Friday 2 October 2015
17.00 - 17.30
Special innovative presentation
Alexandros Kokolakis, General Director of Development and Promotion of CERN-HERMES International Network
On June 1st 2012 the scientific network of CERN-HERMES officially started functioning in the establishments of CERN in Geneva. At that time, both CERN and scientists from the international scientific community, in recognition of my contribution to the establishment of the whole network, suggested that I become a member of the advisory committee of the network and also General Director of Development and Promotion the whole network. One of the aims of the network is the reciprocality of Greece by CERN. In CERN-HERMES, participate research groups from CERN and European Universities. From the Greek side actively participate, the University of Crete, the National Metsovio Polytechnic University, the Universities of Athens, Patras, Alexandroupolis, Nicosia, the Technological Institute of Athens, the National Research center Dimokritos, the Greek Atomic Energy Agency and the University Hospitals of Heraklion, Alexandroupolis and Patras. From the National scientific community, participate 25 universities and research centers from eleven countries.
Evaluating the knowledge I had in the previous months, being informed from deferent research subjects, I was especially interested on the subject of cancer treatment by using protons and decided to submit an official proposal for the establishment of a center for cancer treatment, using protons in Crete. This treatment is technologically the most up to date, and medically the most effective method of treatment using radiation. This method can focus on tumors who are located in great depths and in difficult anatomic points (i.e. tumors of the upper thorax and of the brain). Furthermore, totally destroys genetic material (DNA) of cancer cells and minimizes the reappearance of cancer. Induces only a minimal injury of the by standing normal tissues, in contrast to the photon bundles. The danger of inducing secondary cancers due to radiation by protons is much smaller compared to that from conventional radiotherapy. For this reason, this treatment by protons is used in cases of pediatric cancer. Treatment duration is much shorter related to the referring time of treatment by conventional means.
After a Marathon like effort, I managed to obtain from the Greek authorities the approval of this practical new treatment of malignant tumors of cancer by using protons, for all Greek territory. Now this treatment is a historic reality for our country which gives hope to thousands of patients with cancer and opens the route for the establishment of such a center in our country.
19.00 - 21.00
Invited lecture by Professor Christos Lionis: Evidence-based innovative therapeutic medicine of Cretan plants: some encouraging specific functions and claims
(Only one lecture is presented in every Olympiad)
The Island of Crete was the place where the use of herbal medicine has its roots since the Bronze Age period. Although, the consumption of aromatic plants as component in curing common diseases is still on population’s practices, a new interest was appeared on the basis of studies with a focus on illness behavior as a mutual collaboration between the University of Crete and the University of Leiden, The Netherlands. The antioxidant activity of certain Cretan plants has been documented and it has been shown and reported that herbal extracts are possible to decrease lipid per oxidation in cultured lung cells exposed to iron or ozon. The biological effects and bioactivity of essential oils as well as their antibacterial properties have been previously discussed in the literature. However, it was the first attempt in Europe when a double blind randomized controlled trial examined the effectiveness of an essential-oil extract of three Cretan aromatic plants designed and implemented in rural Crete on patients with upper respiratory tract infection. Descriptive differences were recently reported in favorable direction especially in the virus-positive population, while these results guide at the moment a series of actions for further research and discussion on the potentialities in the therapeutic medicine. A recent joint attempt (Clinic of Social and Family Medicine and Department of Experimental Endocrinology at the School of Medicine, University of Crete) under the support of the National Strategic Reference Framework Program focused on the effectiveness of functional extract of Mentha Spicata encapsulated in yogurt with honey on lipids profile of health patients in rural Crete. The first reported results of a cross-over study which was designed and implemented recently were in a favorite direction and it was in agreement with the animal based study that was carried out in the frame of this project. In conclusion, the two first studies on the Cretan medicinal and aromatic plants support the potentialities of the use of Ethno botanical methodology to move the needle of innovation on viral infections and lipids metabolism.
Innovative presentation by Dr. Sterghios A. Moschos: Ebola Check: Delivering molecular diagnostics at the point of need
The 2013-5 global outbreak of Ebolavirus disease brought to sharp focus the need for diagnostic capacity to be equitably available on a global scale: from the most under-developed areas of resource-limited countries in West Africa to high volume international travel hubs in Europe and the USA. Quick detection of the causal agent of disease is pivotal to containment, contact tracing and clinical action to protect healthcare workers, communities and patients. Nucleic acid testing (NAT) by real time reverse transcription quantitative polymerase chain reaction (RT-PCR) has emerged as the preferred method for reliable patient status confirmation. Presently, this is served through advanced clinical molecular laboratory testing in a <8hr manual process that requires 3.5ml venous blood samples. To meet the demand in West Africa, this has necessitated large-scale mobile laboratory and volunteer biomedical scientist deployment: a solution that has proven eventually adequate, albeit temporary against future re-emergence of this and other haemorrhagic fever disease agents prevalent in the region. The EbolaCheck consortium was formed in August 2014 to address the need for delivering NAT at the point of care. We have developed a novel platform technology that can QUantitatively, RAPidly IDentify (QuRapID) known RNA or DNA targets in viruses, bacteria, or eukaryotic cells directly in crude biofluids, including whole blood, in under 40min using a 5 microliter sample. The portable, battery-operated system lacks microfluidics, pumps or other sensitive/high cost parts making it suitable for the environmental and economic challenges of resource-limited countries. The simple, safe, 5-step sample-to-answer process requires minimal training and informs frontline healthcare workers of diagnostic status, whilst reporting remotely epidemiologically relevant results. Data on biosafety level 2 surrogate Ebolavirus templates presented in encapsulated or enveloped viruses indicate performance comparable to clinical laboratory testing and utility beyond filoviruses. Emerging performance data on live Ebolavirus, non-human primate disease model and patient samples, as well as future development plans will be discussed.
Friday 2 October 2015
09.00 - 10.20
Assessing an avoidable and dispensable reoperative entity: self-referred flawed cleft lip and palate repair
Foroglou P.1, Tsimbonis A.1, Goula C.1, Demiri E.1
1. Dept. of Plastic Surgery-Medical Section-School of Health Sciences-Aristotle University of Thessaloniki-“Papageorgiou” General Hospital-Thessaloniki-Greece
Introduction: The incidence of cleft lip and/or cleft palate (CLP) has reportedly increased from 1:1000 to 1:600 live births and is the commonest congenital birth difference. The main long-term morbidity of this condition is dysfunctional speech and communication impairment, followed by unfavourable surgical outcome
The Island of Crete was the place where the use of herbal medicine has its roots since the Bronze Age period. Although, the consumption of aromatic plants as component in curing common diseases is still on population’s practices, a new interest was appeared on the basis of studies with a focus on illness behavior as a mutual collaboration between the University of Crete and the University of Leiden, The Netherlands. The antioxidant activity of certain Cretan plants has been documented and it has been shown and reported that herbal extracts are possible to decrease lipid per oxidation in cultured lung cells exposed to iron or ozon. The biological effects and bioactivity of essential oils as well as their antibacterial properties have been previously discussed in the literature. However, it was the first attempt in Europe when a double blind randomized controlled trial examined the effectiveness of an essential-oil extract of three Cretan aromatic plants designed and implemented in rural Crete on patients with upper respiratory tract infection. Descriptive differences were recently reported in favorable direction especially in the virus-positive population, while these results guide at the moment a series of actions for further research and discussion on the potentialities in the therapeutic medicine. A recent joint attempt (Clinic of Social and Family Medicine and Department of Experimental Endocrinology at the School of Medicine, University of Crete) under the support of the National Strategic Reference Framework Program focused on the effectiveness of functional extract of Mentha Spicata encapsulated in yogurt with honey on lipids profile of health patients in rural Crete. The first reported results of a cross-over study which was designed and implemented recently were in a favorite direction and it was in agreement with the animal based study that was carried out in the frame of this project. In conclusion, the two first studies on the Cretan medicinal and aromatic plants support the potentialities of the use of Ethno botanical methodology to move the needle of innovation on viral infections and lipids metabolism. 4
1. Nuclear Medicine Unit, D.I.M., University of Bari “Aldo Moro”, Bari, Italy, 2. Department of Pediatric Hematology and Oncology, University of Bari “Aldo Moro”, Bari, Italy, 3. Nuclear Medicine Unit, Department of Biomedical Sciences and of Morphologic and Functional Images, University of Messina, Messin, Italy, 4. Positron Emission Tomography Centre IRMET S.p.A. Euromedicine Inc., Turin, Italy 10
The diagnostic performance of 99mTc-HMPAO radiolabeled leukocytes scintigraphy in the investigation of infections. A single center experience 14
Validation of numerical outputs of IAEA software by the analysis of diuretic nephrogram in children with antenatally detected hydronephrosis 15
Objective: To report the morpho-functional results of Aflibercept (Eylea) intravitreal injection (A-IVI) for wet age related macular degeneration (w-AMD). Subjects and Methods: We retrospectively examined 26 eyes of 26 patients (14 male and 12 female; mean age 80.5; range age 63-91) with a follow-up of 14 months, treated for w-AMD. All the eyes examined, did not receive any type of intravitreal anti-vascular endothelial growth factor (anti-VEGF) before Aflibercept. The morphological analyses included the Optical Coherence Tomography (HD-OCT; Carl Zeiss Meditec, Dublin, CA, USA), Fluoroangiography (Topcon retinal camera, IMAGEnet inc.) while the functional assessment included the best correct visual acuity (BCVA - logarithm of the minimum angle of resolution [LogMar]). The timing of the follow-up was: baseline, 3, 6, 12 months. Every patient received 8 A-IVI according to the protocol (first 3 monthly A-IVI followed by an A-IVI every two months for the first year, regardless the activity of the disease as the guidelines suggested). Statistical analysis was performed using ANOVA test. Results: At the end of the follow-up, 61.5% (16 eyes) improved the BCVA, 23.1% remained stable and 15.4% had a worsening of the BCVA (p-Value<0.02%). All the patients have had a significantly reduction of the central macular thickness at month 12 (P-Value<0.02%) at the automatic OCT measurement (improvement or resolution of the intra-retinal fluid or sub-retinal fluid). In the eyes we observed a worsening of the VA at the end of the follow-up (15.4%), a retinal scar development was detectable at the OCT even though the macula in these eyes resulted dry. Conclusions: The one-year results of A-IVI for w-AMD are statistically significant to improve (61.5%) or to stabilize (23.1%) the visual acuity from the baseline. The VA worsening in the 15.4% of the eyes could be due to the particular aggressivity of the neo-vascular membrane or to the late stage of the disease at the time of the observation and treatment. In fact we observed that the eyes that have had the best VA outcome were those which received an early diagnosis and respective early treatment. From our experience, with 12 months follow-up, A-IVI showed to be a valid treatment for w-AMD in patient who did not receive previous intravitreal anti-VEGF treatment. A long-term follow-up will be useful to evaluate the stability of the treatment. 17
Questions to authors: 18
a) Did your patients accept well your treatment-any side effects? 18
All patients accepted well our treatment with no systemic side effects and only minor complications such as subconjuctival haemorrhage and ocular pain 18
b) Is your treatment valid for dry AMD and what were your exclusion criteria? 18
This treatment is not valid in dry AMD. Exclusion criteria: previous stroke or ischaemic heart disease. 18
Questions to authors:
a) Can you inform us of what are the results from other researchers who have performed your method, even partly?
As stated these operations are individualised for each patient. Facial growth determines the timing of these revisions. They are performed in a tertiary care facility with quartenary input according to international standards and guidelines of specialist care. However, regionally or nationally agreed and/or implemented specialist practice guidelines are often compounded by individual surgeons practicing independently. In the literature there are series that distinguish secondary nasal deformity and cleft lip and palate reoperations. Other studies deal with cleft palate mobility, speech evaluation, fistula rate, orthognathic measurements and facial appearance. As a result of variations between surgical protocols for primary CLP repair internationally, cross-referrals between centres with different practices and patients' moves to different areas or even countries, it is extremely difficult to assess singular lines of treatment for secondary repair or revision surgery.
b) How many patients did you study and what were your results in patients who have been operated for the first time and how many patients you studied and what were the results in patients who have been operated for the second time?
Between 2012 to date there were 5 new self-referred patients candidates for secondary or revision surgery who underwent 11 operations in total. All were initially treated elsewhere. This study focuses on this group solely and assesses their outcome. As per study design any older cases and any new primary CLP cases were excluded. Beyond this evaluation this study also presents the possibility of minimizing or even avoiding revision surgery for which the literature reportedly may amount to as many as 20 operations per patient. In contrast to numerous procedures an approach of careful evaluation, meticulous planning and execution together with full commitment to an agreed surgical strategy between surgeon and patient results in significantly fewer operations and a more favourable outcome.
Assessment of therapeutic response of radioimmunotherapy with yttrium-90-labelled rituximab (chimeric anti-CD20 antibody) in patients with relapsed and refractory B cell NHL-first prospective trial in India
Parul Thakral, C. S. Bal, Arun Malhotra
Department of Nuclear Medicine, All India Institute of Medical sciences, New Delhi, India
Objective: The aim of the study was to evaluate the safety and efficacy of radioimmunotherapy with a human chimeric anti-CD20 antibody labelled with Yttrium-90 (90Y-Rituximab) in patients with B cell Non Hodgkins lymphoma (NHL). Subjects and Methods: Twenty patients with CD20+ B-cell lymphoma in progressive state after at least one line of therapy were included. The patients had undergone a median of 2 (range 2-5) prior standard chemotherapy±immunotherapy regimens.90Y-Rituximab was administered according to approved schedule: a first infusion of rituximab 250mg/m²body weight on days 1 and 8, and either 14MBq/kg (0.4mCi/kg) or 11MBq/kg (0.3mCi/kg) of 90Y-Rituximab on day 8 (maximum dose, 32mCi) depending upon their platelet count. 18F-FDG-PET/CT was performed before treatment and repeated at 1, 3 and 6 months after for response assessment. Hematological assessment was obtained at baseline and weekly after the treatment for 6 weeks or until recovery from nadir. Results: Disease histologies of twenty patients included mainly diffuse large B-cell lymphomas (80%), follicular (10%) and mantle cell lymphoma (10%). No acute adverse effects were observed after the administration of 90Y-Rituximab. Toxicity was primarily haematological. The incidence of grade 3-4 neutropenia, thrombocytopenia and anemia were 30%, 45% and 20% respectively. Overall response rate (ORR) was 55% of which complete response (CR) was observed in 2 patients, stable disease (SD) in 1 patient, partial response (PR) in 8 patients and progressive disease (PD) in 9 patients. Parameters attributed for higher response rates and higher survival rates were histology of follicular or MCL, KPS more than 60 and extranodal disease ≤95cc. Conclusion: Toxicity with 90Y-Rituximab was primarily hematologic, transient and reversible. 90Y-Rituximab therapy was safe and well tolerated in high risk extensively pretreated NHL patients.
Questions to authors:
a) For how long remained the side effects of 90Y-Rituximab in your patients?
