Perinatal asphyxia leads to acute kidney damage and increased renal susceptibility in adulthood.

Perinatal asphyxia (PA) poses a significant threat to multiple organs, particularly the kidneys. Diagnosing PA-associated kidney injury remains challenging and treatment options are inadequate. Furthermore, there is a lack of long-term follow-up data regarding the renal implications of PA. In this study, 7-day-old male Wistar rats were exposed to PA using a gas mixture (4% O2; 20% CO2 in N2 for 15 minutes) to investigate molecular pathways linked to renal tubular damage, hypoxia, angiogenesis, heat-shock response, inflammation, and fibrosis in the kidney. In a second experiment, adult rats with a history of PA were subjected to moderate renal ischemia-reperfusion (IR) injury to test the hypothesis that PA exacerbates renal susceptibility. Our results revealed an increased gene expression of renal injury markers (KIM-1, NGAL), hypoxic- and heat shock factors (HIF-1α, HSF-1, HSP-27), pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, MCP-1), and fibrotic markers (TGF-ß, CTGF, Fibronectin) promptly after PA. Moreover, a machine learning model was identified through Random Forest analysis, demonstrating an impressive classification accuracy (95.5%) for PA. Post-PA rats showed exacerbated functional decline and tubular injury and more intense hypoxic-, heat-shock-, pro-inflammatory-, and pro-fibrotic response after renal IRI compared to controls. In conclusion, PA leads to subclinical kidney injury, which may increase the susceptibility to subsequent renal damage later in life. Additionally, the parameters identified through Random Forest analysis provide a robust foundation for future biomarker research in the context of PA.

Animal Models for Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS): Achievements and Future Perspectives.

BACKGROUND: Since 2012, Associated Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been standing in the limelight of modern liver surgery and numerous questions have been raised regarding this novel approach. On the one hand, ALPPS has proved to be a valuable method in the treatment of hepatic tumors, while on the other hand, there are many controversies, such as high mortality and morbidity rates. Further surgical research is essential for a better understanding of underlying mechanisms and for enhancing patient safety. SUMMARY: Until recently, only 8 animal models have been created with the purpose to mimic ALPPS-induced liver regeneration. From these 7 are rodent (6 rat and 1 mouse) models, while only 1 is a large animal model, which uses pigs. In case of rodent models, portal flow deprivation of 75-90% is achieved via portal vein ligation leaving only the right (20-25%) or left median (10-15%) lobes portally perfused, while liver splitting in general is carried out positioned according to the falciform ligament. As for the swine model, the left lateral and medial lobes (70-75% of total liver volume) are portally ligated, and the right lateral lobe (accounting for 20-24% of the parenchyma) is partially resected in order to reach critical liver volume. Each model is capable of reproducing the accelerated liver regeneration seen in human cases. However, all species have significantly different liver anatomy compared with the human anatomic situation, making clinical translation somewhat difficult. Key Messages: Unfortunately, there are no perfect animal models available for ALPPS research. Small animal models are inexpensive and well suited for basic research, but may only provide limited translational potential to humans. Clinically large animal models may provide more relevant data, but currently no suitable one exists.

[Assessment of the pilot program for cervical cancer screening by health visitors]. / A védonoi méhnyakszurési pilot program értékelése.

INTRODUCTION: Within the tender (6.1.3.A-13/1-2013-0001) supported by the European Union, we wished to involve health visitors into the organized cervical cancer screening program. AIM: The aim of our survey was to assess the satisfaction of health visitors, instructors, and that of the teaching aids. Furthermore, we wished to assess whether the teaching materials met the expectations. METHOD: Satisfaction of the health visitors was assessed by a survey, in four groups of questions. These involved the assessment of the instructors, the teaching aids, evaluation of the further training day, and the compliance with the knowledge of training. Period for completion of the questionnaires lasted from October to December in 2014. We used descriptive statistics for data evaluation. RESULTS: Data of 2148 health visitors was evaluated. They rated the performance of gynecologist-obstetricians 4.65, that of health visitors 4.61, that of public health professionals 4.56, and that of IT specialists 4.52. 98% of the teaching aids were useful for them and the acquired knowledge was appropriate with their expectations. CONCLUSION: The health visitors were satisfied with the theoretical instruction within the pilot program. The professionally well prepared health visitors may contribute to the success of the cervical cancer screening program. Orv. Hetil, 2017, 158(12), 461-467.

[Quality and performance indicators of the pilot program for cervical cancer screening by health visitors]. / A védõnõi méhnyakszûrési pilotprogram minõségi indikátorai és teljesítménymutatói.

