Jósa András Múzeum

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by a hypercoagulable state and recurrent thromboembolism (TE). Patients with triple-positive antiphospholipid antibodies (APAs) are at the highest risk of TE. As standard treatment for these patients, oral anticoagulation therapy (OAT) with vitamin K antagonists (VKAs) is widely used, but inaccurate International Normalized Ratio (INR) measurement due to APA interference can complicate monitoring. Here we report the case of a 19-year-old male patient, with a history of submassive pulmonary embolism at the age of 13. Thrombophilia investigations confirmed type II antithrombin deficiency (Budapest 3 heterozygous) combined with triple-positive APS. He received sustained VKA (warfarin) therapy, but his INR values showed strikingly different results when monitored in two different laboratories (INR 3-4 vs. INR >8 on multiple occasions). Therefore, we aimed to investigate the impact of different thromboplastin reagents on INR values in this triple-positive APS patient receiving VKA therapy. INR measurements were performed using animal-derived (rabbit brain-derived) and recombinant thromboplastins. The effect of purified patient IgG concentrates was examined on INR values using antiphospholipid antibody-negative plasma mixtures. Chromogenic FXa activity (CFXa) was also measured to assess the true anticoagulant effect of VKA. INR values measured using recombinant thromboplastin reagent were consistently higher and less reliable in high APA-titer conditions compared to rabbit brain-derived reagent. CFXa results were more consistent with INR values obtained using rabbit brain-derived thromboplastin. Rabbit brain-derived thromboplastin, less sensitive to APA interference, provided reliable INR monitoring for this high-risk patient. We recommend choosing thromboplastin reagents without interference to APAs, to optimize OAT monitoring in similar cases of patients with high APA-titers.

Abstract We aimed to compare resting Pd/Pa, FFR, and distal RFR values with and without hydrostatic pressure correction. Our main goal was to assess the influence of this correction on cut-off value-based decision-making for each physiological parameter. Data from patients enrolled in two centers of the READY registry (NCT04857762) were analyzed. Center 1 employed catheter and pressure sensor height differences defined from lateral angiographic projection for hydrostatic pressure correction, while Center 2 utilized average pressure differentials from published data. In Center 1, the height difference underlying the hydrostatic pressure correction did not differ significantly from the average values published in previous publication (-5.22±1.1cm for LAD, 2.44±1.1cm for CX, and 1.63±2.8cm for RCA). Consequently, FFR and distal RFR values corrected with average pressure differentials rarely yielded different cut-off-based characterizations compared to individually measured corrections (2.4%). A total of 42 measurements were evaluated in Center 1 (33 patients) and 40 measurements in Center 2 (40 patients). Stenoses were characterized using resting Pd/Pa (0.91 ± 0.05), FFR (0.80 ± 0.08), distal RFR (0.86 ± 0.09) and ΔRFR (0.07 ± 0.07) values. Regarding all the investigated vessels, statistically significant differences were observed in FFR (0.80 ± 0.08 vs 0.81 ± 0.08; p < 0.001), distal RFR (0.86 ± 0.09 vs 0.87 ± 0.09; p < 0.001), and ΔRFR (0.053 ± 0.04 vs 0.047 ± 0.04; p = 0.014) before and after correction. These changes after hydrostatic correction were driven dominantly by the LAD measurements being LAD stenoses constituted the majority of the cases (73.2%). Overall (n=82), hydrostatic pressure correction modified cut-off-based categorization in 24 (29.3%) cases for Pd/Pa, and 19 (23.2%) cases for both distal RFR and FFR measurements. Notably, ΔRFR assessment also changed in 22.2% of cases after correction. Among LAD stenoses (n=60), hydrostatic pressure correction altered cut-off-based characterization in 22 (36.7%), 19 (31.7%), and 17 (28.3%) cases of resting Pd/Pa, distal RFR, and FFR measurements, respectively. Hydrostatic pressure correction offers the potential to enhance the accuracy of intracoronary physiological measurements, especially for LAD stenoses. Our data suggest that the published average pressure differences of each coronary segment can be used for correction.Lateral view and delta RFRIndividual vs Average LAd correction

IntroductionMetabolic syndrome (MetS) is of primary clinical interest because of its harmful impact on the general health and quality of life of patients with psychotic disorders. Paradoxically, MetS is associated with impaired cognitive functions in patients receiving antipsychotics primarily shown to improve cognition (e.g., clozapine and olanzapine).Objectives In this study, we aimed to investigate the relationship between MetS, cognitive functions, and peripheral inflammation.MethodsThe participants were 154 patients with schizophrenia. Fifty-seven patients met the criteria of MetS. We evaluated cognitive functions with the Repeated Battery for the Assessment of Neuropsychological Status (RBANS). The Positive and Negative Syndrome Scale (PANSS) quantified the clinical symptoms. We also measured the plasma levels of IL-6 and C-reactive protein (CRP). In addition to conventional statistics, we also calculated Cohen’s effect size (d) and Bayes Factors (BF10).ResultsResults revealed that patients with MetS exhibited worse cognitive function relative to patients without Mets in attention (d = 0.19, BF10 = 2.3) and delayed memory (d = 0.25, BF10 = 5.7). No significant between-group differences existed in immediate memory, visuospatial functions, and language. The MetS and non-MetS groups did not differ in positive, negative, or general symptoms. Higher IL-6 levels were associated with worse delayed memory (r=-0.56, BF10=34.6).ConclusionsOur results suggest that MetS-associated cognitive dysfunctions are less severe than reported in the literature: it was confined to two cognitive domains, the effect size was small, and the Bayesian evidence level was weak. Peripheral inflammation may mediate the association between MetS and long-term memory dysfunctions.Disclosure of InterestNone Declared

