eight digital radiography systems used for general examinations at Vilnius University Hospital Santaros Klinikos. An anthropomorphic pelvic phantom (CIRS, US) was used to simulate a patient undergoing clinical pelvis radiography. Dose quantities entrance surface dose, dose area product (DAP) and exposure parameters (kVp, mA, mAs) were measured and the effects on the images were evaluated, considering physical contrast to noise ratio (CNR) and observer-based evaluations as image quality metrics. Increasing the tube voltage by 5 kVp from standard protocol led to a reduction in radiation dose (DAP) by 12%–20% with a slight impact on image quality (CNR decreases by 2%–10%). There was an inter-observer variability in image rating across different equipment (kappa value between 0 and 0.3); however, both observers agreed that increasing kVp up to 85–90 kV had no effect on perceived image quality. The results indicate that optimisation strategies should be tailored specifically for each x-ray system since significant performance differences and wide variations in radiation dose exist across various digital radiography systems used in clinical settings. The use of high kVp can be used for dose optimisation in digital pelvis radiography without compromising image diagnostic accuracy.

Comorbidities, Clinical Presentation, Subtypes, and Treatment of HS Patients in Lithuania.

Background: Hidradenitis suppurativa (HS) is a persistent, recurring skin inflammatory condition linked to various comorbidities. Management involves antibiotics, hormone therapy, immune-modulating drugs, surgery, and treatment of comorbidities. The objectives of the study were to assess the comorbidities, clinical presentation subtypes, and applied treatment of patients with HS. Methods: Patients with HS who visited the Centre of Dermatovenereology at Vilnius University Hospital Santaros Klinikos in Lithuania underwent evaluation based on the guidelines of the European Hidradenitis Suppurativa Foundation Registry questionnaire. Results: The study included 49 patients, and 61.22% (n = 30) had comorbidities. A strong positive correlation was found between a family history of inflammatory diseases (69.38% (n = 34)) and the severity of HS according to Hurley stage (r = 0.71 p < 0.05). A statistically significant correlation (r = 0.944, p = 0.02) was found between metabolic comorbidities and Hurley stage. Patients on biologic treatment had a mean IHS4 of 7.38 at the beginning of treatment and 3.22 at follow-up (p < 0.05). For patients not on biologics, the initial IHS4 score was 6.21 and 5.42 at follow-up (p > 0.05). Conclusions: A family history of inflammatory diseases and metabolic comorbidities showed a strong correlation with HS severity. Treatment with biologics showed significant improvement in HS scores compared to systemic antibiotics.

BIOM-01. CARBONIC ANHYDRASE IX INTERPLAY WITH LOCAL AND SYSTEMIC IMMUNE RESPONSE IN PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Brain tumors (BT) remain the leading cause of death among childhood cancers. There is an urgent need to identify novel targets in these patients. BT progression depends on the adaptive responses to hypoxia. Carbonic anhydrase IX (CAIX) helps cancer cells survive in a hypoxic environment and can be potentially as a therapeutic target. The role of CAIX in the interplay between the tumor and immune cells requires in-depth investigation to design effective therapies. METHODS Fresh BT, blood, and intraoperative cerebrospinal fluid (iCSF) samples were collected prospectively from pediatric patients, who underwent brain tumor surgery at Vilnius University Hospital Santaros Klinikos from March 2022 to December 2023. All tumor types were included. Immunohistochemistry (IHC) and flow cytometry (FC) were performed to analyze the expression of CAIX and selected immunological markers in the fresh tumor, iCSF and peripheral blood mononuclear cells (PBMCs). Soluble CAIX content in serum and iCSF was assessed by ELISA. In addition, a retrospective analysis of previously diagnosed pediatric glioma specimens was performed by IHC. RESULTS Twelve patients with heterogeneous BT types have been enrolled prospectively and 17 patients with glioma were reviewed retrospectively. Glioma accounted for 72% (21/29) of all samples. IHC showed that 57% of gliomas were positive for CAIX as well as a moderate correlation between the CAIX score and the expression of CD44, CD206, and CCR2 markers. PD-1/PD-L1 expression was negligible. In the prospective cohort, 83% (10/12) of BT tissue was positive for CAIX by IHC and FC. Soluble CAIX was detectable in 40% of iCSF samples, but not in serum. We found a correlation trend of CAIX expression in the fresh tumor cells and iCSF with increased CCR2 expression on CD45+ PBMCs. CONCLUSIONS This interim analysis showed a correlation between CAIX tumor expression and immune biomarkers, prompting further investigation by enrolling more patients.