There were no side effects such as bleeding or other complications of the therapy. Hematologic nadirs were observed after 4 weeks of the therapy which recovered in 3 weeks.
b) Are there similar papers in India and what are their differences compared to your paper?
There is no similar study from India and this was the first study from India.
In-111-polyclonal HIG identifies patients but not atherosclerotic lesions at risk - a 5 years follow-up
Robert Berent1, Johann Auer2, Susanne Granegger3, Helmut Sinzinger3
1. HerzReha Bad Ischl, Center for Cardiovascular Rehabilitation, Bad Ischl, Austria, 2. Department of Internal Medicine, Hospital Braunau/Inn, Austria, 3. Isotopix, Institute for Nuclear Medicine, Vienna, Austria
There is a strong need for non-invasive detection of human atherosclerotic lesions. One of the radioisotopic approaches using Indium-111-HIG has been shown to accumulate in oxidized LDL-rich foam cells and inflammatory vascular lesions. Earlier human studies in 200 patients, 100 with peripheral vascular disease and 100 with carotid artery disease comparing In-111-HIG scintigraphy with sonographic data revealed a high sensitivity (70-77%) but a very low specificity (33-41%). At this time we concluded the approach “not promising” for human studies. However, clinical follow-up over 5 years now shows that those patients with positive In-111-HIG scintigraphy exhibited a significantly higher vascular morbidity (P<0,01) and mortality (P<0,01), especially in the immediate follow-up period. Retrospective analysis discovered higher CRP and isoprostane (8-epi-prostaglandin (PG)F2) levels in HIG-positive patients at the time of scintigraphy. These findings indicate that In-111-HIG reflecting vascular lesions with a high inflammatory component, probably more prone to rupture, may identify a population at high vascular risk rather than a lesion at risk. The clinical impact of this finding should be assessed in prospective studies.
Questions to authors
a) What are the levels of cholesterol of your patients?
Lipid and lipoprotein values are outlined in table 4. The absolute values for total cholesterol and LDL-cholesterol were comparable in the positive and negative groups, the absolute values always being minimally higher in those patients showing positive scintigraphy.
b) How was peripheral vascular disease diagnosed?
Patients with peripheral vascular disease were admitted to the unit due to symptoms, diagnosis was performed in all of them by means of sonography, 44 patients also had angiography.
Application of Kanban System on a hospital pharmacy
1. Electrical and Computer Engineering, Democritus University of Thrace, University Campus, Xanthi, 67100 Greece
Objective: This paper is a brief overview of principles, views and methods of the Kanban system for the pharmacy of a general hospital. The main goal is the reduction of stores managed by the pharmacy, as well as improvement of the mode of operation. Solutions to problems, such as inadequate storage space. The delay in serving the patients or the clinics and the expiration of various pharmaceutical formulations, stored for a long time, are provided. The philosophy behind the Kanban procurement system and specifically its applicability to a pharmacy underperforming in terms of efficiency, in Greece, are described. Based on the analysis of stock requirements, item stock prices and demand, it is concluded that a significant percentage of the stocked drugs can be procured using the Kanban system. In conclusion: Significant cost savings and operational advantages following the Kanban system will take place. The challenging endeavour is the analysis, design and application of a system that supports the proposed procurement method. Hospital pharmacies in Greece and in other countries that face an economic crisis may largely benefit after using the Kanban system.
Questions to authors:
a) What is the cost benefit in a pharmacy of a hospital of 500 beds if the pharmacy uses your system?
b) Does application of your system needs written permission from hospital authorities?
10.55 - 13.15
Role of 18F-DOPA PET/CT and 131I-MIBG planar scintigraphy in evalating patients with pheochromocytoma
Gurupad P. Bandopadhyaya, Abhishek Kumar, Jyotsana Kumari
Department of Nuclear Medicine & PET, All India Institute of Medical Sciences, New Delhi, India
Objective: The aim of this retrospective study was to evaluate role of 18F-DOPA PET/CT and 131I-MIBG planar scintigraphy in patients with pheochromocytoma Methods: The patients with diagnosis of pheochromocytoma based on radiological and biochemical markers were retrospectively selected for the study. These patients had undergone both 131I-MIBG scintigraphy and 18F-DOPA PET/CT. The imaging findings were compared to patient histopathology reports, biochemical markers and clinical follow up whenever available to establish the diagnosis. Results: 131I-MIBG showed a sensitivity of 68% and specificity of 100%. 18F-DOPA PET/CT showed a sensitivity of 82% and specificity of 100%. 18F-DOPA was better at localizing and finding more no of lesions as compared to 131I-MIBG scintigraphy. 18F-DOPA also is a better study in evaluation of paragangliomas. Conclusions: 18F-DOPA PET/CT seems to be a better modality in comparison to 131I-MIBG scintigraphy in the evaluation of pheochromocytoma/paraganglioma. At this point both these tracers seem to have mutually additive role in these patients and essential investigations with diagnosis and follow-up of this disease.
Questions to authors:
a) Is there any similar study in India and if there is what are the differences of your study?
b) What specifically you mean when you say that both tracers have mutually additive role in your patients?
Yes, 18F-DOPA PET/CT is highly sensitive and specific imaging approach for detection of Pheochromocytoma in comparison to I-131 MIBG and has incremental value. However both the Rps are complimentary to each other.
Pediatric Hodgkin Lymphoma: predictive value of interim 18FDG-PET/CT in therapy response assessment
Cristina Ferrari1, Artor Niccoli Asabella1, Nunzio Merenda1, Corinna Altini1, Margherita Fanelli1, Paola Muggeo2, Francesco De Leonardis2, Teresa Perrillo2, Laura Cassalia3, Angelina Cistaro4, Nicola Santoro2, Giuseppe Rubini1
1. Nuclear Medicine Unit, D.I.M., University of Bari “Aldo Moro”, Bari, Italy, 2. Department of Pediatric Hematology and Oncology, University of Bari “Aldo Moro”, Bari, Italy, 3. Nuclear Medicine Unit, Department of Biomedical Sciences and of Morphologic and Functional Images, University of Messina, Messin, Italy, 4. Positron Emission Tomography Centre IRMET S.p.A. Euromedicine Inc., Turin, Italy
Objective: Interim 18F-FDG PET/CT (PET-2) helps in predicting outcome and tailor treatment in adults with Hodgkin Lymphoma (HL). In contrast, data on pediatric HL patients are rare, with discordant results. Visual analysis using Deauville criteria was proposed to assess PET response. However a 5-point scale did not preclude interobserver reproducibility issues. Alternative approaches were developed to improve the accuracy and reproducibility of PET-2, mainly based on 18F-FDG PET/CT semiquantitative parameters. In the present study we evaluated the clinical usefulness of both methods in HL patients, analyzing PET-2 according to Deauville score (DS) and semiquantitative criteria in a retrospective single center study. Materials and Methods: 30 pediatric patients (16 male: 14 female) affected by HL were prospectively enrolled and underwent to serial 18F-FDG PET/CT: at baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of treatment (PET-3). PET analysis was done visually and semiquantitatively using: ΣSUVmax-0, ΣSUVmean-0, ΣMTV-0, ΣTLG-0 for PET-0; ΣSUVmax-2, ΣSUVmean-2, ΣMTV-2, ΣTLG-2 for PET-2. The PET response assessment was carried visually according to the DS (score 1-3: negative; score 4-5: positive) as well as semiquantitatively by use of absolute decrease in all the parameters from PET-0 to PET-2 (ΔΣSUVmax 0-2, ΔΣSUVmean 0-2, ΔΣMTV 0-2, ΔΣTLG 0-2) and the corresponding Response Indexes (RI% ΣSUVmax 0-2, RI% ΣSUVmean 0-2, RI% ΣMTV 0-2, RI% ΣTLG 0-2). Assessment of response was performed according the Cheson’s Revised Response Criteria considering patients as responders (R) or non-responders (NR). Mean follow up was 24 months (range 3-78). Clinical outcomes were obtained from medical records. T-student test for unpaired groups was performed to compare PET semiquantitative parameters between R and NR. Chi-square and Fisher exact test were performed to evaluate the association among categorical variables. The prognostic capability of 18F-FDG PET/CT was calculated by ROC analysis and expressed as area under curve (AUC). Results: 5/30 (16.67%) patients were NR at the end of therapy based on clinical, CECT and bone marrow biopsy findings. Among them, 2 became R at 40-months follow-up after second-line treatment, another one remained NR while the other two patients died. Visual assessment was: DS=1 in 15/30 (50%) patients, DS=2 in 1/30 (3.3%), DS=3 in 5/30 (16.7%) and DS=4 in 9/30 (30%) patients. Differences between R and NR were statistically significant for ΔΣSUVmax 0-2 (t=2.45, P=0.026) and almost statistically significant for ΔΣSUVmean 0-2 (t=1.88, P=0.071). No significant difference was found for the other parameters. Any association between Deauville evaluation and outcome at the end of therapy was found (Fisher exact test P=0.136). The better AUCs resulted for ΔΣSUVmax 0-2 (0.836; cut-off <12.5, sensitivity 80%, specificity 91%). Conclusion: Despite Deaville Score remains a valid criterion in the evaluation of early response to therapy in adults affected by HL, our preliminary data show that in pediatric patients the semiquantitative evaluation can provide additional data to support the predictive value of interim 18F-FDG PET/CT. In particular, ΔΣSUVmax 0-2 appears to be the best PET parameters in predicting therapy response assessment.
Questions to authors:
a) Did you have inclusion criteria?
Our research study included pediatric patients (age ≤ 16 years old) without previous history of malignancy and/or chemotherapy, with newly diagnosis of Hodgkin’s Lymphoma histologically proven by biopsies of lymphoid tissue, according to the 2008 World Health Organization classification.
b) What is the prevalence of pediatric Hodgkin’s lymphoma related to that in adults?
Hodgkin lymphoma incidence shows a clear bimodal age distribution with the first peak in incidence rates in young adults (15-25-year age group) and the second peak in older men and women (70-80-year age group). HL represents less than 5% of malignancies in children under the age of 15years. In contrast, it represents 16-20% of malignancies in adolescents making it the most common malignancy of this age group. In the Western countries the estimated age-related incidence rates for pediatric Hodgkin Lymphoma are: 29 cases per million per year in adolescents aged 15 to 19; approximately 10 per million per year in 10- to 14-year-olds; 3.5 per million in five- to nine-year-olds; and one per million for ages zero to four years. The childhood form of Hodgkin Lymphoma increases in prevalence in association with larger family size and lower socio-economic status. Rates then decrease until middle age before rising again to reach a second peak in men aged 75-79 and women aged 70-74. An average of 10% of cases were diagnosed in men and women aged 75 years and over.
Role of dopaminergic neurotransmission in pathophysiology of action tremor in Parkinson’s disease
Artor Niccoli Asabella1, Angelo Fabio Gigante2, Cristina Ferrari1, Alessandra Di Palo1, Domenico Rubini1, Emilio Paolo Mossa1, Giovanni Defazio2, Giuseppe Rubini1
1. Nuclear Medicine Unit, D.I.M., University of Bari “Aldo Moro”, Bari, Italy, 2. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Bari, Italy
Objective: Rest Tremor (RT), which occurs in a relaxed and supported limb, is together with rigidity and bradykinesia among the core features of Parkinson’s Disease (PD). In addition to classical RT, many PD patients have Action Tremor (AT) occurring during sustained postures or voluntary movement. Earlier studies showed a good correlation between striatal Dopamine Transporter (DAT) binding, measured with 123I-FP-CIT SPET, and bradykinesia. By contrast, neither rigidity nor RT seems to be closely related to the degree of dopaminergic denervation as measured by DAT imaging. Little is known about the relationship, if any, between the severity of AT and striatal DAT binding. Materials and methods: A cross-sectional study was conducted in 94 patients (57 men and 37 women) with PD staging 1-2 on the Hoehn-Yahr scale. Data on the severity of AT and other motor signs were collected using the Unified Parkinson’s Disease Rating Scale part III. DAT imaging was performed after injection of 123I-FP-CIT. Images were visualized on Workstation Xeleris 3.0 (GE Healthcare) and reconstructed with dedicated software by a nuclear physician blinded about the clinical information of patients. Spearman correlation coefficient was performed to evaluate the relationship between putamen DAT binding and severity of bradykinesia, severity of rigidity, RT and AT respectively. Results: In this group of patients with early PD, putamen DAT binding significantly correlated with the severity of bradykinesia (Spearman r=0.35, P<0.001) but not with the severity of rigidity (Spearman r=0.02, P=0.8), RT (Spearman r=0.05, P=0.6), or AT (Spearman r=-0.03, P=0.7). Multivariable regression analysis adjusted by age, sex, disease duration, and levodopa equivalent daily dose, confirmed the same results. Conclusion: Our study confirms the good correlation between putamen DAT binding and bradykinesia and the lack of correlation between putamen DAT binding and rigidity/RT. In addition, we didn’t found any significant correlation between putamen DAT binding and severity of action tremor, which suggests a contribution of non-dopaminergic mechanisms to the pathophysiology of AT.
Questions to authors:
a) Can you give us a rough description of the PD patients that were included in your study, based on both H-Y and UPDR scales so that we can have a clinical impression of the condition of your patients?
The study group included 57 men and 37 women aged 62.3 (SD 10) years on average. Mean disease duration was 2.3 (SD 1.8) years, mean Hoehn and Yahr staging was 1.8 (SD 0.5) and mean UPDRS-III total score was 20.6 (SD 9.1).
b) Did your adjusted analysis include patients taking Levodopa equivalent for a long period and how long was that?
Thirty-one patients (33%) were drug-naive while 63 patients were on drug therapy for less than one year: 22 patients were taking levodopa and 41 patients were taking dopamine-agonists and/pr MAO-B inhibitors.
