Soluble Receptor for Advanced Glycation End Products (sRAGE) Level and Its Prognostic Significance in Children with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemias are the most common malignancies in childhood. Although its etiology is still unclear, it is thought that disorders in oxidative stress metabolism may contribute to leukemogenesis. Advanced glycation end products (AGEs) are formed as a result of the non-enzymatic binding of sugars to biomolecules. Oxidation reactions are triggered through AGE-Receptor (RAGE) interaction, resulting in the formation of reactive oxygen species. These can play crucial roles in cancer pathogenesis and leukemogenesis. It is thought that sRAGE (soluble RAGE) is the end product of glycation and circulates freely in the circulation by binding to RAGE ligands. We investigate novel leukemia biomarkers and focus on soluble RAGE (sRAGE) for acute lymphoblastic leukemia (ALL) diagnosis and prognosis. Thirty children (1-17 years) diagnosed with ALL were included in the study. Patients were divided into standard, medium, and high risk groups according to the Berlin-Frankfurt-Münster (BFM) treatment protocol. Patients were evaluated twice; at the time of diagnosis and at the sixth month of remission. sRAGE and blood parameters were compared with healthy controls (n = 30, 1-17 years). The sRAGE levels in ALL patients at diagnosis (138.7 ± 177.3 pg/mL) were found to be significantly higher than they were during the sixth month of remission (17.6 ± 21.1 pg/mL) and in healthy controls (22.2 ± 23.7 pg/mL). The cut-off value of the sRAGE level for the diagnosis of ALL was found to be 45 pg/mL in ROC analysis (sensitivity: 73.3%, specificity: 86.7%, AUC: 0.681). At the same time, the sRAGE level was found to be significantly higher in T-ALL patients (490.9 ± 236.9 pg/mL) than in B-ALL patients (84.5 ± 82.7 pg/mL). No significant difference was found in terms of the sRAGE level between standard (45.8± 33.1 pg/mL), medium (212 ± 222.1 pg/mL), and high (143.9 ± 111.5 pg/mL) risk group ALL patients classified according to the BFM protocol. Despite the fact that this was a small, single-center study, our findings highlight the potential use of sRAGE as a biomarker for diagnosing ALL and assessing response to treatment.

COVID-19 in hospitalized infants aged under 3 months: multi-center experiences across Turkey.

To investigate coronavirus disease 2019 (COVID-19) in infants aged 0 to 3 months because there is currently a significant gap in the literature on the subject. A cross-sectional study was conducted with the involvement of 19 medical centers across Turkey and 570 infants. The majority of the patients were male (58.2%), and the three most common symptoms were fever (78.2%), cough (44.6%), and feeding intolerance (39.9%). The results showed that a small percentage of infants had positive blood (0.9%) or urine cultures (10.2%). Most infants presented with fever (78.2%). Children without underlying conditions (UCs) had mostly a complicated respiratory course and a normal chest radiography. Significant more positive urine culture rates were observed in infants with fever. A higher incidence of respiratory support requirements and abnormal chest findings were seen in infants with chronic conditions. These infants also had a longer hospital stay than those without chronic conditions.  Conclusions: Our study discloses the clinical observations and accompanying bacterial infections found in infants aged under 3 months with COVID-19. These findings can shed light on COVID-19 in infancy for physicians because there is limited clinical evidence available. What is Known: • COVID-19 in infants and older children has been seen more mildly than in adults. • The most common symptoms of COVID-19 in infants are fever and cough, as in older children and adults. COVID-19 should be one of the differential diagnoses in infants with fever. What is New: • Although most infants under three months had fever, the clinical course was uneventful and respiratory complications were rarely observed in healthy children. • Infants with underlying conditions had more frequent respiratory support and abnormal chest radiography and stayed longer in the hospital.

Comparison of infants and children with urolithiasis: a large case series.

