Etiology and Factors Affecting Severe Complications and Mortality of Febrile Neutropenia in Children with Acute Leukemia

Objective: Febrile neutropenia (FN) is an important complication that causes high rates of morbidity and mortality in patients with malignancies. We aimed to investigate the etiology, epidemiological distribution and its change over the years, clinical courses, and outcomes of FN in children with acute leukemia. Materials and Methods: We retrospectively analyzed the demographic data, clinical characteristics, laboratory results, severe complications, and mortality rates of pediatric patients with FN between January 2010 and December 2020. Results: In 153 patients, a total of 450 FN episodes (FNEs) occurred. Eighty-four (54.9%) of these patients were male, the median age of the patients was 6.5 (range: 3-12.2) years, and 127 patients (83%) were diagnosed with acute lymphoblastic leukemia. Fever with a focus was found in approximately half of the patients, and an etiology was identified for 38.7% of the patients. The most common fever focus was bloodstream infection (n=74, 16.5%). Etiologically, a bacterial infection was identified in 22.7% (n=102), a viral infection in 13.3% (n=60), and a fungal infection in 5.8% (n=26) of the episodes. Twenty-six (23.2%) of a total of 112 bacteria were multidrug resistant (MDR) The rate of severe complications was 7.8% (n=35) and the mortality rate was 2% (n=9). In logistic regression analysis, refractory/relapsed malignancies and high C-reactive protein (CRP) at first admission were found to be the most important independent risk factors for mortality. Prolonged neutropenia after chemotherapy, diagnosis of acute myeloid leukemia, identification of fever focus or etiological agents, invasive fungal infections, polymicrobial infections, and need for intravenous immunoglobulin treatment increased the frequency of severe complications. Conclusion: We found that there was no significant change in the epidemiological distribution or frequency of resistant bacteria in our center in the last 10 years compared to previous years. Prolonged duration of fever, relapsed/refractory malignancies, presence of fever focus, and high CRP level were significant risk factors for poor clinical course and outcome.

Multisystem inflammatory syndrome in children associated with COVID-19 in 101 cases from Turkey (Turk-MISC study).

AIM: Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey. METHODS: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis. RESULTS: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 µg/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died. CONCLUSION: The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management.

COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group.

Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × µL, p = 0.028; platelet count 166 vs. 216 cells × 103/µL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559). CONCLUSION: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD. WHAT IS KNOWN: • In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. • Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C. WHAT IS NEW: • Half of the patients had clinical features that overlapped with Kawasaki disease. • In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. • Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. • Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.

Evaluation of COVID-19 Disease and the Effect of Trends in Intervention Measures: The Pediatric Perspective from a Tertiary Care Hospital in Turkey.

BACKGROUND: COVID-19 is an emerging disease of global public health concern. AIMS: To evaluate the epidemiological, clinical, laboratory, and radiologic findings and the clinical outcomes of children who were diagnosed with SARS-CoV-2 by polymerase chain reaction (PCR), and to evaluate the effect of the trends in intervention measures. STUDY DESIGN: Between April 2, 2020 and January 16, 2021, children aged 0-18 years who had presented at the pediatric emergency department and were diagnosed with confirmed SARS-CoV-2 by PCR were enrolled. METHODS: Details on demographics, epidemiologic characteristics, clinical findings, laboratory data, and radiologic investigations, hospital admissions, and prognosis were recorded. According to clinical severity, patients were divided into 5 groups as asymptomatic, mild, moderate, severe, or critical. We classified the outbreak into 3 periods. The first was between April 2, 2020, the date when the first pediatric case of our hospital was detected, and June 1, 2020, when restrictive measures were relaxed. The second period was between June 1, 2020 and November 15, 2020, when restrictive measures were reimplemented. The third period was between November 15, 2020 and January 16, 2021. RESULTS: A total of 600 patients [median age: 10.3 years (IQR: 4.4-15.1); 304 females] were enrolled. Among them, 25.0% were asymptomatic, while the 3 most common symptoms among symptomatic cases were fever, cough, and fatigue. There was contact with a COVID-19 PCRpositive individual in 73.5% of the cases, with 76.6% of those being a household contact. There were 23 (3.9%) moderate, severe, or critical cases in terms of clinical severity. The presence of chronic disease, a pathological physical chest examination, and procalcitonin levels of >0.05 ng/mL were identified as predictors of being moderate, severe, or critical. Twenty-four (4.0%) patients were admitted to the hospital; 14 (2.3%) to the ward and 10 (1.6%) to the pediatric intensive care unit. In the second intervention period, we observed a rapidly increasing number of new cases daily, especially in August. From September, an increase was observed, being particularly marked from October to November 18. Since then, there was a decrease in the daily number of cases. CONCLUSION: The majority of the cases were asymptomatic or had a mild clinical presentation. The presence of chronic disease, a pathological physical chest examination, and procalcitonin levels of >0.05 ng/mL were identified as predictors of being moderate, severe, or critical in terms of clinical severity. Strict intervention measures seem to be effective in containing the spread of COVID-19.

[Evaluation of SARS-CoV-2 PCR Positive Cases in the Pediatric Emergency Department]. / Çocuk Acil Serviste SARS-CoV-2 PCR Pozitif Saptanan Olgularin Degerlendirilmesi.