Role of 18F-FDG PET/CT in the evaluation of response to antibiotic therapy in patients affected by infectious spondylodiscitis
Alessandra Di Palo, Artor Niccoli Asabella, Domenico Rubini, Antonio Notaristefano, Nunzio Merenda, Francesca Iuele, Giuseppe Rubini
Nuclear Medicine Unit, D.I.M., University of Bari “Aldo Moro”, Bari, Italy
Objective: Spondylodiscitis is characterized by infection involving the intervertebral disc and adjacent vertebrae. It can occur anywhere in the vertebral column but more commonly involves lumbar spine. Our aim was to evaluate the usefulness of 18F-FDG PET/CT to detect the early response to antibiotic therapy in patients affected by infectious spondylodiscitis and to compare the role of 18F-FDG PET/CT and MRI in post-treatment evaluation. Materials and Methods: 15 patients (12M, 3F), with mean age 65±13 years old, with typical clinical symptoms of Infectious Spondylodiscitis (pain, fever and increase of inflammatory indexes) and confirmed by blood culture or vertebral biopsy underwent within three day-interval a 18F-FDG PET/CT and Magnetic Resonance (MR) at “baseline” and after antibiotic therapy with Teicoplanine, Levofloxacine and Rifampicine. Semiquantitative parameters at 18F-FDG PET/CT “baseline” SUV max1, MTV1 and TLG1 and after therapy SUV max2, MTV2 and TLG2 of involved vertebrae were calculated. Follow-up period of at least three months was available for all patients. T-student test for paired groups was performed to compare baseline and after therapy 18F-FDG PET/CT semiquantitative parameters. Results: According to 18F-FDG PET/CT parameters all patients showed a response to antibiotic therapy. All patients were positive at “baseline” MRI of the spine, while at follow-up, 7/15 patients showed MR signs of infection and were considered “positive”, and 8/15 showed resolution of infectious condition and, therefore they were considered “negative”. A statistical significant difference between 18F-FDG PET/CT “baseline” and after antibiotic therapy was found for all semiquantitative parameters: SUV max (t=5.8, P=0.01); MTV (t=5.17, P=0.001); TLG (t=5,26, P=0,001). The comparison between the “baseline” and “after treatment” 18F-FDG semiquantitative parameters showed a significant reduction of all parameters. This reduction was relevant also in patients with positive post-treatment MRI. This bias is probably due to the tissue remodeling in the very immediate phase post-treatment, resulted positive at MRI and negative at 18F-FDG PET/CT. Clinical follow-up of at least three months confirmed these results. Conclusions: 18F-FDG PET/CT is useful to detect the early response to antibiotic therapy in patients affected by infectious spondylodiscitis. 18F-FDG PET/CT semiquantitative parameters provide critical diagnostic information of the infectious process. 18F-FDG PET/CT should be considered as first-line exam in the diagnosis of spondylodiscitis while MR should be preferred for delayed evaluation.
Questions to authors:
a) Were the patients that were benefited more at first line exam by PET/CT, comparable to age with those not benefited by MR?
Spondylodiscitis has a typical bimodal age distribution (pediatric and older population). However our study group included 15 patients and all of them were older than 50 years old (mean age 6513). For this reason no relationship with age was found neither in the group of 18FDG-PET/CT/MR discordant results nor in the concordant results group.
b) How long was the duration of your work i.e. in how many years you collected your spondylodiscitis patients?
We’ve evaluated 32 patients with suspicious of spondylodiscitis in our Nuclear Medicine Department at University of Bari since 2011. However our research study focused on 15 patients in which spondylodiscitis was confirmed by biopsy and/or blood culture and the follow up period was available.
Notopoulos Athanasios1, Likartsis Christodoulos1, Zaromytidou Evangelia1, Petrou Ioannis1, Meristoudis Georgios1, Alevroudis Emmanouil1, Oikonomou Zoi1, Stavros Tryfon2, Psarras Kyriakos3, Papazoglou Konstantinos4
1. Nuclear Medicine Department, Hippokration General Hospital, Thessaloniki, 2. NHS Department of Chest Medicine, Papanikolaou General Hospital, Thessaloniki, 3. Second Propedeutic Surgery Department, Aristotle University of Thessaloniki, 4. Fifth Department of Surgery, Aristotle University of Thessaloniki, Hellas
Objective: This study aims to evaluate the diagnostic efficacy of 99mTc-HMPAO-labeled white blood cells scintigraphy (RL-WBC scan) in a variety of infectious processes. Despite the technical difficulties of labeling WBCs without altering their viability/pathophysiologic integrity and the lengthy imaging procedure, the RL-WBC scan has gained an evolving role in the detection of occult infection. Methods: Retrospective review of 66 patient files (34 males and 32 females) that underwent this functional imaging test from September 2013 until September 2015. Their mean age was 58.39±18.63 (range: 11-84) years. Twenty seven of them were investigated for fever of unknown origin, 6 with suspicion of inflammatory bowel disease, 9 with aneurysm of celiac artery before or after abdominal endovascular aortic repair, 6 with joint prostheses, 5 with diabetic angiopathy, and 13 had rather undefined symptoms. Results: The mean labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 57.4±8.6. The RL-WBC scan was positive in 39/66 patients, including 16/27 patients with fever of unknown origin and 8/9 patients with aortic aneurysm/graft infection. It showed expected/suspected localization of radioactivity in 23 patients, whereas 11 of them had equivocal signs of infection. In 16 patients, a significant change in patients’ management was conferred, as non-suspected locations of inflammatory process were detected, based on early functional alterations derived from leukocyte recruitment. Conclusion: The RL-WBC scan (i) is extremely useful in the diagnosis of perigraft tissue infection and osteomyelitis (except for spine) with high rate of sensitivity and specificity (≈90%) when timely used, and (ii) may provide valuable information in patients with fever of unknown origin, inflammatory bowel disease or vague symptoms. False positive results have been noticed mainly due to artifacts, co-existent skeletal lesions or in the early postoperative course because of the nonspecific radionuclide uptake in the healing tissue. On the other hand, false negative results may appear in delayed aortic graft infection, etc. Difficulties arise in the discrimination between infection and sterile inflammatory lesions accompanying atheromatosis or grafts/prostheses. Our experience shows that there should take place a closer co-operation between nuclear medicine physicians and clinicians to ensure the rational selection of the patients that would benefit from this complex diagnostic procedure, in order to get the optimal results concerning in vivo inflammation/abscess visualization.
Questions to authors:
a) What are inclusion criteria of your patients?
b) How can you set the diagnosis of sterile inflammatory lessions?
Beatovic S1, Sobic-Saranovic D1, Jaksic E1, Artiko V1, Ajdinovic B2
1. University of Belgrade, Faculty of Medicine, Center for Nuclear Medicine, Clinical Center of Serbia, 2. Military Medical Academy, Belgrade, Serbia
Diuretic nephrogram is important diagnostic tool in the postnatal follow-up of asymptomatic antenatally detected hydronephrosis (HN). In the last decades, two quantitative indicesof renal excretion, output efficiency and the residual kidney counts normalized to the 1-2min counts (normalized residual activity, NORA) have been proposed, that enhance the accuracy of technique to detect kidneys with obstruction. Unfortunately, in many nuclear medicine departments in developing countries the obsolete computer systems do not give the opportunity of sophisticated analysis of nephrogram. Almost a decade ago, the Nuclear Medicine Section of the International Atomic Energy Agency (IAEA) has developed non-commercial software for nephrogram processing on a simple p-computer, which allows access to the developments in this field. However, till now, the software has not been widely implemented in the nuclear medicine institutions in developing countries. Furthermore, the accuracy of numerical outputs of the software has not been assessed in comparison with commercial software. The aims of this study in children were: a) to calculate, by means of the International Atomic Energy Agency (IAEA) software, the values of the technetium-99m mercapto-acetyl-triglycine (99mTc MAG3) parameters in three categories of kidneys: normal kidneys, obstructed kidneys and hypotonic unobstructed kidneys and b) to assess the accuracy of the obtained numerical parameters by comparing with the values published by other authors. Investigation was carried out on a sample of 62 children: 43 boys and 19 girls (median age: 16 months) with antenatally detected HN attributed to pelviureteric junction (PUJ) stenosis. Neither of kidneys had undergone pyeloplasty prior to our investigation. 130 nephrogram curves were analyzed. 22-minutes acquisition with 132 10-sec images was applied. Furosemide was administered after 2min(F+2). Post-void static image was acquired at 60min.Two observers analyzed each study and classified kidneys into three categories. Group 1: 84 kidneys contralateral to hydronephrotic kidney, without structural abnormality on previous diagnostics; group 2: 30 hypotonic non-obstructed kidneys; group 3: 16 obstructed kidneys. Parameters analyzed were: output efficiency (OE), residual kidney counts at 20min normalized to the 1-2min counts (NORA20) and residual kidney counts on post-micturition acquisition normalized to the 1-2min counts (NORAPM). Results were presented as mean±SD. For group 1 they were: OE: 95±1.5%; NORA20: 0.25±0.06; NORAPM: 0.02±0.007. Results for group 2 were: OE: 87±7.8%; NORA20: 0.57±0.19; NORAPM: 0.03±0.02. For group 3: OE: 56±9.6%; NORA20: 2.16±0.33; NORAPM: 0.27±0.13. Linear regression analysis showed significant inverse linear correlation between NORA20 and ROE20 (R = - 0.982; y = 99.6 – 21.1x) at 0.01 level. ROC analysis revealed cutoff values of predicting obstruction at 71%, 1.62 and 0.11 for OE, NORA20 and NORAPM, respectively. In conclusion, we have calculated in children by means of the IAEA software the values of three advanced parameters of the 99mTc MAG3F+2 diuresis nephrogram for normal kidneys, hypotonic non-obstructed and obstructed kidneys. The overall results provided evidence of excellent agreement of obtained results with previously reported values of the quantitative parameters of renal washout. The parameters of IAEA software has been shown to be reliable in assessing kidney drainage. The nuclear medicine section of the IAEA should be encouraged to produce final version of the software and to release it through IAEA Web site.
Questions to authors:
a) Compare better, objectively, the result of your proposal versus the results provided by nuclear medicine departments who do not have sophisticated analysis or give an example.
We can compare results before and after implementation of IAEA software in our department. Before implementation we had rather high percentage of equivocal findings, around 15%. This was due to inability of traditional parameter for characterization of kidney drainage, time to half maximum of nephrogram (T1/2), to distinguish between obstructive and non-obstructive pattern, particularly in the cases of lower relative or total kidney function. Furthermore, the visual interpretation of post-micturition images was subjective, and sometimes we couldn’t conclude whether elimination from kidney was rather good or poor after one hour from the beginning of study. After introduction of these new quantitative parameters based on IAEA software, the more objective criteria were used, and the percent of indeterminate finding has dropped to maximum 5%.
b) For how long you apply this software and what other departments have found in relation to your results?
We applied the software since 2012. In the beginning, the problem had to be resolved to adopt the software to our very old computer system, but now, it is very user-friendly software. Since the implementation in daily practice, we had good feedback from departments of pediatric urology and nephrplogy, as well as from Clinics of Urology Clinical Center of Serbia and Military Medical Academy. The colleagues from these departments found that our reports are more reliable and can help them in deciding about the treatment of their patients. Last year, we made agreement to begin implementation of the software in other nuclear medicine departments, in Serbia particularly in smaller ones.
Saturday 3 October 2015
09.30 – 11.30
Intravitreal aflibercept for the treatment of wet age related macular degeneration: one year experience
Evangelia Papavasileiou1, Vasiliki Zygoura2, Eleni Konstantinou1, Dominic Cortis3
1. Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA, 2. Moorfields Eye Hospital, London, UK, 3. Department of Mathematics, University of Leicester, UK
Objective: To report the morpho-functional results of Aflibercept (Eylea) intravitreal injection (A-IVI) for wet age related macular degeneration (w-AMD). Subjects andMethods: We retrospectively examined 26 eyes of 26 patients (14 male and 12 female; mean age 80.5; range age 63-91) with a follow-up of 14 months, treated for w-AMD. All the eyes examined, did not receive any type of intravitreal anti-vascular endothelial growth factor (anti-VEGF) before Aflibercept. The morphological analyses included the Optical Coherence Tomography (HD-OCT; Carl Zeiss Meditec, Dublin, CA, USA), Fluoroangiography (Topcon retinal camera, IMAGEnet inc.) while the functional assessment included the best correct visual acuity (BCVA - logarithm of the minimum angle of resolution [LogMar]). The timing of the follow-up was: baseline, 3, 6, 12 months. Every patient received 8 A-IVI according to the protocol (first 3 monthly A-IVI followed by an A-IVI every two months for the first year, regardless the activity of the disease as the guidelines suggested). Statistical analysis was performed using ANOVA test. Results: At the end of the follow-up, 61.5% (16 eyes) improved the BCVA, 23.1% remained stable and 15.4% had a worsening of the BCVA (p-Value<0.02%). All the patients have had a significantly reduction of the central macular thickness at month 12 (P-Value<0.02%) at the automatic OCT measurement (improvement or resolution of the intra-retinal fluid or sub-retinal fluid). In the eyes we observed a worsening of the VA at the end of the follow-up (15.4%), a retinal scar development was detectable at the OCT even though the macula in these eyes resulted dry. Conclusions: The one-year results of A-IVI for w-AMD are statistically significant to improve (61.5%) or to stabilize (23.1%) the visual acuity from the baseline. The VA worsening in the 15.4% of the eyes could be due to the particular aggressivity of the neo-vascular membrane or to the late stage of the disease at the time of the observation and treatment. In fact we observed that the eyes that have had the best VA outcome were those which received an early diagnosis and respective early treatment. From our experience, with 12 months follow-up, A-IVI showed to be a valid treatment for w-AMD in patient who did not receive previous intravitreal anti-VEGF treatment. A long-term follow-up will be useful to evaluate the stability of the treatment.
Questions to authors:
a) Did your patients accept well your treatment-any side effects?
All patients accepted well our treatment with no systemic side effects and only minor complications such as subconjuctival haemorrhage and ocular pain
b) Is your treatment valid for dry AMD and what were your exclusion criteria?
This treatment is not valid in dry AMD. Exclusion criteria: previous stroke or ischaemic heart disease.
The role of anti-VEGF treatment in diabetic macular edema
Vasiliki Zygoura1, Evangelia Papavasileiou2, Eleni Konstantinou2, Dominic Cortis3
1. Moorfields Eye Hospital, London, UK, 2. Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA, 3. Department of Mathematics, University of Leicester, UK
Objective: To study the role of anti-VEGF in diabetic macular edema (DMO) treatment measured by changes in visual acuity and retinal thickness and to investigate the reduction or not of the number of intravitreal injections and/or the number of laser sessions in the combination treatment group with laser and anti-VEGF factors. Subjects andMethods: We included 100 patients with diabetic macular edema. Those who had central retinal thickness equal or more than 400μm (group one) underwent combination treatment with anti-VEGF and laser, while those with central retinal thickness less than 400μm (group two) had laser monotherapy. Results: Group one showed better outcomes in terms of visual acuity and retinal thickness compared to group two during the two-year follow up period and this was more obvious during the loading phase (first 4 months). Adding anti-VEGF reduced the laser sessions and the number of intravitreal injections, from 3.86 during the first year to 2.02 during the second year. Conclusions: In our study we were able to show that combination treatment with laser and anti-VEGF was superior to laser monotherapy. We also showed that combination therapy reduced the number of injections during the second year of treatment and the need for laser with better outcomes in terms of BCVA and OCT thickness. Our suggestion is to start treatment with a loading dose of three monthly injections, and laser treatment on the third month. Then we suggest combination treatment with laser and anti-VEGF on a prn basis. Moreover, we found that there is still a role for thermal laser in DMO. For non-central DMO and circinate exudates laser is a reasonable first line treatment.
Questions to authors:
a)Were there cases of patients who did not respond to treatment?
There were a 10% of patients unresponsive to treatment from either group
b) Did your patients accept well your treatment?
Treatment was well accepted with no considerable side effects.
