Novel Noninvasive Paraclinical Study Method for Investigation of Liver Diseases.

Based on a prior university patent, the authors developed a novel type of bioimpedance-based test method to noninvasively detect nonalcoholic fatty liver disease (NAFLD). The development of a new potential NAFLD diagnostic procedure may help to understand the underlying mechanisms between NAFLD and severe liver diseases with a painless and easy-to-use paraclinical examination method, including the additional function to detect even the earlier stages of liver disease. The aim of this study is to present new results and the experiences gathered in relation to NAFLD progress during animal model and human clinical trials.

Serum Total Antioxidant Capacity (TAC) and TAC/Lymphocyte Ratio as Promising Predictive Markers in COVID-19.

SARS-CoV-2 infection might cause a critical disease, and patients' follow-up is based on multiple parameters. Oxidative stress is one of the key factors in the pathogenesis of COVID-19 suggesting that its level could be a prognostic marker. Therefore, we elucidated the predictive value of the serum non-enzymatic total antioxidant capacity (TAC) and that of the newly introduced TAC/lymphocyte ratio in COVID-19. We included 61 COVID-19 (n = 27 ward, n = 34 intensive care unit, ICU) patients and 29 controls in our study. Serum TAC on admission was measured by an enhanced chemiluminescence (ECL) microplate assay previously validated by our research group. TAC levels were higher (p < 0.01) in ICU (median: 407.88 µmol/L) than in ward patients (315.44 µmol/L) and controls (296.60 µmol/L). Besides the classical parameters, both the TAC/lymphocyte ratio and TAC had significant predictive values regarding the severity (AUC-ROC for the TAC/lymphocyte ratio: 0.811; for TAC: 0.728) and acute kidney injury (AUC-ROC for the TAC/lymphocyte ratio: 0.747; for TAC: 0.733) in COVID-19. Moreover, the TAC/lymphocyte ratio had significant predictive value regarding mortality (AUC-ROC: 0.752). Serum TAC and the TAC/lymphocyte ratio might offer valuable information regarding the severity of COVID-19. TAC measured by our ECL microplate assay serves as a promising marker for the prediction of systemic inflammatory diseases.

Michaelis-Menten kinetic modeling of hemoglobin A1c status facilitates personalized glycemic control.

INTRODUCTION: Discrepancy between measured HbA1c and HbA1c calculated from plasma glucose is associated with higher risk for diabetic complications. However, quantification of this difference is inaccurate due to the imperfect linear conversion models. We propose to introduce a mathematical formula that correlates with the observational data and supports individualized glycemic control. METHODS: We analysed 175,437 simultaneous plasma glucose and HbA1c records stored in our laboratory database. Employing the Michaelis-Menten (MM) equation, we compared the calculated HbA1c levels to the measured HbA1c levels. Data from patients with multiple records were used to establish the patients' glycemic status and to assess the predictive power of our MM model. RESULTS: HbA1c levels calculated with the MM equation closely matched the population's average HbA1c levels. The Michaelis constant (Km) had a negative correlation with HbA1c (r2 = 0.403). Using personalized Km values in the MM equation, 85.1% of HbA1c predictions were within 20% error (ADAG calculation: 78.4%). MM prediction also performed better in predicting pathologic HbA1c levels (0.904 AUC vs. 0.849 AUC for ADAG). CONCLUSION: MM equation is an improvement over linear models and could be readily employed in routine diabetes management. Km is a reliable and quantifiable marker to characterize variations in glucose tolerance.

Physical exercise induces mental flow related to catecholamine levels in noncompetitive, but not competitive conditions in men.

