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Bevezetés: Jelenleg nincsenek egyértelmű ajánlások a nem infrarenalis hasi aortaaneurysmák sebészi kezelésének ideális technikájáról. Célkitűzés: Jelenlegi vizsgálatunk célja volt elemezni az intakt fallal rendelkező, nem infrarenalis abdominalis aortaaneurysmák miatt nyitott műtéten átesett betegek mortalitását és a proximalis aortakirekesztés szintjének a posztoperatív eredményekre gyakorolt hatását. Módszer: Retrospektív egyközpontú vizsgálatunk az intakt, nem infrarenalis hasi aortaaneurysmák miatt 2005 és 2017 között a Semmelweis Egyetem Szív- és Érgyógyászati Klinikáján nyitott műtéten átesett betegek eredményeit tekinti át. A tanulmány elsődleges végpontja a 30 napos, 1, 2 és 5 éves mortalitás, másodlagos végpontjai a posztoperatív akut vesekárosodás, valamint a súlyos posztoperatív szövődmények voltak. Az adatokat két csoportban elemeztük a műtét során alkalmazott proximalis aortakirekesztés helye alapján: juxta/pararenalis aortaaneurysmák; inter/suprarenalis aortakirekesztés, suprarenalis aortaaneurysmák; supracoeliacalis kirekesztés. Eredmények: Klinikánkon 94 páciens esett át nyitott aortaműtéten, amely legalább az egyik veseartéria szintje feletti aortakirekesztéssel járt. Az utánkövetési idő 3,14 (IQR: 1,55–5,00) év, a 30 napos, 1, 2 és 5 éves mortalitás 9%, 20%, 27% és 48% volt. A 30 napos és 1 éves mortalitás szignifikánsan alacsonyabb volt a juxta/pararenalis aortaaneurysma miatt operált betegek között. Szignifikánsan többször fordultak elő súlyos posztoperatív szövődmények a suprarenalis aneurysma miatt kezelt páciensek körében a juxta- és pararenalis aneurysma miatt operáltakhoz képest. Az akut vesekárosodás perioperatív incidenciája 54%, a kórházi elbocsátáskor 30% volt. A kórházi bent fekvés ideje alatt jelentősen több akut veseműködési zavart észleltünk a suprarenalis aneurysma miatt operált pácienseknél, a betegek hazabocsátásakor azonban a két csoport között már nem volt szignifikáns különbség. Következtetés: A suprarenalis aortaaneurysmák nyitott műtéte nagyobb morbiditással, korai és középtávú mortalitással jár, mint a juxta/pararenalis aortaaneurysmáké. A preoperatív krónikus veseelégtelenség és a súlyos posztoperatív szövődmények a közép- és hosszú távú mortalitás független prediktív tényezői. Orv Hetil. 2022; 163(37): 1472–1480.

Methane (CH4), which is produced endogenously in animals and plants, was recently suggested to play a role in cellular physiology, potentially influencing the signaling pathways and regulatory mechanisms involved in nitrosative and oxidative stress responses. In addition, it was proposed that the supplementation of CH4 to organisms may be beneficial for the treatment of several diseases, including ischemia, reperfusion injury, and inflammation. However, it is still unclear whether and how CH4 is produced in mammalian cells without the help of microorganisms, and how CH4 might be involved in physiological processes in humans. In this study, we produced the first evidence of the principle that CH4 is formed non-microbially in the human body by applying isotopically labeled methylated sulfur compounds, such as dimethyl sulfoxide (DMSO) and methionine, as carbon precursors to confirm cellular CH4 formation. A volunteer applied isotopically labeled (2H and 13C) DMSO on the skin, orally, and to blood samples. The monitoring of stable isotope values of CH4 convincingly showed the conversion of the methyl groups, as isotopically labeled CH4 was formed during all experiments. Based on these results, we considered several hypotheses about endogenously formed CH4 in humans, including physiological aspects and stress responses involving reactive oxygen species (ROS). While further and broader validation studies are needed, the results may unambiguously serve as a proof of concept for the endogenous formation of CH4 in humans via a radical-driven process. Furthermore, these results might encourage follow-up studies to decipher the potential physiological role of CH4 and its bioactivity in humans in more detail. Of particular importance is the potential to monitor CH4 as an oxidative stress biomarker if the observed large variability of CH4 in breath air is an indicator of physiological stress responses and immune reactions. Finally, the potential role of DMSO as a radical scavenger to counteract oxidative stress caused by ROS might be considered in the health sciences. DMSO has already been investigated for many years, but its potential positive role in medical use remains highly uncertain.

Augmentation cystoplasty is an exemplary multiorgan intervention in urology which is particularly associated with microvascular damage. Our aim was to review the available intravital imaging techniques and data obtained from clinical and experimental microcirculatory studies involving the most important donor organs applied in bladder augmentation. Although numerous direct or indirect methods are available to assess the condition of microvessels the implementation of microcirculatory diagnostic methods in humans is still challenging and the assessment of organ microcirculation in the operating theatre has limitations. Nevertheless, preclinical studies generally report good internal validity and although prospective human protocols with reduced variability are needed, a possible positive impact of microcirculatory diagnostics on the clinical outcomes of urologic surgery can be anticipated.

Összefoglaló. Bevezetés: Az elmúlt évtizedekben számos országban jelentős mértékben változott a hasi aortaaneurysmák sebészi kezelése az eredményesebb ellátás céljából: endovascularis beavatkozások terjedése, nagy betegforgalmú aortacentrumok kialakítása. Célkitűzés: A Magyarországon, infrarenalis aortaaneurysmák miatt végzett beavatkozások rövid távú eredményeinek elemzése elsősorban műtéti technika (endovascularis vs. nyitott aortareconstructio), intézeti betegforgalom (kis vs. nagy betegforgalmú intézet) és időszak (2010–2014 vs. 2015–2019) alapján. Módszer: A Nemzeti Érsebészeti Regiszterben 2010. 01. 01. és 2019. 12. 31. között prospektíven rögzített multicentrikus adatok retrospektív feldolgozása. Eredmények: A regiszterben 3206 infrarenalis aortaaneurysma-műtétet rögzítettek. A második öt évben jelentősen nőtt az endovascularis aortareconstructio aránya a nyitotthoz képest (pKövetkeztetés: Endovascularis aortareconstructio és nagy betegforgalmú intézetek esetében szignifikánsan alacsonyabb perioperatív mortalitás érhető el. Orv Hetil. 2021; 162(31): 1233–1243. Summary. Introduction: The organisation of aortic disease care has changed significantly in many countries over the last decade: centralized, high-volume centers were established. Objective: To analyse the perioperative mortality and the number of the infrarenal aortic aneurysm repairs according to the type of procedure (endovascular vs. open), patient volume (low vs. high) and time period (2010–2014 vs. 2015–2019). Methods: The multicentric data registered prospectively in the Hungarian National Vascular Registry between 01. 01. 2010 and 31. 12. 2019 were analysed retrospectively. Results: 3206 infrarenal aortic aneurysms were recorded. The endovascular-open repair rate was significantly higher (pConclusion: Endovascular repair and aortic surgery in the high-volume institutes result in significantly lower perioperative mortality. Orv Hetil. 2021; 162(31): 1233–1243.

