Comparison of fungemia caused by Candida and non-Candida rare yeasts: a retrospective study from a tertiary care hospital.

Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these yeast infections is recognized, current epidemiological information about these pathogens is limited, and they have variable antifungal susceptibility profiles. In this study, we aimed to evaluate the clinical characteristics for fungemia caused by NCY by comparing with candidemia. The episodes of NCY fungemia between January 2011 and August 2023 were retrospectively evaluated in terms of clinical characteristics, predisposing factor, and outcome. In addition, a candidemia group, including patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to the reference method. A total of 85 patients with fungemia episodes were included: 25 with NCY fungemia and 60 with candidemia. Fluconazole had high minimal inhibitory concentration (MIC) values against almost all NCY isolates. The MIC values for voriconazole, posaconazole, and amphotericin B were ≤ 2 µg/ml, and for caspofungin and anidulafungin were ≥ 1 µg/ml against most of isolates. Hematological malignancies, immunosuppressive therapy, neutropenia and prolonged neutropenia, polymicrobial bacteremia/fungemia, preexposure to antifungal drugs, and breakthrough fungemia were associated with NCY fungemia, whereas intensive care unit admission, diabetes mellitus, urinary catheters, and total parenteral nutrition were associated with candidemia. In conclusion, the majority of fungemia due to NCY species was the problem, particularly in hematology units and patients with hematological malignancy. Preexposure to antifungal drugs likely causes a change in the epidemiology of fungemia in favor of non-albicans Candida and/or NCY.

Among all fungemia episodes, hematological malignancies, immunosuppressive therapy, neutropenia, and preexposure to antifungals were risk factors for non-Candida yeast fungemia; diabetes mellitus, urinary catheters, and total parenteral nutrition were risks for candidemia.

Plasma exchange in acute hemolytic reaction due to ABO-incompatible erythrocyte concentrate transfusions: Single center experience.

OBJECTIVES: Acute hemolytic transfusion reaction (AHTR) due to ABO-incompatible erythrocyte concentrate (EC) is one of the most catastrophic complications of transfusion. Since the hemolysis is intravascular; hemoglobinemia and hemoglobinuria result in disseminated intravascular coagulation (DIC), acute renal failure, shock, and sometimes death. BACKGROUND: Treatment of AHTR is mostly supportive measures. Today there are no clear suggestions about plasma exchange (PE) in these patients. METHODS/MATERIALS: Here we report our experience with six patients diagnosed with AHTR due to ABO-incompatible EC transfusion. RESULTS: We performed PE in 5 of these patients. Although all of our patients were geriatric and most of them had significant comorbidities four out of five patients recovered without an incident. CONCLUSION: Although PE is considered a last-chance treatment when other measures fail in the literature, our experience above indicates that it must be evaluated in every patient with AHTR early in the course. If the patient has cardiac and renal comorbidities, large volume EC is transfused, DAT is negative, plasma color is red and there is macroscopic hemoglobinuria, we suggest performing PE.

An Anomaly with Potential as a New Prognostic Marker in CLL with del(13q): Gain of 16p13.3.

Deletion 13q [del(13q)] is a favorable prognostic marker if it is detected as a sole abnormality in chronic lymphocytic leukemia (CLL). However the clinical courses of cases with isolated del(13q) are quite heterogeneous. In our study, we investigated copy number variations (CNVs), loss of heterozygosity (LOH), and the size of del(13q) in 30 CLL patients with isolated del(13q). We used CGH+SNP microarrays in order to understand the cause of this clinical heterogeneity. We detected del(13q) in 28/30 CLL cases. The size of the deletion varied from 0.34 to 28.81 Mb, and there was no clinical effect of the deletion size. We found new prognostic markers, especially the gain of 16p13.3. These markers have statistically significant associations with short time to first treatment and advanced disease stage. Detecting both CNVs and LOH at the same time is an advantageous feature of aCGH+SNP. However, it is very challenging for the array analysis to detect mosaic anomalies. Therefore, it is very important to confirm the results by FISH. In our study, we detected approximately 9% mosaic del(13q) by microarray. In addition, the gain of 16p13.3 may affect the disease prognosis in CLL. However, additional studies with more patients are needed to confirm these results.

