A comparison of hypersensitivity reactions between intravenous and intramuscular applications of native E. coli asparaginase in children with acute lymphoblastic leukemia.

INTRODUCTION: Asparaginase is an indispensable drug in treating childhood acute lymphoblastic leukemia (ALL). Hypersensitivity reactions (HSR) are the most common side effects and interfere with the antineoplastic activity of the drug. This study aims to compare the intramuscular (IM) and intravenous (IV) administration routes of Native Escherichia coli Lasparaginase (L-ASNase) in terms of hypersensitive reactions. METHODS: L-ASNase was randomly administered IV or IM to newly diagnosed ALL patients and HSR was monitored in all patients for 1 h following the end of the IV infusion and for 2 h following the end of the IM administration of L-ASNase. Based on a retrospective review of clinical charts, reactions were identified. In order to determine the severity of each allergic reaction, we used the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for allergic reactions. RESULTS: A total of 1032 doses of L-ASNase were administered to 85 patients (42 males and 43 females) during the study period. Among 85 patients, 30 reactions were recorded, which means that 35% of the patients reacted. According to the CTCAE, twenty-nine out of 30 reactions (97%) were grade 2, while one (3%) was grade 4. In terms of individual doses, there was a non-significant trend toward increased incidence of reactions with IV administration (3.8% versus 0.9%, p = 0.064). The rate of reactions was higher in patients who received all IV doses (n: 60) as compared to those who received all IM doses (n: 25) (31.7% vs. 3.5%; chi-square= 8.415, p value=0.04). Based on the risk groups and HSR incidence, it was found that high risk group (HRG) patients were significantly more likely to develop HSR compared to the standart risk group (SRG) and intermediate risk group (MRG) patients (chi-square p = 0.003, CI: 95%; odds ratio: 3.12 and 5.91, respectively). CONCLUSIONS: In conclusion, IM administration of L-ASNase causes significantly less HSR to L-ASNase than the IV route. Patients with HRGALL have a higher risk of HSR. Since L-ASNase is still used in many developing countries and there are problems in the supply of Erwinia chrysanthemi ASNase (Erwinia), LASNase can be administered IM to reduce the frequency of HSR.

Comparison of bone marrow biopsy and fluorodeoxyglucose-positron emission tomography for the assessment of bone marrow infiltration in children with Hodgkin's lymphoma.

PURPOSE: To compare bone marrow biopsy (BMB) with [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (PET/CT) imaging in the demonstration of bone marrow involvement in children with Hodgkin's Lymphoma (HL) and to investigate the effectiveness of PET/CT imaging and thus the necessity for BMB at staging. METHODS: Pediatric patients with HL, who underwent both bilateral iliac BMB and PET/CT imaging at disease staging were retrospectively analyzed. In determining bone marrow involvement (BMinv), BMB and/or first/follow-up PET/CT imaging were eligible for review. RESULTS: Fifty-six patients were included. BMinv was detected by PET/CT imaging in 6/56 (10.7%), whereas the proportion was 3/56 (5.3%) in BMB specimens. Bone marrow biopsies and PET/CT images were concordant in 53/56 (94.6%) patients with BMB specimens missing three cases of BMinv detected by PET/CT. When diagnostic accuracy was calculated, sensitivity, specificity, positive predictive value and negative predictive values for PET/CT were 100%, 100%, 100%, 100%, respectively, and the same values for BMB were 50%, 100%, 100%, 94.3%, respectively. CONCLUSIONS: The results of PET/CT and BMB for staging of pediatric HL patients were compatible, and PET/CT imaging was found to provide high diagnostic performance in determining BMinv. In keeping with earlier research, the current study showed that BMB may not be necessary in every patient at staging, and should be reserved for cases where PET/CT is inconclusive.

Clinical, imaging and hemodynamic correlates and prognostic impact of syncope in acute pulmonary embolism: A single-center study.