Quantification of parafoveal capillary network using a semi-automated algorithm
Kapsala Z1, Pallikaris A1, Moschandreas J2, Tsilimbaris MK1
1. Ophthalmology Department, Medical School, University of Crete, Heraklion, 2. Department of Social Medicine, Medical School, University of Crete, Heraklion.
Objective: The quantification of the morphology of the parafoveal capillary network (PCN) in fluorescein angiography (FA) images using a novel semi-automated computerized method. Material and Methods: Using the MatLab R2011 a software we developed an algorithm that detects automatically the parafoveal capillary bed and its branch points as depicted in FA images creating simultaneously an one-pixel-wide skeleton of it. The detection process starts after delineating manually the foveal avascular zone in a cropped 1500μm*1500μm subimage resulting from the original FA image. Thereafter the algorithm calculates the capillary density and the branch points in a circle area with 1000μm radius. The method was also applied on FA images from subjects without diabetes mellitus, diabetics without diabetic retinopathy (DR) signs, patients with non-proliferative DR and patients with proliferative DR in order to assess the PCN morphology metrics for the studied groups. Results: The PCN density and the parafoveal capillary branch points were estimated for the mentioned subject groups and any significant differences among them were assessed as well. Conclusions: The described method could serve as a potential tool for the diagnosis and monitoring of PCN diseases and subclinical abnormalities. The assessed metrics reflect the capillary abnormalities in the central 1000μm area across different DR stages.
Questions to authors:
a) What is the practical objective of your paper research?
b) How prototype is your research even partly, as related to the research of others?
Serum levels of fetuin-a in patients with coronary artery disease corellation with SPECT myocardium scintigraphy
Zissimopoulos Athanassios1, Baloka Lukia3, Nagorni Eleni1, Karathanos Evangelos1, Tsartsarakis Antonios1, Apostolidou Vasiliki1, Thomaidou Andina2 , Tripsianis Gregory4.
1. Nuclear Medicine Department, 2. Cardiology Clinic, Univ. Hospital of Alexandroupolis Democritus University of Thrace, 3. School of Molecular Biology and Genetics, 4. Department of Medical Statistics, Democritus University of Thrace, Alexandroupolis Greece
Objective: The evaluation of Fetuin-Avaluesof the patients with coronary artery disease, as a prognostic factor of the disease, in correlation with SPECT myocardium scintigraphy. Introduction: Fetuin-A an acidic glycoprotein is produced in the liver, as an inhibitor for cysteine protease. The gene is founded in chromosome 3 (3q27). It is involved in various physiological and pathological conditions. These include vascular decalcification, bone metabolism, insulin resistance, protease function control, neurological illnesses, and multiplication of breast cancer cells. Studies on individuals with clinical cardiovascular disease supported that lower levels of fetuine-A are released with coronary artery circulation (CAC) and the function of the heart valve. Patients and Methods: We studied 40 patients, 25 male and 15 female, with a mean age 48±8 years (range 36 to 69), with coronary heart disease, which were subjected to myocardium scintigraphy, in the Nuclear Medicine Dept of University Hospital of Alexandroupolis. At the same time blood samples were drawn for the determination of Fetuin-A Serum fetuin A levels were measured by a commercially available sandwich ELISA (Epitope Diagnostics, Inc., San Diego, CA).Results: The average values of Fetuin-A range between 140-297 mg/L, as it is derived from the current bibliography and our laboratory tests. In normal individuals, pathological values were considered to be under 140mg/L. 25 patients with positive SPECT imaging for myocardium necrosis (scars) had low Fetuin values (45-148mg/L), 10 of them passing away within 6 months, while the rest of them were showing an encumbered clinical condition (P<0.005). 10 patients with reversible ischemia showed relatively low values (125-302mg/L) (P<0.005). 5 patients with a normal myocardiac scintigraphic imaging showed normal values of Fetuin-A (165-508mg/L) (P<0.005). Conclusions: Patients with myocardium necrosis demonstrated very low values of Fetuin. Patients with ischemia show low amounts while patients with a negative Scintigram for ischemia showed normal results of Fetuin. The 10 patients that passed away in 6 months showed very low amounts of Fetuin. Fetuin-A is supported to be a reliable prognostic factor in monitoring patients with coronary heart disease.
Questions to authors:
a) Were your patients with CAD having different stages of the disease, had different levels of fetuin and/or different sizes of infraction? Did your method differentiate between the abovestages and normals? Were your five normal scan patients without CAD?
The answers of the above questions are yes.
b) Has this test with fetuin been published in journals elsewhere?
There are some similar publications worldwide. It's the first publication in Greece and the results are similar.
Preventing cardiac diseases in childhood
Andreas Petropoulos1, Doris Ehringer-Schetitska2, Peter Fritsch3,Eero Jokinen4,Robert Dalla Pozza5,Renate Oberhoffer6 on behalf of the Association for European Paediatric Cardiology Working Group Cardiovascular Prevention
1. Dept. Pediatric Cardiology Merkezi Klinika, Azerbaijan Medical University, Baku, Azerbaijan, 2. Dept. of Paediatrics, Landesklinikum Wiener Neustadt, Austria, 3. Dept. of Paediatric Cardiology, University Children’s Hospital, Graz, Austria, 4. Dept. of Paediatric Cardiology, Children’s Hospital, University of Helsinki, Stenbackinkatu Finland, 5. Dept of Pediatric Cardiology, Ludwig Maximilians-University of Munich, Germany, 6. Institute of Preventive Paediatrics, Technical University of Munich, Uptown Munich, Germany
Objective: The aim of this paper is to describe how some of the above mentioned diseases can be either early detected or prevented. The working Group “Cardiovascular Prevention” of the Association of European Pediatric and Congenital Cardiology (AEPC) focused on some forms of them since its formation in 2011.These areas are: 1. some forms of critical CHD, 2. sudden cardiac death linked to sport activities and 3.detecting- preventing cardio vascular diseases CVD in the young. Introduction: The burden of cardiac disease in childhood is unknown. It will be a sum of 1% of living births in the general population, suffering from Congenital Heart Disease (CHD) + approximately 2.5% of the general population suffering from bicuspid aortic valve diseases + an unknown higher prevalence of acquired diseases. Cardiomyopathies, arrhythmias - sudden cardiac death (SCD), rheumatic heard disease, hypertension and accelerating atherosclerosis are among the most frequent. Adding on, genetic syndromes including cardiac defects, endocarditis and myocarditis we can address a large pediatric population worldwide, suffering from heart disease. Diagnosis and treatment of these diseases are not afforded in many countries worldwide due to luck of human and material resources. Methods-Populations: Measurements of pre and post ductal saturation of oxygen using pulse oximeters, after the first day from birth, can early and cheaply detect critical Ductal Arteriosus dependent pulmonary or systemic and cyanotic CHD, saving lives and decreasing significantly the cost of medical care. This screening test can be applied to all neonates as late as possible after their birth and before released to their homes. A combination of detailed medical history, physical examination and 12 lead ECG, during a pre-participation in sport activities medical screening test can prevent SCD, related to a variety of nosology. This combined screening test can be applied to all children before they are exposed to school or leisure sport activities. Screening to early detect and treating existent risk factors (RF) for CVD as well as preventing obesity and hypertension, contributes in lowering the burden of CVD. Specific screening tests as laboratory measurements of lipids, fasting glucose or regular measurements of Blood Pressure and waist to hip ratio in children with a family history of CVD or other co-morbidity that provokes accelerating atherosclerosis must be done on a regular basis. Results: Since 2010, four European studies reporting the test accuracy of routine pulse oximetry screening, in over 150.000 babies, have delivered new data. A systematic review and meta-analysis of 230.000 screened babies, reported high specificity, moderate sensitivity and a low false-positive rate. Routine screening for critical CHD using pulse oximetry is being increasingly supported and was added to the recommended uniform screening panel in the USA in 2011. Evaluating children with CHD before their involvement in sport activities, so a clear view in what they can and what they can’t to is vital for their safety. For children involved in competitive or leisure sport activities, an initial evaluation and a yearly F/U is vital. In cases of near SCD events an additional thorough investigation and appropriate management is required. Investigating the severity of the existing RF and cooperating with Pediatricians in their treatment (e.g. heredity forms of hyperlipidemias, existing hypertension) of them is essential. Furthermore preventing acceleration of atherosclerosis in patients with: Diabetes Mellitus I, II, chronic renal disease, post Kawasaki disease, post heart transplantation patients, Cardio-Metabolic Syndrome patients, by eradicating RF primordially or by alternating them by opposing a healthy life style or by medicine treatment, has sown in many studies to post pone clinical events in adulthood. Discussion: As many studies have proved the role of preventive measures that can alternate the outcome of cardiac diseases in childhood. AEPC/Preventive Cardiology working group is in the process to publish in the near future guidelines on this topic.
Questions to authors:
a) Did you relate the childrens cardiac diseases with genetic factors?
In cases in which a genetic link can be an etiological factor e.g. in Congenital Heart Diseases such as in complete Atrial Ventricular Defect a possibility of Trisomy 21 is high as 40% so we check a karyotype.
Similarly in conditions as a Long –QT syndrome or Hypertrophic obstructive Cardiomyopathy, we always use genetic investigations to trace possible mutations that have not only epidemiological interest but mostly they serve as prognostic factors in the outcome of these patients. Additionally we check genetically patients with heredity forms of hyperlipidemias to detect the severity of their clinical presentation and to address in a basis of public health the frequency of mutations seen in a specific population. The typical example would be Familial hypercholesterolemia.
b) Did you experience that some children had been diagnosed late-how late-and what was the effect of this delay?
In all the settings we described in our study: 1. CHD, 2. Pre- participation in sports activities in which a cardiac pathology was found, 3. Accelerating atherosclerosis or clustering of RF’s for CVD, we observe frequently late diagnosis. This was due to lack of qualified facilities and specialists mostly in the setting of CHD. In the setting of cardiac disease found in medical evaluations in pre-sport activities it was due to the luck of legislation that would create a uniform approach in Europe regarding, when, how and by whom this evaluation must take place. Finally in preventing atherosclerosis, it is still not clear in the minds of primary pediatricians, general practitioners, family physicians as well as their families of these children that the disease starts in early childhood by the presence of RF’s and accelerates by aging. In critical CHD and life treating arrhythmias a late delay can be fatal. In the setting of atherosclerosis it has been proved that life expectance is jeopardized by 7 to 10 years t list.
Imaging of cardiac amyloidosis by 99mTc-PYP scintigraphy
V. Papantoniou1, MD, PhD, P. Valsamaki1, MD, PhD, Z. Delichas1, MD, J. Papantoniou1, MD, M. Tsiouma1, MD, T. Athanasoulis1, MD, MA. Dimopoulos2, Kastritis2, S. Tsiouris3, MD, PhD, A. Fotopoulos3
1. UGH “ALEXANDRA”, Nuclear Medicine Department Athens, Greece, 2. UGH “ALEXANDRA”, Therapeutic clinic of University of Athens, Athens, Greece, 3. UGH, Nuclear Medicine Department, Ioannina, Greece
Objective: In this pilot study 99mTc-PYP was administered to patients suffering from cardiac amyloidosis, aiming to differentiate scintigraphically between light-chain cardiac amyloidosis (immunoglobulin light-chain amyloidosis – AL) and cardiac amyloidosis related to transthyretin (transthyretin-related amyloidosis – ATTR), and optimize decision therapeutics. Introduction: Whole-body scintigraphy with technetium-99m pyrophosphate (99mTc-PYP) has been used in the past as a diagnostic tool in the assessment of patients with rhabdomyolysis, acute myocardial infarction, soft tissue injury, polymyositis and dermatomyositis. The mechanisms of increased uptake of the radiopharmaceutical in the inflammatory muscles probably include tracer binding in high calcium concentrations in necrotic cells as well as in hydroxyapatite and calcium phosphate crystals in ischemic tissues. Patients and Methods: Twelve patients (8 males, aged [mean ± SD] 70,6 ± 13,2 y; 4 females, aged 65,7 ± 9,9 y) were enrolled for the discrimination between AL and ATTR. Diagnosis was confirmed by biopsy combined with the clinical and laboratory evaluation of the patients. Myocardial scintigraphy (planar and tomographic imaging) was conducted at 1, 2 and/or 3 h after intravenous administration of 555-925 MBq (15-25 mCi) 99mTc-PYP. Myocardial radiotracer uptake was evaluated optically and also by a semiquantitative method. Two rectangular regions of interest (ROIs) were drawn: one over the heart and another over the contralateral hemithorax, to calculate the corresponding heart-to-contralateral (H/CL) count ratio. According to established reference standards, a cutoff H/CL value of 1.5 best discriminates between the two conditions. The results where compared with clinical, laboratory, other imaging and biopsy findings. Results: 99mTc-PYP scintigraphy revealed intense myocardial uptake in visual evaluation that was also verified quantitatively in 6 patients (5 males, 1 female), all of whom had ATTR. No myocardial tracer uptake was found in 4 cases (1 male, 3 females); these were diagnosed with AL. Two AL patients (2 males) had a borderline positive scan on visual evaluation but their H/CL ratios did not exceed 1.5. Discussion: Cardiac amyloidosis is an underestimated and underdiagnosed cause of cardiac insufficiency. Despite being often considered as a solitary entity attributable to extracellular deposition of fibrillary proteins, there exist at least three different pathophysiologic backgrounds, with different clinical course and treatment. In AL cardiac amyloidosis the fibrils consist of light-chain immunoglobulins produced by a clonal plasma cell population in bone marrow and treatment involves chemotherapy. In ATTR, whether familial amyloid cardiomyopathy (ATTRm) or senile systemic amyloidosis (ATTRwt), monomers or dimers of the normally tetrameric protein of transthyretin are deposited in the myocardium. Amyloid deposition can occur in multiple organs (e.g. heart, liver, kidney, skin, eyes, lungs, nervous system) resulting in a variety of clinical manifestations.Cardiac involvement is a progressive disorder resulting in early death due to congestive heart failure and arrhythmias. Cardiac involvement can occur as part of a systemic disease, or as a localized phenomenon.Thus, drugs that stabilize transthyretin and prevent disease progression are necessary. This pilot study investigated the ability of 99mTc-PYP scintigraphy to differentiate between ATTR and AL cardiac amyloidosis. This differentiation is essential, considering the impact on prognosis, treatment and genetic guidance. Further potential uses of this method that worth investigation include disease follow-up, evaluation of response to treatment and prognosis of major adverse cardiac events. Today, definite diagnosis of cardiac amyloid disease is based on endomyocardial biopsy in conjunction with immunohistochemical parameters or, in ambiguous cases, with mass spectroscopy. Scintigraphy with 99mTc-PYP may prove a simple, non-invasive and widely available method in the identification of patients with the ATTR subtype.
Questions to authors:
a) Is your research the first worldwide?