The aim of our analysis was the assessment of the qualitative and performance indicators of a pilot program for health visitors' cervical cancer screening. The analysis involved the data from the Communication module of the Office of the National Chief Medical Officer. In the examined period (October, 2013 - September, 2015) the participation indicators of women aged 25-65, the prevalence rates of human papillomavirus and the cervical intraepithelial neoplasia were determined. In the screening period, the call-in rate was 32.45% nationally, with the compliance of 8.26%. The occurrence of a positive result was 1.85% nationally, with the highest rate in Hajdú-Bihar county (7.24%). HPV infection was detected in 113 cases (0.45%) nationally, HPV prevalence was 37.44/100,000 persons. The willingness for participation among women was low concerning the indicators. Their raising should be an emphasized task for public health in favor of reducing mortality from morbidities.

Liver regeneration after different degrees of portal vein ligation.

BACKGROUND: Selective portal vein ligation (PVL) is followed by ipsilateral atrophy and contralateral hypertrophy of the liver lobes. Although the atrophy-hypertrophy complex induced by PVL is a well-documented phenomenon, the effect of different degrees of extended portal vein occlusion on liver regeneration is not known. The aim of this study was to assess the effects of different degrees of portal occlusion on portal pressure and liver regeneration. MATERIALS AND METHODS: Male Wistar rats (n = 96; 220-250 g) were randomized into three groups and underwent 70%, 80%, or 90% portal vein ligation, respectively. The portal pressure was measured immediately and 24, 48, 72, 120, and 168 h after PVL (n = 6/group/time point). The hepatic lobes and the spleen were weighed, and liver regeneration ratio was calculated. Changes in liver histology and the mitotic activity were assessed on hematoxylin-eosin stained slides. RESULTS: Higher degree of portal occlusion triggered a stronger regenerative response (regeneration ratio of PVL 70%168h = 2.23 ± 0.13, PVL 80%168h = 3.11 ± 0.37, PVL 90%168h = 4.68 ± 0.48) PVL led to an immediate increase in portal pressure, the value of which changed proportionally to the mass of liver tissue deprived of portal perfusion (PVL 70%acute = 17 ± 2 mm Hg, PVL 80%acute = 19 ± 1 mm Hg, PVL 90%acute = 26 ± 4 mm Hg). Findings in histology showed necro-apoptotic lesions in the atrophic liver lobes and increased mitotic cell count in the hypertrophic lobes. The mitotic cell count of PVL 90% peaked earlier and at a significantly higher value than of PVL 70% and PVL 80% (PVL 9024h%: 96.0 ± 3.5 PVL 70%48h: 64.0 ± 2.1, PVL 80%48h: 56.3 ± 4.0). The mitotic index after 24 h showed a strong correlation with the acute portal hypertension. CONCLUSIONS: A higher degree of portal vein occlusion leads to a greater regenerative response, presumably triggered by the proportional increase in portal pressure, which supports the role of the so-called "blood-flow" theory of PVL-triggered liver regeneration.

Alterations in hepatic lobar function in regenerating rat liver.

BACKGROUND: Ligation of a branch of the portal vein redirects portal blood to nonligated lobes resulting in lobar hypertrophy. Although the effect of portal vein ligation on liver volume is well documented, the parallel alterations in liver function are still the subject of controversy. Our aim was to assess the time-dependent reactions of regional hepatic function to portal vein ligation by selective biliary drainage. METHODS: Male Wistar rats (n = 44) underwent 80% portal vein ligation. Before the operation as well as 1, 2, 3, 5, and 7 d after circulation, morphology and function (laboratory blood test; hepatic bile flow; plasma disappearance rate of indocyanine green; and biliary indocyanine green excretion) of the liver were examined. RESULTS: Although portal vein ligation affected liver circulation and morphology to a great extent, serum albumin levels, bilirubin levels, and total hepatic bile flow did not change significantly after the operation. Nevertheless, plasma disappearance rate and biliary indocyanine green excretion indicated a temporary impairment of total liver function with the lowest value on the second day and normalization by the fifth day. Bile production and biliary indocyanine green excretion of ligated lobes decreased rapidly after the operation and remained persistently suppressed, whereas the secretory function of nonligated lobes--after a temporary decline--showed a greater increase than the weight of the lobes. CONCLUSIONS: Portal vein ligation induced temporary impairment of total liver function, followed by rapid recovery mainly by reason of increase in the function of nonligated lobes. Functional increase in nonligated lobes was more pronounced than suggested by the degree of volume gain.

