M. Serban

Ponderas Hospital, Bucureşti, Bucureşti, Romania

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Publications (62)66.23 Total impact

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    ABSTRACT: DCs are potent APCs and key regulators of innate and adaptive immunity. After allo-SCT, their reconstitution in the peripheral blood (PB) to levels similar to those in healthy individuals tends to be slow. We investigate the age- and sex-dependant immune reconstitution of myeloid (mDC) and plasmacytoid DC (pDC) in the PB of 45 children with leukaemia or myelodysplastic syndrome (aged 1-17 years, median 10) after allo-SCT with regard to relapse, acute GVHD (aGVHD) and relapse-free survival. Low pDC/μL PB up to day 60 post SCT are associated with higher incidence of moderate or severe aGVHD (P=0.035), whereas high pDC/μL PB up to day 60 are associated with higher risk of relapse (P<0.001). The time-trend of DCs/μL PB for days 0-200 is a significant predictor of relapse-free survival for both mDCs (P<0.001) and pDCs (P=0.020). Jointly modelling DC reconstitution and complications improves on these simple criteria. Compared with BM, PBSC transplants tend to show slower mDC/pDC reconstitution (P=0.001, 0.031, respectively), but have no direct effect on relapse-free survival. These results suggest an important role for both mDCs and pDCs in the reconstituting immune system. The inclusion of mDCs and pDCs may improve existing models for complication prediction following allo-SCT.Bone Marrow Transplantation advance online publication, 10 November 2014; doi:10.1038/bmt.2014.257.
    Bone marrow transplantation. 11/2014;
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    ABSTRACT: Haemophilic arthropathy is a defining feature and a debilitating condition of persons with haemophilia (PwH) in low resource countries. Orthopaedic surgery is unavoidable for patients with high occurrence of joint damage.
    Hämostaseologie. 11/2014; 34 Suppl 1:S35-6.
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    ABSTRACT: The ability to switch between coagulation factors safely is of common interest to haemophilia patients and treating physicians. This is the first formal prospective comparative evaluation of safety, efficacy and incremental recovery of a plasma-derived FIX (pdFIX) and a recombinant FIX (rFIX) in the same haemophilia B patients following a switch from pdFIX Immunine® to a recently developed rFIX Bax326 product. Patients (aged <65 years) who completed a pretreatment study which prospectively documented the exposure to Immunine® and monitored FIX inhibitors while receiving prophylactic treatment were transitioned into pivotal (patients aged 12–65 years) and paediatric (patients aged <12 years) clinical studies investigating prophylaxis and treatment of bleeding episodes with Bax326. None of the 44 patients developed inhibitory or specific binding anti-FIX antibodies during the course of the studies. A total of 38 unrelated adverse events (AEs) were occurred in 20/44 (45.5%) subjects during the Immunine® study. Following a switch to Bax326, 51 AEs were reported in 25/44 (56.8%) subjects. The incidence of AEs related to Bax326 treatment (two episodes of dysgeusia in one patient) was low (2.3%); there were no serious adverse reactions. The comparison between Immunine® and Bax326 demonstrated analogous haemostatic characteristics and annualized bleeding rates. Overall, there is direct evidence indicating a safe and clinically effective transition from a pdFIX (Immunine®) to a newly developed rFIX (Bax3261) for prophylaxis and treatment of bleeding in previously treated patients of all age cohorts with severe or moderately severe haemophilia B.
    Haemophilia 04/2014; · 3.17 Impact Factor
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    ABSTRACT: To date, few publications report on dendritic cells values in healthy children and mostly are found as control groups in studies focused on either allergic and autoimmune diseases or malignancies. This report provides an overview of 8 publications regarding absolute dendritic cells quantification in the peripheral blood of healthy children by using minimum manipulated samples processed within 24 hours.