Considering that the Department of Clinical Therapeutics in UGH Alexandra constitutes the national reference centre for multiple myeloma patients, we proceeded with our research cooperation in accordance with another pilot study listed in the abstract references. Nevertheless our results include differential uptake patterns, not mentioned in the literature.
b) Did you compare your method with another one to show that your method is better?
First worldwide are to our knowledge our preliminary results indicating that this method seems superior in comparison with another nuclear imaging modality, namely scintigraphy with 99mTc(V)DMSA, in discriminating AL from ATTR cardiac amyloidosis.
18F-FBPA as a tumor specific tracer of L-type amino acid transporter 1 (LAT1): PET evaluation in tumor and inflammation compared to 18F-FDG and 11C-methionine
Tadashi Watabe1,2, Jun Hatazawa1,2
1. Department of Nuclear Medicine and Tracer Kinetics, 2. PET Molecular Imaging Center, Osaka University Graduate School of Medicine, Japan
Objective: 18F-FDG-PET is used worldwide for oncology patients. However, we sometimes encounter false positive cases of 18F-FDG PET, such as moderate uptake in the inflammatory lesion, because 18F-FDG accumulates not only in the cancer cells but also in the inflammatory cells (macrophage, granulation tissue, etc). To overcome this limitation of 18F-FDG, we started to use (4-borono-2-[18F]fluoro-L-phenylalanine) 18F-FBPA, an artificial amino acid tracer which is focusing attention as a tumor specific PET tracer. Physiological accumulation of 18F-FBPA is limited in the kidney and urinary tract in humans, which enable preferable evaluation of uptake in the abdominal organs compared to 11C-methionine (11C-MET). The purpose of this study was to evaluate 18F-FBPA as a tumor specific tracer by in vitro cellular uptake analysis focusing on the selectivity of L-type amino acid transporter 1 (LAT1), which is specifically expressed in tumor cells, and in vivo PET analysis in rat xenograft and inflammation models compared to 18F-FDG and 11C-methionine. Subjects andMethods: Uptake inhibition and efflux experiments were performed in HEK293-LAT1 and LAT2 cells using cold BPA, cold 18F-FBPA, and hot 18F-FBPA to evaluate LAT affinity and transport capacity. Position emission tomography studies were performed in rat xenograft model of C6 glioma 2 weeks after the implantation (n=9, body weight=197±10.5g) and subcutaneous inflammation model 4 days after the injection of turpentine oil (n=9, body weight=197±14.4g). Uptake on static PET images were compared among 18F-FBPA at 60-70min post injection, 18F-FDG at 60-70min, and 11C-MET at 20-30min in the tumors and the inflammatory lesions by maximum standardized uptake value (SUVmax). Results:Cellular uptake analysis showed no significant difference in inhibitory effect and efflux of LAT1 between cold 18F-FBPA and cold BPA, suggesting the same affinity and transport capacity via LAT1. Uptake of 18F-FBPA via LAT1 was superior to LAT2 by the concentration dependent uptake analysis. Position emission tomography analysis using SUVmax showed significantly higher accumulation of 18F-FDG in the tumor and the inflammatory lesions (7.19±2.11 and 4.66±0.63, respectively) compared to 18F-FBPA (3.23±0.40 and 1.86±0.19, respectively) and 11C-MET (3.39±0.43 and 1.63±0.11, respectively) (P<0.01 by Tukey test). No significant difference was observed between 18F-FBPA and 11C-MET. Conclusions: 18F-FBPA showed high selectivity of LAT1 by in vitro cellular uptake analysis, suggesting the potential as a tumor-specific substrate. In vivo PET analysis showed significantly lower uptake of 18F-FBPA and 11C-MET in the inflammatory lesions compared to 18F-FDG, suggesting comparable utility of 18F-FBPA PET to 11C-MET PET in differentiating between the tumor and the inflammation.
Questions to authors:
a) Has your method of synthesizing 18F-FBPA being applied to humans and what your thoughts and expectations-results on this issue?
Now 18F-FBPA is used for the pre-treatment PET evaluation of boron neutron capture therapy (BNCT). In BNCT, boronophenylalanine (BPA), a boron containing career to the tumor target, is administered to the patients and neutrons are irradiated to the target, which resulted in tumor cell killing effect by the alpha particle emitted from the boron-neutron reaction. BPA is reported to be tumor specific compound and kinetics of 18F-FBPA is almost the same as BPA. 18F-FBPA can be used for not only the prediction for the BNCT response but also the tumor specific PET imaging.
b) Is this new synthesis cost effective?
Currently, 18F-FBPA is synthesized from F2 gas target and radioactive yield is not sufficient to perform many patients in one day compared to the oncology tracer which is synthesized from F minus, such as 18F-FDG. 18F-FBPA systhesis from F minus is a quite challenging due to the disturbance by electron cloud. We have successfully developed the synthesis method from F minus although radioactive yield is not enough now. Improvement in the synthesis method will be a key for 18F-FBPA to spread as tumor imaging tracer other than 18F-FDG.
Exploration of mechanisms in nutriepigenomics: Identification of chromatin-modifying compounds from Olea Europaea
Natalie P Bonvino1,2, Nancy B Ray3, Vi T Luu1,4, Julia Liang1,4, Andrew Hung2, Tom C Karagiannis1,4
1. Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia, 3004, 2. Health Innovations Research Institute, School of Applied Sciences, RMIT University, Victoria, Australia, 3001, 3. McCord Research, Coralville, Iowa, USA, 52241, 4. Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia, 3052
Chemical modification of histones represents an important epigenetic mechanism critical for DNA metabolism including, transcription, replication and repair. A well-known example is maintenance of histone acetylation status by the opposing actions of histone acetyltransferase and histone deacetylase enzymes which add and remove acetyl groups on lysine residues on histone tails, respectively. Similarly, histone methyltransferase and histone demethylase enzymes are responsible for adding and removing methyl groups on histone tails, respectively. Further, there is accumulated evidence indicating a histone code where combinations of different chemical modifications on histone tails act in concert to regulate DNA metabolic events. Although numerous compounds have been developed to specifically alter the function of chromatin modifying enzymes (for example, histone deacetylase inhibitors are relatively well-investigated), we are only at the early stages of understanding the epigenetic effects of dietary compounds. Here we used in silicomolecular modelling approaches combined with known experimental affinities for controls, to identify potential chromatin modifying compounds derived from Olea Europaea. Our findings indicate that various compounds derived from Olea Europaea have the ability to bind to the active site of different chromatin modifying enzymes, with an affinity analogous or higher than that for a known positive control. Further, we initiated the process of validating targets using in vitro binding and enzyme activity inhibition assays and provide initial findings of potential epigenetic effects in a clinical context. Overall, our findings can be considered as the first installment of a comprehensive endeavor to catalogue and detail the epigenetic effects of compounds derived from Olea Europaea.
Questions to authors:
a) Can you give us an example or describe better the epigenetic effects from Olea Europaea compounts in a more practical aspect?
b) What are the differences of Olea Europaea to other gens of Olea (not Europaea)?
Neuropsychological Disorders in Patients with Brain Tumor
Afsoun Seddighi1 MD,Amir Nikouei1 MD, Amir Saied Seddighi1 MD, Farzad Ashrafi1 MD,Shabnam Nohesara1 MD
1. Functional Neurosurgery Research Center of Shohada Tajrish Hospital, Shohada Tajrish Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Objective: Very few studies have utilized and even fewer have described specific criteria to assess mental disorders in brain tumor (BT) patients. The purpose of this study was to specifically describe mental disorders in patients with BT and also relate them to tumor characteristics and patients’ psychosocial behavior. We used DSM-IV (Depression, Sleep, and Mood) criteria. Subjects and Methods: From March 2007 to July 2009, 98 patients with BT who were surgically treated were included in this prospective study. The mean age of the patient group was 42.2 years with a range of 18-60 years with a male to female ratio of 1.2. The most common tumor type was glioblastoma multiform (30.3%), followed by meningioma (16.8%) and anaplastic glioma (12.3%). Results: In our study, the prevalence of mild depression was about 30% for males and 38% for females before surgery; however at 3 months after surgery, this amount decreased to 25.6% and 26% for male and female patients respectively. Before tumor operation, the prevalence of major depression was 10.4% for males and 19.7% for females. At 3 months after operation the prevalence of major depression was 12.8% for males, and 6.7% for females. Aggression or suicide attempts were not seen related to depression. Before operative intervention, severe anxiousness as well as severe Obsessive Compulsive Disorder (OCD) symptoms were present in 14.7% of males while at 3 months after operation, prevalence of severe anxiousness and severe OCD symptoms decreased to 4% and 9.3% respectively. In females, 28.7% of the subjects were reported to have severe anxiousness and 25.6% severe OCD symptoms. Three months after surgery, these amounts were 17.6% and 38.7% respectively. Conclusion: Depressive symptoms as well as anxiousness and OCD psychopathology were shown to be prevalent signs among patients with BT. Diagnosis of the previously mentioned symptoms were totally based on DSM-IV criteria and these disorders and their percentiles don’t seem to be related to each other. Due to high variability of tumor stages, statistical analysis of whether the mentioned psychiatric symptoms got worst at the later stages of the tumor genesis was not feasible. Although not measured directly, the psychiatric symptoms seemed to worsen at the later stages of BT. The associated factors were tumor location, patients’ premorbid psychiatric status, cognitive symptoms and adaptive or maladaptive response to stress.
Questions to authors:
a) How do you explain the differences in patients operated and not operated?
Differences in percentage of psychiatric conditions before and after surgery of their brain tumor, i.e. mild depression, major depression, severe anxiousness or obsessive convulsive disorder (OCD) were evaluated by DSM-IV criteria. Mass effect, edema and invasive nature of some brain tumors in frontal lobe as well as derangement of neurotransmitters could have role in these psychological and personality differences.
b) Were your results independently related to patients' financial and social condition or to having a family?
We do not asses either financial or social conditions of our cases.
Using a self-administered virtual reality application for remote cognitive screening
Stelios Zygouris MSc1, 2, Konstantinos Dovas, BSc1, Magda Tsolaki MD, PhD1, 3
1. 3rd Department of Neurology, Aristotle University of Thessaloniki, Greece, 2. CND+, Thessaloniki, Greece, 3. Greek Association of Alzheimer's Disease and Related Disorders, Thessaloniki, Greece
Objective: This study examines the feasibility and diagnostic accuracy of a self-administered virtual reality application for mild cognitive impairment (MCI) detection among Greek older adults by analyzing longitudinal performance data. Subject and method: Two age and education matched groups, healthy older adults (N=6) and MCI patients (N=6) were recruited from day centers for cognitive disorders and provided with a tablet PC with custom software enabling the self-administration of the virtual super market (VSM) cognitive training exercise. The protocol includes 5 administrations in each of the 4 difficulty levels of the exercise preceded by 5 familiarization administrations. The performance of the two groups was compared and correlated with performance in established neuropsychological tests. Results: Average performance differed significantly between healthy (μ = 247,41sec/ sd=89,006) and MCI (μ=454,52sec/ sd=177,604) groups. The use of average performance for MCI detection yielded a sensitivity of 100% and a specificity 83,3%. Average performance correlated significantly with performance in Test of Everyday Attention (TEA) and Ray Osterrieth Complex Figure test (ROCFT). Conclusion: The VR application exhibited very high accuracy in MCI patients and was deemed feasible as all participants were able to operate the tablet and application on their own. Instances of incorrect use did not affect results since they were dismissed as outliers by an included algorithm. Remote MCI detection through VR application could enable older adults to combine cognitive training with cognitive screening while reducing the burden of health services.
Questions to authors:
a) Can you give us more data about the accurcy of VR application in MCA patients?
The metric used for MCI detection was the length of time needed for the correct completion of the virtual reality (VR) exercise. Instances of incorrect use of the application were dismissed by an algorithm so the metric was not affected by mistakes such as forgetting to complete the exercise or accidentally exiting the application. Detection of MCI patients was based on their average performance over 20 administrations. This method yielded a correct classification rate (CCR) of 91,6% with a sensitivity of 100% and a specificity 83,3%. Statistical analysis indicated that there was no significant difference in errors (purchase of unlisted items or wrong quantities of listed items, not buying listed items or paying an incorrect amount of money at checkout) between healthy older adults and MCI patients. The average performance of MCI patients and healthy older adults in each of the 4 difficulty levels of the exercise can also discriminate accurately between the two groups however the overall average performance is preferred as it relies on more data and is less prone to interference from random variations in performance.
b) Can you give us inclusion criteria for including subjects in your study?
Participants were recruited from a cohort of older adults from various socioeconomic backgrounds with SMCs visiting the day centers of the Greek Association of Alzheimer’s Disease and Related Disorders (GAADRD). Recruitment for this study occured between June and September 2014. This cohort of older adults had also participated in a previous study concerning VSM’s diagnostic ability utilizing data from a single administration of the VR exercise, between June and December 2013. All participants were informed about the purpose of the study and provided their consent. Diagnosis was confirmed by a neurologist after a full neurological, neuropsychological, and laboratory assessment. Exclusion criteria were: diagnosis of dementia or another major neurological or psychiatric disorder, illiteracy, health issues such as motor and vision difficulties that could interfere with the use of the exercise, treatment with cholinesterase inhibitors or other drugs that could affect cognitive performance, alcoholism or drug abuse and participation in other studies.
Our experience with the use of new technologies in dementia
Tsolaki M.1,6, Zygouris S1,6., Karagkiozi K.6, Dimitriou T.1, Chatzileontiadis L2., Votis K3., Tzovaras D3., Tsiatsios T4., Dimitriadis S4., Tarnanas I1., Bamidis P5.
