[Management of Stent-graft migration with obstruction of supra-aortic vessel during an endovascular procedure for aortic isthmus rupture]. / Migration d'endoprothèse thoracique avec occlusion des troncs supra-aortiques en per-procédure pour rupture isthmique ; prise en charge.

The endovascular approach is widely used in the management of aortic isthmic rupture. Even if it remains less invasive than conventional surgery, a life-threatening complications are possible. We report the case of a young female patient presenting a stent-graft migration during the deployment with total obstruction of the supra-aortic vessels. We describe the therapeutic management with a cerebral rescue procedure followed by a delayed surgical repair.

[Constrictive pericarditis and disseminated nocardiosis]. / Péricardite constrictive et la nocardiose disséminée.

Human nocardiosis usually involves the respiratory tract or the skin but may disseminate to virtually any organ, it occurs in immunocompromised hosts as well as individuals with no apparent predisposition. Involvement of the pericardium is uncommon, having been reported infrequently in the past, but mandates a special management. This report describes the first case in Europe of a patient with chronic constrictive pericarditis from nocardia brasiliens, successfully treated with pericardiectomy and appropriate antibiotic therapy.

Early postoperative bleeding after isolated coronary bypasses: Changes over a period of 20 years - An observational study.

OBJECTIVES: The objectives were to analyze the evolution of the postoperative bleeding after coronary artery bypass grafting and to determine which factors impacted on this evolution. METHODS: This is a single-center retrospective study including 4590 patients undergoing coronary bypass surgery between 1995 and 2017. The study period was divided into 3 same-sized periods. We analyzed the evolution of the bleeding according to: the chest volume bleeding over the first 24hours, the severity and the rate of transfusion during the hospital stay. Intrahospital outcomes were compared between "minor" and "major" bleedings. The risk factors of major bleeding were analyzed by multiple logistic regression. RESULTS: The chest volume decreased particularly during the first years of the study period. Major bleedings decreased over the periods (7.3%, 4.9% and 3.8% respectively, P<0.0001), as did the rate of transfusion (26.4%, 23.5% and 19.6% respectively, P<0.0001). Major bleedings were correlated with hospital mortality (8.2% versus 1.1%, P<0.0001). The risk factors of major bleeding were the period 1 (1995 to 2003), a renal failure, a resternotomy, the EuroSCORE, the hematocrit prior to cardiopulmonary bypass and the duration of cardiopulmonary bypass. CONCLUSIONS: Postoperative bleeding decreased mainly in the 1990s. Progressive changes in bleeding prevention and blood recovery, surgical techniques, haemoglobin threshold for transfusion decision and practitioners' experience have contributed to these results and must be continued to optimize the postoperative outcomes.

Characterisation of bioenergetic pathways and related regulators by multiple assays in human tumour cells.

BACKGROUND: Alterations in cellular metabolism are considered as hallmarks of cancers, however, to recognize these alterations and understand their mechanisms appropriate techniques are required. Our hypothesis was to determine whether dominant bioenergetic mechanism may be estimated by comparing the substrate utilisation with different methods to detect the labelled carbon incorporation and their application in tumour cells. METHODS: To define the bioenergetic pathways different metabolic tests were applied: (a) measuring CO2 production from [1-(14)C]-glucose and [1-(14)C]-acetate; (b) studying the effect of glucose and acetate on adenylate energy charge; (c) analysing glycolytic and TCA cycle metabolites and the number of incorporated (13)C atoms after [U-(13)C]-glucose/[2-(13)C]-acetate labelling. Based on [1-(14)C]-substrate oxidation two selected cell lines out of seven were analysed in details, in which the highest difference was detected at their substrate utilization. To elucidate the relevance of metabolic characterisation the expression of certain regulatory factors, bioenergetic enzymes, mammalian target of rapamycin (mTOR) complexes (C1/C2) and related targets as important elements at the crossroad of cellular signalling network were also investigated. RESULTS: Both [U-(13)C]-glucose and [1-(14)C]-substrate labelling indicated high glycolytic capacity of tumour cells. However, the ratio of certain (13)C-labelled metabolites showed detailed metabolic differences in the two selected cell lines in further characterisation. The detected differences of GAPDH, ß-F1-ATP-ase expression and adenylate energy charge in HT-1080 and ZR-75.1 tumour cells also confirmed the altered metabolism. Moreover, the highly limited labelling of citrate by [2-(13)C]-acetate-representing a novel functional test in malignant cells-confirmed the defect of TCA cycle of HT-1080 in contrast to ZR-75.1 cells. Noteworthy, the impaired TCA cycle in HT-1080 cells were associated with high mTORC1 activity, negligible protein level and activity of mTORC2, high expression of interleukin-1ß, interleukin-6 and heme oxygenase-1 which may contribute to the compensatory mechanism of TCA deficiency. CONCLUSIONS: The applied methods of energy substrate utilisation and other measurements represent simple assay system using (13)C-acetate and glucose to recognize dominant bioenergetic pathways in tumour cells. These may offer a possibility to characterise metabolic subtypes of human tumours and provide guidelines to find biomarkers for prediction and development of new metabolism related targets in personalized therapy.