Spinal metastatic tumors are common and often cause debilitating symptoms. Image-guided percutaneous thermal ablation (IPTA) has gained significant recognition in managing spinal column tumors due to its exceptional precision and effectiveness. Conventional guidance modalities, including computed tomography, fluoroscopy, and ultrasound, have been important in targeting spinal column tumors while minimizing harm to adjacent critical structures. This study presents a novel approach utilizing a fusion of Cone Beam Computed Tomography with Magnetic Resonance Imaging to guide percutaneous thermal ablation for four patients with secondary spinal column tumors. The visual analog scale (VAS) evaluated procedure effectiveness during an 18-month follow-up. Percutaneous vertebroplasty was performed in two cases, and a thermostat was used during all procedures. Imaging was performed using the Stealth Station navigation system Spine 8 (SSS8) and a 1.5T MRI machine. The fusion of CBCT with MRI allowed precise tumor localization and guidance for thermal ablation. Initial results indicate successful tumor ablation and symptom reduction, emphasizing the potential of CBCT-MRI fusion in spinal column tumor management. This innovative approach is promising in optimizing therapy for secondary spinal column tumors. Further studies are necessary to validate its efficacy and applicability.

The ADNP-gene-related neurodevelopmental disorder Helsmoortel-Van der Aa syndrome is a rare syndromic-intellectual disability-an autism spectrum disorder first described by Helsmoortel and Van der Aa in 2014. Recently, a large cohort including 78 patients and their detailed phenotypes were presented by Van Dijck et al., 2019, who reported developmental delay, speech delay and autism spectrum disorder as nearly constant findings with or without variable cardiological, gastroenterological, urogenital, endocrine and neurological manifestations. Among cardiac malformations, atrial septal defect, patent ductus arteriosus, patent foramen ovale and mitral valve prolapse were the most common findings, but other unspecified defects, such as mild pulmonary valve stenosis, were also described. We present two patients with pathogenic ADNP variants and unusual cardiothoracic manifestations-Bland-White-Garland syndrome, pectus carinatum superiorly along the costochondral junctions and pectus excavatum inferiorly in one patient, and Kawasaki syndrome with pericardiac effusion, coronary artery dilatation and aneurysm in the other-who were successfully treated with intravenous immunoglobulin, corticosteroid and aspirin. Both patients had ectodermal and/or skeletal features overlapping those seen in RASopathies, supporting the observations of Alkhunaizi et al. 2018. on the clinical overlap between Helsmoortel-Van der Aa syndrome and Noonan syndrome. We observed a morphological overlap with the Noonan-like disorder with anagen hair in our patients.

Congenital complete heart block is a rare occurrence. In some cases, it remains asymptomatic until adulthood or in the case of women until pregnancy. It is usually secondary to placental transfer of maternal antibodies and is associated with high mortality and morbidity. We present a case of a parturient who presented in active labor with premature rupture of membranes and decreased fetal movements. We found that the patient had a complete heart block with mild effort intolerance on evaluation. Markers for metabolic and ischemic causes were negative, and we made a provisional diagnosis of congenital complete heart block. The patient underwent a lower section cesarian section under spinal anesthesia with temporary pacemaker backup. Postoperatively, the patient underwent permanent pacemaker implantation. This case report underlines the importance of standard American Society of Anesthesiologists (ASA) monitoring, including a 12-lead electrocardiogram (ECG), which could prove decisive and life-saving in dire circumstances.

A hepatitis C virus (HCV) screening and treatment program was conducted in Hungarian prisons on a voluntary basis. After HCV-RNA testing and genotyping for anti-HCV positives, treatments with direct-acting antiviral agents were commenced by hepatologists who visited the institutions monthly. Patients were supervised by the prisons’ medical staff. Data were retrospectively collected from the Hungarian Hepatitis Treatment Registry, from the Health Registry of Prisons, and from participating hepatologists. Eighty-four percent of Hungarian prisons participated, meaning a total of 5779 individuals (28% of the inmate population) underwent screening. HCV-RNA positivity was confirmed in 317/5779 cases (5.49%); 261/317 (82.3%) started treatment. Ninety-nine percent of them admitted previous intravenous drug use. So far, 220 patients received full treatment and 41 patients are still on treatment. Based on the available end of treatment (EOT) + 24 weeks timepoint data, per protocol sustained virologic response rate was 96.8%. In conclusion, the Hungarian prison screening and treatment program, with the active participation of hepatologists and the prisons’ medical staff, is a well-functioning model. Through the Hungarian experience, we emphasize that the “test-and-treat” principle is feasible and effective at micro-eliminating HCV in prisons, where infection rate, as well as history of intravenous drug usage, are high.

Sleep deprivation (SD) is known to be associated with decreased cognitive performance; however, the underlying mechanisms are poorly understood. As interactions between distinct brain regions depend on mental state, functional brain networks established by these connections typically show a reorganization during task. Hence, analysis of functional connectivity (FC) could reveal the task‐related change in the examined frontal brain networks. Our objective was to assess the impact of SD on static FC in the prefrontal and motor cortices and find whether changes in FC correlate with changes in neuropsychological scores. Healthy young male individuals (n = 10, 27.6 ± 3.7 years of age) participated in the study. A battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and 48 channel functional near‐infrared spectroscopy (fNIRS) measurements were performed before and after 24 hr of SD. Network metrics were obtained by graph theoretical analysis using the fNIRS records in resting state and during finger‐tapping sessions. During task, SD resulted in a significantly smaller decrease in the number and strength of functional connections (characterizing FC) in the frontal cortex. Changes in the global connection strengths correlated with decreased performance in the paired association learning test. These results indicate a global impact of SD on functional brain networks in the frontal lobes.