1. 3rd Department of Neurology, Faculty of Health Sciences, Medical School, Aristotle University of Thessaloniki, 2. School of Electrical & Computer Engineering, Aristotle University of Thessaloniki, 3. Information Technologies Institute, Centre for Research and Technology Hellas, Thessaloniki, Greece. 4. Department of Informatics, Aristotle University of Thessaloniki. 5. Laboratory of Medical Physics, Faculty of Health Sciences, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. 6. Alzheimer Hellas
Objective: There are no medications until today which modify the diseases with cognitive disorders. There are only for symptomatic Alzheimer’s Disease. There is not also one simple way to give the diagnosis in these diseases. Our research teams are implementing high quality next generation services for the Prediction, Early Diagnosis, Monitoring, Management and Support of patients with Cognitive Impairment (MCI, Mild Dementia) and Education and training for all stakeholders. Prediction, Early Diagnosis and Monitoring: The first idea was toResearch and Develop a novel System using motion detection devices, depth cameras, and intelligent objects of everyday use (ranging from cooking implements such as kitchen to furniture (e.g. sofa, bed, etc.) which are appropriately adapted in order to capture changes of subject’s ADL and behavioural patterns (including mobility, nutrition, exercising and medication schedule). We also demonstrated the potential of a virtual supermarket cognitive training game as a screening tool for patients with mild cognitive impairment (MCI) among a sample of older adults. We have indicated that the virtual supermarket (VSM) application displayed a correct classification rate (CCR) of 87.30%, achieving a level of diagnostic accuracy similar to standardized neuropsychological tests, which are the gold standard for MCI screening http://www.en-noisis.gr/Support of patients: Cognitive tasks and cognitive exercises for patients suffering from AD through web-based applications. These exercises have been developed in such a way in order to exploit rich interactive multimedia interfaces (including music) based on human computer interaction principles. To this direction we are implementing a web based portal with supportive services such as (a) on-line monitoring of patient’s progress by health care professionals, (b) statistical representation of patients’ progress. Multimedia enriched cognitive exercises in virtual reality form (i.e. 3D Serious Games) use suitable modalities for such activities through the creation of new brain cells and by assisting the brain to find out alternative methods to execute functions, which are controlled by damaged brain regions. Another program the “robot-programming-as-cognitive-training” approach aims to explore the impact that the activity of programming a friendly robot might have on AD and MCI patients’ condition. http://aspad.csd.auth.gr. Another study aimed at investigating the benefits of combined training on global cognition while assessing the effect of training dosage and exploring the role of several potential effect modifiers. In this multi-center study, 322 older adults with or without neurocognitive disorders (NCDs) were allocated to a computerized, game-based, combined physical and cognitive training group (n=237) or a passive control group (n=85). The results indicate that combined physical and cognitive training improves global cognition in a dose-responsive manner but these benefits may be less pronounced in older adults with more severe NCD. The long-lasting impact of combined training on the incidence and trajectory of NCDs in relation to its severity should be assessed in future long-term trials. www.longlastingmemories.eu. Finally, Symbiosis is a revolutionary system aiming at providing integrated solutions to a series of problems related with Alzheimer. It is the first integrated Alzheimer support system that takes into account patient’s response in an adaptive way that fulfills each patient’s special needs and provides to caregivers and doctors considerable facilitations, unlocking the potential of innovative supporting role.www.youtube.com/watch?v=BDkLz-T-jYE. Education and training for all stakeholders (i.e. health professionals and informal and formal caregivers) through distance education platforms and e-collaboration services. To augment this effort, the research team integrates biofeedback modules for stress measurement in teleconferences in order to support the emotional awareness of the participants. The results on depression, anxiety and burden of caregivers was reduced significantly such as in a face to face intervention. http://aspad.csd.auth.gr. Conclusion: Other sciences in collaboration with medicine can help both patients and caregivers in order to manage better the diseases with cognitive problems.
Questions to authors:
a) Between physical and cognitive training-application which is more important for your favourable results in Alzheimer's dementia?
b) In MRC patients?
In both questions the answer is the above subject has not be studied in our paper.
The role of copeptin in patients with subarachnoid haemorrage
Zissimopoulos Athanassios1, Vogiatzaki Theodosia2, Velissaratou Marion3, Baloka Lukia3, Karathanos Evangelos1, Pistola Anastasia1, Christofis Xristos2, Iatrou Xristos2.
1. Nuclear Medicine Department, 2. Clinic of Anaesthesiology, Univ. Hospital of Alexandroupolis Democritus University of Thrace, 3. School of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis Greece
Objective: The evaluation of copeptineplasma valuesof patients with Subarachnoid haemorrhage hospitalised in the ICU, as a prognostic factor for the severity of the disease. Introduction: Subarachnoid haemorrhage is responsible to a great extend for the death rate of patients who are hospitalised in intense care units (ICU) with haemorrhage. The early detection of its severity plays an important role for the resulting health of the patients. Copeptein (the C-end of vasopressin) in plasma has been used as a prognostic marker in a number of various illnesses, but its prognostic value in intracranial haemorrhage has yet to be valued. Patients and Methods: We studied 32 patients, 21 male, 11 female, (average age 59±7 years), hospitalised in the ICU of Univ. Hospital of Alexandroupolis. Plasma Copeptine values were measured in the Nuclear Medicine Laboratory, with the Radioimmunoassay (RIA) method. The appropriate kit, from Phoenix Pharmaceuticals Inc. (USA), was used. Statistical Analysis: The x2 student test used for statistical analysis. Results: The cut-off value of copeptine ranged between 0.4-4.4pmol/L. 19 patients showing gradual increase of copeptine values, (125-578pmol/L), with a bad prognosis of the illness (P<0.005). 4 of them with extremely high copeptine values died. Decrease of copeptine values for the rest 15 patients were correlated with the improvement of their clinical condition (P<0.005). 11 patients appeared to have high values, followed by the gradual decrease by a range of 85-12pmol/L, and had a good prognosis of the condition. 2 patients with normal values demonstrated to have a good clinical condition. Conclusion: Patients with a gradual increase of copeptine values showed to have bad prognosis of the disease. Four with extremely high copeptine values passed away, while patients showing a gradual decrease of copeptine values had good prognosis. It is supported that copeptine values are a reliable prognostic factor in monitoring patients with intracranial haemorrhage.
Questions to authors:
a) Is it possible that in some of the groups of your patient's the values of copeptin intervened?
Patients with gradual increase of copeptine values in continuous measurements had a bad prognosis of the disease. The patients gradual decrease of copeptine values in continuous measurements had a good prognosis of their condition.
b) Are there other similar publications in Greece or worldwide?
There are some similar publications worldwide but not in Greece.
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Triple negative locally advanced breast cancer: Value of interim FDG PET-CT in predicting the outcome of neoadjuvant therapy (A single centre prospective study)
Swagat Dash, Apoorv Goel, Subham Sogani
Department of Nuclear Medicine and PET/CT, House of Diagnostics, Faridabad, Haryana, India
Objective: Pathological complete response (pCR) to neoadjuvant treatment correlates with improved survival of patients with triple negative locally advanced breast cancer. We prospectively investigated the ability of interim 18F-FDG PET-CT to predict pathological outcomes early. Subjects and Methods: During 48 months, consecutive patients with locally-advanced or large triple negative (ER, PR & HER 2-neu) breast cancer patients without distant metastases were included. All patients received neoadjuvant chemotherapy (NACT). 18F-FDG-PET/CT was performed at baseline (PET 1) and after two cycles of chemotherapy (PET 2). The correlation between pathologic response and SUV parameters (SUVmax at baseline, at two cycles) was examined. Results: Thirty consecutive patients were included. At baseline, 22 patients had PET-positive axillary lymph nodes and in nine of them FDG uptake was higher than in the primary tumor. At surgery, 14 patients (47%) showed residual tumor (non-pCR) while 16 had pCR. There was a strong correlation between the highest residual FDG uptake at PET 2 and pathological response. Any site of residual FDG uptake with a SUVmax >3 whether in breast or axilla was predictive of non-pCR. The risk of non-pCR was 92.3% in patients with any site of residual uptake >3 on interim PET vs. 11.8% in patients with uptake ≤3 (P=0.0001). Conclusions: The level of FDG uptake after two cycles of neoadjuvant chemotherapy predicts residual disease at the completion of neoadjuvant treatment. Because many innovative therapeutic strategies are now available early prediction of poor response is critical.
Questions to authors:
a) What was the age range of your patients related to climacterion?
Age range: 28 to 72, median 47.
b) What were other diagnostic means to diagnose breast cancer besides the three (ER, PR, HER) you mentioned?
All patients underwent breast lesion biopsy (excision or incision) to prove malignancy (histopathologically proven).
Three reasons for on-line remote telemonitoring of patients treated with high doses of radionuclide therapy. Our experience
Matović M1, Jeremić M1, Urošević V2, Ravlić M3, Vlajković M4
1. Department of Nuclear Medicine, Clinical Center Kragujevac and Faculty of Medical Sciences, University of Kragujevac, 2. Polytechnic School in Cacak, University of Kragujevac, 3. Prizma Company, Kragujevac, 4. Department of Nuclear Medicine, Clinical Center Nis and Medical Faculty University of Nis, Serbia
Objective: Following radionuclide therapy, patients usually must remain hospitalised in special “restricted access area” 2-5 days, until radiation in their body drops below a certain level. During this period medical personnel can be faced with some challenges. Based on our previous experience, we used telemedicine approach as solution for it. We have developed comprehensive telemedicine system, which consists of three own developed hardware & software modules which are accessible remotely.Subjects and Methods: Challenge #1Some of patients can experiencing serious complications related to radionuclide therapy or related to co-morbidities, if they have any of it. In some of those cases audio-visual contact with patients and follow-up their vital functions can be of high importance in case of patient needs urgent intervention. Solution #1System for on-line remote monitoring of patients’ vital functions registered with bed side monitor and video surveillance of area which use patients during hospitalisation. This system is established by IP cameras and bedside patient monitor, equipped with appropriate network card and software. Using remote connection (LAN or Internet), a physician can watch at personal computer or mobile phone the waves and vital signs patterns from the bedside monitor, as well as live video from surveillance cameras. It provide prompt intervention in case of emergency.Challenge #2Having in mind the overall costs of radionuclide therapy and patients hospital stay on the one hand, and limited capacity of the hospital premises for radionuclide therapy, on the other, it is of high importance to estimate as early as possible the time period after which the radiation in a patient's body will drop below the limit imposed by the law.Solution #2On-line remote radiation monitoring system, which measures the radiation exposure rate by means of a pancake probe, which is connected to a PTZ (Pan-Tilt-Zoom) device and DVR (Digital Video Recorder). Those devices enables precise positioning of the detector on target region of the patient's body.The positioning of the detector can be visually controlled by a micro camera, placed at the centre of detector's plane. Furthermore, there are three laser pointers placed around the detector in order to mark the area where it is directed.In addition, two ultrasound sensors placed on the edge of the detector holder in order to estimate the exact distance between the probe and the patient’s body. All those devices are controlled by the DVR. The data collected by the detector are acquired and processed by a PC, using customized hardware/software system developed by Italian ThereminoR group.Using remote connection, a physician can watch on-line radiation exposure rate in any time and can use commands of PTZ and DVR device for proper positioning of probe during measurement and control it by micro camera, laser pointers and US sensors. Physician demands from the patients to take the same position for 5 minutes on each hour, during first 10 hours. Those data we use as reference points for further processing by our software. Based on two exponential matematical model, our software estimates the whole process of elimination of radioactivity from the patient’s body, using reference points collected during the first day after radioinuclide therapy. Based on that, physician can predict (on first day after therapy!) when patient will be able to leave the „restricted access area“.Challenge #3Despite strict instructions given to them by physician and nurse before administration of radionuclide therapy, some patients sometimes try to leave “restricted access area”. Solution #3We have developed a system which continuously monitors the corridor which a patient must use in case of an attempt to leave the “restricted access area”.Our system consists of a survey meter equipped with pancake probe directed towards the corridor. The survey meter is connected to a trigger circuit which gives signal in the case when the measeured count rate exceeds previously adjusted value. Trigger circuit is connected to the programmable siren, blinking light, alarm device unit with SIM card and IP surveillance camera. On the siren we previously recorded the voice alarm. In the case when the system is triggered, the patient will hear warning message and see blinking light.When the alarm device is triggered it will call responsible physician and nurse on mobile phone and IP camera simultaneously records this event. System also sending via e_mailappropriate data about each event, when it happens. Conclusion: From our experience gained over the past 4 years, our telemonitoring system dedicated for patients receiving radionuclide therapy, ensures a high level of safety for the patient and medical staff.
Questions to authors:
a) What were the doses-range your patients received and from what diseases they suffered?
Range of doses were 1.85-7.40GBq. We use 131I for thyroid carcinoma therapy as well as 177Lu and 90Y for neuroendocrine tumors therapy.
b) By what percentage your method-system of telemonitoring reduced the level of radiation for patients and staff?
It is not so easy exactly estimate percentage of benefit which we can have using this system. We have monitored more than one and half hundred patients with Bed Side Patients Monitor (BSPM) using our system (Solution #1). Just in few cases we had medical interventions according to received data from BSPM. It is about just few percents, but for each case it is 100%! Using our system (Solutions#2 and #3) we can exactly estimate (on-line, from distance) level of rest radioactivity in patient’s body as well as prevent accidental situation in case of patient try to unauthorised leave “restricted access” premise. It can eliminate any of unnecessary exposure to high radiation, both possible participants, medical personel and other patients! It could be near 100%.
Radioguided surgery using gamma detection probe technology for resection of cerebral glioma
Afsoun Seddighi1 MD, Mohammad Esmail Akbari2 MD, Amir Nikouei1 MD, Alireza Zali1 MD, PhD, Seyed Mahmod Tabatabaei1 MD, PhD, Amir Saied Seddighi1 MD, Elaheh Pirayesh1 MD, Mohammad Mehdi Soleymani1 MD, Shoeib Naimian3 MD, Hesam Rahimi Baqdashti1 MD, Omid Mellati1 MD
1. Functional Neurosurgery Research Center of Shohada Tajrish Hospital, Shohada Tajrish Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 2. Department of Surgery, Shohada Tajrish Hospital, Tehran, Iran, 3. Department of Neurology, Qazvin University of Medical Sciences, Qazvin, Iran
Objective: Using microsurgical procedures without intraoperative imaging, Gross Total Resection (GTR) has so far only been achieved in less than 30% of all cases. Radio-guided surgery (RGS) was introduced in the clinical setting in 1985 in an attempt to facilitate intraoperative tumor detection. There are a few studies in medical literature about this subject. We used gamma probe detection in a manner that increased the extent of tumor resection. Materials and Methods: From January 2013 till February 2014, 22 patients with cerebral glioma were randomized equally into two groups and evaluated. In the first group, 370MBq of methoxy-isobutyl-isonitril (99mTc-MIBI) were injected intravenously in two steps before and during surgery. The microsurgical resection of the tumor was performed as much as possible, and then the tumoral bed was examined by RGS. If the signal was more than 2 times the background, more tissue resection performed where feasible until the signal was diminished. In the control only group, conventional resection of the tumor was performed. The extent of tumor resection was assessed by contrast MRI study. Results: Before surgery, the patients in the first group, as measured by magnetic resonance imaging (MRI), had an average tumor volume of 81.68±9.78cm2 and in the second group 82.63±10.06cm2. There was no significant difference between the preoperative tumor volumes in the two groups. In the first group, in the post-operative MRI, the tumor volume was 5.04±2.69cm2 and in the second group it was 9.5±4.8cm2. Eight out of eleven patients in the radioguided group had radical resection (of more than 95%), but in the control group radical resection was achieved in just 3 out of 11 patients which was significantly higher in radioguided group (P<0.001).Due to the use of GDP, time of finding the tumor area in the radioguided group was significantly less than in the control group (P=0.02). Furthermore, total operation time in the radioguided group, was not statistically more than that in the control group (P=0.88). Conclusions: Current microsurgery neuronavigation system increases the percentage of gross total resection of brain gliomas, but it is not considered a real-time assessment, and is not accurate in determining the borders of glioma to be ablated. In contrast, the addition of radioguided surgery is easy to use, real time effective, not really expensive, and most of all, greatly increases the extent of tumor resection.
Questions to authors:
a) Compared to others similar research, are your results different?