The study aimed to reveal physical exercise conditions and catecholamine response-dependent differences while an individual experiences a flow state (FS) following noncompetitive and competitive running drills. Urine laboratory catecholamine levels were measured using a standard clinical method during pre- and post-physical exercises. The noncompetitive task involved intermittent running drills, from an absolute beginning up through exhaustion. Initially, the drill is performed individually then later competing alongside other runners. Twenty-two males (mean age: 40.27; SD: 5.4; min-max: 31-49 years) were selected in accordance to the following criterion: healthy status without using medication, routine forms of training (running, cycling or swimming) ideally performed with regularity, at least three times per week, 45 min per session. During the noncompetitive task, a high FS experience was associated with a low level of catecholamines, (noradrenaline and adrenaline) while in parallel, the high FS was associated with a low concentration of homovallinic acid. During competitive conditions, the FS-related catecholamine level changes have not yet been found. In conclusion, the low concentration of the circulating catecholamines supports the transient hypofrontality hypothesis regarding the FS experiences. Furthermore, synchronized noradrenaline and adrenaline neurosecretion play an essential role in the manifestation and the prolongation of FS in noncompetitive exercise conditions.

Presepsin: gelsolin ratio, as a promising marker of sepsis-related organ dysfunction: a prospective observational study.

Introduction: We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio. Methods: Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12 h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. PSEP was measured by a chemiluminescence-based POCT method while GSN was determined by an automated immune turbidimetric assay. Data were compared with routine lab and clinical parameters. Patients were categorized by the Sepsis-3 definitions. PSEP:GSN ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic instability, respiratory insufficiency and acute kidney injury (AKI). Results: In our single center prospective observational study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). In contrast to controls, significantly elevated (p < 0.001) admission PSEP:GSN ratios were found in non-septic and septic patients. Regarding 10-day mortality prediction, PSEP:GSN ratios were lower (p < 0.05) in survivors than in non-survivors during follow-up, while the prognostic performance of PSEP:GSN ratio was similar to widely used clinical scores (APACHE II, SAPS II, SOFA). PSEP:GSN ratios were also higher (p < 0.001) in patients with sepsis-related AKI than septic non-AKI patients during follow-up, especially in sepsis-related AKI patients needing renal replacement therapy. Furthermore, increasing PSEP:GSN ratios were in good agreement (p < 0.001) with the dosage and the duration of vasopressor requirement in septic patients. Moreover, PSEP:GSN ratios were markedly greater (p < 0.001) in patients with septic shock than in septic patients without shock. Compared to septic patients requiring oxygen supplementation, substantially elevated (p < 0.001) PSEP:GSN ratios were observed in septic patients with demand for mechanical ventilation, while higher PSEP:GSN ratios (p < 0.001) were also associated with extended periods of mechanical ventilation requirement in septic patients. Conclusion: PSEP:GSN ratio could be a useful complementary marker besides the routinely used SOFA score regarding the diagnosis and short term mortality prediction of sepsis. Furthermore, the significant increase of this biomarker may also indicate the need for prolonged vasopressor or mechanical ventilation requirement of septic patients. PSEP:GSN ratio could yield valuable information regarding the extent of inflammation and the simultaneous depletion of the patient's scavenger capacity during sepsis. Clinical trail registration: NIH U.S. National Library of Medicine, ClinicalTrails.gov. Trial identifier: NCT05060679, (https://clinicaltrials.gov/ct2/show/NCT05060679) 23.03.2022, Retrospectively registered.

Insulin, Testosterone, and Albumin in Term and Preterm Breast Milk, Donor Milk, and Infant Formula.

BACKGROUND: Infants have three options for feeding: their own mother's breast milk, donor milk, or infant formula. Insulin, testosterone, total protein, and albumin levels were measured in breast milk samples from the first 6 months of lactation, in donor milk samples, and in different infant formulas. METHODS: Mothers who gave birth to term (n = 19) or preterm (n = 19) infants were recruited to collect breast milk samples during the first 6 months of lactation. The Breast Milk Collection Center (Unified Health Institution, Pécs, Hungary) provided 96 donor milk (DM) samples for analysis in our study. Insulin, testosterone, total protein, and albumin levels were measured in breast milk, donor milk, and infant formulas. RESULTS: During the first 2 months of lactation, the concentration of insulin was lower (-27.4%) while the testosterone concentration was higher (+20.8%) compared to the period between the 3rd and 6th months only in the preterm breast milk samples. The infant formulas examined did not contain insulin or testosterone. Holder pasteurization (HoP) did not influence the level of testosterone in human milk, although HoP decreased the insulin (-53.6%) and albumin (-38.6%) concentrations. CONCLUSIONS: Diet impacts the hormone intake of infants, underlining the importance of breastfeeding and the possible supplementation of formula-fed infants.