Rotational Thromboelastometry Profile in Children With Chronic Spontaneous Urticaria.

The pathogenesis of chronic spontaneous urticaria (CSU) is incompletely understood. There is a growing interest in the role of the coagulation cascade in chronic urticaria. Rotational thromboelastometry (ROTEM) assay enables the global assessment of coagulation status. In the present study, we aimed to test the coagulation profile in children with CSU using ROTEM and correlate these parameters with those of a healthy group. A total of 24 children with active CSU (11 girls and 13 boys) 8 to 17 years of age and age-matched and sex-matched 30 healthy control participants were enrolled in the study. ROTEM assays (intrinsic thromboelastometry and extrinsic thromboelastometry) were used to measure and analyze coagulation time, clot formation time, and maximum clot firmness. The CSU patients and controls did not differ in age, sex, erythrocyte, neutrophil, and platelet counts. Also, ROTEM parameters did not show any difference between the 2 groups. ROTEM is increasingly being used as a tool for monitoring coagulation status. In this study, ROTEM parameters did not show any difference between CSU patients and the healthy group. Further studies are needed to confirm our findings on a larger number of CSU patients.

Use of rotational thromboelastometry for a global screening of coagulation profile in patients of myeloproliferative neoplasms.

Chronic myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem/progenitor cell characterized by thrombohemorrhagic complications and a tendency to transform into acute leukemia. The pathogenesis of thrombosis in MPN is complex and results from a multifaceted interplay of clinical and disease-related factors. Rotational thromboelastometry (ROTEM) provides the complete and rapid information about all stages of the coagulation process. Here, we assess ROTEM parameters as a screening of coagulation profile in patients with MPNs. In particular, higher mean maximum clot firmness values were found in Essential thrombocythemia and Polycythemia vera patients when compared to healthy controls. Rotational thromboelastometry may be able to detect MPN patients who are susceptible to thrombotic and/or hemorrhagic complications. The predictive value of ROTEM for thrombosis remains to be established to classify subsets of patients at prominent risk who may benefit from prophylaxis with antithrombotic drugs.

Effect of hyperparathyroidism on coagulation: a global assessment by modified rotation thromboelastogram (ROTEM)

Background/aim: Hyperparathyroidism is an endocrine disorder characterized by hypercalcemia. Because of calcium's effects on parathyroid glands, bone, intestines, and kidneys, it has an important place in homeostasis. The results of studies regarding hyperparathyroidism hemostasis are conflicting. Thromboelastography helps to evaluate all steps of hemostatic system. Our aim in this study was to investigate the possible role of hemostatic mechanisms in the development of thrombosis in hyperparathyroid patients with the modified rotation thromboelastogram (ROTEM). Materials and methods: Twenty-two patients with primary hyperparathyroidism (PHPT) and 20 healthy controls were involved. This study was conducted in Eskisehir Osmangazi University Faculty of Medicine, Endocrinology and Hematology clinics for 2 years. The complete blood count, fibrinogen, D-dimer levels, prothrombin time, activated prothrombin time, and ROTEM parameters [clot formation time (CFT), clotting time (CT), and maximum clot formation (MCF)] were determined by two activated tests, INTEM and EXTEM analyses. A thromboelastographic evaluation was performed in the preoperative and postoperative (3 months after surgery) periods. Results: In INTEM assay, the CT (p = 0.012) and CFT (p = 0.07) values were increased in preoperative PHPT patients compared with the control group. Although there was a decrease in the postoperative CT and CFT values, no statistical difference was found. Conclusion: The prolongation of the CT and CFT values were consistent with a hypocoagulable state in patients with PHPT. Hyperparathyroidism causes a hypocoagulable state that can be successfully assessed by ROTEM. Hemostatic changes, do not seem to have an effect on increased cardiovascular mortality.

Evaluation of the Coagulation Profile With Rotational Thromboelastometry in Children With Hereditary Spherocytosis.