Our results were unanimous to other similar researches.
b) Do your results ensure more expected survival than when your technique was not applied as in previous operations?
Radioguided surgery using gamma detection probe minimizes the residue of tumor after excision compared to previous operations, as stated in the results section. Thus depending on literature, greater glioma excision even without chemotherapy and radiotherapy increases the survival, as this technique does.
Voxel based internal dosimetry during radionuclide therapy
Ioannis Vamvakas1, Maria Lyra2
1. MSc, Iaso Hospital Greece, 2. PhD, Ass. Professor, A΄ Radiology Department, Aretaieion Hospital, Greece
Objective: The aim ofthis study is to develop a computer algorithm that calculates absorbed dose at every voxel of quantitative SPECT scintigraphy image and establish a general internal dosimetry protocol for therapy by radionuclides. The case of 131I radioisotope therapy is shown here. Background: Many radionuclides have been used for several decades in cancer treatment. 131I, 90Y, 89Sr, 111In, 177Lu and 223Ra are some of the most widely used radioisotopes. Patient specific dosimetry during radionuclide therapy is essential for the safety of the patient and the efficiency of the treatment. Therapeutic results and side effects can be associated only if the absorbed dose is well estimated. Knowledge of the absorbed dose during radionuclide therapy is the only method that can compare therapeutic results between different therapeutic techniques such as external radiotherapy and radio immunotherapy. Accurate patient specific estimation of the absorbed dose to the tumor and normal tissue can be achieved with voxel based internal dosimetry. Material and methods: SPECT scintigraphy images of known 131I activities were obtained. The known activity of 131I was contained in a cylindrical PMMA phantom with 16 cm diameter. A numerical factor was determined to convert the measured count rate from the SPECT images to activity. The algorithm that calculate absorbed dose at every voxel of the scintigraphy image was developed by MATLAB. MATLAB is a high level computer language with interactive environment and performs mathematical calculations by matrices. The scintigraphy images were imported in MATLAB and were converted to 3- dimensional matrices. Every element of the matrix was assigned with the respective count rate. The matrix was multiplied with the conversion factor and the new elements represented the activity at every voxel. A cumulative activity matrix was made from activity matrices that were obtained at different time points. The absorbed dose at every voxel of the cumulative activity matrix was computed with the convolution method. A 3- dimensional convolution matrix with size 5 x 5 x 5 was created. The elements of this matrix are numerical factors that convert cumulative activity to absorbed dose. The values of these factors were determined from MIRD 17 published data for 131I. The convolution between these two matrices was made using the ‘convn’ function of MATLAB. This function convolves the cumulative activity matrix with the convolution matrix and gives a new matrix with numeric elements that represent absorbed dose at every voxel. Furthermore, regions of interest can be drawn on the images and dose volume histograms and mean absorbed doses can be calculated. Results: SPECT scintigraphy images were obtained for 64 MBq 131I activity. A cumulative activity of 230 GBq*s was calculated and the voxel convolution method showed that mean absorbed dose was 20.6 Gy. Maximum dose of 50 Gy was calculated for the central voxel in the activity. A region of interest was drawn and the dose volume histogram was calculated. The results were compared to MIRDOSE3.1 program. A mean dose of 20.1 Gy was calculated with MIRDOSE3.1 for the same cumulative activity in 0.85 cm diameter. Conclusions: Patient specific voxel internal dosimetry can be performed accurately with MATLAB. Dose volume histograms and mean dose can be calculated. The method has been also applied to177Lupatient specific radionuclide therapies andcan be developed in the future for other therapeuticisotopes.
Questions to authors:
a) Can your dosimetric procedure be duly modified in order to be used in nuclear medicine as a quantitative one?
Our dosimetric procedure can be used in nuclear medicine as a quantitative one. We follow a calibration procedure for the γ – camera in order to convert count rate to activity. A known value of activity is placed into a suitable cylindrical phantom. SPECT scintigraphy image of the known activity is obtained under a specific imaging protocol and the measured count rate is assigned to the known activity. This procedure is repeated for several known activities and a calibration function that converts count rate to activity is obtained.
b) How long it takes to perform this dosimentric procedure in a patient having a superficial and having a deeply located tumor?
The imaging protocol for a dual head γ – camera takes 160 sec to be completed. Circular step and shoot tomography images are obtained according to the following settings:
3 degrees step
32 steps for 180 degrees rotation
5 sec per step
The images are reconstructed by back projection algorithm and corrected for attenuation by Chang method. The imaging protocol takes 160 sec to be completed for superficial and deeply located tumors too.
The diagnostic performance and added value of FDG PET/CT in detection of liver metastases in recurrent colorectal carcinoma patients
Odalovic S, Artiko V, Sobic-Saranovic D, Stojiljkovic M, Petrovic M, Petrovic N, Kozarevic N, Grozdic-Milojevic I, Obradovic V.
Center of Nuclear Medicine, Clinical Center of Serbia, Belgrade
Objective: The aim of this study was to assess the value of 18F-fluorodeoxyglucose (18F-FDG) PET/CT in detection of liver metastases in patients with suspected recurrent colorectal carcinoma, as well as to compare diagnostic performance of 18F-FDG PET/CT with conventional imaging methods (MDCT). Subjects and methods:This study included 73 patients with resected primary colorectal adenocarcinoma referred for 18F-FDG PET/CT to the National PET Center, at the Clinical Center of Serbia, Belgrade, from January 2010 to May 2013, with suspicion of recurrence. The patients underwent 18F-FDG PET/CT examination on a 64-slice hybrid PET/CT scanner (Biograph, TruePoint64, Siemens Medical Solutions, Inc. USA). Prior to 18F-FDG PET/CT all patients underwent contrast-enhanced MDCT. Findings of 18F-FDG PET/CT and MDCT were compared to findings of subsequent histopathological examinations or with results of clinical and imaging follow-up over at least six months. Final diagnosis of liver metastases of colorectal cancer was made either by histopathological examination of specimen after biopsy or surgery, or based on clinical, laboratory and imaging evaluation during first six months after PET/CT scan. Results: In detection of liver metastases 18F-FDG PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 83.3%, 95.3%, 92.6%, 89.1% and 90.4%, respectively. In addition, MDCT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy in detection of liver metastases of 60%, 88.4%, 78.3%, 76% and 76.7%, respectively. There was significant difference in sensitivity (83.3% vs 60%; p=0.045) between these two methods. In addition, significant difference was observed in accuracy between PET/CT and MDCT (90.4% vs 76.7%; p=0.016). The higher specificity in visualization of liver metastases was also achieved by 18F-FDG PET/CT compared to MDCT (95.3% vs 88.4%), but this difference was not significant (p=0.37). Conclusion:18F-FDG PET/CT was highly sensitive, specific and accurate method in detection of liver metastases in patients with suspected recurrent colorectal carcinoma in our study. This hybrid imaging showed superior diagnostic performance in evaluation of suspected colorectal cancer liver metastases compared to conventional imaging.
A generic ABCDE algorithm for radiology image or pathology slide diagnosis
Christina Zioga MD, MSc, MIAC, Xarikleia Destouni, MD, PhD
Cytological laboratory, Theagenio Anticancer Hospital, Thessaloniki Greece
A pathway to the procedure of interpreting radiology images or pathology slides is presented. This simplified mnemonic (Correct ABCDE) can be used as a memory aid determining the order in which diagnosis should be approached. First, before we place the radiology image in front of the lightbox or the slide under the microscope we have to be sure that it is adequately labelled and prepared (Correct). It is also necessary to have or gather all available information concerning the patient and if possible his full medical history (A, Available Information). Once we come across the image, two fundamental questions should be answered: which part of the body does the image concern and – where applicable – if the image is adequate (B, Body). Next, we proceed to answer if we have a neoplastic tissue or not (C, Cancer). We then either form a differential diagnosis list or we reach to a final diagnosis (D, Diagnosis), which is followed by the writing of the report (E, Exhibit). These series of steps (Correct ABCDE) followed as an ad hoc procedure by most radiologists and pathologists, are important in order to achieve a complete and clear diagnosis and report, which is intended to support optimal clinical practice. This ABCDE concept is a generic standard approach which is not limited to specific specimens and can help improve both diagnoses and the quality of the final reports.
Advances in Knowledge Radiology and Pathology ABCDE algorithm:
- is a new structured way to orientate radiology image or pathology slide assessment
describes a generic systematic procedure in radiology or pathology diagnosis and reporting
- is a useful practical and educational tool for educators, medical students, residents, practitioners, pathologists, radiologists and oncologists
- is an approach towards integrating Radiology and Pathology.
Implication for Patient Care
Radiology and Pathology ABCDE algorithm can potentially lead to faster diagnosis and fewer mistakes.
19.00 - 21.00
The role of radionuclide imaging in the diagnosis infected prosthetic joints
L. Brammen1, MD, C. Palestro2, MD, H. Sinzinger3,4, MD
1. Department of Surgery, Division of General Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria, 2. Division of Nuclear Medicine, Long Island Jewish Medical Center, 270-05 76th Ave., New Hyde Park, NY 11040, USA, 3. ISOTOPIX - Institute for Nuclear Medicine, Mariannengasse 30, A-1090, Vienna, Austria, 4.Department of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
A serious complication of joint replacement surgery is infection, which results in prolonged invalidity as well as removal and subsequent re-implantation after lengthy antibiotic therapy. In terms of diagnostic imaging, nuclear medicine has presented several tracers and imaging modalities over the years to be used in prosthetic joint infection. The PubMed/MEDLINE literature database was systematically examined for publications on infection, arthroplasty, joint replacement, prosthetic joint, gallium, labeled leukocytes, sulfur colloid, antimicrobial peptides, positron emission tomography (PET), PET-CT, 18-fluorodeoxyglucose (18F-FDG), 18-fluoride (18F) and single-photon emission computed tomography (SPECT-CT). This was determined to be a comprehensive review, not a meta-analysis of prosthetic joint infection and diagnostic imaging in the field of nuclear medicine. Prosthetic joint replacement is more frequently being employed as a way of improving the quality of life in an ever-ageing population. Complications following joint replacement surgery include aseptic or mechanical loosening, as well as polyethylene wear and prosthetic joint infection. The rate of infection is estimated to be between 1-3%. The therapeutic management of these complications lies in the ability to differentiate between infection and aseptic mechanical loosening. Given that plain radiographs are neither sensitive nor specific to infection and computer tomography, as well as magnetic resonance imaging are limited due to metal-induced artifacts, radionuclide imaging has come to aid in the diagnostic imaging in the failed joint replacement. However, each modality has its advantages and disadvantages, thus there is no gold standard technique of radionuclide imaging. Nevertheless, radiolabelled leukocyte scintigraphy has proven itself to be the gold standard in neutrophil-based infection processes. Several studies have examined the role of PET using radiotracers such as 18F-FDG, 67-Gallium and 18F, as well as SPECT-CT in diagnosing prosthetic joint infections. Other radiotracers, such as antigranulocyte antibodies and fragments, as well as radiolabeled antibodies and antimicrobial peptide have yet to confirm their role in diagnostic imaging of the failed joint replacement. Nuclear medicine plays a vital role in diagnosing prosthetic joint infections. WBC/bone marrow imaging is the best available diagnostic imaging test. Newer imaging modalities, such as SPECT-CT may in the future, play a larger role in diagnosing prosthetic joint infections. The roles of 18F-PET and 18F-FDG-PET have yet to still be determined.
Questions to authors:
a) Can you suggest what are the false negative results by using the leukocites scintigraphy and the FDG scintigraphy in infected prosthetic joints?
False negative results produced by leukocyte scintigraphy can be due to either aseptic inflammation, i.E. non-neutrophil dominated response, or prior long-term antibiotic treatment. Given that leukocyte scintigraphy is most sensitive in neutrophil-dominated responses, chronic inflammation, which is characterized by less distinct neutrophil recruitment and edema, will decrease the sensitivity of this diagnostic imaging. In addition, since long-term antibiotic treatment may also affect the neutrophil response, it has been hypothesized that this may also decrease sensitivity. In terms of FDG scintigraphy, I would say we are more concerned about false positive results than false negative. False positive readings due to non-specific FDG-uptake may be due to artifacts adjacent to prostheses, as well as healing tissues up to 6 months following surgery, varicose veins, bone fractures and atherosclerotic lesions.
b) What is the role of clinical symptoms-signs in the same diagnosis?
The role of clinical symptoms/signs in the same diagnosis plays an subordinate role. Infected prosthetic joints can either present acutely with obvious signs and symptoms, such as pain, swelling, erythema, however, it can also present with few, if any, of these signs and symptoms. Given that the presentation varies, diagnosis is also challenging. There is no single test sensitive enough to diagnose prosthetic joint infection on its own and therefore diagnosis is based on a combination of clinical, serologic, laboratory and imaging findings.
Brain capillaries in Alzheimer’s disease
Stavros J.Baloyannis MD, PhD, Professor Emeritus
Aristotelian University o Thessaloniki, Greece, Research Institute for Alzheimer’s disease, Aristotelian University, Greece
Alzheimer’s disease is the most common cause of irreversible dementia, affecting mostly the presenile and senile age, shaping a tragic profile in the epilogue of the life of the suffering people. Due to the severity and the social impact of the disease an ongoing research activity is in climax nowadays, associated with many legal, social, ethical, humanitarian, philosophical and economic considerations. From the neuropathological point of view the disease is characterized by dendritic pathology, loss of synapses and dendritic spines, affecting mostly selective neuronal networks of critical importance for memory and cognition, such as the basal forebrain cholinergic system, the medial temporal regions, the hippocampus and many neocortical association areas. Tau pathology consisted of intracellular accumulation of neuroﬁbrillary tangles of hyperphosphorilated tau protein and accumulation of Aβ-peptide’s deposits, deﬁned as neuritic plaques, are the principal neuropathological diagnostic criteria of the disease. The neurotoxic properties of the oligomerics of the Aβ-peptide and tau mediated neurodegeneration are among the main causative factors of impaired synaptic plasticity,neuronal loss, dendritic alterations and tremendous synaptic loss.The gradual degeneration of the organelles, particularly mitochondria, smooth endoplasmic reticulum and Golgi apparatus, visualized clearly by electron microscopy (EM), emphasize the importance of the oxidative stress and amyloid toxicity in the pathogenetic cascade of the disease.The vascular factor may be an important component of the whole spectrum of the pathogenesis of AD. It is of substantial importance the concept that the structural alterations of the brain capillaries, may contribute in the pathology of AD, given that the disruption of the BBB may induce exacerbation of AD pathology, by promoting inflammation around the blood capillaries and in the neuropile space diffusely. From the morphological point of view, silver impregnation techniques revealed a marked tortuosity of the capillaries in early cases of AD. In addition, the distance between two branch points is longer in capillaries of AD brains, whereas the branch point density as well as the ratio of the branch point density to astrocytic density is substantially decreased in AD in comparison with age matched normal controls. EM revealed, that the most frequent morphological alterations of the brain capillaries in AD consist of thickness, splitting and duplication of the basement membrane, reduction of the length of tight junctions, decrease of the number of tight junctions per vessel length, associated as a rule, with morphological alterations of the mitochondria of the endothelial cells, the pericytes and the perivascular astrocytic processes. The number of the pinocytotic vesicles is substantially increase in the endothelium of the brain capillaries in AD in comparison with age matched normal controls. Endothelial cells play a very important role in the transport systems in the brain. Subsequently, the dysfunction of the endothelial cells and the disruption of the BBB may induce serious impairment in the transport system. The dysfunction of the brain capillaries may result in releasing neurotoxic factors, such as thrombin, pro-inflammatory cytokines, nitric oxide and leukocyte adhesion molecules, and in abnormal regulation of Aβ-peptide homeostasis in the brain. The impairment of the brain capillaries in structures of the brain, which are crucial for the homeostatic equilibrium, such as the hypothalamic nuclei, may induce autonomic dysfunction, which usually occur in the advanced stages of AD, affecting dramatically the viability of the patients. Degeneration of the pericytes is also observed emphasizing even more the importance of the vascular factor in AD.Pericytes may serve as integrators, coordinators and effectors of blood–brain barrier structure and maintenance, and play a key role in microvascular stability, capillary density and angiogenesis. The correlation between AD pathology and vascular pathology, at the level of brain capillaries and BBB, raises the rational question, whether the efficient treatment of the vascular factor might be beneficial for the patients who suffer from AD.It is reasonable that any protection of the brain capillaries at the initial stages of the disease might contribute in the abbreviation of the long chain of pathological alteration, which occur following the disruption of the BBB, which serves as the essential interface between the vascular system and the brain.