Observation Safely Reduces the Use of the Computerized Tomography in Medium-to-Low-Risk Patients with Suspected Acute Appendicitis: Results of a Randomized Controlled Trial.

Objectives-The objective was to compare the effectiveness of observation in standard-of-care computed tomography (CT) in adult patients with suspected acute appendicitis (AA). Methods-Patients with clinically suspected AA and inconclusive diagnosis after primary clinical examination, laboratory examination, and transabdominal ultrasound (TUS) were eligible for the study, and they were randomized (1:1) to parallel groups: observation-group patients were observed for 8-12 h and then, repeated clinical and laboratory examinations and TUS were performed; CT group (control group) patients underwent abdominopelvic CT scan. The study utilized Statistical Analysis System 9.2 for data analysis, including tests, logistic regression, ROC analysis, and significance evaluation. Patients were enrolled in the study at Vilnius University Hospital Santaros Klinikos in Lithuania between December 2018 and June 2021. Results-A total of 160 patients (59 men, 101 women), with a mean age of 33.7 ± 14.71, were included, with 80 patients in each group. Observation resulted in a reduced likelihood of a CT scan compared with the CT group (36.3% vs. 100% p < 0.05). One diagnostic laparoscopy was performed in the observation group; there were no cases of negative appendectomy (NA) in the CT group. Both conditional CT and observation pathways resulted in high sensitivity and specificity (97.7% and 94.6% vs. 96.7% and 95.8%). Conclusions-Observation including the repeated evaluation of laboratory results and TUS significantly reduces the number of CT scans without increasing NA numbers or the number of complicated cases.

Carotid Plaques and Hypertension as Risk Factors for Cardiovascular Disease and All-Cause Mortality in Middle-Aged Adults.

Background/Objectives: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. We aim to investigate the synergistic effects of hypertension and carotid plaques on cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology Department of Vilnius University Hospital Santaros Klinikos between 2012 and 2021. The study recruited participants aged 40-65 who did not have overt cardiovascular disease (CVD) and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. Results: The participants were monitored for 4-10 years for CVD events and all-cause mortality. Among 6138 participants, 954 (16%) experienced CVD events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events or all-cause mortality. Conclusions: The risk of CVD events or all-cause mortality was not significantly increased by the combination of hypertension and carotid plaque. Cardiovascular events depend on the extent of atherosclerosis in the carotid arteries.

Deep learning‐based aggregate analysis to identify cut‐off points for decision‐making in pancreatic cancer detection

AbstractThis study addresses the problem of detecting pancreatic cancer by classifying computed tomography (CT) images into cancerous and non‐cancerous classes using the proposed deep learning‐based aggregate analysis framework. The application of deep learning, as a branch of machine learning and artificial intelligence, to specific medical challenges can lead to the early detection of diseases, thus accelerating the process towards timely and effective intervention. The concept of classification is to reasonably select an optimal cut‐off point, which is used as a threshold for evaluating the model results. The choice of this point is key to ensure efficient evaluation of the classification results, which directly affects the diagnostic accuracy. A significant aspect of this research is the incorporation of private CT images from Vilnius University Hospital Santaros Klinikos, combined with publicly available data sets. To investigate the capabilities of the deep learning‐based framework and to maximize pancreatic cancer diagnostic performance, experimental studies were carried out combining data from different sources. Classification accuracy metrics such as the Youden index, (0, 1)‐criterion, Matthew's correlation coefficient, the F1 score, LR+, LR−, balanced accuracy, and g‐mean were used to find the optimal cut‐off point in order to balance sensitivity and specificity. By carefully analyzing and comparing the obtained results, we aim to develop a reliable system that will not only improve the accuracy of pancreatic cancer detection but also have wider application in the early diagnosis of other malignancies.

