Tanulással összefüggő előagyi rendszerek madarakban = Learning-associated forebrain systems in birds

A kutatóprogram a viselkedés motivációjának idegi alapjait vizsgálja multidiszciplináris megközelítéssel, madár idegrendszeri modell felhasználásával. A vizsgálatból extrapolálható eredmények felhasználhatók az emlős viszonyok leírására és értelmezésére is. A kutatócsoport korábbi nemzetközi tapasztalataira épülő program megvalósításával a következő területeken értünk el eredményeket: (1) A tanulással és motivációval összefüggő agyterületek (thalamus, septum, nucl. accumbens, ventralis tegmentalis area) funkciós morfológiai jellemzése. Ezen belül a jutalmazásban és addikcióban kulcsszerepet játszó nucleus accumbens pontos lokalizációja, szubdiviziói és kapcsolatrendszerének feltárása madarakon, valamint az amygdalo-accumbens pályarendszer elhárító tanulásban játszott szerepének igazolása; (2) Dopaminerg és dopaminoceptív neuronrendszerek szerepe háziszárnyas tanulási és motivációs folyamataiban. Dopamin receptor antagonisták hatása a memória retenciójára. Striato-tegmentalis pályarendszerek és szelektív projekciókkal rendelkező neuronjaik jellemzése. (3) A serkentő neurotranszmitterek és a dopamin striatalis kölcsönhatása, motivációban, döntéshozatalban és tanulásban játszott szerepe. Az aszpartát sajátos magatartásfüggő szerepének kimutatása a striatum és a törzsdúcok neurális hálózatában. (4) Cannabinoid receptorok megoszlása és a tanulási folyamatra gyakorolt hatása. | In the research program we investigated the neural foundations of motivation, using multidisciplinary approach and the avian nervous system as a model. The results extrapolated from the study may be adapted also for the description and interpretation of mammalian systems. Based upon international experience of the group, progress has been made primarily in the following areas: (1) Functional morphological characterisation of learning and behaviour associated brain regions (thalamus, septum, nucl. accumbens, ventral tegmental area). In particular, precise localization of the nucleus accumbens, its subdivisions and connectivity, and evidence for the role of amygdalo-accumbens pathway in avoidance learning. (2) The role of dopaminergic and dopaminoceptive neuronal systems in learning and motivation of domestic chicks. Effect of dopamine receptor antagonists on memory retention. Characterisation of striato-tegmental pathways and neurons with selective projections. (3) Striatal interaction between excitatory transmitter amino acids and dopamine, its role in motivation, decision-making and learning. Verification of specific behaviour-linked effect of the excitatory transmitter aspartate in the neural circuits of striatum and basal ganglia. (4) Tissue distribution of cannabinoid receptors and their effect on the learning process

Aging and Comorbidities in Acute Pancreatitis II.: A Cohort-Analysis of 1203 Prospectively Collected Cases

Introduction: Our meta-analysis indicated that aging influences the outcomes of acute pancreatitis (AP), however, a potential role for comorbidities was implicated, as well. Here, we aimed to determine how age and comorbidities modify the outcomes in AP in a cohort-analysis of Hungarian AP cases.Materials and Methods: Data of patients diagnosed with AP by the revised Atlanta criteria were extracted from the Hungarian Registry for Pancreatic Patients. Outcomes of interest were mortality, severity, length of hospitalization, local, and systemic complications of AP. Comorbidities were measured by means of Charlson Comorbidity Index (CCI) covering pre-existing chronic conditions. Non-parametric univariate and multivariate statistics were used in statistical analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.Results: A total of 1203 patients from 18 centers were included. Median age at admission was 58 years (range: 18–95 years), median CCI was 2 (range: 0–10). Only severe comorbidities (CCI ≥ 3) predicted mortality (OR = 4.48; CI: 1.57–12.80). Although severe comorbidities predicted AP severity (OR = 2.10, CI: 1.08–4.09), middle (35–64 years) and old age (≥65 years) were strong predictors with borderline significance, as well (OR = 7.40, CI: 0.99–55.31 and OR = 6.92, CI: 0.91–52.70, respectively). Similarly, middle and old age predicted a length of hospitalization ≥9 days. Interestingly, the middle-aged patients (35–64 years) were three times more likely to develop pancreatic necrosis than young adults (OR = 3.21, CI: 1.26–8.19), whereas the old-aged (≥65 years) were almost nine times more likely to develop systemic complications than young adults (OR = 8.93, CI: 1.20–66.80), though having severe comorbidities (CCI ≥ 3) was a predisposing factor, as well.Conclusion: Our results proved that both aging and comorbidities modify the outcomes of AP. Comorbidities determine mortality whereas both comorbidities and aging predict severity of AP. Regarding complications, middle-aged patients are the most likely to develop local complications; in contrast, those having severe comorbidities are prone to develop systemic complications. Studies validating the implementation of CCI-based predictive scores are awaited