[Inequalities in cervical screening practices]. / Egyenlotlenségek a méhnyakszurésben.

Theoretically, the cytology-based cervical screening is capable of early detection of precancerous epithelial lesions of cervix uteri and its cancer, and of early referral to treatment. In this way, screening can inmprove the quality of life of the patients and reduce mortality from the target disease. Unfortunately, this often remains unexploited, because there might be inequalities on both "supply" and "demand" side of screening. In addition to the geopolitical situation of a country, inequalities might result from differences in the health care systems, and heavy access to the screening services. On the other hand, the socioeconomic status, the health-conciousness of the target population, and their knowledge and information of the benefits and potential harms of screening examination might have a bearing on the acceptance or refusal of the offered screening. Efforts need to be made to increase the uptake of cervical screening programmes.

[Factors influencing the participation in colorectal screening]. / Vastagbélszurés: a lakossági részvételt befolyásoló tényezok.

Participation of the target population in coloretal screening is generally low. In addition to demographic and socio-economic factors, the health care system and- in particular - family doctors play an important role. Further, the rate of participation is influenced by psychological, cognitive and behavioural factors, too. The paper analyses factors related to colorectal screening behaviour and potential interventions designed to screening uptake.

[Implementation status of cervical screening in Europe]. / A rákellenes méhnyakszurés helyzete Európában.

Following the recommendation of the Council of the European Union, almost all governments made a policy statement on the introduction of cytology-based cervical screening for the health care system. However, the status of implementation is uneven. In the majority of the developed countries an organised model of screening recommended by the relevant international professional organisations are in use, while occasional screening is applied in some other countries. Screening strategies (i.e. age range, screening intervals), coverage of the target population, and compliance rates vary significantly. The screening activities are in a planning phase is some less developed Central-Eastern and South European countries. In Hungary, the transition from the traditional "gynaecological cancer screening" into the recommended organised cervical screening is in progress; the active involvement of the district health visitors in the cervical screening would provide further improvement.

[Attendance of the fourth (2008-2009) screening round of the Hungarian organized, nationwide breast cancer screening program]. / A szervezett országos emloszurési program negyedik (2008-2009) szurési körének részvételi arányai.

INTRODUCTION: Organised, nationwide screening for breast cancer with mammography in the age group between 45 and 65 years with 2 years screening interval started in Hungary in January 2002. AIM: The aim of this study is to analyze the attendance rate of nationwide breast screening programme for the 2008-2009 years. METHOD: The data derive from the database of the National Health Insurance Fund Administration. The ratio of women in the age group 45-65 years was calculated having either a screening mammography or a diagnostic mammography in the 4th screening round of the programme. RESULTS: In the years 2000-2001, 7.6% of the women had an opportunistic screening mammography while in 2008-2009 31.2% of the target population had screening mammography within the organized programme. During the same periods 20.2% (2000-2001) and 20.4% (2008-2009) of women had a diagnostic mammography. Thus the total (screening and diagnostic) coverage of mammography increased from 26.6% (2000-2001) to 50.1% (2008-2009). The attendance rate failed to change between 2002 and 2009. CONCLUSIONS: In order to decrease the mortality due to breast cancer, the attendance rate of mammography screening programme should be increased. Orv. Hetil., 154(50), 1975-1983.

[Participation rates in the third round (2006-2007) of the breast cancer screening program in Hungary]. / A szervezett emloszurési program harmadik (2006-2007) szurési ciklusának részvételi arányai.

Organised, nationwide screening for breast cancer with mammography in the age group of 45-65 years with 2 years screening interval started in Hungary in January 2002. The aim of this study is to analyse the attendance rate of breast screening programme for the 2006/2007 years, including the analysis of the ratio of screening and diagnostic mammography examinations. The data derive from the financial database of the National Health Insurance Fund Administration (NHIFA) covering the 8 years period between 2000 and 2007. The ratio of women in the age group of 45-65 years was calculated having either a screening mammography or a diagnostic mammography. The analysis was carried out for the years 2000-2001 before and 2006-2007 after the implementation of nationwide organised programme. In the years 2000-2001 7.26% of the women aged 45-65 years had an opportunistic screening mammography while in 2006-2007 29.4% of the target population had screening mammography within the organised programme. During the same periods 19.8% (2000-2001) and 21.8% (2006-2007) of women aged 45-65 years had a diagnostic mammography. Thus the total (screening and diagnostic) coverage of mammography increased from 26.2% (2000-2001) to 49.7% (2006-2007). The attendance of the Hungarian organised breast cancer screening programme slightly declined in 2006-2007 compared to 2002-2003/2004-2005, and to achieve the expected results in mortality decrease a further improvement of the uptake is necessary.