Prevalence and trends of contact sensitization in patients with psoriasis in Lithuania

BackgroundPsoriasis and allergic contact dermatitis (ACD) are two very common dermatoses. The relationship between them has not yet been fully understood. Contact dermatitis can be an additional cause of epidermal disruption in psoriasis patients, resulting in poor management of the disease. ObjectiveTo analyze the tendencies of contact sensitization in a cohort of psoriasis patients with suspected ACD. MethodsPsoriasis patients (n=85) with suspected contact dermatitis underwent patch testing with European Baseline allergen series S-1000 in Vilnius University Hospital Santaros Klinikos Centre of Dermatovenereology from August 2020 to August 2021. Their results are presented in this study. ResultsThe patch test was positive in 43.5% (n=37) of patients. Contact sensitization was more prevalent in patients with mild psoriasis, as characterized by PASI scores ≤10, compared to those with moderate-to-severe psoriasis (p<0.05). Generalized psoriasis and nail involvement were more common among non-sensitized patients (p<0.05). Most common contact allergens among sensitized patients were nickel (II) sulphate, formaldehyde, and potassium dichromate. ConclusionAn inverse trend was observed between psoriasis severity and contact sensitization. Extended psoriatic involvement was uncommon in sensitized patients.

Belief in omens and superstitions among patients with chronic neurological disorders.

Chronic neurological disorders may affect various cognitive processes, including religiosity or superstitious belief. We investigated whether superstitious beliefs are equally prevalent in patients with Parkinson's disease (PD), people with epilepsy (PWE), patients with multiple sclerosis (MS) and healthy controls (HCs). From late 2014 to early 2023 we conducted a cross-sectional in-person anonymous paper-based survey at the tertiary clinic of Vilnius University Hospital Santaros Klinikos among outpatients and HCs by asking them to ascribe meaning or report belief for 27 culturally adapted statements (9 omens and 18 superstitions). The sum of items that a respondent believes in was labeled the superstition index (SI). The SI was compared between groups by means of the Kruskal-Wallis (H) test and negative binomial regression modeling. A two-step cluster analysis was performed to discern different subgroups based on answers to the items of the SI. There were 553 respondents who completed the questionnaire (183 PWE, 124 patients with PD, 133 with MS and 113 HCs). Complete SI scores were collected for 479 (86.6%) participants and they were lower in patients with PD (n = 96, Md = 1, IQR = 0-5.75) in comparison to those with epilepsy (n = 155, Md = 6, IQR = 1-14), MS (n = 120, Md = 4, IQR = 0-12) or HCs (n = 108, Md = 4.5, IQR = 1-10), H (3) = 26.780, p < 0.001. In a negative binomial regression model (n = 394, likelihood ratio χ2 = 35.178, p < 0.001), adjusted for sex, place of residence, income and education, female sex was the only characteristic associated with the SI (β = 0.423, OR = 1.526, 95% CI = 1.148 to 2.028). Both female sex (β = 0.422, OR = 1.525, 95% CI = 1.148 to 2.026) and Parkinson's disease (β = -0.428, OR = 0.652, 95% CI = 0.432 to 0.984) were significant predictors of the SI when age was removed from the model. Two-step cluster analysis resulted in individuals with PD being grouped into "extreme non-believer," "non-believer" and "believer" rather than "non-believer" and "believer" clusters characteristic for PWE, patients with MS and HCs. Our study suggests that individuals with PD believe in less superstitions than patients with MS, PWE or HCs. The results of this investigation should be independently confirmed after adjusting for PD-specific variables.

Twinning to reduce research and innovation inequalities in paediatric solid tumours across Europe

Inequalities in research and innovations affect childhood cancer survival across Europe. Vilnius University Hospital Santaros Klinikos (VULSK, the coordinator) and eight research-intensive institutions from seven European countries implemented the TREL project (Twinning in Research and Education to improve survival in childhood solid tumours in Lithuania) supported by the Horizon 2020 Widening programme. TREL aimed to enhance translational, clinical, and survivorship research in paediatric CNS, neuroblastoma, and renal tumours to improve future treatment outcomes in Lithuania. From January 2021 to December 2023, 49 VULSK professionals and 55 peers from partner institutions collaborated in this twinning program. Achievements after three years were: nine educational events, the initiation of basic and clinical research on fertility preservation, ten VULSK researchers joining international research groups, six signed agreements to participate in international academic clinical trials and the implementation of the European Survivorship Passport. Thirty patients received individual treatment recommendations following multidisciplinary discussions with experts from partner institutions. Twenty-five rare genetic variants were classified by the twinning bioinformatician teams with direct consequences on patient management. In conclusion, coordination of the Horizon 2020 project enhanced VULKS’s research capacities, networking channels and attractiveness for industry and academia-initiated innovative actions that will improve survival rates in the long run.