Background: We aimed to determine the clinical, echocardiographic and hemodynamic correlates of syncope as a presenting symptom in pulmonary embolism and its impact on in-hospital and long-term outcomes. Methods: Between July 2012 and October 2019, a total of 641 patients with PE (277 males, 364 females; median age: 65 years; range, 51 to 74 years) in whom the diagnostic work-up and risk-based management were performed according to the current pulmonary embolism guidelines were retrospectively analyzed. Clinical, laboratory and imaging data of the patients were obtained from hospital database system. Results: Syncope was noted in 193 (30.2%) of patients on admission, and was associated with a significantly higher-risk status manifested by elevated troponin and D-dimer levels, a higher Pulmonary Embolism Severity Index scores, deterioration of right-to-left ventricular diameter ratio, right ventricular longitudinal contraction measures, the higher Qanadli score, and higher rates of thrombolytic therapies (p<0.001) and rheolytic-thrombectomy (p=0.037) therapies. In-hospital mortality (p=0.007) and minor bleeding (p<0.001) were significantly higher in syncope subgroup. Multivariate logistic regression analysis showed that higher Pulmonary Embolism Severity Index scores and right-to-left ventricular diameter ratio were independently associated with syncope, while aging and increased heart rate predicted in-hospital mortality. Malignancy and right-to-left ventricular diameter ratio at discharge, but not syncope, were independent predictors of cumulative mortality during follow-up. Conclusion: Syncope as the presenting symptom is associated with a higher risk due to more severe obstructive pressure load and right ventricular dysfunction requiring more proactive strategies in patients with pulmonary embolism. However, with appropriate risk-based therapies, neither in-hospital mortality nor long-term mortality can be predicted by syncope.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

A Rare Lymphoproliferative Disease: Castleman Disease

Castleman disease is a rare lymphoproliferative disease also known as angiofollicular lymph node hyperplasia. It is classified as hyaline vascular and plasmacytic variants histologically but characteristics of both types can coexist. Most unicentric cases of the disease are hyaline vascular while most multicentric cases are of the plasmacytic type. Although the pathogenesis is not completely understood, the role of interleukin (IL)-6 in unicentric disease and the roles of IL-6 and human herpes virus-8 in multicentric disease are well defined. Unicentric disease is typically localized and symptoms are minimal and treated locally. Multicentric disease is systemic and clinically characterized by generalized lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms. Systemic therapies are primarily given. Several malignant diseases including lymphomas, POEMS syndrome, follicular dendritic cell sarcomas, paraneoplastic pemphigus, Kaposi sarcoma, and amyloidosis can be associated with Castleman disease. In this paper, recent information about Castleman disease, which is a rare disease, is summarized.

Temporal association of contamination obsession on the prehospital delay of STEMI during COVID-19 pandemic.

BACKGROUND: One of the modifiable risk factors for ST elevation myocardial infarction is prehospital delay. The purpose of our study was to look at the effect of contamination contamination obsession on prehospital delay compared with other measurements during the Covid-19 pandemic. METHOD: A total of 139 patients with acute STEMI admitted to our heart center from 20 March 2020 to 20 June 2020 were included in this study. If the time interval between the estimated onset of symptoms and admission to the emergency room was >120 min, it was considered as a prehospital delay. The Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and Padua Inventory-Washington State University Revision (PI-WSUR) test were used to assess Contamination-Obbsessive compulsive disorder (C-OCD). RESULT: The same period STEMI count compared to the previous year decreased 25%. The duration of symptoms onset to hospital admission was longer in the first month compared to second and third months (180 (120-360), 120 (60-180), and 105 (60-180), respectively; P = 0.012). Multivariable logistic regression (model-2) was used to examine the association between 7 candidate predictors (age, gender, diabetes mellitus (DM), hypertension, smoking, pain-onset time, and coronary artery disease (CAD) history), PI-WSUR C-OCD, and admission month with prehospital delay. Among variables, PI-WSUR C-OCD and admission month were independently associated with prehospital delay (OR 5.36 (2.11-13.61) (P = 0.01); 0.26 (0.09-0.87) p < 0.001] respectively]. CONCLUSION: Our study confirmed that contamination obsession was associated with prehospital delay of STEMI patients, however anxiety and depression level was not associated during the pandemic.

Comparison of outcomes of children with acute lymphoblastic leukemia treated with BMF protocol across 2 decades.