Wintertime surgery increases the risk of conversion to hip arthroplasty after internal fixation of femoral neck fracture.

UNLABELLED: The study demonstrates that wintertime surgeries are associated with impaired fracture healing and increases the risk of conversion to hip arthroplasty after osteosynthesis of femoral neck fracture. Furthermore, the results raise the possibility of association between seasonal changes in vitamin D levels and impaired fracture healing of femoral neck fracture. INTRODUCTION: Although the changes of vitamin D level and calcitropic hormones influencing bone metabolism are seasonal, the effect of seasons on hip fracture healing is unknown. We assessed the effects of seasonal periodicity on conversion to hip arthroplasty after primary osteosynthesis of femoral neck fracture. METHODS: This nationwide retrospective observational cohort study involved 2779 patients aged ≥ 60 years who underwent internal screw fixation for primary femoral neck fracture and were discharged in 2000. Cases requiring conversion to arthroplasty during the 8-year follow-up derived from the Hungarian health insurance database were registered. Risk factors assessed included sex, age, fracture type, season of primary surgery and surgical delay. Competing-risks regression analysis was used for data analyses. RESULTS: During the observation period, 190 conversions to hip arthroplasty (6.8%) were identified, yielding an overall incidence of 19.5 per 1000 person-years. The crude incidence rates of conversions after osteosynthesis in winter, spring, summer and fall were 28.6, 17.8, 16.9 and 14.7 per 1000 person-years, respectively. Besides younger age, female sex and intracapsular fracture displacement, wintertime primary osteosynthesis significantly increased the risk of conversion (fall vs. winter, hazard ratio (HR): 0.50, 95% confidence interval [95% CI 0.33-0.76]; spring vs. winter, HR: 0.63, [95% CI 0.44-0.92]; summer vs. winter, HR: 0.62, [95% CI 0.42-0.91]). CONCLUSIONS: Our study demonstrate that wintertime primary osteosynthesis increases the risk of conversion surgeries. The results may help improving the outcome of primary fixation of femoral neck fractures.

Correlation between risk factors and subsequent surgical management following internal fixation of intracapsular femoral neck fractures in patients under the age of 60 years.

PURPOSE: Regarding intracapsular femoral neck fractures, the main focus of research is the correlation between fracture-related complications and prognostic factors. To evaluate the correlation between complications required surgery (fracture-related treatment) and, among others, several less extensively investigated prognostic factors (day of surgery, co-morbidities, hospital type) in a 2-year period following internal fixation in patients under the age of 60 years with intracapsular femoral neck fracture. METHODS: A retrospective analysis of femoral neck fractures occurring in Hungary in 2000 was undertaken, based on data obtained from the National Health Insurance Fund Administration. The data were validated and completed by a questionnaire carried out in all of the 60 institutions enrolled. The effects of prognostic factors were analyzed by uni- and multivariate logistic regression in three groups: all fracture-related treatments and non-prosthetic (NPT) and prosthetic treatments (PT). RESULTS: Out of 413 patients, 17.9% required further fracture-related treatment. In 7.7% of patients, NPT and in 10.2% of patients, PT was performed. Fracture displacement (odds ratio [OR] = 2.24), weekend surgery (OR = 2.35), infections (OR = 3.68), central nervous system-related co-morbidities (OR = 3.64), and the county hospital level of management (OR = 2.36) were associated with significantly increased risk for further surgery. CONCLUSIONS: To reduce the influence of risk factors, standardization of the substantive traumatologic and orthopedic professional guidelines, as well as the introduction of the "common orthopedic-trauma patient care" (British model) are suggested. To achieve high-quality standardized patient management, personal and material conditions are required to be accessible every day of the week. In the presence of co-morbidities, reduction of their harmful effects should be a major consideration by focusing on the patient in the peri-operative periods.