Clinical Features and Predictors of Lethal Outcome in Tick-Borne Encephalitis: A Retrospective Study from Lithuania

Background. In Lithuania, the incidence rate of tick-borne encephalitis (TBE) increases and remains the highest in the whole Europe. Diverse clinical manifestations cause difficulties in diagnosing and treating this infectious disease. The aim of the study was to analyze clinical manifestations of the TBE and to indicate predictive variables for unfavorable outcome.&#x0D; Methods. A retrospective study of case histories of patients diagnosed with TBE and treated at the Vilnius University Hospital Santaros Klinikos in the years 2019-2021. Demographic variables, symptoms and clinical form of the disease, laboratory values, and aspects of treatment were recorded.&#x0D; Results. Six hundred and seven case histories were analyzed. Of these, 588 case histories were included in the final analysis. Men made up 56.97% of the population studied. The median age of the patients was 54 years (18-86). The median length of hospitalization was 9 days (1-50). Seventeen (2.89%) patients were immunized against TBE, the others were not immunized (401, 68.20%) or their immunization status was unknown (170, 28.91%). The most common symptoms were headache (509, 86.56%) followed by febrile fever (403, 68.54%), fatigue (400, 68.03%), and dizziness (394, 67.01%). The most prevalent clinical form of TBE cases was meningoencephalitis (387, 76.18%) followed by meningitis (88, 17.32%), meningoencephalomyelitis (29, 5.71%), and encephalitis (4, 0.79%). Patients with the meningoencephalomyelitic form of TBE less often had headache on admission, more often had diabetes, and had fewer lymphocytes in the CSF (all p&lt;0.05). Six patients (1.02%) died. The latter patients were significantly older (71 vs. 53 years, p=0.003), had higher protein concentration and cytosis in the CSF (1.04 vs. 0.70 g/L, p=0.006 and 422 vs. 84 cells per milliliter, p=0.003, respectively), whereas the percentage of lymphocytes in the CSF was lower (62% vs. 81%, p&lt;0.001). Univariate analysis showed that older age, absence of headache and fatigue, higher cytosis and percentage of neutrophils in the CSF may be prognostic variables for the lethal outcome of the disease. Multivariate analysis showed that the absence of fatigue and higher pleocytosis were significant predictors of unfavorable outcome.&#x0D; Conclusions. Clinical forms of TBE differ based on symptoms and laboratory values. Symptoms and laboratory results may prognose the outcome of the disease.

Rare c.302C>T TTR Variant Associated with Transthyretin Amyloidosis.

Background and Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a rare disease caused by pathogenic variants in the transthyretin (TTR) gene. More than 140 different disease-causing variants in TTR have been reported. Only a few individuals with a rare TTR variant, c.302C>T, p.(Ala101Val) (historically known as p.(Ala81Val)), primarily associated with cardiac ATTRv, have been described. Therefore, our aim was to analyze the clinical characteristics of individuals with the identified c.302C>T TTR variant at our center. Materials and Methods: We analyzed data from individuals with ATTRv who were diagnosed and treated at Vilnius University Hospital Santaros Klinikos. ATTRv was confirmed by negative hematological analysis for monoclonal protein, positive tissue biopsy or bone scintigraphy and a pathogenic TTR variant. Results: During 2018-2021, the TTR NM_000371.3:c.302C>T, NP_000362.1:p.(Ala101Val) variant was found in one individual in a homozygous state and in three individuals in a heterozygous state. The age of onset of symptoms ranged from 44 to 74 years. The earliest onset of symptoms was in the individual with the homozygous variant. A history of carpal tunnel syndrome was identified in two individuals. On ECG, three individuals had low QRS voltage in limb leads. All individuals had elevated NT-proBNP and hsTroponine I levels on baseline laboratory tests and concentric left ventricular hypertrophy on transthoracic echocardiography. The individual with the homozygous c.302C>T TTR variant had the most pronounced polyneuropathy with tetraparesis. Other patients with the heterozygous variant had more significant amyloid cardiomyopathy. When screening family members, the c.302C>T TTR variant was identified in two phenotypically negative relatives at the ages of 33 and 47 years. Conclusions: c.302C>T is a rare TTR variant associated with ATTRv cardiomyopathy. The homozygous state of this variant was not reported before, and is associated with earlier disease onset and neurological involvement compared to the heterozygote state.