    Klinische Pädiatrie 10/2013; · 1.90 Impact Factor
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    ABSTRACT: Obesity is accompanied by increased arterial stiffness, left ventricular (LV) hypertrophy, and diastolic dysfunction, all associated with a negative prognosis. The evolution of LV mass, function, and arterial elasticity after laparoscopic sleeve gastrectomy (LSG) was unknown, and this is what we have investigated. Thirty-four consecutive obese subjects (mean age, 39 ± 11 years; 35.2 % men), scheduled for LSG, were studied before, at 6 and 12 months after surgery. The body mass index (BMI) decreased from 43.6 ± 11.9 to 32.1 ± 7.4 and to 28.9 ± 5.8 kg/m(2) at 6 and 12 months after surgery (all p < 0.05). The baseline LV mass index was correlated with age, BMI, waist circumference, blood glucose level, systemic hypertension stage, and with aortic distensibility, strain, and stiffness index (all p < 0.05). Aortic distensibility increased by 110 %, aortic strain by 58 %, and aortic stiffness index decreased by 88 % at 6 months after LSG (all p 6 months-baseline < 0.05) and all the parameters had similar values at 12 months postoperatively (all p 12-6 months = NS). LV hypertrophy prevalence decreased from 61.8 to 47.1 % and to 32.3 % at 6 and 12 months after surgery (all p < 0.05). The proportion of patients with LV diastolic dysfunction decreased from 52.9 to 23.5 % at 6 months (p 6 months-baseline < 0.01) and to 20.6 % at 12 months postoperatively (p 12 -6 months = 0.7). Significant improvements of aortic elasticity and of LV diastolic function were recorded at 6 months, and they were maintained at 12 months after LSG. The LV hypertrophy showed also a favorable evolution: it has been slightly improved 6 months after surgery and further ameliorated 1 year postoperatively.
    Obesity Surgery 10/2013; · 3.10 Impact Factor
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    ABSTRACT: The aim of this study was to determine the clinical conditions of patients with haemophilia within Europe as recommended by the European Commission. In this multicentre, cross-sectional, ambispective study, conducted within 21 European countries patients' clinical data were collected, amongst others haemophilia type, severity, treatment pattern, use of factor products, bleeding, orthopaedic joint scores and infections. A total of 1400 patients, 84.3% with haemophilia A and 15.7% with haemophilia B were enrolled by 42 centres between 2004 and 2006. Thereof, 417 were children (30.0%) and 983 were adults (70.0%). About 70% of patients had severe factor deficiency (<1%). More than half of the adults were carriers of chronic infections (12.6% HIV, 55.8% HCV), compared to only 3.8% children (no HIV, 2.9% HCV). Patients were grouped according to per capita amount of clotting factor used in patients' region of residence in 2005: region 1: >5 IU; region 2: 2-5 IU; region 3: <2 IU. Paediatric and adult patients in region 3 had median numbers of three and eight joint bleeds, respectively, with worse joint scores compared to region 1 with zero and one bleed. Prophylactic therapy was used in only 31.3% children and 8.9% adults with severe haemophilia in region 3 compared to 93.7% and 54.1%, respectively, in region 1. Statistical analysis revealed that residence in areas with low factor consumption/availability is the most prominent risk factor for joint disease. Access of European patients with haemophilia to optimal care with safe factor VIII concentrates is limited and depends on the region of residence.
    Haemophilia 05/2012; 18(5):729-37. · 3.17 Impact Factor
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    ABSTRACT: Haemophilia, a lifelong congenital bleeding disease, is a highly demanding disorder, due to the costs of its replacement therapy. In the absence of this pivotal treatment, life expectancy and quality of life are deleteriously affected. As illustration, we present a 14 years long follow-up of a patient with severe haemophilia A, treated sporadically with fresh plasma, cryoprecipitate and factor concentrates, who developed a giant iliopsoas pseudotumor. Since he was an infant, under on demand therapy with fresh frozen plasma, cryoprecipitate and low doses of factor concentrates he presented many spontaneous bleedings, developing multiple disabling arthropathies. At the age of 14 years, an iliopsoas hematoma occurred, which relapsed several times, developing an iliopsoas pseudotumour. After 5 years, sepsis with Klebsiella was diagnosed. A CT scan revealed fistula between the pseudotumor and the gut. Under antibiotics, the evolution of sepsis improved, but over a period of 10 months 5 episodes of haematemesis and melena, followed by one episode of macroscopic haematuria occurred; two months later he developed an inguino-crural mass, which fistulized through the abdominal wall. A mixt german-romanian team solved the clinical concern. After 108 hospitalization days and consumption of 104840 IU factor VIII he left the clinic in good condition. One year later, the temporary colostomy with anus praeter was closed. The follow-up reveals now, after almost 10 years with favourable outcome, that the patient is well, active within his family and profession.