We evaluated the demographic features, etiologic risk factors, treatment strategies, and outcome of the infants and children with urolithiasis (UL). A retrospective multicenter study was conducted including 23 Pediatric Nephrology centers in Turkey. The medical records of 2513 children with UL were reviewed. One thousand, three hundred and four boys and 1209 girls (1.1:1) were reported. The mean age at diagnosis was 39.5 ± 35 months (0.4-231 months), and 1262 patients (50.2%) were in the first year of life (infants). Most of the cases with infantile UL were diagnosed incidentally. Microlithiasis (< 3 mm) was found in 794 patients (31.6%), and 64.5% of the patients with microlithiasis were infants. Stones were located in the pelvis-calyces in 63.2% (n: 1530) of the cases. The most common stone type was calcium oxalate (64.6%). Hypocitraturia was the most common metabolic risk factor (MRF) in children older than 12 months, but in infancy, hypercalciuria was more common. Fifty-five percent of the patients had received at least one medical treatment, mostly potassium citrate. At the end of a year's follow-up, most of the patients with microlithiasis (85%) showed spontaneous remission. The rate of spontaneous stone resolution in infants was higher than in children. Spontaneous remission rate was higher in cases with MRF ( - ) stones than in MRF ( +) stones. However, remission rate with medical treatment was higher in cases with MRF ( +) stones. This study represents the results of a large series of infants and children with UL and showed that there are several differences such as underlying metabolic and anatomic abnormalities, clinical course, and stone remission rates between infants and children with urinary stone disease.

Effects of azithromycin on ventricular repolarization in children with COVID-19.

Introduction: Azithromycin is used to treat pediatric COVID-19 patients. It can also prolong the QT interval in adults. This study assessed the effects of azithromycin on ventricular repolarization in children with COVID-19. Method: The study prospectively enrolled children with COVID-19 who received azithromycin between July and August 2020. An electrocardiogram was performed before, one, three, and five days post-treatment. Using ImageJ®, the following parameters were measured: QT max, QT min, Tp-e max, and Tp-e min. The parameters QTc max, QTc min, Tp-ec max, Tp-ec min, QTcd, Tp-ecd, and the QTc/Tp-ec ratio were calculated using Bazett's formula. Results: The study included 105 pediatric patients (mean age 9.8±5.3 years). The pretreatment heart rate was higher than after treatment (before 92 [79-108]/min vs. Day 1 82 [69-108)]/min vs. Day 3 80 [68-92.2]/min vs. Day 5 81 [70-92]/min; p=0.05). Conclusion: Azithromycin does not affect the ventricular repolarization parameters on ECG in pediatric COVID-19 cases.

Introdução: A azitromicina (AZ) é utilizada no tratamento da COVID-19 em pediatria. Como este fármaco pode prolongar o intervalo QT nos adultos, este estudo avaliou os efeitos da AZ na repolarização ventricular de crianças com COVID-19. Método: Este estudo prospetivo incluiu crianças com COVID-19 que foram tratadas com AZ em julho-agosto 2020. Foi efetuado um eletrocardiograma (ECG) antes e um, 3 e 5 dias após o tratamento. Utilizando ImageJ ®, foram medidos os parâmetros seguintes: QT max, QT min, Tp-e max, e Tp-e min. Os parâmetros QTc min, Tp-ec max, Tp-ec min, QTcd, Tp-ecd e QTc/Tp-ec ratio foram calculados utilizando a fórmula Bazett. Resultados: O estudo incluiu 105 doentes pediátricos (idade média 9,8±5,3 anos). A frequência cardíaca no pré-tratamento foi mais elevada do que após o tratamento (antes 92 [79­108]/min versus dia 1 82 [69­108)]/min versus dia 3 80 [68­92,2]/min versus dia 5 81 [70­92]/min; p=0,05). Conclusão: A AZ não afeta os parâmetros de repolarização ventricular no ECG nos casos pediátricos da COVID-19.

Therapeutic Plasma Exchange in Pediatric Intensive Care Unit: A Single-center Experience.

AIM AND OBJECTIVE: To examine the clinical characteristics, indications, and complications of patients undergoing therapeutic plasma exchange (TPE) in our pediatric intensive care unit (PICU). MATERIALS AND METHODS: Patients who underwent therapeutic plasma exchange between January 2018 and January 2020 in the PICU were included in the study. Demographic, clinical, and laboratory data of patients were obtained retrospectively from medical records. A venous catheter was placed into subclavian, femoral, or jugular veins. The number of plasmapheresis sessions for each patient was determined by observing the course of the disease and clinical improvement. Patients were monitored for vital signs during the plasmapheresis process. Complications directly associated with TPE were recorded. RESULTS: During the 2-year study period, 105 TPE sessions were performed in 25 patients (15 males/10 females). The median age was 84 months (6-204), and the median body weight was 32 kg (8-75). Renal disorders and sepsis were the most common group, and about 48% of patients were in these groups. The most common diagnoses were sepsis with multi-organ dysfunction syndrome in seven patients and followed by hemolytic uremic syndrome (five patients) and Guillain-Barre syndrome (three patients). Nausea (6.7%) and hypocalcemia (6.7%) were the most common complications of patients associated with the procedure. Premature discontinuation of the procedure were not seen due to complications. Complications were treated with symptomatic therapy. CONCLUSION: TPE is an effective treatment that can be safely used for pediatric patients with developments in PICUs. Nevertheless, TPE should be performed by experienced staff at a specialized center to minimize the risk of complications. HOW TO CITE THIS ARTICLE: Özsoylu S, Dursun A, Çelik B. Therapeutic Plasma Exchange in Pediatric Intensive Care Unit: A Single-center Experience. Indian J Crit Care Med 2021;25(10):1189-1192.