Human anti-60 kD heat shock protein autoantibodies are characterized by basic features of natural autoantibodies.

Anti-human Hsp60 autoantibodies--known risk factor of atherosclerosis--were investigated in a mouse model and in samples of healthy subjects: polyreactivity, presence in cord blood samples of healthy newborns and life-long stability were tested. In IgM hybridoma panel from mouse spleens, polyreactivity of anti-Hsp60 autoantibodies was studied. In healthy pregnant women, umbilical vein and maternal blood samples were collected after childbirth, anti-Hsp-60 and -65 IgM and IgG levels were measured. Life-long stability of anti-Hsp-60 levels was studied on healthy patients during 5 years. ELISA was used in all studies. Polyreactivity of IgM clones of newborn mice and lifelong stability of these autoantibodies in healthy adults were established. IgM anti-Hsp60 autoantibodies in cord blood of healthy human infants were present, however, there was no correlation between maternal and cord blood IgM anti-Hsp60 concentrations. It is proposed that presence of anti-Hsp60 autoantibodies--as part of the natural autoantibody repertoire--may be an inherited trait. Level of anti-Hsp60 autoantibodies may be an independent, innate risk factor of atherosclerosis for the adulthood.

Notch-regulation upon Dll4-stimulation of TGFb-induced apoptosis and gene expression in human B-cell non-Hodgkin lymphomas.

Notch-signalling has been implicated as a pathogenetic factor and a therapeutical target in T-cell leukaemias and in some lymphomas of B-cell origin. Our aim was to investigate the role of Notch-signalling in apoptosis regulation in human non-Hodgkin B-cell lymphoma (B-NHL) cell lines and in primary chronic lymhocytic leukaemia (CLL) cells using Delta-like 4 (Dll4) ligand mediated Notch activation and gamma-secretase inhibitor (GSI) mediated Notch inhibition in vitro. The potential cross-talk of Notch with the transforming growth factor-beta (TGFb) pathway in apoptosis induction was also explored, and the effect of GSI on drug-induced apoptosis was assessed. Modulation of Notch-signalling by itself did not change the rate of apoptosis in B-NHL cell lines and in CLL cells. TGFb-induced apoptosis was decreased - but not completely abolished - by GSI in TGFb-sensitive cell lines, but resistance to the apoptotic effects of TGFb were not reversed by Notch activation or inhibition. Drug-induced apoptosis was not modified by GSI. We identified Hairy/Enhancer of Split (HES)-1 as a TGFb target gene in selected - TGFb-sensitive - B-NHL cell lines. TGFb-induced HES-1 was only partially Notch-dependent in later phases. Apoptosis regulation by TGFb and GSI was not dependent on the transcriptional regulation of c-myc. In conclusion, our data does not support a unifying role of Notch in regulating apoptosis in B-NHL, but warns that gamma-secretase inhibitors may actually counteract apoptosis in some cases.

Epidemiology of osteoporosis related fractures in Hungary from the nationwide health insurance database, 1999-2003.

UNLABELLED: The Hungarian national health insurance database was screened for fractures of patients aged 50-100, 1999-2003. On average, there were 343 hip, 1,579 forearm, 342 proximal humerus, 48 inpatient vertebral and 2,459 other fractures/100,000 inhabitants/year. INTRODUCTION: The incidence of fractures differs among populations. Our aim was to study the incidence of fractures in Hungary, focusing on classical osteoporotic sites and to compare the results with those of other European countries. METHODS: The Hungarian National Health Insurance Fund database, covering 100% of the population, was screened for fractures of patients aged 50-100, 1999-2003. The search of vertebral fractures was restricted to those admitted to hospital. A gender and age-matched comparison was performed with available data from Europe. RESULTS: There were mean 343 hip, 1,579 forearm, 342 proximal humerus, 48 inpatient vertebral and 2,459 other fractures/100,000 inhabitants/year; the female/male ratio was between 1.2-2.4. Multiple fractures occurred in 23.1% of the cases. Hip fracture incidence in Hungary lies between the rates of northern and southern countries of Europe. CONCLUSIONS: Our study offers nationwide epidemiological data on fractures in Hungary. The incidence of fractures increased by age, regardless of the type of fracture. Incidence of hip fractures in Hungary fits in the previously established geographic trends in Europe. Our results fulfil a need for fracture data from Central Europe.

