Circadian ritmusos biológiai folyamatok mechanizmusának vizsgálata madár tobozmirigy modellen. = Mechanisms of circadian rhythmic biological processes - studies on avian pineal gland.

Kimutattuk, hogy a csirke tobozmirigyben a filogenetikailag ismertebb óragének többsége, a Clock, Bmal1, Bmal2, Per1, Per2, Per3, Cry1 és Cry2 expresszálódik. A Cry1, Cry2, Bmal2 és a Clock óragének mRNS-eit sikerült kimutatni 15 napos csirke embriók tobozmirigyeiből is, valamint a kikelt állatokban mért mRNS ritmushoz fázisban hasonló mintázatot mértünk 18 napos csirke embriókban is. Az óragének expressziós mintázatát mind az éjszaka alkalmazott megvilágítás, mind az in vitro alkalmazott PACAP kezelés megváltoztatta. Kimutattuk, hogy a MT és cAMP koncentrációjának napszakos ritmusa a 16-18. embrionális napokon jelenik meg in vitro körülmények között is. A ritmikus szekréció kialakulása azonban periodikus ingerek nélkül késik. Igazoltuk, hogy bár a tobozmirigy fény-receptorai már a 14. embrionális napon is működőképesek, a fényingernek még nincs direkt, in vitro a corpus pinealéra gyakorolt szinkronizáló hatása. Ugyanakkor a 18. embrionális naptól kezdve a csirke tobozmirigy már a rendkívül alacsony intenzitású (10 lux) megvilágítással is vezérelhető. Eredményeink szerint mind a PACAP, mind a VIP már a 13. embrionális napon fokozza a cAMP és a melatonin termelést, de a ritmus fejlődését, illetve annak fázisát nem változtatja meg. Kimutattuk, hogy a tobozmirigy in vitro MT szekrécióját a környezeti hőmérséklet periodikusan alkalmazott, mindössze három órás megváltoztatása is módosítja, a hőmérséklet változására adott válasz azonban az állat életkorának függvénye. | We have demonstrated that most of the known, philogenetically conserved clock genes (Clock, Bmal1, Bmal2, Per1, Per2, Per3, Cry1 and Cry2) are expressed in the chicken pineal gland. Expression of Cry1, Cry2, Bmal2 and Clock mRNA-s were shown also in the pineal glands of chicken embryos. Similar 24-h pattern of clock gene expression were detected in 18 day old chicken embryos and in post hatched chickens (6 weeks old). The expression patterns of clock genes were altered by light exposure at subjective night and also by in vitro PACAP administration. It was shown, that the circadian rhythm of both MT secretion and cAMP efflux appears on the 16-18th embryonic days, even in vitro. Without periodic environmental stimuli, the development of the MT rhythm was delayed. Although the light receptors of the pineal gland were found to be responsive to light from the 14th embryonic day, the illumination did not have a synchronizing effect on the in vitro MT secretion at this age. However, from the 18th day, the pineal MT secretion could be controlled by illumination with even the very low intensity (10 lux). Our results showed that both PACAP and VIP induced an increase in both cAMP and MT secretion already from the 13th day of embryonic life, but none of these drugs influenced the development or the phase of the MT rhythm. It was presented that the in vitro MT secretion could be modified age-dependently by only 3 hour-long daily alterations of environmental temperature

Egy diagnosztikus kihívás: paraduodenalis pancreatitis. Két eset bemutatása = A diagnostic challenge: paraduodenal pancreatitis. Two case reports