Metabolic-Associated Fatty Liver Disease is associated with Acute Pancreatitis with More Severe Course: Post hoc Analysis of a Prospectively Collected International Registry

Non-alcoholic fatty liver disease (NAFLD) is a proven risk factor for acute pancreatitis (AP). However, NAFLD has recently been redefined as metabolic-associated fatty liver disease (MAFLD). In this post hoc analysis, we quantified the effect of MAFLD on the outcomes of AP.We identified our patients from the multicentric, prospective International Acute Pancreatitis Registry of the Hungarian Pancreatic Study Group. Next, we compared AP patients with and without MAFLD and the individual components of MAFLD regarding in-hospital mortality and AP severity based on the revised Atlanta classification. Lastly, we calculated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regression analysis.MAFLD had a high prevalence in AP, 39% (801/2053). MAFLD increased the odds of moderate-to-severe AP (OR = 1.43, CI: 1.09-1.89). However, the odds of in-hospital mortality (OR = 0.89, CI: 0.42-1.89) and severe AP (OR = 1.70, CI: 0.97-3.01) were not higher in the MAFLD group. Out of the three diagnostic criteria of MAFLD, the highest odds of severe AP was in the group based on metabolic risk abnormalities (OR = 2.68, CI: 1.39-5.09). In addition, the presence of one, two, and three diagnostic criteria dose-dependently increased the odds of moderate-to-severe AP (OR = 1.23, CI: 0.88-1.70, OR = 1.38, CI: 0.93-2.04, and OR = 3.04, CI: 1.63-5.70, respectively) and severe AP (OR = 1.13, CI: 0.54-2.27, OR = 2.08, CI: 0.97-4.35, and OR = 4.76, CI: 1.50-15.4, respectively). Furthermore, in patients with alcohol abuse and aged ≥60 years, the effect of MAFLD became insignificant.MAFLD is associated with AP severity, which varies based on the components of its diagnostic criteria. Furthermore, MAFLD shows a dose-dependent effect on the outcomes of AP

Multiple Hits in Acute Pancreatitis: Components of Metabolic Syndrome Synergize Each Other's Deteriorating Effects

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Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis: a cross-sectional multicentre international study with experimental animal model

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare

Detailed characteristics of post-discharge mortality in acute pancreatitis

The in-hospital survival of patients suffering from acute pancreatitis (AP) is 95-98%. However, there is growing evidence that patients discharged after AP may be at risk of serious morbidity and mortality. Here, we aimed to investigate the risk, causes, and predictors of the most severe consequence of the post-AP period: mortality.2,613, well-characterized patients from twenty-five centers were collected and followed by the Hungarian Pancreatic Study Group between 2012 and 2021. A general and a hospital-based population was used as the control group.After an AP episode patients have an approximately three-fold higher incidence rate of mortality than the general population (0.0404vs.0.0130 person-years). First-year mortality after discharge was almost double than in-hospital mortality (5.5%vs.3.5%), with 3.0% occurring in the first 90-day period. Age, comorbidities, and severity were the most significant independent risk factors for death following AP. Furthermore, multivariate analysis identified creatinine, glucose, and pleural fluid on admission as independent risk factors associated with post-discharge mortality. In the first 90-day period, cardiac failure and AP-related sepsis were among the main causes of death following discharge, while cancer-related cachexia and non-AP-related infection were the key causes in the later phase.Almost as many patients in our cohort die in the first 90-day period after discharge as during their hospital stay. Evaluation of cardiovascular status, follow-up of local complications, and cachexia-preventing oncological care should be an essential part of post-AP patient care. Future study protocols in AP must include at least a 90-day follow-up period after discharge