Albeit previous experiments suggest potential anti‐inflammatory effect of exogenous methane (CH4) in various organs, the mechanism of its bioactivity is not entirely understood. We aimed to investigate the potential mitochondrial effects and the underlying mechanisms of CH4 in rat cardiomyocytes and mitochondria under simulated ischaemia/reperfusion (sI/R) conditions. Three‐day‐old cultured cardiomyocytes were treated with 2.2% CH4‐artificial air mixture during 2‐hour‐long reoxygenation following 4‐hour‐long anoxia (sI/R and sI/R + CH4, n = 6‐6), with normoxic groups serving as controls (SH and SH + CH4; n = 6‐6). Mitochondrial functions were investigated with high‐resolution respirometry, and mitochondrial membrane injury was detected by cytochrome c release and apoptotic characteristics by using TUNEL staining. CH4 admixture had no effect on complex II (CII)‐linked respiration under normoxia but significantly decreased the complex I (CI)‐linked oxygen consumption. Nevertheless, addition of CH4 in the sI/R + CH4 group significantly reduced the respiratory activity of CII in contrast to CI and the CH4 treatment diminished mitochondrial H2O2 production. Substrate‐induced changes to membrane potential were partially preserved by CH4, and additionally, cytochrome c release and apoptosis of cardiomyocytes were reduced in the CH4‐treated group. In conclusion, the addition of CH4 decreases mitochondrial ROS generation via blockade of electron transport at CI and reduces anoxia‐reoxygenation‐induced mitochondrial dysfunction and cardiomyocyte injury in vitro.

Összefoglaló. Az alsó húgyutak fő funkciója a vizelet tárolása és ürítése, amely működések zavara az úgynevezett alsó húgyúti tünetegyüttes kialakulásához vezet, ami a kiváltó októl függően vizeletürítési zavarral és vizeletretencióval is járhat. Kezeletlen esetekben a felső húgyutak károsodása következik be a magas hólyagnyomás által kiváltott vesicoureteralis reflux következtében, amely ureter- és veseüregrendszeri tágulat kialakulására, illetve fertőzésekre és kőképződésre hajlamosít. A vizelettárolási/vizeletürítési zavarokat három fő csoportba sorolhatjuk, úgymint stressz- (terheléses) inkontinencia , hiperaktív hólyag (nedves/száraz) és neurogén hólyag. A jelen összefoglaló közlemény tárgyát képező neurogén hólyag egy gyűjtőfogalom, mely magában foglal minden, releváns neurológiai kórkép talaján kialakult vizelettárolási és vizeletürítési zavart. Mivel a húgyhólyag mellett a záróizomzat és a hátsó húgycső is érintett, ezt a kórképet napjainkban „neurogén alsó húgyúti diszfunkció” elnevezéssel is szokás illetni. A kórállapotot a neurológiai diszfunkciók széles spektruma okozhatja, kezdve a helyi funkcionális zavartól a helyi idegi sérülésen át a felső és alsó motoneuron-sérülésig vagy a centrális degeneratív folyamatokig. Az eltérő etiológia ellenére a klinikai tünetek rendszerint két alapvető klinikai típusban manifesztálódhatnak: túlműködő (fokozott detrusorkontraktilitást okozó automata) hólyag vagy alulműködő hólyag formájában. Tekintettel a neurogén alsó húgyúti diszfunkció következtében létrejövő felső húgyúti komplikációkra, a közlemény egyik célja a betegség diagnózisát segítő algoritmus bemutatása a legújabb nemzetközi szakirodalmi ismeretek alapján. A neurogén hólyag kezelése jobbára nem terjedhet ki a kiváltó ok kezelésére, ezért a jelen összefoglaló másik célja azon gyógyszeres és invazív terápiás beavatkozások összefoglalása, melyek a felső húgyutak védelmét szolgálják az alacsony hólyagnyomás fenntartása révén. Orv Hetil. 2021; 162(4): 135–143. Summary. Storage and urination are the main functions of the lower urinary tract and its lesions lead to the so-called lower urinary tract syndrome causing either urinary incontinence or retention. In untreated cases, the upper urinary tract becomes injured via a vesicoureteral reflux resulting from increased bladder pressure and resultant dilations of the ureter and the renal pelvis which predispose to infection and stone formation. Lower urinary tract storage/urination disorders can be classified as stress incontinence, hyperactive bladder (wet/dry) and neurogenic bladder. Neurogenic bladder which is the subject of this review, is a collective term that encompasses all urinary storage and emptying disorders which develop on the basis of neurological diseases. Being not only the bladder, but also the sphincter and posterior urethra (generally termed as the “bladder outlet”) affected, nowadays this condition is referred to as “neurogenic lower urinary tract dysfunction”. A wide range of neurological dysfunctions could contribute to the development of this condition, ranging from local dysfunction (autonomic dysreflexia) or local nerve injury to upper/lower motoneuron injury or central degenerative processes. Regardless of the diverse etiology, the clinical symptoms eventually manifest in two major forms, i.e., overacting (automatic bladder with increased detrusor contractility) and underactive bladder. Considering the severity of complication occurring in the upper urinary tract in response to the pathophysiological changes in the lower urinary tract, one of the aims of this paper was to present an algorithm aiming to build up a state of the art diagnosis of the disease based on current international literature data. Since treatment of the neurogenic bladder usually can not target elimination of the underlying cause, the other goal of the present paper is to summarize the pharmacological treatment regimen and invasive therapeutic interventions that protect the upper urinary tract by maintaining low pressure values in the bladder. Orv Hetil. 2021; 162(4): 135–143.