    Hamostaseologie 01/2012; 32 Suppl 1:S43-4. · 1.59 Impact Factor
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    ABSTRACT: A number of 513 consecutive patients (494-haemophilia A and 19-haemophilia B) from eight haemophilia treatment centers have been investigated with Bethesda assay for the presence of factor VIII or IX inhibitors. The overall prevalence of inhibitors was 15.20%, 18.48% in severe, 5.60% in moderate and 12.24% in mild forms. The prevalence was higher than reported in most of the western countries. The age at start of substitution (p = 0.9775), the frequent switching of factor concentrates (p = 0.8931) were not relevant factors for the development of inhibitors. It is worth to be mentioned the unexpectedly occurrence of inhibitors in prior inhibitor negative (6/72) patients (during surgical interventions) probably due to their previous scarce substitution, occurrence which seems not being connected with the continuous infusion modality of factor VIII administration (p = 0.8341). In controversial situations, in the field of low titer (≤ 1 BU/ml) inhibitors for a reliable interpretation of the results the performance of recovery index and half-life time assessment of FVIII/IX was undertaken.
    Hamostaseologie 11/2011; 31 Suppl 1:S20-3. · 1.59 Impact Factor
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    ABSTRACT: Portopulmonary hypertension is a form of pulmonary arterial hypertension that has gained interest in recent years with the development of liver transplantation techniques and new pulmonary vasodilator therapies. Portopulmonary hypertension is defined as pulmonary artery hypertension associated with portal hypertension with or without advanced hepatic disease. Echocardiography plays a major role in screening for portopulmonary hypertension but right heart catheterization remains the gold standard for diagnosis. The treatment of patients with portopulmonary hypertension consists of general measures that apply to all patients that carry the diagnosis of pulmonary hypertension and specific vasodilator therapies. These new therapies showed encouraging results in patients who would otherwise have a contraindication for liver transplantation. The review presents a summary of the current knowledge on the epidemiology, diagnosis, treatment and prognosis of patients with portopulmonary hypertension.
    European Journal of Internal Medicine 10/2011; 22(5):441-7. · 2.30 Impact Factor
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    ABSTRACT: Plasma-derived factor IX (FIX) concentrate remains an important choice for replacement therapy in haemophilia B patients. Haemonine is a high purity double-virus inactivated human plasma-derived coagulation FIX concentrate (pdFIX). Aim was to evaluate the clinical efficacy, safety and pharmacokinetic properties of Haemonine in three prospective, open-label uncontrolled studies and a compassionate use program in previously treated patients with severe haemophilia B. Long-term efficacy and safety were investigated in 29 patients treated prophylactically and, in addition, treatment on-demand (TOD) in the case of acute haemorrhage. Pharmacokinetic properties were assessed in 14 patients at baseline and after 3 months of regular treatment. Pharmacokinetic parameters were in accordance with published data and remained nearly unchanged over time, notably recovery and half-life. Mean terminal elimination half-life was 27.6 h and 25.0 h, mean incremental recovery (IU dL(-1) /IU kg(-1)) was 1.55 and 1.60, at baseline and 3 months, respectively. Haemonine was shown to be effective in preventing and controlling bleeds. 55.2% (16/29) of patients were free of bleeds under prophylaxis. 38 haemorrhages occurred, 42% (16/38) required treatment and 87.5% (14/16) resolved after a single infusion, 12.5% after 2 infusions. All responses reported on haemorrhages were rated as 'excellent' or 'good'. Moreover, 'excellent' haemostatic efficacy was demonstrated in 12 surgeries with no complications. Few adverse events (AEs) and no thrombogenic complication, nor induction of FIX inhibitory antibodies were observed. Haemonine is effective, safe and well tolerated in long-term prophylaxis, TOD and when applied after minor and major surgeries.