Use of blood products during the first months of COVID-19 pandemic period: A single center report.

The novel coronavirus (SARS-CoV-2) outbreak exerted a serious effect on healthcare. Between 1st of January and May 31, 2020 due to the special regulations in Hungary, the number of reported COVID-19 infections were relatively low (3876 cases). The inpatient and outpatient care and the blood supply were significantly affected by the implemented regulations. The aim of this study was to evaluate the use of blood products amid the first five months of the pandemic situation. This investigation has observed a significant reduction of hospitalizations (37.35%). Analyzing individually the included units, pre-transfusion hemoglobin concentrations of transfused patients presented slight modifications, which were not statistically significant. The special regulations resulted major changes in the frequency of diagnoses at admissions in case of the Department of Surgery, while in case of the other specialities (Division of Hematology and Department of Anesthesiology and Intensive Therapy), there were no major changes compared to pre-pandemic period. Considering each department separately, transfused red blood cell concentrates (RBC) per patient, and the proportion of transfused patients did not change significantly. However, the combination of these modifications resulted in the significant decrease in RBC transfusions (p < 0.0001) compared to the pre-pandemic baseline. With regard to platelet and fresh frozen plasma (FFP), their usage was significantly reduced (44.40% platelet concentrates and 34.27% FFP). Our results indicate that the pandemic had an important effect on the blood product usage at the included departments by introducing different patient care policies and the temporary deferral of the elective surgical interventions. Despite the challenging circumstances of blood collection and blood product supply, the hospitalized patients received adequate care.

Characterization of Danube Swabian population samples on a high-resolution genome-wide basis.

BACKGROUND: German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans arrived in Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150 year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Swabian individuals living in the Dunaszekcso-Bár area, in Danube side villages of Southwest Hungary. These Swabians, according to self-declaration, did not admix with other ethnic groups for 3-6 succeeding generations. Using Illumina Infinium 720 K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples. RESULTS: Haplotype-based analyses like identity by descent segment analysis show that the investigated Danube Swabians possess significant German and other West European ancestry, but their Hungarian ancestry is also prominent. Our results suggest that their main source of ancestry can be traced back to Western Europe, presumably to the region of Germany. CONCLUSION: This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns.

Plasma Levels and Renal Handling of Amino Acids Contribute to Determination of Risk of Mortality or Feed of Ventilation in Patients with COVID-19.

COVID-19 infection may lead to serious complications, e.g., need for mechanical ventilation or death in some cases. A retrospective analysis of patients referred to our COVID Emergency Department, indiscriminately, was performed. A routine lab analysis measured amino acids in plasma and urine of patients. Data of surviving and deceased patients and those requiring or not requiring mechanical ventilation were compared, and logistic regression analyses have been performed. Deceased patients were older, had higher blood glucose, potassium, AST, LDH, troponin, d-dimer, hsCRP, procalcitonin, interleukin-6 levels (p < 0.05 for all). They had lower plasma serine, glycine, threonine, tryptophan levels (p < 0.01), higher tyrosine and phenylalanine levels (p < 0.05), and higher fractional excretion of arginine, methionine, and proline (p < 0.05) than survivors. In a regression model, age, severity score of COVID-pneumonia, plasma levels of threonine and phenylalanine were predictors of in-hospital mortality. There was a difference in ventilated vs. non-ventilated patients in CT-scores, glucose, and renal function (p < 0.001). Using logistic regression, CT-score, troponin, plasma level, and fractional excretion of glycine were predictors of ventilation. Plasma levels and renal excretion of certain amino acids are associated with the outcome of COVID-19 infection beside other parameters such as the CT-score or age.

Reward Dependence-Moderated Noradrenergic and Hormonal Responses During Noncompetitive and Competitive Physical Activities.