Introduction: Solid evidence is not available on the ideal technique of surgical repair (open or endovascular) of noninfrarenal abdominal aortic aneurysms. Objective: Our aim was to analyze the postoperative effect of mortality and the level of proximal cross-clamping of the patients who underwent open surgical aortic repair of non-infrarenal abdominal aortic aneurysms with intact wall. Method: This is a retrospective, single-centre study, which reviews the results of open surgical repair, performed for intact non-infrarenal abdominal aorta aneurysms between 2005 and 2017. Aneurysms were analyzed in two groups, based on the level of aortic cross-damping: juxta-pararenal aortic aneurysm group with inter- or suprarenal aortic cross-clamping and suprarenal aortic aneurysm group with supraceliac aortic cross-clamping. Primary endpoints were 30-day, 1-, 2- and 5-year mortality. Secondary endpoints were postoperative acute kidney injury, including hemodialysis, and major postoperative complications. Results: In our clinic, 94 patients underwent open surgical aortic repair with cross-clamping above at least one renal artery. The median follow-up was 3.14 (1.55-5.00) years. The overall 30-day, 1-, 2- and 5-year mortality were 9%, 20%, 27% and 48%, respectively. The mortality was significantly lower in the juxta/pararenal abdominal aortic aneurism group at 30 day and 1 year. The overall perioperative incidence of acute kidney injury was 54% and 30% at discharge. Significantly more in-hospital acute renal dysfunction was noticed in the patients with suprarenal aortic aneurysm than with juxta/pararenal aneurysm, however, the difference was not significant at discharge. Major postoperative complications were more frequent in the suprarenal aneurysm group. Conclusion: Open surgical repair of abdominal aortic aneurysms with supraceliac aortic cross-clamping is associated with significantly higher morbidity, early and mid-term mortality than the repair of juxta/pararenal aneurysms. Chronic kidney disease and major postoperative complications are independent factors of mid- and long-term mortality.Bevezetés: Jelenleg nincsenek egyértelmű ajánlások a nem infrarenalis hasi aortaaneurysmák sebészi kezelésének ideális technikájáról. Célkitűzés: Jelenlegi vizsgálatunk célja volt elemezni az intakt fallal rendelkező, nem infrarenalis abdominalis aortaaneurysmák miatt nyitott műtéten átesett betegek mortalitását és a proximalis aortakirekesztés szintjének a posztoperatív eredményekre gyakorolt hatását. Módszer: Retrospektív egyközpontú vizsgálatunk az intakt, nem infrarenalis hasi aortaaneurysmák miatt 2005 és 2017 között a Semmelweis Egyetem Szív- és Érgyógyászati Klinikáján nyitott műtéten átesett betegek eredményeit tekinti át. A tanulmány elsődleges végpontja a 30 napos, 1, 2 és 5 éves mortalitás, másodlagos végpontjai a posztoperatív akut vesekárosodás, valamint a súlyos posztoperatív szövődmények voltak. Az adatokat két csoportban elemeztük a műtét során alkalmazott proximalis aortakirekesztés helye alapján: juxta/pararenalis aortaaneurysmák; inter/suprarenalis aortakirekesztés, suprarenalis aortaaneurysmák; supracoeliacalis kirekesztés. Eredmények: Klinikánkon 94 páciens esett át nyitott aortaműtéten, amely legalább az egyik veseartéria szintje feletti aortakirekesztéssel járt. Az utánkövetési idő 3,14 (IQR: 1,55–5,00) év, a 30 napos, 1, 2 és 5 éves mortalitás 9%, 20%, 27% és 48% volt. A 30 napos és 1 éves mortalitás szignifikánsan alacsonyabb volt a juxta/pararenalis aortaaneurysma miatt operált betegek között. Szignifikánsan többször fordultak elő súlyos posztoperatív szövődmények a suprarenalis aneurysma miatt kezelt páciensek körében a juxta- és pararenalis aneurysma miatt operáltakhoz képest. Az akut vesekárosodás perioperatív incidenciája 54%, a kórházi elbocsátáskor 30% volt. A kórházi bent fekvés ideje alatt jelentősen több akut veseműködési zavart észleltünk a suprarenalis aneurysma miatt operált pácienseknél, a betegek hazabocsátásakor azonban a két csoport között már nem volt szignifikáns különbség. Következtetés: A suprarenalis aortaaneurysmák nyitott műtéte nagyobb morbiditással, korai és középtávú mortalitással jár, mint a juxta/pararenalis aortaaneurysmáké. A preoperatív krónikus veseelégtelenség és a súlyos posztoperatív szövődmények a közép- és hosszú távú mortalitás független prediktív tényezői. Orv Hetil. 2022; 163(37): 1472–1480.

Absztrakt: Az egészségügyi, orvosi szimulációs oktatás alapja, hogy klinikai szituációkat, gyakorlati feladatokat modellez szimulátorok, számítástechnikai megoldások, esetleg humán szereplők segítségével. Így az oktatott a legvalósághűbb környezetben sajátíthatja el a készségeket. A közleményben bemutatjuk a szimulációs oktatás múltját, technológiai hátterét, valamint a szimulációs oktatás jelenlegi helyzetét Magyarországon, melynek megkérdőjelezhetetlen szerepe van az egészségügyi felsőoktatásban. Számos pozitív hatása van hallgatók és oktatók számára, továbbá az intézetek számára is számtalan előnyt tartogat. Az egységek feladata, hogy hidat teremtsen az elméleti és a gyakorlati képzés között, felkészítve a hallgatókat a valódi orvosegészségügyi életpálya kihívásaira. Bár a terület több évszázada ismert módszertan az orvos- és egészségtudományi képzésben, csak a XXI. században indult jelentős fejlődésnek a technológia robbanásszerű előrehaladásának köszönhetően. Az innovatív megoldások révén egyre élethűbben lehet modellezni bonyolultabb orvosi feladatokat is. Már hazánkban is használják az oktatás során a 3D nyomtatott segédeszközöket, virtuális- és kiterjesztettvalóság-megoldásokat. A magyarországi „Skill Labor Hálózat” fejlesztése mellett a szimulációs oktatás hazai módszertanának kialakítása is megkezdődött, ennek sikerességét jelzi több, oktatást segítő kézikönyv megjelenése is. A hálózat négy egyetemi skillközpontot és 16 oktató kórházat foglal magában. A skill-laborok eddig hiányzó láncszemek voltak az elméleti és a klinikai oktatás között, melyekben magas szakmai színvonalú gyakorlati készségeket sajátíthatnak el a hallgatók mind a graduális, mind a posztgraduális képzés során. A kezdeti fejlesztések sikeresnek tekinthetők, ezt tükrözi a nagy érdeklődés, a résztvevők száma és a hallgatók pozitív visszajelzései is. Közleményünk átfogó jelleggel betekintést ad a magyarországi egészségügyi szimulációs oktatás jelenlegi helyzetébe, illetve felveti a potenciális fejlesztési irányokat, gyakorlati példákkal szemléltetve. Orv Hetil. 2020; 161(26): 1078–1087.

Aims Our aim was to develop a machine learning (ML)-based risk stratification system to predict 1-, 2-, 3-, 4-, and 5-year all-cause mortality from pre-implant parameters of patients undergoing cardiac resynchronization therapy (CRT). Methods and results Multiple ML models were trained on a retrospective database of 1510 patients undergoing CRT implantation to predict 1- to 5-year all-cause mortality. Thirty-three pre-implant clinical features were selected to train the models. The best performing model [SEMMELWEIS-CRT score (perSonalizEd assessMent of estiMatEd risk of mortaLity With machinE learnIng in patientS undergoing CRT implantation)], along with pre-existing scores (Seattle Heart Failure Model, VALID-CRT, EAARN, ScREEN, and CRT-score), was tested on an independent cohort of 158 patients. There were 805 (53%) deaths in the training cohort and 80 (51%) deaths in the test cohort during the 5-year follow-up period. Among the trained classifiers, random forest demonstrated the best performance. For the prediction of 1-, 2-, 3-, 4-, and 5-year mortality, the areas under the receiver operating characteristic curves of the SEMMELWEIS-CRT score were 0.768 (95% CI: 0.674–0.861; P Conclusion The SEMMELWEIS-CRT score (available at semmelweiscrtscore.com) exhibited good discriminative capabilities for the prediction of all-cause death in CRT patients and outperformed the already existing risk scores. By capturing the non-linear association of predictors, the utilization of ML approaches may facilitate optimal candidate selection and prognostication of patients undergoing CRT implantation.

Mammalian methanogenesis is regarded as an indicator of carbohydrate fermentation by anaerobic gastrointestinal flora. Once generated by microbes or released by a non-bacterial process, methane is generally considered to be biologically inactive. However, recent studies have provided evidence for methane bioactivity in various in vivo settings. The administration of methane either in gas form or solutions has been shown to have anti-inflammatory and neuroprotective effects in an array of experimental conditions, such as ischemia/reperfusion, endotoxemia and sepsis. It has also been demonstrated that exogenous methane influences the key regulatory mechanisms and cellular signalling pathways involved in oxidative and nitrosative stress responses. This review offers an insight into the latest findings on the multi-faceted organ protective activity of exogenous methane treatments with special emphasis on its versatile effects demonstrated in sepsis models.