Tubular calcium, magnesium, and phosphate excretion during therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy: A prospective study.

OBJECTIVES: Hypocalcemia, hypomagnesemia, and hyperphosphatemia are common electrolyte disturbances in perinatal asphyxia (PA). Different reasons have been proposed for these electrolyte disturbances. This study investigated the effect of the urinary excretion of calcium (Ca), magnesium (Mg), and phosphorus (P) on the serum levels of these substances in babies who were treated using therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) caused by PA. This study sheds light on the pathophysiology that may cause changes in the serum values of these electrolytes. METHODS: This study included 21 healthy newborns (control group) and 38 patients (HIE group) who had undergone therapeutic hypothermia due to HIE. Only infants with a gestational age of 36 weeks and above and a birth weight of 2000 g and above were evaluated. The urine and serum Ca, Mg, P, and creatinine levels of all infants were evaluated at 24, 48, and 72 h. RESULTS: The lower serum Ca value and the higher serum P value of the HIE group were found to be statistically significant compared to the control group (p<0.05). There was no significant difference in serum Mg values between the groups. However, hypomagnesemia was detected in five patients from the HIE group. The urine excretion of FeCa and FeMg at 24 h, and FeP excretion at 48 and 72 h were found to be significantly higher in the HIE group compared to the control group. CONCLUSIONS: This study determined that the urinary excretion of Ca, Mg, and P has an effect on the serum Ca, Mg, and P levels of infants with HIE.

A nationwide retrospective study in Turkish children with nephrocalcinosis.

BACKGROUND: Nephrocalcinosis (NC) is defined as calcium deposition in the kidney parenchyma and tubules. This study aims to determine the etiology, risk factors, and follow-up results of patients with NC in Turkey. METHODS: Patients diagnosed with NC in the pediatric nephrology Department Units of 19 centers from all geographical regions of Turkey over a 10-year period (2010-2019) were included in the study. The medical records from the centers were reviewed and demographic data, admission complaints, medical history, systemic and genetic disorders, risk factors for NC, treatment details, and presence of NC after one-year follow-up, were recorded retrospectively. RESULTS: The study sample included 195 patients (88 females, 107 males). The mean age at diagnosis was 39.44 ± 47.25 (0.5-208) months; 82/190 patients (43.2%) were diagnosed incidentally; 46/195 patients (23.6%) had an underlying disease; idiopathic hypercalciuria was detected in 75/195 (38.4%) patients. The most common systemic diseases were distal renal tubular acidosis in 11/46 patients (23.9%), primary hyperoxaluria in 9/46 patients (19.6%) and Bartter syndrome in 7/46 patients (15.3%). After one year of follow-up, NC resolved in 56/159 patients (35.2%) and they all did not have an underlying systemic disease. DISCUSSION: The most common presentation of NC was incidental. Distal renal tubular acidosis and primary hyperoxaluria were the main systemic diseases leading to NC, while hypercalciuria was the most common metabolic risk factor. Nephrocalcinosis was found to remain in most of the patients at a one-year follow-up. It may resolve particularly in patients with no underlying systemic disease.

