The role of proangiogenic cytokines in predicting sepsis in febrile neutropenic children with cancer.

BACKGROUND: We assessed the relationship between sepsis occurrence and the serum levels of angiopoietin (Ang-1, Ang-2), vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in pediatric patients with cancer-related febrile neutropenia. METHODS: Fifty-two children with malignant tumors who experienced 86 episodes of febrile neutropenia (FN) were examined between June 2016 and June 2018. Each FN episode was considered a separate event and the total number of FNs were recorded (86 FN episodes = FN group). The control group consisted of 21 healthy children. Ang-1, Ang-2, VEGF-A and sFlt-1 were measured at the baseline and 48th hour of each FN episode -alongside routine characterization of inflammation (C-reactive protein; white blood cell and absolute neutrophil count). RESULTS: Among the episodes, 29 (34.5%) developed sepsis while 57 were classified as non-complicated FN. The baseline values of patients and controls were significantly different for Ang-1, Ang-2, VEGF and sFlt-1 values (all, p < 0.05). In the subgroup with sepsis, Ang-2 values were higher than in the subgroup without sepsis (p = 0.017). In predicting sepsis, Ang-2 had 60.7% sensitivity and 66.7% specificity at the 74.6 cut-off value (AUC: 0.662 [95%CI: 0.541 - 0.783], p = 0.022), Ang-2 / Ang-1 ratio had 65.5% sensitivity and 60.0% specificity at the 0.405 cut-off value (AUC: 0.633 [95%CI: 0.513 - 0.753], p = 0.046). CONCLUSIONS: Our results reveal that Ang-2 and Ang-2/Ang-1 were higher in the sepsis group and Ang-2 might be a biomarker to indicate the risk of sepsis in patients with FN and/or cancer.

Serum interleukin-33 and soluble suppression of tumorigenicity 2 in pediatric leukemia with febrile neutropenia.

The purpose of this study was to evaluate the association between interleukin-33 (IL-33) and its receptor Soluble Suppression of Tumorigenicity-2 (sST2) levels and bacterial infections during febrile neutropenia (FN) in pediatric patients with acute lymphoblastic leukemia (ALL). In this prospective, case-control study, participants were divided into 3 groups: ALL patients with FN (Group A), ALL patients without neutropenia and fever (Group B), and healthy children without infection and chronic disease (Group C). There were 30 cases in each group. Blood samples for IL-33 and sST2 have been drawn from patients in Group A before the initiation of treatment and on days 1 and 5 of treatment, and from patients in Groups B and C at initiation. At admission, mean IL-33 level (39.02 ± 26.40 ng/L) in Group B and mean sST2 level (185.3 ± 371.49 ng/ml) in Group A were significantly higher than the other groups (p = 0.038, p < 0.001, respectively). No difference was observed in the mean IL-33 and sST2 levels in the 5-day follow-up of patients in Group A (p = 0.82, p = 0.86, respectively). IL-33 and sST2 levels were not associated with fever duration, neutropenia duration or length of hospitalization. While C-reactive protein (CRP) was significantly higher in patients with positive blood culture (p = 0.021), IL-33 (p = 0.49) and sST2 (p = 0.21) levels were not associated with culture positivity.  Conclusion: IL-33 and sST2 levels were not found valuable as diagnostic and prognostic markers to predict bacterial sepsis in patients with FN. What is Known: • Neutropenic patients are at high risk of serious bacterial and viral infections, but the admission symptom is often only fever. • Febrile neutropenia has a high mortality rate if not treated effectively. What is New: • Febrile neutropenia is not only caused by bacterial infections. Therefore, new biomarkers should be identified to prevent overuse of antibiotics. • Specific biomarkers are needed to diagnose bacterial sepsis in the early phase of febrile neutropenia.

Evaluation of coagulation parameters and impact of transfusion on coagulation in patients with beta thalassemia major.