The aim of this study was to reveal whether increased reward dependence (RD) plays a role in the catecholamine neurotransmitter release and testosterone hormone regulation during physical activities among healthy trained participants. Twenty-two male participants (mean age: 40.27 ± 5.4 years) participated in this study. Two conditions were constructed, namely, a noncompetitive and a competitive running task (RT), which were separated by a 2-week interval. Urine and blood samples were collected prior to and following the running tasks. Noradrenaline (NA), adrenaline (A), dopamine (D), and their metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA), were measured from urine, while testosterone levels were analyzed from blood samples. RD was assessed using the Cloninger's Personality Inventory (PI). Mental health was evaluated using the WHO Well-Being, Beck Depression, and Perceived Life Stress Questionnaires. According to our findings, levels of NA, A, D, VMA, and testosterone released underwent an increase following physical exertion, independently from the competitive condition of the RT, while HVA levels experienced a decrease. However, we found that testosterone levels showed a significantly lower tendency to elevate in the competitive RT, compared with the noncompetitive condition (p = 0.02). In contrast, HVA values were higher in the competitive compared with the noncompetitive condition (p = 0.031), both before and after the exercise. Considering the factor RD, in noncompetitive RT, its higher values were associated with elevated NA levels (p = 0.007); however, this correlation could not be detected during the competitive condition (p = 0.233). Among male runners, the NA and testosterone levels could be predicted to the degree of RD by analyzing competitive and noncompetitive physical exercises.

Thyroxine and Thyroid-Stimulating Hormone in Own Mother's Milk, Donor Milk, and Infant Formula.

Breastfeeding is widely supported in clinical and home practices, and it is known that different forms of infant feeding differ in hormone content. Thyroid hormones have essential physiological roles. In our study, we examined thyroid-stimulating hormone (TSH), thyroxine, and albumin levels in breast milk produced for term (n = 16) or preterm (n = 15) infants throughout the first 6 months of lactation. Moreover, we analyzed these components in donor human milk and in three different infant formulas. Term and preterm breast milk samples were collected monthly. The two groups had similar levels of TSH (18.4 ± 1.4 vs. 24.7 ± 2.9 nU/L), but term milk contained higher amounts of thyroxine (11,245.5 ± 73.8 vs. 671.6 ± 61.2 nmol/L) during the examination period. The albumin level was significantly higher in preterm breast milk than in term breast milk (328.6 ± 17.1 vs. 264.2 ± 6.8 mg/L). In preterm breast milk we detected downward trends in the levels of TSH (-30.2%) and thyroxine (-29.2%) in the 3rd through 6th month compared to the first 2 months of lactation. Microbiological safety of donor milk was ensured by Holder pasteurization (HoP). From the Breast Milk Collection Center of Pécs, Hungary, we enrolled 44 donor mothers into the study. HoP decreased TSH (-73.8%), thyroxine (-22.4%), and albumin (-20.9%) concentrations. Infant formulas used by the Neonatal Intensive Care Unit of the University of Pécs were found to not contain the investigated hormones, but their albumin levels were similar to the breast milk samples. The present study shows the lack of thyroid hormones in infant formulas compared to human milk and raises the question of whether formula-fed infants should be supplemented with thyroid hormones.

Genome-Wide Marker Data-Based Comparative Population Analysis of Szeklers From Korond, Transylvania, and From Transylvania Living Non-Szekler Hungarians.

Genome-wide genotype data from 48 carefully selected population samples of Transylvania-living Szeklers and non-Szekler Hungarians were analyzed by comparative analysis. Our analyses involved contemporary Hungarians living in Hungary, other Europeans, and Eurasian samples counting 530 individuals altogether. The source of the Szekler samples was the commune of Korond, Transylvania. The analyzed non-Szekler Hungarian samples were collected from villages with a history dating back to the era of the Árpád Dynasty. Population structure by principal component analysis and ancestry analysis also revealed a great within-group similarity of the analyzed Szeklers and non-Szekler Transylvanian Hungarians. These groups also showed similar genetic patterns with each other. Haplotype analyses using identity-by-descent segment discovering tools showed that average pairwise identity-by-descent sharing is similar in the investigated populations, but the Korond Szekler samples had higher average sharing with the Hungarians from Hungary than non-Szekler Transylvanian Hungarians. Average sharing results showed that both groups are isolated compared to other Europeans, and pointed out that the non-Szekler Transylvanian Hungarian inhabitants of the investigated Árpád Age villages are more isolated than investigated Szeklers from Korond. This was confirmed by our autozygosity analysis as well. Identity-by-descent segment analyses and 4-population tests also confirmed that these Hungarian-speaking Transylvanian ethnic groups are strongly related to Hungarians living in Hungary.