In December 2019, a previously unknown type of coronavirus was detected in China and named as "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)". The World Health Organization has named the SARS-CoV-2 related as coronavirus disease-2019 (COVID-19) and declared it as a pandemic. There is a limited data about the COVID-19 disease for the pediatric patients. In this study, it was aimed to evaluate the epidemiological, clinical, laboratory and radiologic findings, treatment and clinical outcomes of patients admitted to the pediatric emergency department with the suspicion of COVID-19. Between March 11 and June 16, 2020, patients aged between 1 month-18 years admitted to the pediatric emergency department and who have an indication for sampling for the polymerase chain reaction (PCR) method with the suspicion of COVID-19 according to the current guidelines published by the Ministry of Health were included in the study. The demographic characteristics, symptoms, durations and the history of contact with the suspected/definite COVID-19 cases were questioned in the patients with positive results. Physical examination, laboratory and imaging data of the patients were recorded. According to clinical severity, patients were divided into five groups. Treatment methods, ward/intensive care unit admission, length of stay at hospital, and prognosis were recorded. Of the 237 patients included in the study, 45 (18.9%) of the samples were positive and 192 (81.1%) were negative. There was a history of contact with COVID-19 positive case in 38 (85.6%) of COVID-19 PCR positive patients. The mean time for onset of symptoms after contact was 3.5 ± 1.7 days. Twenty-one of the patients (46.6%) were asymptomatic and the most common symptom was fever (34.1%) and cough (27.3%). Of the patients whose laboratory tests were requested, lymphopenia wasdetected in 50% and 52.3% of procalcitonin, 23.5% of C-reactive protein and 64.7% of D-dimer values were found to be high. Chest radiography was obtained from 45.4% of the patients; 90.0% were evaluated as normal, bronchovascular change, pleural effusion and consolidation were detected in one of each (5.0%) patient. Thorax computed tomography (CT) was obtained from 4 (9.0%) patients. One patient had normal CT findings, two patients had consolidation, one patient had peripheral ground-glass appearance and one patient had pleural effusion. Antibiotics were started in 38.6% of the patients and the most commonly used antibiotic was azithromycin (34.1%). Oseltamivir was started in one (2.3%) patient, and 10 (24.7%) patients were treated with hydroxychloroquine. There were no serious and critical cases according to the clinical severity. Pediatric patients constitute a small part of COVID-19 individuals in the community, and a significant part of them are asymptomatic, and patients who are symptomatic present with a mild clinic. In our study, most of the patients had a history of contact with COVID-19 positive cases, therefore, it should be questioned when evaluating a pediatric patient. There were no specific findings for COVID-19 positive patients in terms of laboratory and radiology.

[A Case of Congenital Syphilis and Prozone Phenomenon]. / Konjenital Sifilis Olgusu ve Prozon Fenomeni.

The screening for syphilis during pregnancy is important to prevent intrauterine transmission and complications. Prozone phenomenon may cause a false negative result in non-treponemal syphilis tests, which complicates an accurate diagnosis. In this case report a newborn syphilis case was presented to emphasize the importance of reverse algorithm in diagnosis and the prozone phenomenon which can cause problems in rapid plasma reagin (RPR) test. The 2920 g infant patient was born from a 24-year-old mother with no known diseases, at the 35th week of gestation by cesarean section due to premature rupture of membranes. The initial physical examination of the newborn revealed erythema and exfoliation of the bilateral hands and feet. Laboratory results revealed CRP: 90 mg/L, WBC: 19.2 x 103/µl, hemoglobin: 9.5 g/dl, platelet count: 214 x 103/µl, HIV-Ag/Ab: non-reactive, anti-Toxoplasma gondii IgM and IgG: negative, anti-cytomegalovirus IgM: negative, anti-cytomegalovirus IgG: positive (128.7 AU/ml), anti-Rubella IgM: negative, anti-Rubella IgG: positive (26 IU/ml), anti-Treponema pallidum (anti-T.pallidum) antibody [IgM and IgG by the chemiluminescence microparticle enzyme immunoassay (Architect Syphilis TP; Abbott Japan Co, Japan)]: positive (Signal Cut Off value (S/CO): 28.35), and RPR (Omega Diagnostics, UK): negative. All of the above ELISA tests were performed by using Architect (Abbott Diagnostics, Wiesbaden, Germany) kits. When the RPR test was repeated with serial dilutions of the serum in order to detect prozone phenomenon, positive reaction was detected starting from 1:2 and ending at 1:64 dilution. It was determined that the mother was not tested for syphilis during her pregnancy. When both the mother and the father were tested for syphilis, the mother's anti-T.pallidum total antibody test result was reactive (S/CO: 30.52) and the RPR was positive at 1:32 dilution, while the father's anti-T.pallidum total antibody test result was reactive (S/CO: 16.05) and the RPR was negative. A four-fold difference between the maternal and infant RPR dilutions is required by the guidelines for a laboratory diagnosis of congenital syphilis. Although this criterion was not met in the newborn, the case was accepted as congenital syphilis due to clinical findings. Congenital syphilis must be considered in the differential diagnosis in the presence of skin manifestations at the birth and early neonatal period. Accurate and early diagnosis of the disease is important to start appropriate treatment and prevent complications. As described in the presented case, the use of reverse syphilis test algorithm will enable to reach the correct diagnosis of the infection. If the result of the treponemal test is positive and the RPR test is negative, prozone phenomenon should be considered and the RPR test should be repeated with serial serum dilutions.