There have been several studies that have shown that patients with beta thalassemia major are at a higher risk of thrombosis due to the procoagulant activity of thalassemic erythrocytes, decreased liver synthetic function, increased platelet activity and vascular endothelial activation attributed to chronic oxidative stress, although there are no established tests to predict thrombotic risk in TM patients. In this study, we evaluated whether or not the platelet function analyser (PFA-200) and thrombin generation test (TGT) would be useful tools to identify hypercoagulability and risk of thrombosis in thalassemia major patients. The study included 50 patients with thalassemia major and 104 healthy control group. Pretransfusion and posttransfusion PFA-200 and TGT results were compared with control group. We found that median C/ADP and C/EPI values in the thalassemia major group were greater in both the pre and posttransfusion samples than the C/ADP and C/EPI results from the control group. The TGT results showed there was no difference between control group and the results from the thalassemia major group. The TGT and PFA-200 testing did not identify hypercoagulability nor identify clear testing parameters to predict a thalassemia major patient's risk of thrombosis. There may be other mechanisms/causes yet unidentified that could better explain thalassemia major patient's increased risk from thromboembolic events.

Effect of Folic Acid on Cisplatin-Induced Ototoxicity: A Functional and Morphological Study.

OBJECTIVES: The aim of our study was to investigate the effects of folic acid on cisplatin-induced ototoxicity. MATERIALS AND METHODS: Thirty Wistar albino rats were divided into five groups. Group I received intraperitoneal cisplatin (IP) 10 mg/kg/day and IP folic acid 10 mg/kg/day; Group II received IP cisplatin 10 mg/kg/day and IP physiological saline; Group III received IP cisplatin 10 mg/kg/day and intratympanic (IT) folic acid 0.15 mL/day; Group IV received IP cisplatin 10 mg/kg/day and IT physiological saline; and Group V received IT folic acid 0.15 mL/day. Before and after drug administration, plasma homocysteine, folic acid levels, and auditory brainstem evoked responses (ABR) were measured. The rats were then sacrificed, and the inner ears were processed for electron microscopy. RESULTS: The differences of ABR thresholds in Group I compared to Group II were significantly smaller at 4 kHz, 8 kHz, and 16 kHz, whereas they were smaller but not statistically significant at 12 kHz in ABR. The differences of ABR thresholds in Group III compared to Group IV were significantly smaller at 12 kHz, and smaller but not statistically significant at 4 kHz, 8 kHz, and 16 kHz. Cisplatin treatment resulted in the degeneration of the cells of the organ of Corti, stria vascularis, and spiral ganglion. The cells of the organ of Corti, stria vascularis, and spiral ganglion showed a partially preserved morphology in both Group I and Group III. CONCLUSION: Our study results suggests that folic acid is a potential agent in preventing cisplatin-induced ototoxicity.

Test-1 analyzer and conventional Westergren method for erythrocyte sedimentation rate: A comparative study between two laboratories.

BACKGROUND: Measurement of the length of sedimentation reaction in blood (LSRB), also called erythrocyte sedimentation rate (ESR), is a widely used hematology test. This study intends to compare ESR levels measured by Test-1 method and International Council for Standardization in Hematology's (ICSH) reference method, and analyzes the effect of hematocrit (Hct) on ESR results. MATERIAL AND METHODS: A total of 755 patients from 2 hospitals were included in the study, and samples with EDTA were studied by Test-1 method for ESR measurement and total blood count, whereas citrated samples were studied with reference Westergren method. Then, 2 methods were compared. Distribution of ESR results according to the ESR(≤20, >20 mm/h) and Hct(≥35%, <35%) levels and hospital type was analyzed. ESR levels with Hct levels<35% were corrected with Fabry's formula. RESULTS: The mean and SD values for the Test-1 method, reference Westergren method, and corrected ESR measurement were 21.30 ± 18.39, 28.59 ± 25.82, and 24.92 ± 20.58 mm/h, respectively. Within the whole group, the correlation coefficient (r) was .77 (.7-.80) with a significance level P < .001. Passing-Bablok regression analysis of the methods resulted in a regression equation y = 1.00 (95% Cl: 0.43-1.88) + 0.75 (95% Cl: 0.70-0.78)x while the significance of linearity was acceptable (P < .01). All subgroup linear regression analyses revealed that the correlation was acceptable, except ESR > 20 mm/h group, Hct < 35% group, and corrected ESR group (significance level were P > .10). CONCLUSION: The study showed that the role of the hospital and the capacity of testing are important in choosing the instrument for measuring ESR. Furthermore, the patient profile, especially malignancy possibility and Hct level, may be important for instrument selection.