    Haemophilia 08/2011; 18(2):175-81. · 3.17 Impact Factor
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    ABSTRACT: Purpose To describe the enzymatic profile of plasma matrix metalloproteinases (MMP7 and MMP9) and their tissue inhibitors (TIMP1 and TIMP2) in different categories of patients (pts.) with coronary artery disease (CAD), and their relationship with clinical status, left ventricular (LV) function and remodelling. Methods Total MMP7, active fraction of MMP9, TIMP1 and TIMP2 were determined in 68 consecutive pts with confirmed CAD (Group A, 56.6 ± 9.9 years, 75% men) and compared with a control group of 23 pts. with normal coronary arteries (Group B, 58.1 ± 10.7 years, 56.5% men). LVEF was calculated by Simpson's method. We calculated global longitudinal (L), circumferential (C) and radial (R) strain (S) and strain rate (SR) values as the average of segmental values by 2D strain analyses. Results The active form of MMP9 differed significantly between group A and B, as did the MMP9/TIMP1 and MMP9/TIMP2 ratios (8.78 ± 10.0 ng/ml vs 3.33 ± 4.0 ng/ml p = 0.016; 5.43 ± 3.4 v 0.85 ± 0.9, p = 0.039 and 11.60 ± 5.2 v 3.71 ± 1.0, p = 0.022, respectively). Group A included 35 pts. with acute coronary syndromes (ACS) and 33 pts. with stable angina (SA), with similar profile of LVEF and number of coronary arteries involved. The were no significant differences in MMP9, MMP9/TIMP1 and MMP/TIMP2 ratio between normal and SA group, but only between normal and ACS group (p = 0.02 for MMP9). In group A, only MMP7, TIMP1/MMP7 and TIMP2/MMP7 ratio corellated with markers of systolic function: LVEF (p<0.05 for all), and global LS (r = 0.31, r = 0.40, r = 0.23, p = 0.023, respectively, p<0.05 for all). There were no significant correlations between MMP or TIMP and global C and R-S or SR. Conclusion There were no significant changes in extracellular matrix markers in pts. with chronic stable ischemia vs normals. Only active form of MMP9 and its ratio with TIMP differed significantly in ACS. Total MMP7 and its ratio with TIMP correlated with parameters of LV systolic function even in pts. with normal LVEF.
    Archives of Cardiovascular Diseases Supplements 01/2011; 3(1):16-16.
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    ABSTRACT: To describe the enzymatic profile of plasma matrix metalloproteinases (MMP-7 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in different categories of patients (pts.) with coronary artery disease (CAD), and their relationship with clinical status, left ventricular (LV) function and remodelling. Total plasma MMP7, active fraction of MMP9, TIMP1 and TIMP2 were determined in 68 consecutive pts with confirmed CAD (Group A, 56.6 +/- 9 y, 75% men, LVEF 56.4 +/- 11%) and compared with a control group of 23 pts. without cardiovascular disease and normal coronary arteries (Group B, 58.1 +/- 10 y, 56.5% men, LVEF 58.7 +/- 5%). LVEF and wall motion index (WMI) were computed. Diastolic function parameters were evaluated: mitral E/A ratio, E/E'septal ratio. We calculated global longitudinal (L), circumferential (C) and radial (R) strain (S) and strain rate (SR) values as the average of segmental values, by 2D strain analysis. The active form of MMP9 differed significantly between group A and B, as did the MMP9/TIMP1 and MMP9/TIMP2 ratios (8.78 +/- 10.0 ng/ml vs 3.33 +/- 4.0 ng/ml; 5.43 +/- 3.4 vs 0.85 +/- 0.9, and 11.60 +/- 5.2 vs 3.71 +/- 1.0, respectively, p < 0.04 for all). Group A included 35 pts. with acute coronary syndromes (ACS) and 33 pts. with stable angina (SA), with similar profile of LVEF and number of coronary arteries involved. There were no significant differences in plasma MMP9, MMP9/TIMP1 and MMP/TIMP2 ratio between normal and SA group, but only between normal and ACS group (p = 0.02 for MMP9). In group A, only MMP7, TIMP1/MMP7 and TIMP2/MMP7 ratio correlated with markers of systolic function: LVEF, WMI and global LS. There were no significant changes in extracellular matrix markers in pts. with chronic stable ischemia vs normals. Only active form of MMP9 and its ratio with TIMP differed significantly in ACS. Total MMP7 and its ratio with TIMP correlated with parameters of LV systolic function even in pts. with normal LVEF.
    Romanian journal of internal medicine = Revue roumaine de médecine interne 01/2010; 48(2):141-9.