The importance of angiotensin II type 1 receptor gene polymorphism to losartan treatment in improving glomerulopathy in type 1 diabetic patients
Boris Ajdinovic1, Tamara Dragovic2, Zvonko Magic3, Nikola Kocev4
1. Military Medical Academy, Institute of Nuclear Medicine, 2. Clinic of Endocrinology, 3. Institute for Medical Research, Belgrade, Serbia; School of Medicine, Belgrade University, 4. Institute for Informatics and Statistics, Belgrade, Serbia
Objective: Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. Aim of this study was to examine if renoprotective response to losartan therapy, in patients with diabetic nephropathy, depends on 1166 A/C gene polymorphism for its target receptor, angiotensin II type 1 receptor (AT1R). Subjects andMethods: The study included 35 patients with diabetes mellitus type 1 and high urinary albumin excretion rate (>30mg/24h) genotyped for the 1166 A/C gene polymorphism for the AT1R. The participants were segregated into three genotype groups according to combinations of A or C allele: AA-16, AC-15 and CC-4 patients. The patients received losartan 50mg daily for 4 weeks, following 100mg daily for 8 weeks. At baseline and after losartan therapy period, blood pressure, GFR (Gates method) and filtration fraction (FF) were calculated. FF was calculated by dividing GFR by ERPF (Schlegels method). Results: GFR remained unchanged in all genotype groups. FF was significantly reduced from baseline by 0.018±0.024 (P=0.012) only in the AC group. In the AA genotype FF was reduced from baseline by 0.017±0.03 (P=0.052) and in the CC group by 0.01±0.008 (P=0.092). In the AA group, systolic blood pressure declined from 136±24mmHg at baseline, to an average of 121±18mmHg at the end of the study (P=0.001). The AC group achived reduction from 131±10mmHg at baseline to 115±7mmHg (P=0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86±13mmHg at baseline to 78±8mmHg (P=0.004), and in the AC genotype from 88±5mmHg at baseline to 11.7±5.6mmHg during the investigation period (P=0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (P=0.066). Conclusion: The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy.
Sitagliptin reduces urinary microalbumin in experimental model of diabetic nephropathy
Tsavdaridis Ioannis1,2, Papadimitriou Dimochristos1,3, Karanikola Dora1,4, Kalousis Kostas1,5, Katsouda Areti 1,3, Mironidou-Tzouveleki Maria1,6
1. A' Laboratory of Pharmacology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Greece, 2. MD, Pathologist, Diabetologist, 3. Medical student, 4. DMD, PhD, 5. MD, Plastic surgeon, MSc, 6. MD, Anaesthesiologist, Professor of Pharmacology, PhD
Objective: The term Diabetic kidney disease (DKD) refers to any disease of the kidney that is a result of long-term hyperglycemia caused either by diabetes mellitus type 1 (DT1) or type 2 (DT2). When DKD coexists with macro albuminuria or proteinuria the condition is called diabetic nephropathy. DKD is the primary cause of renal failure since it is responsible for the 44% of new cases presented in the U.S.A. in 2008. Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase and is used as a treatment for diabetes since 2006. Through the inhibition of the enzyme’s action sitagliptin prevents the degradation of GLP-1 which is an endogenous peptide with significant hypoglycemic actions, particularly postprandial. The proven hypoglycemic actions of sitagliptin led the researchers to further study the possible effects sitagliptin may have on the complications of diabetes mellitus such as diabetic nephropathy. The purpose of the study is to examine the effect of sitagliptin on diabetic nephropathy using biochemical parameters for assessment. Methods: 27 db/db mice were used in total. They were about 4 weeks old. The mice were randomly divided into 3 groups each one consisting of 9 mice, the first 2 groups received sitagliptin treatment over a period of 32 weeks while the third did not receive any treatment. In the first group the mice received 200mg sitagliptin per Kg of body weight and in the second 10mg per Kg. At the end of the 32 weeks period the serum glucose, urea, creatinine, cholesterol, LDL, HDL, hsCRP and triglycerides as well as the urinary creatinine and microalbumin were measured in all 3 groups. Results: The first group (received 200mg/kg) in comparison to the third group (control group) exhibited a reduction in the biochemical parameters measured: glucose -12.35% (P=0.16), urea -17.18% (P=0.61), creatinine -0.81% (P=0.95 ), cholesterol -19.28% (P=0,09), HDL -12,25% (P=0.26), LDL -31.2% (P=0.25), triglycerides -13,9% (P=0.37), hsCRP -49.8% (P=0.06), microalbumin -37.8% (P<0.0001). Conclusion: The administration of sitagliptin reduces in a statistically significant manner the urinary microalbumin. In addition, hsCRP was greatly reduced but the reduction did not reach the required significance level. The other biochemical data presented a reduction which could not be considered as statistically significant. However, it should be mentioned that the exact mechanisms by which sitagliptin achieves this reduction in the biochemical parameters measured, except for the glucose reduction, remain unclear. Although it is suggested that the reduction of glucotoxicity due to sitagliptin treatment is the main reason for those results, the effects of sitagliptin on inflammation, protection of the endothelium and reduction of arterial blood pressure might play a facilitating role.
Questions to authors:
a) What werethe levels ofglucosethat causedkidney disease?
Hyperglycemia is associated with the severity of renal disease in humans. Some studies suggest that this pathophysiological association is also present in mice. The mice model of diabetic nephropathy used in this study display important similarities with the human kidney disease. The mice that were used carried a mutant autosomal recessive gene (db) encoding the protein of the leptin receptor. The binding of leptin to the abnormal receptor, which bears a point mutation, results in the activation of pathological metabolic pathways. In particular the activation of the abnormal leptin receptor in the hypothalamus, leads to overeating, obesity and finally high serum levels of leptin and insulin. The homozygous mice (db/db) for the mutated gene exhibit hyperinsulinemia starting at the 10th day of their life and mild hyperglycemia starting around the 4th week. Between the 8th and 10th week hyperglycemia is clearly established. After the 5th or 6th month of their life their weight and insulin serum levels decline due to the degeneration of pancreatic islets. Between the 2nd and 4th month glomerular hypertrophy of a class of 20% to 30% is observed as a result of hemodynamic changes in the glomerulus. After the 4th month an expansion of the mesangium is observed and reaches three times the normal levels. The mean value of the urinary albumin is between 68 to 600μg/24h versus 4-21μg/24h of the heterozygous mice of the same age. The levels of albuminuria do not appear to be increasing in accordance with the mice age and they appear to be the same between 8-25 weeks. Hyalinosis of arterioles without tubulointerstitial fibrosis is also present. However, it should be outlined that, there is no specific threshold to glucose serum levels at which kidney disease is initiated, therefore we can only assume that the histopathological changes of the disease had occurred in the mice we used (db/db) because of their diabetic nephropathy model and their age. The mean glucose serum levels of the first group of mice (200mg sitagliptin/kg) was 313.75μg/dL while in the control group it was 357μg/dL.
b) How severe or light were the clinical symptoms?
Diabetic nephropathy in humans is a microangiopathy associated primarily with the risk of developing chronic kidney disease (CKD) and secondarily with cardiovascular complications (macroangiopathy). In general, it is a clinical syndrome characterized by proteinuria and progressive reduction in GFR.
GFR (mL/min/1,73m2 BSA)
Kidney disease stages
Association with diabetic nephropathy
GFR=normal or ↑ and proteinuria → diabetic nephropathy
Established changes in the structure and function of the kidney. If proteinuria exists → diabetic nephropathy
and proteinuria → diabetic nephropathy
Existing microalbuminuria is probably not a result of diabetes mellitus. If microalbuminuria exists → diabetic nephropathy
<15 or dialysis
Final stages of kidney disease.
Existing microalbuminuria is probably not a result of diabetes mellitus
Classificationofdiabeticnephropathy according to theglomerular filtration rate(GFR) in humans.
Patients suffering from diabetic nephropathy initially appear microalbuminuria which if left untreated can lead to albuminuria at levels of nephrotic syndrome (>3gr/24h) and finally develop into CKD. It is suggested that these stages also occur in mice suffering from diabetic nephropathy and that there is a strong correlation between the severity of disease and the urinary albumin levels. Unfortunately mice models of diabetic nephropathy is not ideal for studying the progression of the disease and its clinical manifestations over time. It should be noted that there is no "normal" limits of urinary albumin levels in mice and that there are significant differences in urinary albumin levels of different strains of mice used in experiments. The mean urinary microalbumin levels of the first group of mice (200mg sitagliptin/kg) was 45.61μg/dL while in the control group it was 73.4μg/dL. In overall, taking into consideration the age of the mice, the model of diabetic nephropathy used and the mean urinary microalbumin levels of the control group compared with that of the first group, we can conclude that the mice suffered from kidney disease and that the severity of the clinical symptoms of the disease was decreased using sitagliptin, in a statistically important way (P <0.0001).
The impact of low back and neck pain on dentistry students in Northern Greece
E. Samoladas, S.I. Stavridis, K. Tsitas, K. Xanthopoulou, K. Apostolidou, I. Hatzokos
2nd Orthopaedic Dpt, Aristotle University of Thessaloniki, “G. Gennimatas” General Hospital
Objective: Dentistry students and dentists comprise a unique group of professionals, whose everyday professional activity requires long hours of standing and working in position considered “unhealthy” for low-back and neck. Our aim was to explore the factors involved in the appearance of low-back and neck pain in dentistry students as well as the impact of the pain on the students professional and everyday activities. Materials and Methods: A questionnairewas sent via e-mail to all dentistry students of the xx semester of our university. The questionnaire included 43 questions regarding demographical data, history (spinal injury, other comorbidities), daily activities (exercise, smoking, alcohol and caffeine consumption, use of cell phone, etc), professional activities (length and type of dental work), pattern and intensity of pain and personal pain evaluation. A statistical analysis of the gathered data was performed. Results: All students having suffered a spinal trauma or indicating any other comorbidities that could cause severe pain of the spine were excluded from the study. 55 students (21 male, 34 female) were included in the study. Our data showed that increased alcohol consumption and prolonged use of cell phone were connected to increased levels of pain. The students reported that the most frequent onset of pain was one hour after starting to work in standing position, while the majority believed that their working habits were involved in the appearance and the intensity of neck and law-back pain. Conclusion: Our findings indicate that among dentists and dentistry students there appears to be a causative relation between their professional activities and the experienced spinal pain. The findings may be useful in a possible future restructuring of the educational program in dental schools, as well as in improving the ergonomics of dentistry working units.
Can tumor necrosis factor a (TNF-a) and interleukin 6 (IL-6) be used as prognostic markers of infection following ureteroscopic lithrotripsy and extracorporeal shock wave lithotripsy for ureteral stones?
A. Bantis1, G. Tsakaldimis1, A. Zissimopoulos2, Ch. Kalaitzis1, S. Gianakopoulos1, M. Pitiakoudis3, A. Polichronidis3, S. Touloupidis1
1. Urology Department, 2. Department of Nuclear Medicine, 3. Department General Surgery University General Hospital of Alexandroupolis
Objective: Ureteroscopic lithotripsy (URS) and Extracorporeal shock wave lithotripsy (ESWL) are highly effective for the treatment of uretral lithiasis and remain the treatment option for the majority of patients for more than two decades. In the present study we aimed to evaluate the levels of serum tumor necrosis factor A (TNFa) and interleucin 6 (IL6) in patients undergoing ESWL and URS. Subjects and Methods: A total number of seventy patients were involved in our study. Thirty patients (17 males, 13 females), with a mean age of 43 had underwent ESWL and thirty patients (19 males, 11 females), with a mean age of 47 (range: 26-68) underwent URS lithotripsy. 10 healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF-and IL-6 were obtained before URS and ESWL and after the procedure at 1, 24, and 48 hours and at 2, 24, and 48 hours, respectively. The pre ESWL/URS and post ESWL/URS levels were compared and correlated with possible tissue damage. According to ESWL procedure we found that serumTNF-a levels were significantly increased after one hour (P<0,001) and after 24hours (P=0.007). Furthermore, IL-6was significantly increased at 2 (P< 0,001), 24 and 48 hours post ESWL (P=0,003 and 0,002) respectively. For URS serum TNF-a levels were statistical significantly correlated preoperatively with one hour (P=0,0083) and 48 hours (P<0,001) after URS and IL-6 with 2 and 24 hours (P<0,001).In 3 patients for URS and 1 for ESWL we observed post procedure fever (>38.5C0). All those patients had preoperatively high values of TNF-a and Il-6 that increased at 1 and 2-hours respectively. We conclude that high pre ESWL/URS levels of serum TNF-a and IL-6 may indicate a predisposition for post ESWL/URS inflammation and infection following URS lithotripsy or ESWL procedure.
Questions to authors
Question 1: Which were the inclusion criteria for your patients?
Negative urine examen, normal blood serum tests, ureter stone in median and upper ureter for ESWL and proximal and median for URS, no anticoagulants, no renal insufficiency, normal ECG.
Question 2: Which is the clinical benefit of the study according to your results for patients undergoing URS or ESWL for their stone disease and are there other similar publications in Greece or worldwide?
The clinical benefit of this study was to identify which patients are predisposed to urinary infection (or/and sepsis) post URS and ESWL regardless of the serum or urine laboratory tests. To my knowledge there are no similar publications in Greece or worldwide.