Pirmosios Baltijos šalyse taikomos robotinės chirurgijos sistemos „Versius“ daugiadisciplinis diegimas

On June, 2023, Vilnius University Hospital Santaros Klinikos started robotic-assisted operations using VERSIUS robotic surgery system (CMR, Cambridge, UK) and performed 29 robotic surgeries within the first 3 weeks. This surgical system was purchased with funding from the European Regional Development Fund. Comprehensive three-month-long learning courses were organized for a total number of 32 persons, forming 8 independent teams, each consisting of 2 surgeons and 2 nurses. Learning courses consisted of online theoretical training modules, a one-week learning course including technical skills training with a simulator and dry runs as well as cadaveric surgical cases. Furthermore, an additional learning module included dry runs in the operating room prior to the first surgeries, following live and online proctored surgical cases. This enabled a rapid and smooth introduction of the robotic surgical system into clinical practice without putting patients at risk. Abdominal surgeons, urologists, and gynecologists have already performed surgeries using the VERSIUS surgical system and no major complications have been reported. Thoracic surgeons are underway to begin thoracic robotic-assisted surgeries, completing the multidisciplinary VERSIUS surgical system implementation process. Our goal is to share initial experience with robotic VERSIUS surgical system and evaluate its implementation in Vilnius University Hospital Santaros Klinikos.

Assessment of the disease severity in patients hospitalized for COVID-19 based on the National Early Warning Score (NEWS) using statistical and machine learning methods: An electronic health records database analysis.

The coronavirus disease 2019 (COVID-19) was a cause of concern in the healthcare system and increased the need for disease severity indicators. However, they still vary in use to evaluate in-hospital outcomes and severity. The National Early Warning Score (NEWS) is routinely used to evaluate patient health status at the hospital. Further research is needed to ensure if NEWS can be a good instrument for an overall health status assessment with or without additional information like laboratory tests, intensive care needs, and history of chronic diseases. To evaluate if NEWS can be an indicator to measure COVID-19 patient status in-hospital. We used the fully anonymized Electronic Health Records (EHR) characterizing patients admitted to the hospital with COVID-19. Data was obtained from Vilnius University Hospital Santaros Klinikos EHR system (SANTA-HIS) from 01-03-2020 to 31-12-2022. The study sample included 3875 patients. We created several statistical and machine learning models for discrimination between in-hospital death/discharge for evaluation NEWS as a disease severity measure for COVID-19 patients. In these models, two variable sets were considered: median NEWS and its combination with clinical parameters and medians of laboratory test results. Assessment of models' performance was based on the scoring metrics: accuracy, sensitivity, specificity, area under the ROC curve (AUC), and F1-score. Our analysis revealed that NEWS predictive ability for describing patient health status during the stay in the hospital can be increased by adding the patient's age at hospitalization, gender, clinical and laboratory variables (0.853 sensitivity, 0.992 specificity and F1-score - 0.859) in comparison with single NEWS (0.603, 0.995, 0.719, respectively). A comparison of different models showed that stepwise logistic regression was the best method for in-hospital mortality classification. Our findings suggest employing models like ours for advisory routine usage. Our model demonstrated incremental value for COVID-19 patient's status evaluation.

Can family members reliably assess mood and suicidal ideation in individuals with epilepsy?

BackgroundRoutine detection of depression, anxiety and suicidal ideation in people with epilepsy (PWE) remains suboptimal. We investigated the level of agreement between PWE and their proxies when evaluating these psychiatric symptoms. MethodsFrom October 2021 to March 2022, we conducted a cross-sectional anonymous survey at Vilnius University Hospital Santaros Klinikos (Vilnius, Lithuania). Persons accompanying PWE completed different scales measuring symptoms of depression and anxiety and evaluated suicidal ideation among PWE (defined as a non-zero score of the suicide item of the Beck depression inventory (BDI) or as a score > 1 of the item 4 of the Neurological Disorders Depression Inventory for Epilepsy, NDDI-E). Agreement between PWE and their proxies was measured using the Wilcoxon test for paired samples and Pearson’s correlation analysis. ResultsThe study included 140 PWE (mean age 41.0 ± 18.1, 71 (50.7 %) female) and 140 proxies (mean age 49.0 ± 15.01, 105 (75.0 %) female, 57 (40.7 %) were parents, 51 (36.4 %) – spouses, 15 (10.7 %) – partners, 11 (7.9 %) – children and 6 (4.3 %) – siblings of PWE). There were no statistical differences in paired scores of the BDI, Hospital Anxiety and Depression scale, Generalized Anxiety Disorder scale-7, and the NDDI-E (p > 0.05). Proxies reported statistically higher scores on the Geriatric Depression Scale (Z = − 2.026, p = 0.043) than PWE. The correlation between PWE and proxy evaluations for all instruments was moderate (varying from r = 0.500 to r = 0.688, p < 0.001). For most psychometric scales proxies became less accurate with higher scale scores for anxiety and depression and tended to underestimate the level of such symptoms (correlation between scale results and signed (PWE − proxy) mismatch varied from r = 0.368 to r = 0.641, p < 0.001). The measure of proxy-PWE agreement on suicidal ideation was low (Cohen’s Κ = 0.192, p = 0.025); proxies missed 63 % (NDDI-E) to 70 % (BDI) of cases of suicidal ideation. ConclusionCompanions of PWE provided comparable reports of participant anxiety and depression on a group level but tended to underestimate psychiatric symptoms as their scale scores became higher. Proxies significantly underreported suicidal ideation in those people who did express it. While proxy reporting should not be used interchangeably on an individual level, its use in group studies may be useful and ought to be investigated further.