[Gynecological screening or cervical screening? Conflicts between clinical and public health viewpoints]. / Nogyógyászati rákszurés vagy méhnyakszurés? Klinikai és népegészségügyi nézopontok ütközése.

The "gynecological screening" that is composed of complex gynecological examination including colposcopy and cytological examinations has traditionally been incorporated into the gynecological protocol and practice. Over the past few decades, unfortunately, this screening practice has entrenched in the mind both of the gynecological community and the general public. As a result, the government-supported, organized cervical screening program of the population has come to a standstill. In order to adjust the cervical screening practice to the international public health recommendations in which cytology is the only screening test applied, the authors decided to involve primary care nurses and health visitors in smear taking, and to refer those with abnormal findings to a gynecologist for further clinical examination.

The effect of Cyclophilin D depletion on liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy.

AIM: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created. METHODS: Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed. RESULTS: The CypD KO group displayed improved mitochondrial function, as both ATP production (P < 0.001) and oxygen consumption (P < 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor γ co-activator 1-α (PGC1-α) was also elevated in the CypD KO group (P < 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P < 0.001). CONCLUSIONS: Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS.

[Controversial issues in colorectal screening in Hungary: conflict of clinical and public health viewpoints]. / A vastag- és végbéldaganatok szurésének vitatott kérdései: klinikai és népegészségügyi nézopontok ütközése.

In Hungary, mortality rates from colorectal cancer are dramatically high, therefore the reduction by population screening as a public health measure is considered as one of the priorities of National Public Health Program. In the beginning, a human-specific immunological test was applied in the "model programs", as a screening tool, to detect the occult blood in the stool; compliance was 32% in average. However, the objectives of the model programs have not been achieved, because, among other reasons, a debate on the method of choice and the strategy to follow have divided the professional public opinion. In this study the debated issues are critically discussed, being convinced that, at present, population screening seems to be the most promising way to alleviate the burden of colorectal cancer.

[All you should know about intraductal papillary mucinous neoplasm (IPMN)]. / Az intraduktális papilláris mucinózus neoplázia (IPMN) jellegzetességei.

In an increasingly aging Western society, the treatment of the malignant diseases became the greatest challenge of medicine in the 21st century. Among these, pancreatic ductal adenocarcinoma (PDAC) is of particular interest which, in spite of modern oncology treatments, is a malignancy with an unfavorable prognosis. Underlying the poor survival rates, relatively late-stage recognition, limitations of surgical removal, and ineffective oncological treatments can be mentioned. Its importance is further enhanced by its growing incidence. As a consequence of these reasons, there is an increasing effort for the early detection of invasive tumors, the central part of which is the detection and clinical addressing of precancerous conditions in the pancreas. Of these, intraductal papillary mucinous neoplasia (IPMN) has a paramount importance. In this review, we present the latest evidence-based knowledge of the etiological factors, epidemiological features, pathomorphological manifestations, most up-to-date diagnosis and treatment of IPMN.

The Role of Farnesoid X Receptor in Accelerated Liver Regeneration in Rats Subjected to ALPPS.

BACKGROUND: the role of bile acid (BA)-induced farnesoid X receptor (Fxr) signaling in liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was investigated in a rat model. METHODS: Male Wistar rats underwent portal vein ligation (PVL) (n = 30) or ALPPS (n = 30). Animals were sacrificed pre-operatively and at 24, 48, 72, or 168 h after intervention. Regeneration rate, Ki67 index, hemodynamic changes in the hepatic circulation, and BA levels were assessed. Transcriptome analysis of molecular regulators involved in the Fxr signaling pathway, BA transport, and BA production was performed. RESULTS: ALLPS induced more extensive liver regeneration (p < 0.001) and elevation of systemic and portal BA levels (p < 0.05) than PVL. The mRNA levels of proteins participating in hepatic Fxr signaling were comparable between the intervention groups. More profound activation of the intestinal Fxr pathway was observed 24 h after ALPPS compared to PVL. CONCLUSION: Our study elaborates on a possible linkage between BA-induced Fxr signaling and accelerated liver regeneration induced by ALPPS in rats. ALPPS could trigger liver regeneration via intestinal Fxr signaling cascades instead of hepatic Fxr signaling, thereby deviating from the mechanism of BA-mediated regeneration following one-stage hepatectomy.

The effects of physical prehabilitation: Improved liver regeneration and mitochondrial function after ALPPS operation in a rodent model.