  • Archives of Cardiovascular Diseases Supplements 01/2010; 2(1):105-106.
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    ABSTRACT: Treatment of haemophiliacs with inhibitors is of great concern in low-income countries confronting shortage in substitutive treatment. Invasive interventions on these patients represent a major challenge due to the fact that costs are significantly higher in comparison to similar procedures conducted on patients without inhibitors. Objective: In the context of insufficient availability of clotting factor, we aimed at highlighting the experience of surgical treatment in inhibitor patients. We analyzed the indications, types of performed interventions and outcomes. Patients, methods: This single center, retrospective analysis has been conducted on 7 inhibitor patients registered and treated in Haemophilia Center of Timisoara over ten years (1997-2007): six patients with severe hemophilia A (3 - high titer, 3 - low titer), one patient with von Willebrand disease (low titer).Three patients developed inhibitors only after 2-5 days post surgery. Results: A total of 15 invasive procedures were carried out: 2 orthopedic interventions (1 arthrodesis, 1 arthroscopic synovectomy), 2 urogenital interventions (1 surgical testicular detorsion, 1 orchiectomy), 4 limb amputations (2 bilateral upper and 2 lower limb amputation), 2 pseudotumour (PT) surgery interventions, 5 drainages (2 massive pyohaemothorax, 1 drainage of shank haematoma, 1 drainage of compressive forearm haematoma, 1 drainage of thigh haematoma). Haemostasis was achieved in patients with low level inhibitors (< 5 BU/ml) with high doses of FVIII concentrates; in those with high inhibitor level (> 5 BU/ml), surgery was managed using by-passing agents. Supplementation with local fibrin glue and intravenous or local antifibrinolytic agents was given in 68.75% of interventions. Postoperative complications consisted of haemorrhagic shock in 13.33% of interventions and infection in 6.66%. Haemostatic outcome was evaluated by blood loss and duration of treatment, compared to expectations for non-inhibitor patients. The outcome was excellent and good in 66.66% of interventions, and fair in 33.33%. Discussion, conclusion: Indication of invasive procedures in haemophiliacs with inhibitors was limited to life and/or limb-threatening situations. In low-income countries, inhibitor and recovery of FVIII monitoring is mandatory in the postoperative follow-up of patients with low or no substitution prior to surgery due to false negative results at the preoperative investigation.
    Hamostaseologie 10/2009; 29 Suppl 1:S39-41. · 1.59 Impact Factor
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    ABSTRACT: Adiponectin may play an important role in the interplay between metabolic changes and cardiovascular risks. Our aim was to establish if plasma adiponectin can be used to detect the metabolic syndrome (MetS) in women without a history of major cardiovascular events and to evaluate its correlation with the global cardiovascular risk expressed by the Reynolds risk score (RRS). 148 consecutive women without a history of cardiovascular events with or without MetS have been investigated. Clinical risks factors as well as plasma levels of lipids, fasting glucose and adiponectin were determined. As expected, circulating adiponectin was lower in women with MetS: 26.8 +/- 20.4 versus 44.3 +/- 26.7 microg/ml (p < 0.001) and inversely related to the number of MetS features (r = -0.33, p < 0.001). The latter was further associated with the total cardiovascular risk calculated using RRS (r = 0.49, p < 0.001). However, there was no relationship between circulating adiponectin and this score (r = -0.14, p = NS). Plasma adiponectin levels are significantly lower in women with MetS, but as a stand-alone tool plasma adiponectin may be of little value in the diagnosis MetS. Circulating adiponectin levels are not associated with the global cardiovascular risk calculated using RRS.
    Cardiology 10/2009; 115(1):64-70. · 1.52 Impact Factor
  • Ejc Supplements - EJC SUPPL. 01/2009; 7(2):230-230.