Evaluation of Ischemia-Modified Albumin in Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is considered a chronic gastrointestinal inflammatory disease with unknown etiology. Oxidative stress has been demonstrated to play a critical role in the pathophysiology of IBD. We aimed to investigate the effect of the ischemia-modified albumin (IMA) and CRP levels on the pathophysiology and activities of IBD and its subgroups. METHODS: The study included 39 patients with Crohn's disease (CD) and 41 patients with ulcerative colitis (UC). Thirty-three healthy volunteers participated in the study as the control group. The IMA concentrations were determined by colorimetric method. RESULTS: IMA levels were significantly higher in IBD than in the controls (p = 0.02). In the subgroups of IBD, IMA levels were significantly lower in the control group and CD group than in UC (p < 0.001 and p < 0.001, respectively) while IMA levels were significant higher in the UC when compared with the CD group (p < 0.001). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly higher in the CD group compared to the control group (p < 0.01 and p < 0.02, respectively). CONCLUSIONS: Higher IMA level, which is a marker of oxidative stress in diseases with inflammation, indicates that inflammation and oxidative stress are related in the pathogenesis of IBD.

The Role of Interleukin-33 as an Inflammatory Marker in Differential Diagnosis of Idiopathic Granulomatous Mastitis and Breast Cancer.

INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast disease that can clinically and radiographically mimic breast carcinoma and bacterial mastitis. The aim of this study is to investigate the importance of levels of the inflammation markers, interleukin-33 (IL-33), soluble ST2 receptor of IL-33 (sST2), procalcitonin (PCT), and CRP on differential diagnosis of IGM and breast cancer (BC). METHODS: 25 patients with IGM and 32 patients with primary BC who applied to General Surgery Clinic, and 30 healthy volunteer women with similar demographic condition were enrolled in the study. While the IL-33, sST2, and PCT levels were measured with ELISA method, other biochemical parameters were studied with autoanalyzer. RESULTS: IL-33, sST2 levels were significantly higher in both BC and IGM groups than in control (p < 0.001). More importantly, the IL-33 levels of IGM group were found to be significantly higher when compared to the group with BC (p < 0.001). Accordingly the sST2 levels of the patients with IGM were significantly lower than the patients with BC (p < 0.001). There was no statistical significance between PCT levels BC and IGM groups (p > 0.05). CONCLUSION: The results of our study suggest that measurement of IL-33 and its receptor sST2 levels, alongside radiological studies can help distinguishing IGM from BC. Findings of our study need to be supported with additional studies.

Lower serotonin level and higher rate of fibromyalgia syndrome with advancing pregnancy.