Acute lymphoblastic leukemia is the most common malignancy of childhood. The aim of this study is to compare the outcome of children with acute lymphoblastic leukemia treated with BFM protocol over two decades at our center. We retrospectively examined the files of 421 patients by dividing them into two groups by decade of treatment, 1995-2005 and 2006-2015. After excluding 117 patients, overall, 304 patients were included in the analysis. From the first to the second decade, the proportion of patients over 12 years of age increased from 7.1% to 16.8% (p < 0.04), the high-risk group increased from 15.5% to 19.5% and patients with central nervous system leukemia increased from 5.2% to 11.4%. The relapse rate remained relatively unchanged during this period (from 12.9% to 12.7%), while the mortality rate decreased from 18.7% to 15.4% (p > 0.05) and the death rate during remission induction treatment decreased from 3.9% to 0.7%. The mortality rate of high-risk and standard-risk patients decreased from 62.5% to 34.5% (p < 0.05) and 11.1% to 3.0% (p > 0.05), respectively. The 5-year overall survival and event-free survival rates for standard-, medium- and high-risk patients were 92.7% ± 6.0%, 87.9% ± 4.7%, and 54.7% ± 13.3% and 92.5% ± 6.3%, 83.2% ± 5.5%, and 48.7% ± 14.7%, respectively. For the cohort, the 5-year overall survival rate was 83.2% ± 4.1% and the event-free survival rate was 79.9% ± 4.7%. These results demonstrate the impact of a standard protocol, experience of staff, achieving better risk stratification on treatment success.

Relative Fat Mass Index can be solution for obesity paradox in coronary artery disease severity prediction calculated by SYNTAX Score.

BACKGROUND: The relation between body mass index (BMI) and coronary artery disease (CAD) extension remains controversial. A new score was developed to estimate body fat percentage (BFP) known as Relative Fat Mass (RFM) Index. This study aimed to evaluate the value of RFM Index in predicting the severity of the CAD, compared with other anthropometric measurements. METHODS: A total of 325 patients with chronic CAD were investigated. RFM, BFP, BMI and other anthropometric characteristics of patients were measured before angiography. CAD severity was determined by SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery trial (SYNTAX) Score. The association between SYNTAX Score and variables was evaluated using linear regression models. In order to compare the model performance, R-squared (R2), Akaike's information criterion, Bayesian information criterion and root mean square error were used. RESULTS: Univariate linear regression outcome variable, SYNTAX was used to determine whether there was any relationship between variables. Independent variables were included in the multivariable linear logistic regression models. The analysis showed that in model 1, RFM (ß coefficient: 2.31 (0.90 to 3.71), p=0.001)), diabetes mellitus (ß coefficient: 3.72 (1.67 to 3.76), p=0.004)), haemoglobin (ß coefficient: -2.12 (-3.70 to -0.53), p=0.03) and age (ß coefficient: 1.83 (0.29 to 3.37), p=0.02)) were statistically significant. The adjusted R2 values in model 1 were higher than model 2 (BFP) and model 3 (BMI) (0.155, 0.137 and 0.130, respectively), and χ2 values of RFM were higher than BFP and BMI (10.5, 3.4 and 1.0, respectively). CONCLUSION: RFM Index is a more reliable and compatible marker of obesity in showing the severity of CAD compared to BMI.

The effect of P wave indices on new onset atrial fibrillation after trans-catheter aortic valve replacement.

OBJECTIVES: Data is scarce regarding the relation between P wave indices and new onset atrial fibrillation (NOAF) after trans-catheter aortic valve replacement (TAVR). AIMS: The present study aimed to find out certain characteristics of P wave that may predict NOAF after TAVR procedure. METHOD: Patients with severe calcific aortic stenosis who had undergone TAVR procedure between 2013 and 2019 in two centers were investigated. P wave abnormalities that have been resumed to reflect impaired atrial conduction; partial and advanced inter atrial block (IAB), P-wave terminal force in lead V1, P wave dispersion, reduced amplitude of P- wave in lead I, P wave peak time in D2 and V1 were evaluated on pre- procedural 12 derivation surface electrocardiography (ECG). The relationship between these parameters and incidence of NOAF during index hospitalization was evaluated. RESULTS: A total of 227 consecutive patients (median age 79 [74-83]; 134 [59%] female) were included in the study. NOAF occurred in 46 (20.3%) patients. P wave duration, P wave dispersion, number of patients with partial and advanced IAB, left atrium diameter, STS score were higher in NOAF patients. Use of general anesthesia and history of prior open heart surgery were also more frequent in NOAF group. In multivariable logistic regression analysis; advanced IAB (OR 6.413 [2.555-16.095] p < 0.01), P wave dispersion (OR 3.544 [1.431-8.780] p = 0.006) and use of general anesthesia (OR 2.736 [1.225-6.109] p = 0.014) were independent predictors of NOAF. CONCLUSION: Among P wave abnormalities evaluated on pre-procedural 12-derivation surface ECG, advanced IAB and P wave dispersion may predict NOAF after TAVR procedure.