HMR Mutations Drive Poor Prognosis in Myelofibrosis Patients with Lower JAK2V617F Allele Burden but Not in Those with Higher Allele Burden: Results of a Multicenter Study

JAK2V617F is the most common driver mutation in myelofibrosis (MF), followed by CALR and MPL alterations. Clinical variables included in the International Prognostic Scoring System (IPSS), Dynamic IPSS (DIPSS), and DIPSS plus, as well as JAK2V617F allele burden are all well-established prognostic factors influencing the survival of MF patients. In addition, ASXL1, EZH2, SRSF2, IDH and U2AF1 mutations are classified as high-molecular risk (HMR) mutations in this context because of their close association with disease progression and leukemic transformation. However, the relationship between JAK2V617F allele burden and HMR mutations remains unclear. To address this, we recruited 122 MF patients (discovery cohort) diagnosed at the National Taiwan University Hospital (Taipei, Taiwan) who had available mutation profile determined by next-generation sequencing. For external validation, 82 MF patients from the Christie Hospital (Manchester, U.K.) and 51 MF patients from the Cleveland Clinic (Ohio, U.S.A.) and Vilnius University Hospital Santaros Klinikos (Vilnius, Lithuania) were enrolled. The median age of the discovery cohort was 61 years. JAK2V617F was the most common driver mutation (64.8%), followed by CALR (18%) and MPL mutations (9%). ASXL1 mutation was the most common (37%) genetic alteration other than driver mutations, followed by TET2 (16%) and EZH2 mutations (12%). Overall, 55 patients (45%) had at least one HMR mutation ( ASXL1, EZH2, SRSF2, IDH and U2AF1). With a median follow-up of 28.2 months, the median overall survival (OS) of the discovery cohort was not reached (NR) and was well risk-stratified by current prognostication systems, including IPSS, DIPSS plus, MIPSS70, and GIPSS. Notably, patients with at least one HMR mutation had significantly shorter leukemia-free survival (LFS) and OS than those without (both p&amp;lt;0.001). Next, we divided the 79 JAK2-mutated patients into lower- and higher-allele burden groups ( JAK2low and JAK2high) using the median (75%), as the cutoff. Concurring with previous reports ( Tefferi et al, Leukemia 2008; and Guglielmelli et al, Blood 2009), JAK2low patients had significantly inferior OS than JAK2high patients (median, 53 months vs NR, p=0.037). Among all JAK2-mutated patients, those with HMR mutations had a significantly shorter OS than those without (50 months vs NR, p&amp;lt;0.001). When considering HMR mutations and JAK2V617F allele burden together, the presence of HMR alterations conferred worse LFS and OS in JAK2low but not in JAK2high patients (HMR vs without HMR among JAK2low patients, p&amp;lt;0.001 and p&amp;lt;0.001; and JAK2high, p=0.822 and p=0.699, respectively). By and large, patients with concurrent HMR mutations and lower JAK2V617F allele burden had a distinctively inferior OS than those with other constellations of genomic lesions ( p&amp;lt;0.001, Figure 1A). This group of patients also had the shortest survival among the total cohort including both JAK2-mutated and wild patients ( p&amp;lt;0.001). The discriminating power of integrating HMR/ JAK2 allele burden for LFS and OS remained valid in the UK cohort (HMR vs without HMR: JAK2low, p=0.013 and p=0.012; and JAK2high, p=0.337 and p=0.600, respectively) and the US/Lithuania cohort (HMR vs without HMR: JAK2low, p=0.016 and p=0.013; and JAK2high, p=0.643 and p=0.446, respectively). Co-occurrence tests in the discovery and validation cohorts revealed that there was no shared mutational co-occurrence pattern among the 3 cohorts, excluding the potential confounding influence of specific concurrent mutations. More strikingly, time-dependent ROC curve analyses suggested that integrating JAK2 allele burden with HMR mutations could be complementary to current risk stratification systems in predicting LFS and OS of MF patients (Figure 1B) across 3 cohorts. Finally, HMR/ JAK2low was identified as an independent adverse prognostic factor by multivariable analysis, irrespective of age, risk stratification systems, and other mutations. In summary, we observe that HMR mutations accompanied by a lower mutant JAK2V617F allele burden identified a distinct MF population with significantly reduced survival and high risk of leukemic transformation, with independent prognostic relevance extrapolated to and validated in two independent cohorts. Experimental studies are ongoing to ascertain the underlying mechanistic basis and resolve the clonal architecture of this distinct MF genomic grouping.