OBJECTIVE: The aim of the study is to investigate the relationship between changes in serotonin levels during pregnancy and fibromyalgia syndrome (FS) and the relationships between FS and the physical/psychological state, biochemical and hormonal parameters, which may be related to the musculoskeletal system. STUDY DESIGN: This study is a prospective case-control study conducted with 277 pregnant women at the obstetric unit of Ankara University Faculty of Medicine, in the period between January and June 2015. FS was determined based on the presence or absence of the 2010 ACR diagnostic criteria and all the volunteers were asked to answer the questionnaires as Fibromyalgia Impact Criteria (FIQ), Widespread Pain Index (WPI), Symptom Severity Scale (SS), Beck Depression Inventory and Visual Analog Scale (VAS). Biochemical and hormonal markers (glucose, TSH, T4, Ca (calcium), P (phosphate), PTH (parathyroid hormone) and serotonin levels) relating to muscle and bone metabolism were measured. RESULTS: In the presence of fibromyalgia, the physical and psychological parameters are negatively affected (p < 0.001). There was no significant difference between the fibromyalgia and control groups in terms of glucose, Ca (calcium), P (phosphorus), PTH (parathyroid hormone), TSH (thyroid stimulant hormone), fT4 (free T4) levels (p = 0.060, 0.799, 0.074, 0.104, 0.797, 0.929, respectively). A reduction in serotonin levels may contribute to the development of fibromyalgia but this was not statistically significant. The Beck Depression Inventory scale statistically showed that increasing scores also increase the risk of fibromyalgia (p <0.001). CONCLUSION: Our study has shown that serotonin levels in women with FS are lower than the control group and that serotonin levels reduce as pregnancy progresses. Anxiety and depression in pregnant women with FS are higher than the control group. The presence of depression increases the likelihood of developing FS at a statistically significant level. Serotonin impairment also increases the chance of developing FS, but this correlation has not been shown to be statistically significant.

Evaluation of proinflammatory cytokine and neopterin levels in women with papillary thyroid carcinoma.

INTRODUCTION: Papillary thyroid cancer is a disease that has been associated with chronic inflammation. The purpose of this study is to measure the production of the proinflammatory cytokines IL-1ß, IL-6 and IL-8 and neopterin, which is a novel biomarker for cellular immune response in papillary thyroid cancer. MATERIALS AND METHODS: The serum IL-1ß, IL-6, IL-8 and neopterin values of 31 papillary thyroid cancer patients undergoing bilateral total thyroidectomy were measured before and 20 days after surgery. The values were compared with those of 39 healthy controls. RESULTS: Serum IL-1ß levels were similar across groups. IL-6 (p<0.001), IL-8 (p = 0.015) and neopterin levels (p = 0.002) were higher in presurgical samples and returned to normal following surgery. CONCLUSIONS: The proinflammatory cytokines IL-6 and IL-8, but not IL-1ß, were produced in greater amounts in papillary thyroid cancer. Serum neopterin seems to be a valid biological marker supporting the presence of papillary thyroid cancer.

Muscle strength, motor performance, cardiac and muscle biomarkers in detection of muscle side effects during and after acute lymphoblastic leukemia treatment in children.

Muscle side effects have not been frequently assessed in childhood acute lymphoblastic leukemia (ALL) patients. Our objective was to determine the early and late muscle side effects during childhood ALL treatment. To this end, we examined the early muscle side effects in 15 newly diagnosed "therapy patients" (group I), and the late side effects in 18 ALL survivors "off therapy patients" (group II). Muscle side effects were assessed by measuring hand grip strength (HGS), the "timed up and go" (TUG) test, creatine phosphokinase, myoglobin, plasma electrolytes, cardiac troponin I before and after induction chemotherapy in group I. The same parameters and cranial radiotherapy dose were examined in group II at a single timepoint. Cumulative doses of chemotherapy were calculated, and echocardiograms were obtained for each group. As a result, we found that the HGS and TUG measures of group I at the end of induction were poorer than measures of the first admission, control subjects, and group II. Low HGS measures had been normalized over time, but the TUG measures remained poor. Overt rhabdomyolysis and pyomyositis were not detected in any of the patients. These results suggested that muscle side effect monitoring might be helpful in the follow-up of children with ALL.

A feasible shortcut for the mobilization outcome: Steady state CD34 positive hematopoietic stem cells.

Predicting success of hematopoietic cell mobilization is an important issue for transplant physicians. We examined the steady state peripheral blood CD34+ cell count to predict ability to mobilize adequate hematopoietic progenitor cells in 63 myeloma and lymphoma patients. The median steady state CD34+ cell number was 1.56/µL (0.03-5.76). Although counting steady state CD34+ is definitely cost effective to predict the successful mobilization, we could not find a threshold steady state CD34 count of any value predicting successful mobilization.