Background Ischemic preconditioning (IPC) can provide a defense against ischemia–reperfusion (IR)-induced acute inflammation and barrier dysfunction in many organs. Because nitric oxide (NO) has been implicated as a trigger or mediator in the IPC mechanism and because neuronal NO synthase (nNOS) is a dominant isoform of NOS in the gastrointestinal tract, our aim was to investigate the role of nNOS in IPC-induced protection after mesenteric IR. Materials and methods Intestinal IR was induced in sodium pentobarbital–anesthetized dogs by clamping the superior mesenteric artery for 60 min followed by 2 h of reperfusion (IR group; n = 7). In further groups, IPC was used (three cycles of 5-min ischemia/5-min reperfusion periods) before IR in the presence or absence of selective inhibition of nNOS with 7-nitroindazole (5 mg/kg, intravenously, in a bolus 15 min before IPC, n = 6 each). Changes in mesenteric vascular resistance, intramucosal pH (pHi), and small bowel motility were monitored. Plasma nitrite/nitrate levels, intestinal NO synthase activity, leukocyte accumulation, mast cell degranulation, and histologic injury were also determined. Results Ischemia significantly decreased mesenteric vascular resistance and pHi, whereas IR induced a temporary bowel hypermotility and acute inflammatory reaction. IPC facilitated pHi recovery, attenuated motility dysfunction, elevated NOS-dependent NO production, and reduced leukocyte accumulation, mast cell degranulation, and mucosal injury. Pretreatment with 7-nitroindazole halted the IPC-induced increase in NO availability, pHi recovery, and the anti-inflammatory and morphologic effects. Conclusions Our data demonstrate that NO generated by intestinal nNOS plays a pivotal role in IPC-linked tissue protection by inhibiting an IR-related acute inflammatory response.

We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of fecal peritonitis in rodents. Saline or fecal suspensions with a standardized dose range of bacterial colony-forming units (CFUs) were injected intraperitoneally into Sprague–Dawley rats. The qualitative composition of the initial inoculum and the ascites was analyzed separately by MALDI-TOF mass spectrometry. Invasive monitoring was conducted in separate anesthetized groups (n = 12–13/group) after 12, 24, 48 and 72 h to determine rat-specific organ failure assessment (ROFA) scores. Death and ROFA scores peaked at 24 h. At this time, 20% mortality occurred in animals receiving a monomicrobial E. coli suspension, and ROFA scores were significantly higher in the monomicrobial subgroup than in the polymicrobial one (median 6.5; 5.0–7.0 and 5.0; 4.75–5.0, respectively). ROFA scores dropped after 48 h, accompanied by a steady decrease in ascites CFUs and a shift towards intra-abdominal monomicrobial E. coli cultures. Furthermore, we found a relationship between ascites CFUs and the evolving change in ROFA scores throughout the study. Hence, quantitatively identical bacterial loads with mono- or polymicrobial dominance lead to a different degree of sepsis severity and divergent outcomes. Initial and intraperitoneal microbiological testing should be used to improve translational research success.

Introduction Incontinence (up to 20%) and erectile dysfunction (up to 70%) occur frequently after radical prostatectomy (RP) in patients with localized prostate cancer. Human amniotic membrane (HAM) can improve tissue regeneration and functional outcome after RP owing to the growth factors and unique immune tolerance. Preliminary studies showed the potential value of HAM in the reconstruction of the urinary tract and nerve protection during RP. Methods A protocol is developed for a prospective, randomized, single-blind, single-surgeon, placebo-controlled exploration study of the efficacy and safety of dehydrated human amnion membrane placed around the neurovascular bundle (NVB) and vesicourethral anastomosis (VUA) during RP for the treatment of localized prostate cancer. Eligible for inclusion are patients with localized prostate cancer, requiring a surgical procedure and exclusion of preoperative incontinence and erectile dysfunction. The patients are randomized 1:1 to HAM vs. placebo and blinded during the study period. According to the T test with an alpha of 0.05 and a power of 80% and expecting a dropout of 20% of the patients, an adjusted sample size per arm of 164 patients is required. Planned Outcomes The primary outcome is a postoperative continence measured as 24-h pad test up to 12 months postoperatively. Secondary outcomes are potency, time of postoperative catheter removal, postoperative complications, and biochemical recurrence. The protocol for this randomized exploration study defines the conditions to assess the efficacy and safety of HAM application during RP in order to improve the postoperative functional outcome. This trial should pave the way for future studies of tissue engineering in an effort to reduce the morbidity of RP. Trial Registration Clinicaltrials.gov, identifier NCT03864939.

Background and Aims. Resynchronization therapy (CRT) improves mortality and induces reverse remodeling in heart failure (HF) patients with reduced ejection fraction and wide QRS. Nonetheless, some patients do not improve despite the optimal medical therapy and right indications for device implantation. Therefore, finding biomarkers suitable for identification of those patients is crucial. Vitamin D plays a classic hormonal role in the regulation of bone metabolism and also has physiological functions in wide range of nonskeletal tissues. Based on recent studies, low levels of vitamin D seem to directly contribute to pathogenesis and worsening of HF. We planned to assess the role of vitamin D levels on clinical outcomes of HF patients undergoing CRT. Methods and Results. We enrolled 136 HF patients undergoing CRT. Total plasma vitamin D levels were measured at baseline and 6 months later. Primary endpoint was 5-year all-cause mortality; secondary endpoint was lack of good clinical response, defined as less than 15% increase of left ventricular ejection fraction after six months. During follow-up, 58 patients reached the primary, and 45 patients reached the secondary endpoint. Vitamin D levels less than 24.13 ng/mL predicted 5-year mortality (p=0.045) and poor clinical response (p=0.03) after adjusting to all significant baseline predictors. Conclusion. Our study showed that vitamin D deficiency has a significant impact in heart failure patients; it is an independent predictor of lack of midterm clinical response and long-term mortality in patients undergoing CRT. Therefore, monitoring vitamin D status of heart failure patients could be of clinical significance.

Objectives Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure. Design Randomized, controlled in vivo animal study. Setting University research laboratory. Subjects Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg). Interventions In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes. Measurements and main results Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson's r = 0.669 or r = 0.632, respectively). Conclusions we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.

Abstract: Introduction: Levels of cardiac necroenzymes, high-sensitive troponin (hsTnT) and creatine kinase muscle-brain (CKMB) increase as a result of a myocardial damage following catheter ablation. Aim: To analyze the mid-term alteration of hsTnT and CKMB levels following radiofrequency ablation (RFCA) for atrial fibrillation (AF), atrial flutter (AFlu), AV-nodal reentry tachycardia (AVNRT) and electrophysiological studies (EPS) without ablation. Method: Patients undergoing RFCA for various indications and EPS were consecutively enrolled in our prospective study. Concentrations of hsTnT and CKMB were measured from serial blood samples directly before and after the procedure, 4 and 20 hours later and at 3 months follow-up. Results: Forty-seven patients (10 EPS, 12 AVNRT, 13 AFlu, 12 AF) with mean age of 55 ± 13 were included. hsTnT levels increased significantly in all groups after the procedures, while CKMB changed only in the AF group. hsTnT exceeded the reference value in all patients with ablation and in 80% of patients with EPS 4 hours post-ablation. Peak average hsTnT levels for EPS, AVNRT, AFlu were 24 ± 11, 260 ± 218 and 541 ± 233 ng/L, respectively. The highest hsTnT level was measured in the AF group (799 ± 433 ng/L). We found a positive correlation between hsTnT levels and ablation time after RFCA. Conclusions: The hsTnT levels significantly change after EPS and RFCA, in all patients who underwent ablation, and in 80% of those with EPS had hsTnT positivity in the early post-procedural phase. hsTnT levels depended significantly on the type of the subgroups and correlated with the ablation time. Awareness of those observations is essential to correctly interpret elevated hsTnT levels following RFCA. Orv Hetil. 2019; 160(14): 540–548.