Low-dose Immune Tolerance Induction in Hemophilia: A Single-Center Experience.

INTRODUCTION: The development of inhibitors against factors VIII/IX is the most serious complication in hemophilia. The best treatment strategy for inhibitor eradication is immune tolerance induction (ITI). The aim of this study was to evaluate patients treated with low-dose ITI at a single center with limited resources. MATERIALS AND METHODS: In total, 29 (8.05%) of 360 hemophilia A patients exhibited inhibitors. The data from hemophilia patients with inhibitors undergoing ITI between 1999 and 2017 were collected and analyzed. RESULTS: Seventeen ITIs administered to 15 hemophilia A patients with inhibitors were analyzed, and the data from 13 ITIs conducted in 12 patients were evaluated. The median age at ITI onset was 10 years (range: 1.25 to 52 y). The maximum inhibitor titer before ITI was 30 Bethesda Units (BU) (range: 4.48 to 135), and the median inhibitor titer was 1.25 BU (range: 0 to 5.6) at the onset of ITI. The median time interval between the inhibitor development and ITI onset was 60 months (range: 7 to 264 mo). The median inhibitor titer during ITI was 3.4 BU (range: 0 to 158.7). At the end of the treatment, 4 of the 12 patients (33.3%) exhibited a complete response, 4 (33.3%) had partial responses (with continuing ITI), and 4 (33.3%) exhibited ITI failure. CONCLUSIONS: Treatment of hemophilia patients with inhibitors is challenging, and ITI is the best treatment method; however, a high-dose daily ITI regimen cannot be given to every patient in every country due to its high cost. Our results show that low-dose ITI may be a choice for selected patients with inhibitors.

Pediatric Stroke: A Single-Center Experience.

The aim of this study was to evaluate the clinical characteristics, risk factors, treatment, and outcomes of pediatric stroke cases. A total of 118 patients diagnosed with arterial ischemic stroke (AIS), hemorrhagic stroke, and sinovenous thrombosis (SVT) between January 2000 and December 2011 were included. Neonatal cases were excluded. Demographic and clinical findings were retrospectively examined from medical records. We identified 118 patients with stroke. The age of the patients ranged from 1 to 215 months (17.92 y), with a mean age of 5.19±5.25 years. AIS accounted for the majority of cases (n=69, 58.5%), and the major etiology was cardiac disease (17%). Hemorrhagic stroke accounted for 19.5% (n=23) of the cases, and late hemorrhagic disease of the newborn was the major etiology (43%, n=10). SVT accounted for 22% (n=26) of the cases, and the major etiology was otitis media-mastoiditis (27%, n=7). Hemiplegia and headache were the most frequent symptoms for AIS and SVT, respectively. Stroke is rare in children compared with adults; however, it is detected more frequently with better imaging techniques and increased awareness. We found that children with AIS presented more commonly with hemiplegia and children with SVT with headache and strabismus. We did not find an association between thrombophilia and stroke.

The effect of time between angiography and coronary artery bypass grafting on postoperative acute kidney injury in patients with diabetes mellitus.

BACKGROUND: This study aims to investigate the effect of time interval between coronary angiography and coronary artery bypass grafting surgery on postoperative acute kidney injury in patients with diabetes mellitus. METHODS: Between December 2013 and November 2016, a total of 421 diabetic patients (274 males, 147 females; mean age 60±9.2 years; range, 31 to 84 years) who underwent coronary artery bypass grafting were included in the study. Data including demographic characteristics of the patients, comorbidities, medical, and surgical histories, previous coronary angiographies, and operative and laboratory results were retrospectively analyzed. The patients were divided into two groups as those with acute kidney injury (n=108) and those without acute kidney injury (n=313). The Risk, Injury, Failure, Loss, End-Stage Kidney Disease (RIFLE) criteria were used to define acute kidney injury. The patients were further classified into three subgroups according to the time interval: 0-3 days, 4-7 days, and >7 days. RESULTS: There was no statistically significant difference in the median time between coronary angiography and coronary artery bypass grafting between the patients with and without acute kidney injury (11.5 and 12.0 days; respectively p=0.871). There was no significant difference in the risk factors for acute kidney injury among the subgroups. Multivariate analysis revealed that previous myocardial infarction (odds ratio [OR]: 5.192, 95% confidence interval [CI]: 2.176-12.38; p<0.001) and the increase in the creatinine levels in the first postoperative day (OR: 4.102 and 95% CI: 1.278- 13.17; p=0.018) were independent predictors of acute kidney injury. CONCLUSION: Coronary artery bypass grafting can be performed without any delay after coronary angiography without an increase in the postoperative risk of acute kidney injury in patients with diabetes mellitus.