The characteristics and prognostic role of acute abdominal on-admission pain in acute pancreatitis: A prospective cohort analysis of 1432 cases.

INTRODUCTION: Pain is the most common symptom in acute pancreatitis (AP) and is among the diagnostic criteria. Therefore, we aimed to characterize acute abdominal pain in AP. METHODS: The Hungarian Pancreatic Study Group prospectively collected multicentre clinical data on 1435 adult AP patients between 2012 and 2017. Pain was characterized by its intensity (mild or intense), duration prior to admission (hours), localization (nine regions of the abdomen) and type (sharp, dull or cramping). RESULTS: 97.3% of patients (n = 1394) had pain on admission. Of the initial population with acute abdominal pain, 727 patients answered questions about pain intensity, 1148 about pain type, 1134 about pain localization and 1202 about pain duration. Pain was mostly intense (70%, n = 511/727), characterized by cramping (61%, n = 705/1148), mostly starting less than 24 h prior to admission (56.7%, n = 682/1202). Interestingly, 50.9% of the patients (n = 577/1134) had atypical pain, which means pain other than epigastric or belt-like upper abdominal pain. We observed a higher proportion of peripancreatic fluid collection (19.5% vs. 11.0%; p = 0.009) and oedematous pancreas (8.4% vs. 3.1%; p = 0.016) with intense pain. Sharp pain was associated with AP severity (OR = 2.481 95% CI: 1.550-3.969) and increased mortality (OR = 2.263, 95% CI: 1.199-4.059) compared to other types. Longstanding pain (>72 h) on admission was not associated with outcomes. Pain characteristics showed little association with the patient's baseline characteristics. CONCLUSION: A comprehensive patient interview should include questions about pain characteristics, including pain type. Patients with sharp and intense pain might need special monitoring and tailored pain management. SIGNIFICANCE: Acute abdominal pain is the leading presenting symptom in acute pancreatitis; however, we currently lack specific guidelines for pain assessment and management. In our cohort analysis, intense and sharp pain on admission was associated with higher odds for severe AP and several systemic and local complications. Therefore, a comprehensive patient interview should include questions about pain characteristics and patients with intense and sharp pain might need closer monitoring.

Nationwide effectiveness of five SARS-CoV-2 vaccines in Hungary-the HUN-VE study.

OBJECTIVES: The Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. This observational study (HUN-VE: Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million vaccinated individuals. METHODS: Incidence rates of SARS-CoV-2 infection and COVID-19-related mortality were calculated using data from the National Public Health Centre surveillance database. Estimated vaccine effectiveness was calculated as 1 - incidence rate ratio ≥7 days after the second dose for each available vaccine versus an unvaccinated control group using mixed-effect negative binomial regression controlling for age, sex and calendar day. RESULTS: Between 22 January 2021 and 10 June 2021, 3 740 066 Hungarian individuals received two doses of the BNT162b2 (Pfizer-BioNTech), HB02 (Sinopharm), Gam-COVID-Vac (Sputnik-V), AZD1222 (AstraZeneca), or mRNA-1273 (Moderna) vaccines. Incidence rates of SARS-CoV-2 infection and COVID-19-related death were 1.73-9.3/100 000 person-days and 0.04-0.65/100 000 person-days in the fully vaccinated population, respectively. Estimated adjusted effectiveness varied between 68.7% (95% CI 67.2%-70.1%) and 88.7% (95% CI 86.6%-90.4%) against SARS-CoV-2 infection, and between 87.8% (95% CI 86.1%-89.4%) and 97.5% (95% CI 95.6%-98.6%) against COVID-19-related death, with 100% effectiveness in individuals aged 16-44 years for all vaccines. CONCLUSIONS: Our observational study demonstrated the high or very high effectiveness of five different vaccines in the prevention SARS-CoV-2 infection and COVID-19-related death.