OBJECTIVES Extracorporeal circulation induces cellular and humoral inflammatory reactions, thus possibly leading to detrimental secondary inflammatory responses. Previous data have demonstrated the bioactive potential of methane and confirmed its anti-inflammatory effects in model experiments. Our goal was to investigate the in vivo consequences of exogenous methane administration on extracorporeal circulation-induced inflammation. METHODS Two groups of anaesthetized Vietnamese minipigs (non-treated and methane treated, n = 5 each) were included. Standard central cannulation was performed, and extracorporeal circulation was maintained for 120 min without cardiac arrest or ischaemia, followed by an additional 120-min observation period with haemodynamic monitoring. In the methane-treated group, 2.5% v/v methane–normoxic air mixture was added to the oxygenator sweep gas. Blood samples through the central venous line and tissue biopsies from the heart, ileum and kidney were taken at the end point to determine the whole blood superoxide production (chemiluminometry) and the activity of xanthine-oxidoreductase and myeloperoxidase, with substrate-specific reactions. RESULTS Methane treatment resulted in significantly higher renal blood flow during the extracorporeal circulation period compared to the non-treated group (63.9 ± 16.4 vs 29.0 ± 9.3 ml/min). Whole blood superoxide production (548 ± 179 vs 1283 ± 193 Relative Light Unit (RLU)), ileal myeloperoxidase (2.23 ± 0.2 vs 3.26 ± 0.6 mU/(mg protein)) and cardiac (1.5 ± 0.6 vs 4.7 ± 2.5 pmol/min/mg), ileal (2.2 ± 0.6 vs 7.0 ± 3.4 pmol/min/mg) and renal (1.2 ± 0.8 vs 13.3 ± 8.0 pmol/min/mg) xanthine-oxidoreductase activity were significantly lower in the treated group. CONCLUSIONS The addition of bioactive gases, such as methane, through the oxygenator of the extracorporeal circuit represents a novel strategy to influence the inflammatory effects of extracorporeal perfusion in cardiac surgical procedures.

INTRODUCTION AND OBJECTIVES Cardiac resynchronization therapy (CRT) is beneficial for selected heart failure (HF) patients, although nonresponse to therapy is still prevalent. We investigated a set of novel biomarkers associated with various pathophysiological pathways of HF. Our purpose was to assess their ability to predict clinical outcomes after CRT. METHODS We studied 136 chronic HF patients undergoing CRT. We measured the plasma levels of fractalkine, pentraxin-3, hepatocyte growth factor (HGF), carbohydrate antigen-125, and matrix metalloproteinase-9 before and 6 months after CRT. The primary endpoint of the study was 5-year all-cause mortality, and we considered the absence of 6-month reverse remodelling (defined as at least a 15% decrease in end-systolic volume) as a secondary endpoint. RESULTS Fifty-eight patients died during the 5-year follow-up period and 66 patients were categorized as nonresponders. In multivariable models, only an increased HGF was an independent predictor of both mortality (HR, 1.35; 95%CI, 1.11-1.64; P=.003; per 1 standard deviation increase) and the absence of reverse remodelling (OR, 1.83; 95%CI, 1.10-3.04; P=.01; per 1 standard deviation increase). Applying HGF to the basic multivariable model of both mortality (net reclassification improvement=0.69; 95%CI, 0.39-0.99; P

Resumen Introduccion y objetivos La terapia de resincronizacion cardiaca (TRC) es beneficiosa para pacientes seleccionados con insuficiencia cardiaca (IC), aunque la ausencia de respuesta a la terapia es aun prevalente. Se investiga un conjunto de nuevos biomarcadores asociados a varias vias fisiopatologicas de la IC. El proposito fue valorar su capacidad para predecir los resultados clinicos con la TRC. Metodos Se estudio a 136 pacientes con IC cronica y TRC. Se midieron los valores plasmaticos de fractalquina, pentraxina-3, factor de crecimiento hepatocitario (HGF), el antigeno carbohidrato 125 y la metaloproteinasa de matriz 9 tanto antes como 6 meses despues del inicio de la TRC. El objetivo primario del estudio fue la mortalidad por todas las causas a 5 anos, y se considero la ausencia de remodelado inverso a los 6 meses (definido como al menos un 15% de descenso del volumen telesistolico) como un objetivo secundario. Resultados Cincuenta y ocho pacientes fallecieron a lo largo de los 5 anos de seguimiento y 66 pacientes se categorizaron como no respondedores. En modelos multivariables, solo un aumento del HGF resulto un predictor independiente, tanto de mortalidad (HR = 1,35; IC95%, 1,11-1,64; p = 0,003; por cada unidad de incremento de la desviacion estandar) como de ausencia de remodelado inverso (OR = 1,83; IC95%, 1,10-3,04; p = 0,01; por cada unidad de incremento de la desviacion estandar). Aplicando el HGF al modelo basico multivariable tanto de mortalidad (mejora neta de reclasificacion = 0,69; IC95%, 0,39-0,99; p Conclusiones De los biomarcadores investigados, solo el HGF predijo los resultados clinicos despues de la TRC independientemente de otros parametros. Los analisis de reclasificacion mostraron que las mediciones de HGF podrian ser utiles para mejorar la seleccion de pacientes.

Augmentation cystoplasty is an exemplary multiorgan intervention in urology which is particularly associated with microvascular damage. Our aim was to review the available intravital imaging techniques and data obtained from clinical and experimental microcirculatory studies involving the most important donor organs applied in bladder augmentation. Although numerous direct or indirect methods are available to assess the condition of microvessels the implementation of microcirculatory diagnostic methods in humans is still challenging and the assessment of organ microcirculation in the operating theatre has limitations. Nevertheless, preclinical studies generally report good internal validity and although prospective human protocols with reduced variability are needed, a possible positive impact of microcirculatory diagnostics on the clinical outcomes of urologic surgery can be anticipated.