BACKGROUND: To identify the role of physical prehabilitation (PP) in liver regeneration, mitochondrial function, biogenesis, and inflammatory response was investigated after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in a rodent model. METHODS: Male Wistar rats (n = 60) underwent ALPPS. Animals were divided (n = 30) to the physical prehabilitation group (PP) and sedentary group (S). The animals were exsanguinated before (0 hour) and 24, 48, 72, or 168 hours after the operation. Regeneration rate and proliferation index were assessed. Mitochondrial function, biogenesis, and inflammatory response were evaluated. RESULTS: Regeneration rate and Ki67 index were significantly increased in the PP group compared to the S group (P < .001). Due to the changes in oxidative capacity and ATP production rate, the P/O ratio of PP group compared to the S group was significantly increased (P < .05). PP group was characterized by accelerated mitochondrial biogenesis and less intense inflammatory response compared to the S group. CONCLUSIONS: To our knowledge, this is the first demonstration of the beneficial effects of PP on liver regeneration, mitochondrial function, biogenesis, and the inflammatory response after ALPPS.

[Quality and performance indicators of colorectal cancer screening pilot program in Csongrád County, Hungary]. / A Csongrád megyei vastagbélszûrési pilot program minõségi indikátorai és teljesítménymutatói.

Colorectal cancer is a major social and economic burden for developed countries. Our analysis aimed to evaluate the quality and performance indicators of colorectal cancer screening pilot program. The colon cancer screening pilot program was carried out in 2015 involving an average-risk population aged 50-69 in Csongrád county, Hungary. The analysis involved data from the Communication module of the Office of the National Chief Medical Officer. We recorded 21.1% invitation rate (22,130 persons), 51.2% attendance and 47.3% participation rates, with a higher female participation rate (p<0.001). Participation rate was far lower than the expected 65%. The rate of non-negative results (13.1%) exceeds the international reference rate. Participation rate on the colonoscopy screening (90.1%) reached the expected value. Compared to the number of actual colonoscopies performed, adenomas were found in 2.5% and malignant lesions in 0.3% of the cases. Our results highlight the deficiencies regarding the follow-up and data recording of screening results in the IT system as well as the lack of communication between the GP and the diagnostic laboratories.

[Attendance in the second phase (2004-2005) of the Hungarian organized breast cancer screening program]. / A szervezett emlôszûrési program második ciklusának (2004-2005) részvételi arányai.

AIM: Organised, nationwide screening for breast cancer with mammography in the age group of 45-65 years with a 2-year screening interval started in Hungary in January 2002. The aim of this study is to analyze the attendance rate of breast screening programme, including the analysis of the ratio of screening and diagnostic mammography examinations. DATA AND METHODS: The data derive from the financial database of the National Health Insurance Fund Administration (NHIFA) covering the 6-year period between 2000-2006. The ratio of women in the age group of 45-65 years was calculated having either a screening mammography or a diagnostic mammography. The analysis was carried out for the years 2000-2001 before and 2002-2003, 2004-2005 after the implementation of nationwide organised programme. RESULTS: In the years 2000-2001 7.26% of the women aged 45-65 had an opportunistic screening mammography, while in 2002-2003 34% and in 2004-2005 29.5% of the target population had screening mammography within the organised programme. During the same periods 19.8% (2000-2001), 22.1% (2002-2003) and 23.2% (2004-2005) of women aged 45-65 had a diagnostic mammography. Thus the total (screening and diagnostic) coverage of mammography increased from 26.2% (2000-2001) to 53.5% (2002-2003) and 50.8% (2004-2005). CONCLUSIONS: Attendance of the Hungarian organised breast cancer screening programme slightly declined in 2004-2005, and to achieve the expected results in decline of mortality further improvement of attendance is necessary.

[Is the mass screening for prostate cancer justifiable?]. / Indokolt-e a népegészségügyi prosztataszurés?

In Hungary, prostate cancer is a major public health problem, therefore screening should be considered to reduce the number of deaths. Screening tests are available, i.e. prostate-specific antigen (PSA) and digital-rectal examination, nevertheless their sensitivity, specificity and positive predictive value are far from being perfect. Evidences from non-randomized screening trials suggest possible benefit but randomized controlled trials are still needed for conclusive evidence. The screening might cause more harm than good due to overdiagnosis and overtreatment as a result of limited specificity of the test. According to authors' point of view, opportunistic screening as part of diagnostics of patients having symptoms indicative of prostatic disorder is fully justified but mass screening of population of average risk should not be introduced until supportive evidence is available from the ongoing randomized-controlled screening trials.