Hypoalbuminemia affects one third of acute pancreatitis patients and is independently associated with severity and mortality.

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (< 35 g/L) was 19% on admission and 35.7% during hospitalization. Hypoalbuminemia dose-dependently increased the risk of severity, mortality, local complications and organ failure and is associated with longer hospital stay. The predictive value of hypoalbuminemia on admission was poor for severity and mortality. Severe hypoalbuminemia (< 25 g/L) represented an independent risk factor for severity (OR 48.761; CI 25.276-98.908) and mortality (OR 16.83; CI 8.32-35.13). Albumin loss during AP was strongly associated with severity (p < 0.001) and mortality (p = 0.002). Hypoalbuminemia represents an independent risk factor for severity and mortality in AP, and it shows a dose-dependent relationship with local complications, organ failure and length of stay.

Effect of SARS-CoV-2 pandemic on blood product usage at the University of Pécs / A SARS-CoV-2-pandémia hatása a vérkészítmény-felhasználásra a Pécsi Tudományegyetemen.

Összefoglaló. Bevezetés: A COVID-19-világjárvány betegellátásra gyakorolt hatása hazánkban is jelentos. A vérellátást nehezítette a járványügyi intézkedések következményeként a véradási események elmaradása, a csökkent véradási hajlandóság, továbbá a nehezen megítélheto vérkészítményigény . A "Patient Blood Management" irányelveinek az orvosi gyakorlatban történo egyre szélesebb köru alkalmazása elosegíti az optimális vérkészítmény-felhasználást a transzfúziók lehetoség szerinti elkerülésével. Célkituzés és módszer: Vizsgálatunk célja a Pécsi Tudományegyetem Klinikai Központjának Janus Pannonius Klinikai Tömbjében a vérkészítmény-felhasználás változásainak felmérése volt a 2020. év elso öt hónapjában. Eredmények: A járványügyi intézkedéseket követo idoszakban szignifikánsan csökkent a hospitalizált betegeknek (34,08%), a transzfúziót igénylo betegeknek (39,69%) és a felhasznált vörösvérsejt-készítményeknek (46,41%) a száma, valamint az egy betegre jutó felhasznált vörösvérsejt-koncentrátum átlaga (2,61-rol 1,97-re) is. Közel 30%-os arányban csökkent a felhasznált friss fagyasztott plazma egységeinek és a thrombocytakoncentrátumoknak a száma is. Következtetés: A szigorú korlátozások életbe léptetését követoen a nehézségek ellenére sikerült elegendo mennyiségu vérkészítményt biztosítani a betegeknek. Az Országos Vérellátó Szolgálat Pécsi Regionális Vérellátó Központja munkatársainak és a klinikusok erofeszítéseinek köszönhetoen a vérkészítményigény és -kínálat között új egyensúly alakult ki, mely megfelelo ellátást biztosított a feltétlenül szükséges transzfúziók kivitelezéséhez. Orv Hetil. 2021; 162(43): 1717-1723. INTRODUCTION: The impact of COVID-19 pandemic on patient care is pronounced also in Hungary. Blood supply was hindered by the reduction of public blood donation events, the reduced willingness to donate, and the difficult predictability of blood product demand as a result of the epidemiological regulations. The wider application of Patient Blood Management guidelines in the medical practice will promote optimal blood product utilization by avoiding transfusions where possible. OBJECTIVE AND METHOD: The aim of our study was to assess the changes in the usage of blood products in the first five months of 2020 at the Clinical Center of the University of Pécs, Janus Pannonius Clinical Building. RESULTS: In the period following the epidemiological measures, we found reduction in the number of hospitalized patients (34.08%), in the number of patients requiring transfusion (39.69%) and in the number of red blood cell products used (46.41%). The number of transfused red blood cell concentrates per patient was also significantly reduced (from 2.61 to 1.97) in this period. The number of transfused fresh frozen plasma units and platelet concentrates also decreased by approximately 30%. CONCLUSION: After the implementation of the strict restrictions, despite the difficulties, it was possible to provide patients with sufficient blood products. Due to the efforts of both the Regional Blood Transfusion Center of Pécs of the Hungarian National Blood Transfusion Service and of the clinicians, a new balance was established between the demand and the supply of blood products, which provided adequate care for the necessary transfusions. Orv Hetil. 2021; 162(43): 1717-1723.