Despite their clinical effectiveness, a growing body of evidence has shown that many classes of antibiotics lead to mitochondrial dysfunction. Ceftriaxone and Rifaximin are first choice perioperative antibiotics in gastrointestinal surgery targeting fundamental processes of intestinal bacteria; however, may also have negative consequences for the host cells. In this study, we investigated their direct effect on mitochondrial functions in vitro, together with their impact on ileum, colon and liver tissue. Additionally, their impact on the gastrointestinal microbiome was studied in vivo, in a rat model. Rifaximin significantly impaired the oxidative phosphorylation capacity (OxPhos) and leak respiration in the ileal mucosa, in line with increased oxidative tissue damage and histological changes following treatment. Ceftriaxone prophylaxis led to similar changes in the colon mucosa. The composition and diversity of bacterial communities differed extensively in response to antibiotic pre-treatment. However, the relative abundances of the toxin producing species were not increased. We have confirmed the harmful effects of prophylactic doses of Rifaximin and Ceftriaxone on the intestinal mucosa and that these effects were related to the mitochondrial dysfunction. These experiments raise awareness of mitochondrial side effects of these antibiotics that may be of clinical importance when evaluating their adverse effects on bowel mucosa.

Összefoglaló. Bevezetés: Az elmúlt évtizedekben számos országban jelentős mértékben változott a hasi aortaaneurysmák sebészi kezelése az eredményesebb ellátás céljából: endovascularis beavatkozások terjedése, nagy betegforgalmú aortacentrumok kialakítása. Célkitűzés: A Magyarországon, infrarenalis aortaaneurysmák miatt végzett beavatkozások rövid távú eredményeinek elemzése elsősorban műtéti technika (endovascularis vs. nyitott aortareconstructio), intézeti betegforgalom (kis vs. nagy betegforgalmú intézet) és időszak (2010-2014 vs. 2015-2019) alapján. Módszer: A Nemzeti Érsebészeti Regiszterben 2010. 01. 01. és 2019. 12. 31. között prospektíven rögzített multicentrikus adatok retrospektív feldolgozása. Eredmények: A regiszterben 3206 infrarenalis aortaaneurysma-műtétet rögzítettek. A második öt évben jelentősen nőtt az endovascularis aortareconstructio aránya a nyitotthoz képest (p0,0001), illetve a nagy betegforgalmú intézetek szignifikánsan több rupturált aortaaneurysmát láttak el, mint a kis betegforgalmú intézetek (p0,0001) az első öt évhez viszonyítva. A perioperatív mortalitás rupturált aortaaneurysma miatt a nagy betegforgalmú intézetekben végzett nyitott aortareconstructio esetén szignifikánsan alacsonyabb volt a kis betegforgalmú intézetekkel szemben az első öt évben (p = 0,0011), illetve a nagy betegforgalmú intézetekben végzett endovascularis aortareconstructio esetén szignifikánsan alacsonyabb volt a nyitottal szemben a második öt évben (p = 0,029). A nem rupturált aortaaneurysma-műtétek perioperatív mortalitása a nagy betegforgalmú intézetekben végzett nyitott aortareconstructio esetén szignifikánsan alacsonyabb volt a kis betegforgalmú intézetekhez képest az első és a második öt évben is (p = 0,0007; p = 0,004). Mind a nagy, mind a kis betegforgalmú intézetekben végzett endovascularis aortareconstructio esetén szignifikánsan alacsonyabb volt a perioperatív mortalitás a második öt évben (p0,0001; p0,0001). A rupturált és a nem rupturált aortaaneurysmák perioperatív mortalitásának független rizikófaktora az intézetek betegforgalma (p = 0,006; p = 0,004), a betegek életkora (p0,0001; p = 0,001), a preoperatív renalis megbetegedés (p = 0,007; p = 0,007), a transzfúzióigény (p0,0001; p0,0001), illetve nem rupturált aortaaneurysmák esetében a műtéti technika (p0,0001) is. Következtetés: Endovascularis aortareconstructio és nagy betegforgalmú intézetek esetében szignifikánsan alacsonyabb perioperatív mortalitás érhető el. Orv Hetil. 2021; 162(31): 1233-1243.The organisation of aortic disease care has changed significantly in many countries over the last decade: centralized, high-volume centers were established.To analyse the perioperative mortality and the number of the infrarenal aortic aneurysm repairs according to the type of procedure (endovascular vs. open), patient volume (low vs. high) and time period (2010-2014 vs. 2015-2019).The multicentric data registered prospectively in the Hungarian National Vascular Registry between 01. 01. 2010 and 31. 12. 2019 were analysed retrospectively.3206 infrarenal aortic aneurysms were recorded. The endovascular-open repair rate was significantly higher (p0.0001) and the high-volume institutes managed significantly more ruptured aneurysms (p0.0001) in the second period. The perioperative mortality of the open repair of ruptured aneurysms was significantly lower in the high-volume institutes than in the low-volume ones in the first period (p = 0.0011), and the mortality of endovascular repair was significantly lower compared with open repair in the high-volume institutes in the second period (p = 0.029). The perioperative mortality of the open repair of non-ruptured aneurysm was significantly lower in the high-volume institutes in both periods (p = 0.0007; p = 0.004). Furthermore, the mortality of endovascular repair was significantly lower compared with open repair both in the high- and the low-volume institutes in the second period (p0.0001; p0.0001). Patient volume (p = 0.006; p = 0.004), age (p0.0001; p = 0.001), preoperative renal insufficiency (p = 0.007; p = 0.007) and the need of blood transfusion (p0.0001; p0.0001) were independent risk factors of the perioperative mortality of ruptured and non-ruptured aneurysms. Type of the procedure was also an independent risk factor in the case of non-ruptured aneurysms (p0.0001).Endovascular repair and aortic surgery in the high-volume institutes result in significantly lower perioperative mortality. Orv Hetil. 2021; 162(31): 1233-1243.

Introduction: Sepsis is a dysregulated host response to infection with macro- and microhemodynamic deterioration. Kynurenic acid (KYNA) is a metabolite of the kynurenine pathway of tryptophan catabolism with pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenously administered KYNA or the synthetic analog SZR-72 affects the microcirculation and mitochondrial function in a clinically relevant rodent model of intraabdominal sepsis.Methods: Male Sprague–Dawley rats (n = 8/group) were subjected to fecal peritonitis (0.6 g kg−1 feces ip) or a sham operation. Septic animals were treated with sterile saline or received ip KYNA or SZR-72 (160 μmol kg−1 each) 16 and 22 h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic dysfunctions (PaO2/FiO2 ratio, mean arterial pressure, urea, AST/ALT ratio and lactate levels, respectively) based on the Rat Organ Failure Assessment (ROFA) score. The ratio of perfused vessels (PPV) of the ileal serosa was quantified with the intravital imaging technique. Complex I- and II-linked (CI; CII) oxidative phosphorylation capacities (OXPHOS) and mitochondrial membrane potential (ΔΨmt) were evaluated by High-Resolution FluoRespirometry (O2k, Oroboros, Austria) in liver biopsies. Plasma endothelin-1 (ET-1), IL-6, intestinal nitrotyrosine (NT) and xanthine oxidoreductase (XOR) activities were measured as inflammatory markers.Results: Sepsis was characterized by an increased ROFA score (5.3 ± 1.3 vs. 1.3 ± 0.7), increased ET-1, IL-6, NT and XOR levels, and decreased serosal PPV (65 ± 12% vs. 87 ± 7%), ΔΨmt and CI–CII-linked OXPHOS (73 ± 16 vs. 158 ± 14, and 189 ± 67 vs. 328 ± 81, respectively) as compared to controls. Both KYNA and SZR-72 reduced systemic inflammatory activation; KYNA treatment decreased serosal perfusion heterogeneity, restored PPV (85 ± 11%) and complex II-linked OXPHOS (307 ± 38), whereas SZR-72 improved both CI- and CII-linked OXPHOS (CI: 117 ± 18; CII: 445 ± 107) without effects on PPV 24 h after sepsis induction.Conclusion: Treatment with SZR-72 directly modulates mitochondrial respiration, leading to improved conversion of ADP to ATP, while administration of KYNA restores microcirculatory dysfunction. The results suggest that microcirculatory and mitochondrial resuscitation with KYNA or the synthetic analog SZR-72 might be an appropriate supportive tool in sepsis therapy.