Hereditary spherocytosis (HS) is a familial hemolytic disorder associated with a variety of mutations that lead to defects in red blood cell (RBC) membrane proteins. There is increasing evidence that hypercoagulability occurs in chronic hemolytic anemia. In this study, changes in the coagulation profile in children with HS were investigated using rotational thromboelastometry. A total of 21 children with HS and 28 healthy children were enrolled in the study between October 2010 and October 2018. Complete blood count, prothrombin time, activated partial thromboplastin time, and fibrinogen level were ascertained, while rotational thromboelastometry assays were used to measure and analyze coagulation time, clot formation time, and maximum clot firmness. There was no difference between the 2 groups in terms of age and sex. The values of hemoglobin and RBC in the patient group were statistically significantly lower than those in the control group (P<0.01, <0.0001, respectively), and the values of platelet count, mean corpuscular hemoglobin concentration, and RBC distribution width were statistically significantly higher than those in the control group (P<0.05, 0.001, <0.0001, respectively). There was no statistically significant difference between the 2 groups in terms of prothrombin time, activated partial thromboplastin time, fibrinogen levels, coagulation time, clot formation time, and maximum clot firmness values. In contrast to other chronic hemolytic anemias, no predisposition to hypercoagulability has been shown in the coagulation profile of children with HS without splenectomy.

Circulating endothelial cells in Behçet's disease: is there a relationship with vascular involvement?

OBJECTIVES: Circulating endothelial cells (CEC) are identified in conditions with vascular damage such as systemic vasculitis. Our aim was to investigate if EPC, CEC, and/or its subgroups activated CEC (aCEC) or resting CEC (rCEC) related with vascular involvement in Behçet's disease (BD). METHODS: In total 60 patients were included in this study, divided into 4 groups: 1) Behçet patients with a history of vascular involvement: vascular BD; 2) Behçet patients with mucocutaneus involvement: mucocutaneus BD; 3) patients with history of thrombosis due to other causes: thrombosis; 4) 20 healthy controls were also included: control group. Percentages of CEC, aCEC, rCEC and EPCs in peripheral blood mononuclear cells were measured by flow cytometry. RESULTS: CEC (3.75 (1.80-7.20), 1.80 (0.70-3.53), 3.50 (1.83-7.23), 2.45 (1.28- 4.60)) and aCEC (2.40 (1.28-4.28), 1.10 (0.77-2.20), 3.15 (1.48-7.20), 3.20 (1.15-9.80) levels were did not show a statistically significant difference between groups (p:0.077 and p:0.054, respectively). EPC and rCEC levels were higher in vascular BD and thrombosis groups than mucocutaneus BD and control groups (EPC:10.5 (7.20-18.3), 11.6 (7.30-20.9) vs. 7.15 (5.55-8.25), 10.2 (5.93-18.6), rCEC: 5.35 (3.13-7.90), 6.45 (4.60-10.8) vs. 4.95 (3.05-7.55), 3.40 (1.88-4.30), p:0.042 and p:0.007, respectively). CONCLUSIONS: CEC, EPC, aCEC and rCEC may have role in the assessment of vascular involvement in BD. Longitudinal studies would be needed to identify the utility of these cells for the follow up and risk stratification of BD patients with vascular involvement for recurrences or identify BD patients at risk of vascular involvement.

Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG).

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.

The effect of clinical characteristics on the performance of galactomannan and PCR for the diagnosis of invasive aspergillosis in febrile neutropenic patients.