Absztrakt: A paraduodenalis, vagy groove pancreatitis egy kevéssé ismert krónikus hasnyálmirigygyulladás-típus, mely malignitást utánozva sokszor differenciáldiagnosztikai nehézségeket okoz. Közleményünkben két esetet mutatunk be: mindkét esetben műtéti reszekcióra volt szükség a biztos diagnózishoz, az inadekvát preoperatív szövettani mintavétel és a klinikai kép miatt. A képalkotó vizsgálatok az első esetben malignitás gyanúját vetették fel, a második esetben gyomorürülési zavar indikálta a reszekciót. Irodalmi áttekintést adunk az elváltozás klinikopatológiájáról, beleértve annak epidemiológiáját, klinikai megjelenését és az alkalmazható diagnosztikus módszereket, a betegség makroszkópos és mikroszkópos patomorfológiáját. Kialakulásának háttere összetett: az alkohol patogenetikai szerepe mellett a pancreaticus ductalis rendszer anatómiai variációi, a dorsalis pancreas inkomplett involúciójából származó duodenumfali pancreasszigetek vagy az elváltozás részeként gyakran megfigyelt Brunner-mirigy-hyperplasia is szerepet játszhat a minor papilla területén jelentkező pancreasnedv-elfolyási zavarban, mely a jellegzetes lokalizációjú gyulladáshoz vezet. A legfrissebb kutatások génpolimorfizmusok hajlamosító szerepét is kimutatták a hasnyálmirigy gyulladásos folyamataiban. A paraduodenalis pancreatitis differenciáldiagnosztikájának kérdése mellett a terápiás lehetőségekről is szót ejtünk, kiemelve a sikeres elkülönítés esetén jó hatásfokkal alkalmazható konzervatív kezelés lehetőségét. Orv Hetil. 2019; 160(22): 873–879. | Abstract: The paraduodenal, or groove pancreatitis is a lesser-known type of chronic pancreatitis, often mimicking malignancy, hence resulting in serious differential diagnostic challenges. Herein we report two cases of this entity. Both required analysis of the surgical specimen in order to ensure the diagnosis due to inadequate preoperative histological sampling and a vague clinical presentation. In the first case, strong suspicion of malignancy following imaging, while in the second, severe gastric outlet stenosis indicated the resection. In our report, we give a clinicopathological summary from the literature of this entity, including its epidemiology, clinical presentation and applicable diagnostic methods as well as macroscopic and microscopic pathomorphology. The pathogenesis of this disease is complex. Beside the role of alcohol, anatomic variations of the pancreatic ductal system, pancreatic islets in duodenal wall resulting from incomplete involution of dorsal pancreas, or Brunner gland hyperplasia (often observed as part of the lesion) can all play a role in the disturbance of pancreatic fluid discharge in the minor papilla area, eventually leading to this specific localised inflammation. In addition, recent investigations revealed a susceptible role of genetic polymorphism in the persistent inflammatory disorders of the pancreas. Besides summarizing the differential diagnostic aspects, we also discuss therapeutic possibilities, underlining the conservative methods, which can be used with good efficacy after a successful identification of this entity. Orv Hetil. 2019; 160(22): 873–879

Infliximabterápia mellett kialakuló appendicitis perianalis Crohn-betegben = Acute appendicitis in a patient with perianal Crohn’s disease receiving infliximab

Absztrakt: A Crohn-betegek akut hasi panaszai gyakori forrásai a nehéz differenciáldiagnosztikai helyzeteknek. Különösen igaz ez a biológiai terápiában részesülő, remisszióban lévő betegek esetében. Az akut exacerbatio mellett más gyakori kórképekre, például az oly hasonló tünettannal fellépő, igen gyakran atípusos megjelenésű akut appendicitis jelenlétére minden korosztályban gondolni kell. Infliximabterápia mellett remisszióban lévő perianalis Crohn-betegség esetében az akutan kialakuló ileocaecalis manifesztáció valószínűsége alacsony – még akkor is, ha a laboratóriumi és képalkotó vizsgálatok ezt látszanak alátámasztani. Esetünkben egy perianalis Crohn-betegség miatt infliximabterápiában részesülő középkorú nőbetegnél a remisszió ideje alatt fellépő akut hasi tünetek miatt műtétet indikáltunk, mely perforált appendicitist igazolt. Orv Hetil. 2018; 159(10): 405–409. | Abstract: The differential diagnosis of acute abdominal complaints is challenging in Crohn’s disease. This is particularly true in patients in remission induced by biological therapy. In addition to the acute relapse of Crohn’s disease, other common causes, such as acute appendicitis exhibiting similar and often atypical course, should be taken into consideration irrespective of the age. An ileocecal flare-up is unlikely to occur in patients with perianal Crohn’s disease in remission induced by infliximab even if laboratory and radiological findings point towards this diagnosis. We report the case of a middle-aged woman in remission induced by infliximab who developed acute abdominal symptoms due to perforated appendicitis. Orv Hetil. 2018; 159(10): 405–409

Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended

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

Early prediction of acute necrotizing pancreatitis by artificial intelligence : a prospective cohort-analysis of 2387 cases

Pancreatic necrosis is a consistent prognostic factor in acute pancreatitis (AP). However, the clinical scores currently in use are either too complicated or require data that are unavailable on admission or lack sufficient predictive value. We therefore aimed to develop a tool to aid in necrosis prediction. The XGBoost machine learning algorithm processed data from 2387 patients with AP. The confidence of the model was estimated by a bootstrapping method and interpreted via the 10th and the 90th percentiles of the prediction scores. Shapley Additive exPlanations (SHAP) values were calculated to quantify the contribution of each variable provided. Finally, the model was implemented as an online application using the Streamlit Python-based framework. The XGBoost classifier provided an AUC value of 0.757. Glucose, C-reactive protein, alkaline phosphatase, gender and total white blood cell count have the most impact on prediction based on the SHAP values. The relationship between the size of the training dataset and model performance shows that prediction performance can be improved. This study combines necrosis prediction and artificial intelligence. The predictive potential of this model is comparable to the current clinical scoring systems and has several advantages over them

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.Peer reviewe