Összefoglaló. Az alsó húgyutak fő funkciója a vizelet tárolása és ürítése, amely működések zavara az úgynevezett alsó húgyúti tünetegyüttes kialakulásához vezet, ami a kiváltó októl függően vizeletürítési zavarral és vizeletretencióval is járhat. Kezeletlen esetekben a felső húgyutak károsodása következik be a magas hólyagnyomás által kiváltott vesicoureteralis reflux következtében, amely ureter- és veseüregrendszeri tágulat kialakulására, illetve fertőzésekre és kőképződésre hajlamosít. A vizelettárolási/vizeletürítési zavarokat három fő csoportba sorolhatjuk, úgymint stressz- (terheléses) inkontinencia , hiperaktív hólyag (nedves/száraz) és neurogén hólyag. A jelen összefoglaló közlemény tárgyát képező neurogén hólyag egy gyűjtőfogalom, mely magában foglal minden, releváns neurológiai kórkép talaján kialakult vizelettárolási és vizeletürítési zavart. Mivel a húgyhólyag mellett a záróizomzat és a hátsó húgycső is érintett, ezt a kórképet napjainkban "neurogén alsó húgyúti diszfunkció" elnevezéssel is szokás illetni. A kórállapotot a neurológiai diszfunkciók széles spektruma okozhatja, kezdve a helyi funkcionális zavartól a helyi idegi sérülésen át a felső és alsó motoneuron-sérülésig vagy a centrális degeneratív folyamatokig. Az eltérő etiológia ellenére a klinikai tünetek rendszerint két alapvető klinikai típusban manifesztálódhatnak: túlműködő (fokozott detrusorkontraktilitást okozó automata) hólyag vagy alulműködő hólyag formájában. Tekintettel a neurogén alsó húgyúti diszfunkció következtében létrejövő felső húgyúti komplikációkra, a közlemény egyik célja a betegség diagnózisát segítő algoritmus bemutatása a legújabb nemzetközi szakirodalmi ismeretek alapján. A neurogén hólyag kezelése jobbára nem terjedhet ki a kiváltó ok kezelésére, ezért a jelen összefoglaló másik célja azon gyógyszeres és invazív terápiás beavatkozások összefoglalása, melyek a felső húgyutak védelmét szolgálják az alacsony hólyagnyomás fenntartása révén. Orv Hetil. 2021; 162(4): 135-143. Summary. Storage and urination are the main functions of the lower urinary tract and its lesions lead to the so-called lower urinary tract syndrome causing either urinary incontinence or retention. In untreated cases, the upper urinary tract becomes injured via a vesicoureteral reflux resulting from increased bladder pressure and resultant dilations of the ureter and the renal pelvis which predispose to infection and stone formation. Lower urinary tract storage/urination disorders can be classified as stress incontinence, hyperactive bladder (wet/dry) and neurogenic bladder. Neurogenic bladder which is the subject of this review, is a collective term that encompasses all urinary storage and emptying disorders which develop on the basis of neurological diseases. Being not only the bladder, but also the sphincter and posterior urethra (generally termed as the "bladder outlet") affected, nowadays this condition is referred to as "neurogenic lower urinary tract dysfunction". A wide range of neurological dysfunctions could contribute to the development of this condition, ranging from local dysfunction (autonomic dysreflexia) or local nerve injury to upper/lower motoneuron injury or central degenerative processes. Regardless of the diverse etiology, the clinical symptoms eventually manifest in two major forms, i.e., overacting (automatic bladder with increased detrusor contractility) and underactive bladder. Considering the severity of complication occurring in the upper urinary tract in response to the pathophysiological changes in the lower urinary tract, one of the aims of this paper was to present an algorithm aiming to build up a state of the art diagnosis of the disease based on current international literature data. Since treatment of the neurogenic bladder usually can not target elimination of the underlying cause, the other goal of the present paper is to summarize the pharmacological treatment regimen and invasive therapeutic interventions that protect the upper urinary tract by maintaining low pressure values in the bladder. Orv Hetil. 2021; 162(4): 135-143.

BACKGROUND Maintenance of cell viability during cold storage is a key issue in organ transplantation. Methane (CH4) bioactivity has recently been recognized in ischemia/reperfusion conditions; we therefore hypothesized that cold storage in CH4-enriched preservation solution can provide an increased defense against organ dysfunction during experimental heart transplantation (HTX). METHODS The hearts of donor Lewis rats were stored for 60 minutes in cold histidine-tryptophan-ketoglutarate (Custodiol [CS]) or CH4-saturated CS solution (CS-CH4) (n = 12 each). Standard heterotopic HTX was performed, and 60 minutes later, the left ventricular (LV) pressure-volume relationships LV systolic pressure (LVSP), systolic pressure increment (dP/dtmax), diastolic pressure decrement, and coronary blood flow (CBF) were measured. Tissue samples were taken to detect proinflammatory parameters, structural damage (by light microscopy), endoplasmic reticulum (ER) stress, and apoptosis markers (CCAAT/enhancer binding protein [C/EBP] homologous protein, GRP78, glycogen synthase kinase-3β, very low-density lipoprotein receptor, caspase 3 and 9, B-cell lymphoma 2, and bcl-2-like protein 4), whereas mitochondrial functional changes were analyzed by high-resolution respirometry. RESULTS LVSP and dP/dtmax increased significantly at the largest pre-load volumes in CS-CH4 grafts as compared with the CS group (114.5 ± 16.6 mm Hg vs 82.8 ± 4.6 mm Hg and 3,133 ± 430 mm Hg/s vs 1,739 ± 169 mm Hg/s, respectively); the diastolic function and CBF (2.4 ± 0.4 ml/min/g vs 1.3 ± 0.3 ml/min/g) also improved. Mitochondrial oxidative phosphorylation capacity was more preserved (58.5 ± 9.4 pmol/s/ml vs 27.7 ± 6.6 pmol/s/ml), and cytochrome c release was reduced in CS-CH4 storage. Signs of HTX-caused myocardial damage, level of ER stress, and the transcription of proapoptotic proteins were significantly lower in CS-CH4 grafts. CONCLUSION The addition of CH4 during 1 hour of cold storage improved early in vitro graft function and reduced mitochondrial dysfunction and activation of inflammation. Evidence shows that CH4 reduced ER stress–linked proapoptotic signaling.