Rapid diagnosis and early treatment of invasive aspergillosis is crucial for the management of the patients with haematological malignancy. We evaluated 358 sera from 78 febrile neutropenic episodes in patient with invasive aspergillosis (IA) (one proven, 17 probable, and 60 possible) and 83 episodes in patients with no IA according to the EORTC/MSG criteria. Patient's specimens were tested by Mycassay Aspergillus PCR (first commercial real-time PCR test) and in house real-time PCR to investigate the presence of Aspergillus DNA, and by ELISA for detect the galactomannan (GM) antigen. We systematically investigated the medical background that can be effective on the test results. The hospitalisation period was longer in proven/probable episodes when compared with no IA (P = 0.001) and possible episodes. With regard to duration of neutropenia, the differences between both proven/probable with no IA (P = 0.023) and possible with no IA (P = 0.002) were highly significant. Similarly, the rates of T cell suppressant therapy in group proven/probable and possible episodes were significantly higher than in no IA (P = 0.005). There are significant differences in the performance of GM and PCR-based tests among studies, and standardisation is required. Therefore, it can be useful to determine the effective factors on these tests. The use of larger volume of sera improved the performance of real-time PCR for detection of Aspergillus DNA in high-risk adult patients in the present study. Some host factors such as duration of neutropenia and administration of T cell suppressants related to the development of IA.

The utility of thromboelastometry in prophylactic platelet transfusion for hematological malignancies.

There is still debate on how platelet transfusions should be used to prevent severe bleeding. The aim of our study is to assess the clinical efficacy of thromboelastometry in reducing number of prophylactic platelet transfusions in patients with hematological malignancies. One hundred hematological malignancy patients were included in the study. Six units random donor platelets (RDPs) was given to the first group, three units RDPs was given to the second group, one unit single donor platelets (SDPs) was given to the third group, and 1/2 unit SDPs was given to the fourth group. Before and 15 minutes after transfusion, rotation thromboelastometry (ROTEM) was performed (Pentapharm GmbH, Munich, Germany). ROTEM(®) parameters did not show any statistical difference between 'low dose' and 'high dose' random or single donor platelet transfusions. Therefore, low dose platelet transfusion can be considered because of its reduced adverse transfusion reactions and economic burden.

Are the high serum interleukin-6 and vascular endothelial growth factor levels useful prognostic markers in aggressive non-hodgkin lymphoma patients?

OBJECTIVE: Pro-inflammatory and pro-angiogenic cytokines play an important role in the pathogenesis of lymphoma, and recent studies have shown that cytokines can be used as prognostic markers. Non-Hodgkin lymphoma (NHL) patients with high levels of serum interleukin-6 (s-IL6) and serum vascular endothelial growth factor (s-VEGF) have poor prognosis and shorter survival time. We aimed to determine pre-treatment levels of s-IL6 and s-VEGF and their relation with known prognostic markers, especially International Prognostic Index (IPI) scores, and to examine their effects on overall survival in newly diagnosed, untreated aggressive NHL patients. MATERIALS AND METHODS: The study included 51 newly diagnosed NHL patients and 17 healthy controls. Blood samples were obtained to study s-IL6 and s-VEGF cytokine levels. RESULTS: Patients with aggressive NHL diagnosis had higher s-VEGF and s-IL6 levels than the healthy population. If the s-IL6 levels of patients were above the cut-off levels, the overall survival time was shorter. There was no relation between s-VEGF and overall survival time. CONCLUSION: s-IL6 is an independent prognostic factor that may be included in IPI risk classification. In addition to the s-IL6 level, age, erythrocyte sedimentation rate, beta-2 microglobulin, WHO performance status, and IPI score are independent prognostic factors that are effective, especially for overall survival, in the clinical follow-up of NHL patients.

Utility of flow cytometric κ and λ light chain analysis of peripheral blood.

PURPOSE: Monoclonality in the peripheral blood can be shown by flow cytometric analysis of kappa (κ) and lambda (λ) light chain ratio of B lymphocytes. We aimed to show the utility of this method in patients with unknown causes of lymphadenopathy and/or splenomegaly. METHODS: This method was performed in 81 adult patients with undefined causes of lymphadenopathy and splenomegaly. RESULTS: 18 (22%) of these patients had clonality and all of them were diagnosed as B cell lymphoma later. None of the patients with benign causes had clonality in the peripheral blood. We could not find any relationship between presence of clonality and type and stage of lymphoma and bone marrow involvement. CONCLUSION: This method is easy to perform, cheap and non-invasive and yet it can give valuable information about the malignant nature of a suspected disease. If there is a sign of clonality in the peripheral blood, more invasive diagnostic procedures should be performed rather than watch and wait.