Rehabilitation of cognition and psychosocial well-being - a better life with epilepsy (ReCaP-ABLE): a protocol for a randomized waitlist-controlled trial.

Despite advances in the understanding of cognitive dysfunction among people with epilepsy (PWE), evidence for cognitive rehabilitation in epilepsy (CoRE) remains scarce. We present the protocol of a randomized waitlist-controlled trial (ClinicalTrials.gov ID NCT05934786) of a psychological-behavioral intervention aiming to ameliorate quality of life as well as cognitive functioning in a mixed PWE sample. The study is set at Vilnius University Hospital Santaros Klinikos and will offer adult PWE six individual and two group sessions led by a certified psychologist and directed toward improving memory, attention, self-regulation, mood and quality of life. The trial is expected to address major gaps in the literature by providing novel evidence on the effectiveness of CoRE in patients with genetic generalized epilepsies, the importance of epilepsy-specific factors for the response to CoRE, the impact of CoRE on long-term memory as well as its maintenance effects.

Retrospective study of spontaneous subarachnoid haemorrhage: vasospasm and other complications (Part III)

Background. Acute subarachnoid haemorrhage (SAH) is a dangerous condition: roughly 50% of patients die within 30 days, nearly 25% develop significant neuropsychological and cognitive deficits, about 10% suffer from other complications, and only around 15% recover fully. One of the main causes of mortality is cerebral vasospasm (CVS), a cause of delayed cerebral ischaemia (DCI), which can lead to secondary cerebral infarction. Thus, early detection of CVS is crucial for improving patient outcomes.The aim of this study was to analyse the demographic and clinical (including complications) data of patients diagnosed with SAH, to evaluate the diagnostic methods, and to investigate the prevalence and treatment of complications.Materials and methods. This retrospective study included 102 patients diagnosed with spontaneous SAH, aged at least 18 years, who were treated in the Vilnius University Hospital Santaros Klinikos (VUL SK) in 2014-2017. The obtained VUL SK data were selected by the I60 ICD-10-CM code and depersonalized. Head computerized tomography (CT), CT angiography (CTA), digital subtraction angiography (DSA), transcranial color-coded duplex sonography (TCCS), and magnetic resonance angiography (MRA) were used to evaluate the cerebral arteries.Results. In 102 patients (mean age 58±16 years; 55% female), the most common cause of spontaneous SAH was ruptured aneurysm, the most common arterial sites were the middle cerebral artery (36%), anterior cerebral artery and/or communicating artery (together 33%), and internal carotid artery (20%). In-hospital mortality was as high as 21%. All patients underwent head CT, 78% CTA, 33% DSA, 8% TCCS, and 1% MRA. 71% patients experienced SAH complications: 66% acute, 27% chronic. The most common acute complications were cerebral oedema (34%), rebleeding (29%), and acute ischaemia (23%), the most common chronic complications hydrocephalus (11%), DCI (9%), and CVS (8%).Conclusions. CVS was diagnosed considerably less frequently in this study compared to other studies. While the diagnosis rates of ischaemia and hyponatremia were likewise significantly lower in this study compared to those in others, they are in line with the CVS diagnosis rate. Aside from the CVS and CVS-related complications, all the other SAH complications were roughly within the range of the other studies.