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    ABSTRACT: Introduction: European Study of Clinical, Health economic and Quality of Life outcomes in Haemophilia treatment (ESCHQoL) - Analysis of resource consumption Background: Determination of resource consumption is the basic information for health economic analyses. In this study resource consumption associated with haemophilia was measured and quantified. Methods and Patients: ESCHQoL was designed as a retrospective/prospective multicentre, multinational cohort study. Patients (pts) were consecutively enrolled. This analysis focused on data from patient diaries. Results: 1,073 diaries were analyzed(752 adults: 35.6 ± 14.2 years; 321 children: 10.6 ± 3.5). 549 adults, 213 children with severe haemophilia. 55% pts had in 6 months on average 8 Comprehensive Care Center visits, 30% pts consulted 5-times their GP. In 6 months 17% pts were hospitalised (8.0 days on average). 19% pts had physiotherapy, on average 15-times in 6 months. 344 pts had 15 days, 27% care givers on average 14 days lost of productivity in 6 months. Mean factor consumption for adults varied from approx. 400 IU per kg/year up to 4.000 IU per kg/year. Children: mean values ranged from 500 IU per kg/year up to 6.600 IU per kg/year. Conclusion: ESCHQoL showed that high resource consumption is associated with haemophilia. Factor use varies between European countries. These results are the basis for future cost analyses and discussions on resource allocation.
    Journal of thrombosis and haemostasis. 01/2009; 7(Suppl. 2):810-810.
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    ABSTRACT: Clinical expression of inadequately treated haemophilia is dominated by orthopedic complications, requiring invasive or non-invasive interventions. In Romania, with under dosed and late introduced "on demand" substitution, we aimed at highlighting the experience of orthopedic treatment and its outcome. Single center retrospective analysis regarding orthopedic interventions and their outcomes was conducted on 59 hemophilia A, B, and von Willebrand disease patients, between 2002 and 2007. The majority of interventions, invasive (60.71%) and non-invasive (39.28%), were elective, only two being emergencies. Postoperative functional evolution after synovectomies was good in 68.28%, fair in 24.39%, satisfactory in 7.31%. Results of 33 non-invasive (extensive releases) procedures were very good in 27.27%, good in 63.63%, poor in 9.09%. DISCUSSION, CONCLUSIONS: The important number and complexity of orthopedic interventions are proving the precarious musculoskeletal state in persons with hemophilia, demonstrating the need of improving substitution, at least with discontinue prophylaxis in patients with severe forms.
    Hamostaseologie 11/2008; 28 Suppl 1:S52-4. · 1.59 Impact Factor
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    ABSTRACT: The Shone's complex, defined by four cardiovascular defects such as a supravalvular mitral membrane, valvular mitral stenosis by a parachute mitral valve, subaortic stenosis, and aortic coarctation, is a rare entity, which occurs most frequently in its incomplete form. We report the case of a 19-year-old female patient who presented at the emergency room for progressively worsening dyspnoea, orthopnoea, fever, and productive cough, due to bronchopneumonia. Echocardiography revealed the co-existence of aortic coarctation with bicuspid aortic valves, mitral supravalvular ring, and dysplastic mitral valves producing severe mitral stenosis and severe pulmonary hypertension. Although wide spectrum antibiotics were administered from the first day of hospitalization, the patient developed severe sepsis and died. The components of the Shone's complex diagnosed by echocardiography were confirmed at pathology.
    European Heart Journal – Cardiovascular Imaging 08/2008; 9(6):865-7. · 3.67 Impact Factor
  • Ultraschall in Der Medizin - ULTRASCHALL MED. 01/2008; 29.

Publication Stats

52 Citations
66.23 Total Impact Points

Institutions

  • 2013
    • Ponderas Hospital
      Bucureşti, Bucureşti, Romania
  • 2012
    • Ludwig-Maximilian-University of Munich
      • Department of Transfusion Medicine, Cell Therapeutics and Haemostasis
      München, Bavaria, Germany
  • 2007–2012
    • Victor Babes University of Medicine and Pharmacy of Timisoara
      Freidorf, Timiş, Romania
  • 2011
    • Spitalul Clinic de Urgenta pentru Copii Louis Turcanu Timisoara
      Freidorf, Timiş, Romania
  • 2006–2011
    • Prof. Dr. C.C. Iliescu Institute for Emergency Cardiovascular Diseases
      Bucureşti, Bucureşti, Romania
  • 2002–2009
    • Carol Davila University of Medicine and Pharmacy
      • Faculty of Medicine
      Bucureşti, Bucureşti, Romania
    • Spitalul Universitar de Urgenta Bucuresti
      Bucureşti, Hunedoara, Romania