Bone marrow examination in patients with immune thrombocytopenia: is there anything different in older patients?

Immune thrombocytopenia (ITP) is a disorder characterised by immune-mediated accelerated platelet destruction and suppressed platelet production. In the bone marrow examinations of patients with ITP, some investigators found megakaryocyte numbers to be increased while others have found them to be normal. Although recent guidelines recommend against bone marrow examinations in typical ITP patients, the recent introduction of thrombopoietin receptor agonists as an effective treatment for ITP has refocused attention on abnormalities of bone marrow megakaryocytes. In this study, we retrospectively analysed the bone marrow aspiration, flow cytometry-CD45 side scatter (SSC) and biopsy results of our patients with ITP by dividing them into two groups according to age (<60 yr and ≥60 yr). Ninety eight newly diagnosed ITP patients were included in the study. CD45 SSC results were recorded as percentages of normoblasts, granulocytes, lymphocytes, monocytes and myeloid/erythroid ratio. Length of the biopsy specimen, cellularity, presence of dysplasia or fibrosis with number, morphology and distribution of megakaryocytes were recorded. In group 1, there were 49 patients. Mean age was 41.31 ± 12.77 yr. In group 2, there were 49 patients. Mean age was 70.78 ± 7.88 yr. Megakaryocyte numbers on bone marrow aspirates were not recorded in most patients, so we could not comment on this point. Flow cytometry results and bone marrow findings were similar between two groups. In conclusion, there is no difference between bone marrow examinations of young and older patients with ITP, and biopsy should not be recommended in typical ITP patients as already mentioned in guidelines.

Cardiac and pulmonary thrombosis during multidrug treatment in an idiopathic thrombocytopenic purpura patient.

Glucocorticosteroids, intravenous immunoglobulins, vincristine, danazol, and eltrombopag are used in refractory chronic idiopathic thrombocytopenic purpura (ITP). All those treatment modalities are susceptible for thrombosis generation. There is an increased risk of thrombosis in the diseases' natural course. The case we present is a resistant chronic ITP patient who developed pulmonary and intracardiac thrombosis during multidrug treatment. Risk of concomitant usage of drugs and rapid increase in platelet count are discussed.

Isolated Granulocytic Sarcoma of the Breast after Allogeneic Stem Cell Transplantation: A Rare Involvement Also Detected by 18FDG-PET/CT.

Granulocytic sarcoma is a tumor consisting of myeloid blasts with or without maturation that occurs at an anatomical site other than bone marrow. Most frequently affected sites are skin, lymph nodes, gastrointestinal tract, bone, soft tissue and testes. AML may manifest as granulocytic sarcoma at diagnosis or relapse. Although it has been considered to be rare relapse as granulocytic sarcoma after stem cell transplantation is being increasingly reported. However it is rare without bone marrow involvement and in AML M6 subtype. Breast is also a rare involvement. We report a 30-year-old woman with AML M6 relapsed 16 months after allogeneic stem cell transplantation as a granulocytic sarcoma in right breast without bone marrow involvement. She was treated with systemic chemotherapy but died of sepsis. 18FDG-PET/CT images were also obtained and detected lesions other than detected by breast ultrasound. The incidence of granulocytic sarcoma may increase if suspected or new diagnostic modalities are performed.

Thrombelastographic evaluation of the influence of 2-RBC apheresis on donor's coagulation system.

Rotation thrombelastogram (ROTEM®/TEG®) assays allow rapid global assessment of hemostatic function using whole blood. Since published data about the effects of automated red cell collection on coagulation system are scarce, we aimed to investigate the effects of 2-RBC apheresis on donor's coagulation system using ROTEM® assays. In INTEM assay, CFT was significantly shortened 24h after apheresis compared with baseline value (p<0.05) and MCF was significantly prolonged immediately after apheresis and 24h after apheresis compared with baseline value (p<0.05 and p<0.01, respectively). In EXTEM assay, CFT was significantly prolonged immediately after apheresis and 24h after apheresis compared with baseline value (p=0.001 and p<0.001, respectively) and MCF was significantly prolonged 24h after apheresis compared with baseline value (p<0,001). Our results demonstrate thromboelastographic signs of hypercoagulability in donors undergoing 2-RBC apheresis.