Renal manifestations in children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant neurocutaneous syndrome affecting various parts of the body, including the renovascular and urinary systems. We evaluated the renovascular, urinary, glomerular, and tubular functions of children with NF1. We compared blood pressures, urinary findings, and renal glomerular and tubular functions in children with NF1 with those of a healthy age- and gender-matched control group. We evaluated 46 NF1 patients and 33 healthy controls. The mean ages of the NF1 group (female/male: 20/26) and the control group (female/male: 15/18) were 10.1 ± 4.6 and 10.6 ± 4.3 years respectively. Six NF1 patients were hypertensive. The mean blood pressures of the NF1 group were significantly higher than those of the control group. Renal artery stenosis was detected in one NF1 patient. Urinary tract anomalies were evident in 21.7% of NF1 but only 9% of control subjects. The mean estimated glomerular filtration rate (eGFR) of the NF1 group was significantly lower than that of the control group. Six NF1 patients evidenced eGFRs < 90 mL/min. In the NF1 group, tubular phosphorus reabsorption was significantly lower and uric acid excretion significantly higher than in the control group.Conclusion: Hypertension, urinary tract anomalies, and impaired renal function were more common in NF1 patients than healthy controls. Regular blood pressure measurements and evaluation of urinary tract and kidney function are essential for NF1 patients. What is Known: • NF1 is most commonly associated with systemic hypertension due to renal artery vasculopathy and the development of a pheochromocytoma. • Hydronephrosis and bladder involvement have been documented in NF1. What is New: • Renal glomerular and tubular functions may be affected in NF1.

Is medical treatment necessary for infants with small urinary stones?

Urinary stone disease is a common condition. We investigated the usefulness of medical treatment for infants with urinary stones 5 mm or smaller. The study included 197 infants (86 girls and 111 boys) with urolithiasis ≤ 5 mm who were referred to our Department of Nephrology between 2014 and 2016. Infants with metabolic or anatomical risk factors requiring medical treatment were excluded from the study. We retrospectively reviewed urine and serum metabolic profiles and compared stone resolution rates in patients who did and did not receive treatment. The mean age at diagnosis was 5.2 months (range, 14 days to 12 months). The most common complaint was restlessness (n = 92, 46.7%), and 49 infants (24.9%) were asymptomatic. Multiple stones were detected in 166 infants (84.3%). Hypomagnesuria, hypocitraturia, and hypercalciuria were present in 25.3, 19.7, and 18.7% of patients, respectively. Stones < 3 mm (microlithiasis) were detected in 97 infants (49.2%), and 100 (50.8%) patients had 3-5 mm stones. In total, 130 infants (66.5%) received regular treatment and 67 (33.5%) were not treated. Stone resolution was significantly higher in the group receiving K-citrate treatment at the 6th month follow-up, while there were no significantly difference between the two groups at the 12th month control. No previous studies have investigated treatment outcomes in infants with 3-5 mm urinary stones. According to our results, K-citrate treatment may accelerate the resolution of the stone in infants with stones smaller than 5 mm.

Effect of zinc supplementation on hemogram parameters and circulating concentrations of homocysteine, vitamin B12, and folate in zinc-deficient children and adolescents.

BACKGROUND: Zinc deficiency may exacerbate some pathologies and may also explain alterations in circulating concentrations of various molecules. Zinc has previously been reported to affect plasma concentrations of vitamin B12, homocysteine, and folate; however, the current evidence is inconclusive. We aimed to evaluate plasma zinc, hemoglobin, red blood cell count, mean corpuscular volume, ferritin, vitamin B12, folate, and homocysteine concentrations during and after zinc supplementation for treatment of zinc deficiency. METHODS: This prospective, open-label, single-arm study included children who presented to outpatient clinics with symptoms of growth retardation, anorexia or frequent infections, and who were considered deficient based on plasma zinc concentrations (<70 mcg/dl). Zinc supplementation of 15 mg per day was administered to all participants, and fasting blood samples collected 3 months later were analyzed for plasma zinc, vitamin B12, homocysteine, and folate concentrations. RESULTS: Eighty-three children (27 males and 26 females) admitted to the outpatient clinics with anorexia, growth retardation, and complaints of frequent infections. The mean age of the children was 9.64 ± 5.05 (min-max, 1-15) years, and the mean plasma zinc concentration before zinc supplementation was 61.7 ± 6.3 mcg/dl. Zinc concentrations were significantly elevated after zinc sulfate supplementation for 3 months, at 107.1 ± 18.8 mcg/dl (p < 0.01). Hemoglobin (p < 0.01), mean corpuscular volume (p < 0.01), and ferritin (p = 0.049) levels were significantly increased after zinc supplementation, but no significant difference was found in red blood cell count (p = 0.83). Vitamin B12 and homocysteine concentrations were significantly decreased after zinc treatment (743.5 ± 498.8 vs 373.3 ± 128 mcg/dl p < 0.01; and 11.2 ± 5.3 vs 6.7 ± 3.4 mcg/dl p < 0.01, respectively). However, the change in folate concentrations was not significant (p = 0.05). CONCLUSIONS: Anemia was not detected in patients with zinc deficiency, but ferritin level significantly increased after zinc treatment. Therefore, it can be said that zinc therapy has a positive effect on iron absorption. Elevations in vitamin B12 and homocysteine may be associated with zinc deficiency, and these elevations may in turn influence the prognoses of liver, kidney, cardiorespiratory, and neoplastic conditions. This can be corrected through appropriate zinc supplementation.