Urinary actin, as a potential marker of sepsis-related acute kidney injury: A pilot study.

INTRODUCTION: A major complication of sepsis is the development of acute kidney injury (AKI). Recently, it was shown that intracellular actin released from damaged tissues appears in the urine of patients with multiple organ dysfunction syndrome. Our aims were to measure urinary actin (u-actin) concentrations of septic and control patients and to test if u-actin levels could predict AKI and mortality. METHODS: Blood and urine samples were collected from septic and sepsis-related AKI patients at three time points (T1-3): T1: within 24 hours after admission; T2: second day morning; T3: third day morning of follow-up. Patients with malignancies needing palliative care, end-stage renal disease or kidney transplantation were excluded. Serum and u-actin levels were determined by quantitative Western blot. Patients were categorized by the Sepsis-3 and KDIGO AKI classifications. RESULTS: In our study, 17 septic, 43 sepsis-induced AKI and 24 control patients were enrolled. U-actin levels were higher in septic patients compared with controls during follow-up (p<0.001). At T1, the septic and sepsis-related AKI groups also showed differences (p<0.001), yet this increase was not statistically significant at T2 and T3. We also detected significantly elevated u-actin concentrations in AKI-2 and AKI-3 septic patients compared with AKI-1 septic patients (p<0.05) at T1 and T3, along with a significant increase in AKI-2 septic patients compared with AKI-1 septic patients at T2 (p<0.01). This tendency remained the same when referring u-actin to urine creatinine. Parameters of first-day septic patient samples could discriminate AKI from non-AKI state (AUC ROC, p<0.001): u-actin: 0.876; se-creatinine: 0.875. Derived cut-off value for u-actin was 2.63 µg/L (sensitivity: 86.0%, specificity: 82.4%). CONCLUSION: U-actin may be a complementary diagnostic biomarker to se-creatinine in sepsis-related AKI while higher u-actin levels also seem to reflect the severity of AKI. Further investigations may elucidate the importance of u-actin release in sepsis-related AKI.

O-GlcNAcylation in early stages of chronic lymphocytic leukemia: Protocol development for flow cytometry.

BACKGROUND: Recent studies proved that metabolic changes in malignant disorders have an impact on protein glycosylation, however, only a few attempts have been made so far to use O-GlcNAc analysis as a prognostic tool. Glucose metabolism is reported to be altered in hematological malignancies thus, we hypothesized that monitoring intracellular O-GlcNAc levels in Rai stage 0-I (Binet A) CLL patients could give deeper insights regarding subtle metabolic changes of progression which are not completely detected by the routine follow-up procedures. OBJECTIVE: In this proof of concept study we established a flow cytometric detection method for the assessment of O-GlcNAcylation as a possible prognostic marker in CLL malignancy which was supported by fluorescence microscopy. METHODS: Healthy volunteers and CLL patients were recruited for this study. Lymphocytes were isolated, fixed and permeabilised by various methods to find the optimal experimental condition for O-GlcNAc detection by flow cytometry. O-GlcNAc levels were measured and compared to lymphocyte count and various blood parameters including plasma glucose level. RESULTS: The protocol we developed includes red blood cell lysis, formalin fixation, 0.1% Tween 20 permeabilisation and employs standardized cell number per sample and unstained controls. We have found significant correlation between O-GlcNAc levels and WBC (R2= 0.8535, p< 0.0029) and lymphocyte count (R2= 0.9225, p< 0.0006) in CLL patients. Interestingly, there was no such correlation in healthy individuals (R2= 0.05664 for O-GlcNAc vs WBC and R2= 0.04379 for O-GlcNAc vs lymphocytes). CONCLUSION: Analyzing O-GlcNAc changes in malignant disorders, specifically in malignant hematologic diseases such as CLL, could be a useful tool to monitor the progression of the disease.