Three-Dimensional Structural Phenotype of the Optic Nerve Head as a Function of Glaucoma Severity

The 3-dimensional (3-D) structural phenotype of glaucoma as a function of severity was thoroughly described and analyzed, enhancing understanding of its intricate pathology beyond current clinical knowledge. To describe the 3-D structural differences in both connective and neural tissues of the optic nerve head (ONH) between different glaucoma stages using traditional and artificial intelligence-driven approaches. This cross-sectional, clinic-based study recruited 541 Chinese individuals receiving standard clinical care at Singapore National Eye Centre, Singapore, and 112 White participants of a prospective observational study at Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania. The study was conducted from May 2022 to January 2023. All participants had their ONH imaged using spectral-domain optical coherence tomography and had their visual field assessed by standard automated perimetry. (1) Clinician-defined 3-D structural parameters of the ONH and (2) 3-D structural landmarks identified by geometric deep learning that differentiated ONHs among 4 groups: no glaucoma, mild glaucoma (mean deviation [MD], ≥-6.00 dB), moderate glaucoma (MD, -6.01 to -12.00 dB), and advanced glaucoma (MD, <-12.00 dB). Study participants included 213 individuals without glaucoma (mean age, 63.4 years; 95% CI, 62.5-64.3 years; 126 females [59.2%]; 213 Chinese [100%] and 0 White individuals), 204 with mild glaucoma (mean age, 66.9 years; 95% CI, 66.0-67.8 years; 91 females [44.6%]; 178 Chinese [87.3%] and 26 White [12.7%] individuals), 118 with moderate glaucoma (mean age, 68.1 years; 95% CI, 66.8-69.4 years; 49 females [41.5%]; 97 Chinese [82.2%] and 21 White [17.8%] individuals), and 118 with advanced glaucoma (mean age, 68.5 years; 95% CI, 67.1-69.9 years; 43 females [36.4%]; 53 Chinese [44.9%] and 65 White [55.1%] individuals). The majority of ONH structural differences occurred in the early glaucoma stage, followed by a plateau effect in the later stages. Using a deep neural network, 3-D ONH structural differences were found to be present in both neural and connective tissues. Specifically, a mean of 57.4% (95% CI, 54.9%-59.9%, for no to mild glaucoma), 38.7% (95% CI, 36.9%-40.5%, for mild to moderate glaucoma), and 53.1 (95% CI, 50.8%-55.4%, for moderate to advanced glaucoma) of ONH landmarks that showed major structural differences were located in neural tissues with the remaining located in connective tissues. This study uncovered complex 3-D structural differences of the ONH in both neural and connective tissues as a function of glaucoma severity. Future longitudinal studies should seek to establish a connection between specific 3-D ONH structural changes and fast visual field deterioration and aim to improve the early detection of patients with rapid visual field loss in routine clinical care.

Evaluation of oncofertility care in childhood cancer patients: the EU-Horizon 2020 twinning project TREL initiative.

The 5-year survival rate of childhood cancer exceeds 80%, however, many survivors develop late effects including infertility. The aim of this study was to evaluate the current status of oncofertility care at Vilnius University Hospital Santaros Klinikos (VULSK) within the framework of the EU-Horizon 2020 TREL project. All parents or patients aged 12-17.9 years treated from July 1, 2021 until July 1, 2022 were invited to complete an oncofertility-care-evaluation questionnaire. After completing the questionnaire, patients were triaged to low-risk (LR) or high-risk (HR) of gonadal damage using a risk stratification tool (triage). Data was assessed using descriptive statistics. Questionnaires were completed by 48 parents and 13 children triaged as 36 (59%) LR and 25 (41%) HR patients. Most HR respondents (21/25, 84%) were not counseled by a fertility specialist. Six boys (4 HR, 2 LR) were counseled, none of the girls was counseled. Three HR boys underwent sperm cryopreservation. Only 17 (27.9%, 9 HR, 8 LR) respondents correctly estimated their risk. All counseled boys (n = 6) agreed the risk for fertility impairment had been mentioned as compared to 49.1% (n = 27) of uncounseled. All counseled respondents agreed they knew enough about fertility (vs. 42%). Respondents counseled by a fertility specialist were provided more information on fertility than uncounseled. HR patients were not sufficiently counseled by a fertility specialist. Based on the current experience oncofertility care at VULSK will be improved.