Abnormality of regulatory T-cells in remission and non-remission idiopathic thrombocytopaenic purpura patients.

Primer immunologic defect in patients with idiopathic thrombocytopaenic purpura (ITP) result from autoreactive B-lymphocytes secreting antiplatelet antibodies. Dysfunctional cellular immunity has also great importance in ITP pathogenesis. CD4(+)CD25(+) regulatory T-cells have immunoregulatory features and it is able to inhibit CD4(+)CD25(-) and CD8(+) responses. ITP is also an autoimmune disease; the CD4(+)CD25(+) T-cell levels of the patients decrease during the active state. According to our findings, immunosuppressive treatments increase the CD4(+)CD25(+) Treg cell levels in the non-remission ITP patients. However, this level is not enough to overcome the resistance. CD4(+)CD25(-)Foxp3(+) and CD4(+)Foxp3(+) Treg cells are responsible for the pathogenesis of the non-remission ITP patients and other factors exist, which are responsible for the resistance of ITP treatment.

Regulatory T cells in Behçet's disease: is there a correlation with disease activity? Does regulatory T cell type matter?

The aim of this study was to investigate the percentage of regulatory T cells and the correlation with clinical activity in Behçet's disease. Forty Behçet's disease (BD) patients, 18 males and 22 females, were included in the study. The patients were diagnosed according to the published BD criteria. Twenty age- and sex-matched volunteer healthy donors were also included. At the time of sampling, clinical activity was assessed for activity signs and symptoms according to the BD Current Activity Form. We considered active those patients with a clinical activity index equal to and/or above 2. Eleven patients had active disease and the remaining were considered as clinically inactive. We have studied the percentages of CD4+CD25+FOXP3+, CD4+CD25+ and CD4+FOXP3+regulatory T cells by flow cytometry and investigated the correlation with disease activity. Percentage of CD4+CD25+FOXP3+Treg in active patients was lower than clinically inactive patients and healthy controls. Percentage of CD4+CD25+Treg was not different between active and inactive patients and healthy controls. Percentage of CD4+FOXP3+Treg was lower than healthy controls in clinically active patients but was not different for inactive group and healthy controls. Patients were active when CD4+CD25+FOXP3+Treg was ≤1.19 %, CD4+CD25+Treg was ≤2.68 %, and CD4+FOXP3+Treg was ≤2.60. CD4+CD25+FOXP3+Treg and CD4+FOXP3+Treg were found negatively correlated with disease activity. Peripheral blood regulatory T cells are decreased in clinically active Behçet's disease patients. The advances in our understanding of the interactions between distinct subsets of Treg and clinical activity might help in modulating BD treatment.

Clinical significance of reticulocyte hemoglobin content in the diagnosis of iron deficiency anemia.

OBJECTIVE: The aim of this study was to evaluate the clinical significance of reticulocyte hemoglobin content (CHr) in the diagnosis of iron deficiency anemia (IDA) and to compare it with other conventional iron parameters. MATERIALS AND METHODS: A total of 32 female patients with IDA (serum hemoglobin <120 g/L and serum ferritin <20 ng/ mL) and 18 female patients with iron deficiency (serum hemoglobin > 120 g/L and serum ferritin <20 ng/mL) were enrolled. RESULTS: CHr was 24.95±3.92 pg in female patients with IDA and 29.93±2.96 pg in female patients with iron deficiency. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, serum iron, and transferrin saturation and a significant negative correlation with transferrin and total iron-binding capacity. The cut-off value of CHr for detecting IDA was 29 pg. CONCLUSION: Our data demonstrate that CHr is a useful parameter that can be confidently used in the diagnosis of IDA, and a CHr cut-off value of 29 pg predicts IDA. CONFLICT OF INTEREST: None declared.