Assessment of Hair Zinc in the School Children in Kayseri, Turkey.

Zinc is an essential micronutrient for the organism and is critical for the functional and structural integrity of cells. Determination of the amount of trace element concentrations in tissues such as hair samples have been used for the evaluation of the metabolic status especially in children. Unlike serum zinc, concentrations of zinc in hair are more stable and indicative of variations over time. The purpose of this study is to assess the zinc status of healthy school-age children in Kayseri (Turkey) by measuring the zinc level in hair samples and its association with BMI and the frequency of intake of zinc-rich foods. A total of 527 healthy children, including preadolescent (n = 360) aged 6-10 years and adolescent (n = 167) aged 11-15 years were included in this study. Hair samples were analyzed for zinc content by the inductively coupled plasma-mass spectrophotometry. Analysis of 527 healthy children showed that the mean hair zinc level was 186 ± 77 µg/g. Mean hair zinc level was lower in preadolescent age group than adolescents. There was no significant relationship between the monthly income of the family and the zinc-rich food intake and the zinc level of the hair. Our study shows that samples for analysis of zinc can be obtained with a noninvasive method for determining cases of deficiency during periods of rapid growth. However, further studies are needed to determine the normal tissue zinc level in healthy children, especially in our country and including different geographical regions.

Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department.

BACKGROUND: The objective of this research was to evaluate the potential clinical utility of baseline hematological parameters measured on admission as adjuncts in the identification of complicated and uncomplicated appendicitis in children. METHODS: The records of a total of 334 pediatric patients who underwent curative surgery for acute appendicitis (AA) between 2015 and 2016 were retrospectively investigated. The patients were categorized as complicated or uncomplicated appendicitis based on the histopathological reports. The clinical features and baseline hematological parameters of leukocyte count, neutrophil percentage, thrombocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and platelet distribution width (PDW) of the groups were compared. RESULTS: Complicated AA was determined in 36 (10.8%) patients. The white blood cell count (WBC) (p<.001), neutrophil percentage (p<.001), NLR (p<.001), and PLR (p=.004) were higher in the complicated appendicitis group compared with the uncomplicated group, while the RDW, MPV, and PDW levels were uninformative. Analysis of receiver operating characteristic curves yielded the cut-off values of 14.870 cell/mm3 for WBC (area under the curve [AUC]: 0.675; sensitivity: 86.1%; specificity: 41.6%), 10.4 for NLR (AUC: 0.717; sensitivity: 61.1%; specificity: 73.2%), and 284 for PLR (AUC: 0.647; sensitivity: 42%; specificity: 86%) were found to be the best predictive values for the determination of complicated acute appendicitis. CONCLUSION: The present study demonstrated that AA patients with higher NLR and PLR levels might be more likely to develop a complication. The NLR and PLR values combined with a physical examination, imaging studies, and other laboratory tests may help clinicians to identify high-risk AA patients in the emergency department.

Acute renal failure due to severe hypercalcemia and nephrocalcinosis treated with two doses of pamidronate in an infant with Williams-Beuren syndrome.

Bastug F, Nalçacioglu H, Bas VN, Tekatli-Çelik B, Çetinkaya H, Yel S. Acute renal failure due to severe hypercalcemia and nephrocalcinosis treated with two doses of pamidronate in an infant with Williams-Beuren syndrome. Turk J Pediatr 2018; 60: 210-215. Infantile hypercalcemia has been reported in 15% of infants and children with Williams-Beuren syndrome (WBS) and has generally mild clinical symptoms. However, the need for pamidronate treatment in a few infants with severe hypercalcemia associated with WBS has been reported in literature. Many disorders, such as primary hyperoxaluria, associated with nephrocalcinosis can lead to renal failure, but there are only a few reports in infants with WBS who have decreased renal function and nephrocalsinosis. We present a 23-month-old girl with WBS (confirmed with fluorescent in situ hybridization probes) who presented with acute renal failure with severe symptomatic hypercalcemia and nephrocalcinosis, which responded to two infusions of pamidronate.