Early occurrence of pseudocysts in acute pancreatitis - A multicenter international cohort analysis of 2275 cases.

BACKGROUND: Pseudocysts being the most frequent local complications of acute pancreatitis (AP) have substantial effect on the disease course, hospitalization and quality of life of the patient. Our study aimed to understand the effects of pre-existing (OLD-P) and newly developed (NEW-P) pseudocysts on AP. METHODS: Data were extracted from the Acute Pancreatitis Registry organized by the Hungarian Pancreatic Study Group (HPSG). 2275 of 2461 patients had uploaded information concerning pancreatic morphology assessed by imaging technique. Patients were divided into "no pseudocyst" (NO-P) group, "old pseudocyst" (OLD-P) group, or "newly developed pseudocyst" (NEW-P) groups. RESULTS: The median time of new pseudocyst development was nine days from hospital admission and eleven days from the beginning of the abdominal pain. More NEW-P cases were severe (15.9% vs 4.7% in the NO-P group p < 0.001), with longer length of hospitalization (LoH) (median: 14 days versus 8 days, p < 0.001), and were associated with several changed laboratory parameters. OLD-P was associated with male gender (72.2% vs. 56.1%, p = 0.0014), alcoholic etiology (35.2% vs. 19.8% in the NO-P group), longer hospitalization (median: 10 days, p < 0.001), a previous episode of AP (p < 0.001), pre-existing diagnosis of chronic pancreatitis (CP) (p < 0.001), current smoking (p < 0.001), and increased alcohol consumption (unit/week) (p = 0.014). CONCLUSION: Most of the new pseudocysts develop within two weeks. Newly developing pseudocysts are associated with a more severe disease course and increased length of hospitalization. Pre-existing pseudocysts are associated with higher alcohol consumption and smoking. Because CP is more frequently associated with a pre-existing pseudocyst, these patients need closer attention after AP.

Involvement of the Catecholamine Pathway in Glioblastoma Development.

Glioblastoma (GBM) is the most aggressive tumor of the central nervous system (CNS). The standard of care improves the overall survival of patients only by a few months. Explorations of new therapeutic targets related to molecular properties of the tumor are under way. Even though neurotransmitters and their receptors normally function as mediators of interneuronal communication, growing data suggest that these molecules are also involved in modulating the development and growth of GBM by acting on neuronal and glioblastoma stem cells. In our previous DNA CpG methylation studies, gene ontology analyses revealed the involvement of the monoamine pathway in sequential GBM. In this follow-up study, we quantitated the expression levels of four selected catecholamine pathway markers (alpha 1D adrenergic receptor-ADRA1D; adrenergic beta receptor kinase 1 or G protein-coupled receptor kinase 2-ADRBK1/GRK2; dopamine receptor D2-DRD2; and synaptic vesicle monoamine transporter-SLC18A2) by immunohistochemistry, and compared the histological scores with the methylation levels within the promoters + genes of these markers in 21 pairs of sequential GBM and in controls. Subsequently, we also determined the promoter and gene methylation levels of the same markers in an independent database cohort of sequential GBM pairs. These analyses revealed partial inverse correlations between the catecholamine protein expression and promoter + gene methylation levels, when the tumor and control samples were compared. However, we found no differences in the promoter + gene methylation levels of these markers in either our own or in the database primary-recurrent GBM pairs, despite the higher protein expression of all markers in the primary samples. This observation suggests that regulation of catecholamine expression is only partially related to CpG methylation within the promoter + gene regions, and additional mechanisms may also influence the expression of these markers in progressive GBM. These analyses underscore the involvement of certain catecholamine pathway markers in GBM development and suggest that these molecules mediating or modulating tumor growth merit further exploration.