[Experiences with the Introduction of Diagnosis Related Groups (DRG) in the Hungarian Ophthalmology]. / Erfahrungen der Umsetzung von Diagnosis Related Groups (DRG) in der ungarischen Augenheilkunde.

OBJECTIVE: The aim of our investigation is to analyse the effect of the introduction of the DRG (Diagnosis Related Groups) principle on the financing of ophthalmology care including the analysis of market share of ophthalmology. DATA AND METHODS: Data of the study derive from the financial database of the Hungarian National Health Insurance Fund Administration (OEP) containing the monthly activity reports of health care providers. The financing of acute hospital care in Hungary is based on a case-mix system called Homogeneous Disease Groups (Homogén Betegségcsoportok, HBCS). The analysis covers the period between 1995 and 2003. We used the following indicators in order to analyse the market share of ophthalmology: financial cases (patients), DRG costweights and nursing days (length of stay). RESULTS: From the DRG costweights - serving as a base value for financing - the market share of ophthalmology was 3.3 - 3.5 % in 1995 - 1996, but decreased to 2.6 - 2.7 % in 1997 - 1998, and after a gradual increase since 1999 it went up to 3.4 % in 2002 - 2003. The market share of ophthalmology from financial cases (patients) increased from 3.1 - 3.2 % in 1995 - 1996 to 3.8 - 3.9 % in 2002 - 2003. From the total number of nursing days ophthalmology had a market share of 2.4 - 2.6 % in 1995 - 1996, which showed a further decrease to 2.2 - 2.3 % in 2002 - 2003. The average length of stay in ophthalmology decreased from 8 days (1995) to 4 days (2003). CONCLUSION: The frequent changes of the Hungarian DRG system had a significant effect on the financing of Hungarian ophthalmology care. The continuous changes in the regulation of financing and reimbursement represent a big challenge for ophthalmology.

Activity of the notch-signalling pathway in circulating human chronic lymphocytic leukaemia cells.

Dysregulation of the Notch-pathway has been implicated in the pathogenesis of chronic lymphocytic leukaemia (B-CLL). We characterized the mRNA expression of Notch pathway elements in circulating normal B- and B-CLL cells, and compared expression profiles with clinical and prognostic data. Similar expression profiles were found in normal B-cells and B-CLL cells, however, most B-CLL samples showed lower Hairy/Enhancer of Split-1 expression than normal B-cells, which suggests that the pathway is not over-activated in B-CLL. The expression of Notch-pathway genes did not correlate with other prognostic factors of B-CLL. The importance of Notch-signalling in CLL cells in lymphatic tissue microenvironments remains to be determined.

The organisation and results of first screening round of the Hungarian nationwide organised breast cancer screening programme.

BACKGROUND: The aim of this paper is to give an overview of organisational issues of the Hungarian nationwide organised breast cancer screening programme and to provide the results of the first screening round of the programme for the years 2002-2003. PATIENTS AND METHODS: Data were derived from the financial database of the National Health Insurance Fund Administration covering the period 2000-2003. Women who underwent mammography screening were included into the study. RESULTS: Uptake of the organised screening programme in 2002-2003 was 45.09%, while the recall rate was 7.23%. Malignant cases represented 65.38% of total surgeries and 0.36% of total number of screened women yielding a cancer detection rate 3.6 per 1000 screened women. Malignant cases of 10.78% were identified as ductal carcinoma in situ, while 89.22% was invasive cancer. Benign to malignant ratio was 0.54 : 1. CONCLUSION: There is therefore an urgent need to closely monitor performance and to review programme policies and procedures with the aim of increasing both the participation rate and the proportion of women eligible to attend screening.