Causes of Hypochromic Microcytic Anemia in Children and Evaluation of Laboratory Parameters in the Differentiation.

Most common causes of microcytic anemia in children are iron deficiency anemia (IDA) and thalassemia. Differentiation of these and detection of coexistence is essential for genetic counseling and to set a treatment plan. Aim is to characterize the frequency of IDA and thalassemia trait (TT) in children presenting with hypochromic, microcytic anemia and to define the significance of blood count parameters in differential diagnosis. Of the 200 enrolled, 107 were male (53.5%). In total 154 had IDA (77%), 27 had ß-TT (13.5%), and in 11 (5.5%) both conditions coexisted. Eight patients had α-thalassemia gene mutations, 3 of these also had IDA. RBC, MCV, Mentzer index, serum iron, TIBC, ferritin were significantly different between IDA and ß-TT patients (P<0.001); however, RDW was not different between the 2 groups (P>0.05). Sensitivity and specificity of Mentzer index for the detection of ß-TT were 100% and 69.4%, respectively. The positive and negative predictive values of Mentzer index in diagnosing ß-TT were 36.6% and 100%, respectively. Differential diagnosis of microcytic anemia is important in children, especially in regions where IDA and thalassemia are both prevalent. We found that 7% of children referred to our clinic for hypochromic, microcytic anemia had both TT and IDA. Our data showed that serum iron, ferritin, TIBC, MCV, and Mentzer index were all valuable markers in diagnosing IDA and were significantly different compared with ß-TT patients; RDW was not different between the 2 groups.

Hemophagocytic Lymphohistiocytosis Associated With Visceral Leishmaniasis.

This is the report of a 2-year-old boy who presented with fever, cytopenia, and splenomegaly. The patient was diagnosed with hemophagocytic lymphohistiocytosis (HLH) and treated with HLH-2004 protocol. Repeated bone marrow aspiration showed amastigotes on follow-up. In endemic countries, visceral leishmaniasis should be considered in the differential diagnosis to avoid chemotherapy toxicity.

Extrinsic compression of left main coronary artery by aneurysmal pulmonary artery in severe pulmonary hypertension: its correlates, clinical impact, and management strategies.

Aims: Although left main coronary artery (LMCA) compression (Co) by pulmonary artery (PA) aneurysm (A) has been reported in some pulmonary hypertension (PH) series, clinical importance and management of this complication remain to be determined. In this single-centre prospective study, we evaluated correlates, clinical impact, and management strategies of LMCA-Co in patients with PH. Methods and results: Our study group comprised 269 (female 166, age 52.9 ± 17.3 years) out of 498 patients with confirmed PH who underwent coronary angiography (CA) because of the PAA on echocardiography, angina or incidentally detected LMCA-Co during diagnostic evaluation with multidetector computed tomography. The LMCA-Co ≥ 50% was documented in 22 patients (8.2%) who underwent CA, and stenosis were between 70% and 90% in 14 of these. Univariate comparisons revealed that a younger age, a D-shaped septum, a higher PA systolic, diastolic, and mean pressures and pulmonary vascular resistance, a larger PA diameter, a smaller aortic diameter and pulmonary arterial hypertension associated with patent-ductus arteriosus, atrial or ventricular septal defects were significantly associated with LMCA-Co. Bare-metal stents were implanted in 12 patients and 1 patient underwent PAA and atrial septal defect surgery and another one declined LMCA stenting procedure. Conclusion: Our study demonstrates that LMCA-Co is one of the most important and potentially lethal complications of severe PH, and alertness for this risk seems to be necessary in specific circumstances related with PAA. However, long-term benefit from stenting in this setting remains as a controversy.