Background: Internal hemorrhage is a medical emergency, which requires immediate causal therapy, but the recognition may be difficult. The reactive changes of the mesenteric circulation may be part of the earliest hemodynamic responses to bleeding. Methane is present in the luminal atmosphere; thus, we hypothesized that it can track the intestinal circulatory changes, induced by hemorrhage, non-invasively. Our goal was to validate and compare the sensitivity of this method with an established technique using sublingual microcirculatory monitoring in a large animal model of controlled, graded hemorrhage and the early phase of following fluid resuscitation. Materials and Methods: The experiments were performed on anesthetized, ventilated Vietnamese minipigs (approval number: V/148/2013; n = 6). The animals were gradually bled seven times consecutively of 5% of their estimated blood volume (BV) each, followed by gradual fluid resuscitation with colloid (hydroxyethyl starch; 5% of the estimated BV/dose) until 80 mmHg mean arterial pressure was achieved. After each step, macrohemodynamic parameters were recorded, and exhaled methane level was monitored continuously with a custom-built photoacoustic laser-spectroscopy unit. The microcirculation of the sublingual area, ileal serosa, and mucosa was examined by intravital videomicroscopy (Cytocam-IDF, Braedius). Results: Mesenteric perfusion was significantly reduced by a 5% blood loss, whereas microperfusion in the oral cavity deteriorated after a 25% loss. A statistically significant correlation was found between exhaled methane levels, superior mesenteric artery flow (r = 0.93), or microcirculatory changes in the ileal serosa (ρ = 0.78) and mucosa (r = 0.77). After resuscitation, the ileal mucosal microcirculation increased rapidly [De Backer score (DBS): 2.36 ± 0.42 vs. 8.6 ± 2.1 mm-1], whereas serosal perfusion changed gradually and with a lower amplitude (DBS: 2.51 ± 0.48 vs. 5.73 ± 0.75). Sublingual perfusion correlated with mucosal (r = 0.74) and serosal (r = 0.66) mesenteric microperfusion during the hemorrhage phase but not during the resuscitation phase. Conclusion: Detection of exhaled methane levels is of diagnostic significance during experimental hemorrhage as it indicates blood loss earlier than sublingual microcirculatory changes and in the early phase of fluid resuscitation, the exhaled methane values change in association with the mesenteric perfusion and the microcirculation of the ileum.

Simulation-based medical education aims to model clinical situations and tasks using simulators, computers or even human beings. By using this system, the students are able to learn and master technical, also non-technical skills in lifelike situations. This publication contains a historical review of simulation-based education system, and its actualities in Hungary. Simulation has an unquestionable role in medical education. It is beneficial for the students, for the teachers, and for the teaching hospitals as well, since it saves clinical equipment and reduces the human burden. Its main purpose is to establish connection between theoretical and practical competencies, preparing the students for real medical challenges. Simulation has been a known teaching method for centuries, but only the 21st century brought real breakthrough due to the sudden development of technology. As a result of the recent years' innovative development and accepted innovative solutions, the modeling of complex medical procedures turned into more realistic. In Hungary, 3D-printed tools, virtual reality and augmented reality approaches are already adopted for education purposes. The national simulation network contains 3 universities and 16 hospitals. The initial developments are shown to be successful, as simulation-based training is progressively involved in undergraduate and post-graduate education, and the overall feedback is positive from the involved students. The evolvement of comprehensive national methodology for education has started also, by publishing reference books. This review is about the state of the national simulation education and offers development possibilities. Orv Hetil. 2020; 161(26): 1078-1087.

Petra Hartmann,1 Edina Butt,2 Ágnes Fehér,1 Ágnes Lilla Szilágyi,1 Kurszán Dávid Jász,1 Boglárka Balázs,3 Mónika Bakonyi,3 Szilvia Berkó,3 Gábor Erős,4 Mihály Boros,1 Gyöngyi Horváth,5 Endre Varga,2 Erzsébet Csányi3 1Institute of Surgical Research, University of Szeged, Szeged, Hungary; 2Department of Traumatology, University of Szeged, Szeged, Hungary; 3Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary; 4Department of Pathology, University of Szeged, Szeged, Hungary; 5Department of Physiology, University of Szeged, Szeged, Hungary Purpose: Since electroporation (EP) can increase the permeability of biological membranes, we hypothesized that it offers an opportunity to enhance the transdermal delivery of drugs for intra-articular indications. Our aim was to compare the anti-inflammatory and analgesic efficacy of EP-combined topical administration of diclofenac sodium hydrogel (50 mg mL-1 in 230 μL volume) with that of an equivalent dose of oral (75 mg kg-1) and simple topical administration. Methods: Arthritis was induced with the injection of 2% λ-carrageenan and 4% kaolin into the right knee joints of male Sprague Dawley rats. EP was applied for 8 min with 900 V high-voltage pulses for 5 ms followed by a 20 ms break. Drug penetration into the synovial fluid and plasma was detected by high-performance liquid chromatography. Leukocyte–endothelial interactions were visualized by intravital videomicroscopy on the internal surface of the synovium. Inflammation-induced thermal and mechanical hyperalgesia reactions, knee joint edema, and inflammatory enzyme activities were assessed at 24 and 48 h after arthritis induction. Results: EP significantly increased the plasma level of diclofenac as compared with the topical controls 10 min after the 2% λ-carrageenan and 4% kaolin injection. Increased leukocyte–endothelial interactions were accompanied by joint inflammation, which was significantly reduced by oral and EP diclofenac (by 45% and by 30%, respectively) and only slightly ameliorated by simple topical diclofenac treatment (by 18%). The arthritis-related secondary hyperalgesic reactions were significantly ameliorated by oral and EP-enhanced topical diclofenac treatments. The knee cross-section area (which increased by 35%) was also reduced with both approaches. However, simple topical application did not influence the development of joint edema and secondary hyperalgesia. Conclusion: The study provides evidence for the first time of the potent anti-inflammatory and analgesic effects of EP-enhanced topical diclofenac during arthritis. The therapeutic benefit provided by EP is comparable with that of oral diclofenac; EP is a useful alternative to conventional routes of administration. Keywords: diclofenac, transdermal delivery, HPLC, intravital videomicroscopy

Our aim was to characterize the main components of the nitrosative response with quantitative changes of the nitrergic myenteric neurons in adjacent intestinal segments after transient superior mesenteric artery occlusion. We also tested the hypothesis that exogenous methane may modulate the evolution of nitroxidation by influencing xanthine oxidoreductase (XOR) activity. The microcirculatory consequences of a 50 min ischemia or ischemia-reperfusion were investigated in anesthetized rats (n = 124) inhaling normoxic air with or without 2.2% methane. XOR activities, nitrogen monoxide (NO), nitrite/nitrate (NOx), and nitrotyrosine levels were measured, together with relative nitrergic neuron ratios from duodenum, ileum and colon samples. The effects of methane on XOR were also examined in vitro. The intramural flow stopped only in the ileum during ischemia. The highest baseline XOR activity was found in the duodenum, which increased further during ischemia. NO and nitrotyrosine levels rose, and the nNOS-immunopositive neuron ratio and NOx level both dropped. Reperfusion uniformly elevated XOR activity and nitrotyrosine formation, with the highest level attained in the duodenum, where the nitrergic neuron ratio remained depressed. These alterations were eliminated in methane-treated animals, XOR activity and nitrotyrosine formation decreased in all sites, and the duodenal nitrergic neuron ratio was re-established. The inhibitory effect of methane on XOR-linked nitrate reductase activity was also demonstrated in vitro. With segment-specific microcirculatory alterations, the risk for nitrosative stress is highest in transiently hypoxic tissues with high endogenous XOR activities. The XOR-inhibitory effect of methane can reduce nitroxidation and protects the nitrergic neuron population in such conditions.