Successful management of intrauterine twin and concomitant cervical pregnancy: a case report.

Use of in vitro fertilization techniques increases the frequency of pathological implantation. However, simultaneous pregnancies are a rarity. Ectopic implantation of the embryo may occur in the cervical canal. This is the first case report, which describes successful management of an intrauterine twin pregnancy which occurred simultaneously with a cervical pregnancy. Diagnostic and therapeutic options are discussed along with the outcome of pregnancies. The cervical pregnancy was removed by aspiration, without dilation of cervical canal, which saved the lives of intrauterine fetuses and preserved fertility for following pregnancies. Finally we review the advanced methods in the literature.

TGF beta 1 induces caspase-dependent but death-receptor independent apoptosis in lymphoid cells.

Transforming growth factor beta 1 (TGF beta 1) is an antiproliferative and proapoptotic cytokine for normal B-cells, however many B-cell lymphomas have lost their response to TGF beta 1. The aim of this study was to identify the sequence of events in apoptosis induced by TGF beta 1 in an EBV negative, human B-cell lymphoma line (HT58). The proportion of apoptotic cells increased gradually (up to 72 hr) at an optimal dose range of 0.5-1.0 ng/ml. The induced cell death required the action of downstream caspases. Caspase activation was accompanied by an increase in the permeability of mitochondrial membranes, but there was no change in the expression of certain members of Bcl-2 family (Bcl-2, Bax, Bcl-XL). Similarly, none of the death receptors or ligands were involved in apoptosis induction. Further study will include the participation of TGF beta 1 target genes in the pore formation of mitochondrial membranes and/or the elimination of a putative survival signal.

Expression of metastasis associated proteins, CD44v6 and NM23-H1, in pediatric acute lymphoblastic leukemia.

Two metastasis-associated proteins, CD44v6 and NM23-H1, are expressed by normal lymphoid cells, the former serving as activation marker and the latter as a constitutive protein. CD44v6 is considered as a marker of poor prognosis of various hematological cancers but its expression was not demonstrated in childhood acute lymphoblastic leukaemia (ALL). On the other hand, NM23-H1 is considered as a differentiation inhibitory factor in various hematological cancers and as a marker of poor prognosis. Therefore we analyzed the expression of CD44v6 and NM23-H1 in the bone marrow of sixteen pediatric ALL patients using immunocytochemistry. For the first time, we have demonstrated the expression of CD44v6 protein epitopes on leukemic cells in a proportion of ALL cases (6 out of 16), primarily in the medium/high risk group (except one case), suggesting a possible association to an unfavourable outcome. On the other hand, NM23-H1 protein expression was maintained in leukaemic cells in 50% of both low and medium/high risk ALL cases. The majority of the pediatric ALL cases expressed only one of the metastasis-associated proteins (10 out of 16). This feature is similar to the observations made in several adult solid cancers. The potential of CD44v6 expression in leukaemic cells as prognosticator in pediatric ALL should be evaluated in a larger clinical trial.

[The role of syndecans in lymphoid systems] / Syndecan-expresszió és a lymphoid rendszer.

Syndecans, transmembrane heparan sulfate proteoglycans, play an important role in cell-cell and cell-matrix interactions, as receptors/co-receptors of matrix elements, cytokines, growth factors. These functions are partly non-specific and due to the heparan sulfate chains attached to the ectodomain, and partly specific related to the transmembrane and cytoplasmic domains of the core protein. In hemopoietic cells syndecan-1 is expressed in certain B cells, in pre-B cells and plasma cells. In lymphoproliferative diseases this normal syndecan-1 expression of plasma cells is retained in myelomas/plasmocytomas, other lymphoplasmocytic NHL subtypes and primary effusional lymphomas. Syndecan-1 expression is probably gained in B-CLL, and lost in other NHLs of pre- or post-follicular origin. These results suggest that the expression of syndecan is essential for some NHLs, probably ensuring the required connections to the microenvironment. From a diagnostic point of view, syndecan-1 is a very useful phenotypic marker to identify cells with plasmocytic differentiation. The importance of syndecan expression in CLL and Hodgkin-lymphoma still requires further studies.