Adolescence-onset atypical hemolytic uremic syndrome: is it different from infant-onset?

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, mostly complement-mediated thrombotic microangiopathy. The majority of patients are infants. In contrast to infantile-onset aHUS, the clinical and genetic characteristics of adolescence-onset aHUS have not been sufficiently addressed to date. METHODS: A total of 28 patients (21 girls, 7 boys) who were diagnosed as aHUS between the ages of ≥10 years and <18 years were included in this study. All available data in the Turkish Pediatric aHUS registry were collected and analyzed. RESULTS: The mean age at diagnosis was 12.8±2.3 years. Extra-renal involvement was noted in 13 patients (46.4%); neurological involvement was the most common (32%). A total of 21 patients (75%) required kidney replacement therapy. Five patients (17.8%) received only plasma therapy and 23 (82%) of the patients received eculizumab. Hematologic remission and renal remission were achieved in 25 (89.3%) and 17 (60.7%) of the patients, respectively. Compared with the infantile-onset aHUS patients, adolescent patients had a lower complete remission rate during the first episode (p = 0.002). Genetic analyses were performed in all and a genetic variant was detected in 39.3% of the patients. The mean follow-up duration was 4.9±2.6 years. At the last visit, adolescent patients had lower eGFR levels (p = 0.03) and higher rates of chronic kidney disease stage 5 when compared to infantile-onset aHUS patients (p = 0.04). CONCLUSIONS: Adolescence-onset aHUS is a rare disease but tends to cause more permanent renal dysfunction than infantile-onset aHUS. These results may modify the management approaches in these patients.

Effect of hyperchloremia on mortality of pediatric trauma patients: a retrospective cohort study.

BACKGROUND: Hyperchloremia is often encountered due to the frequent administration of intravenous fluids in critically ill patients with conditions such as shock or hypotension in the pediatric intensive care unit, and high serum levels of chloride are associated with poor clinical outcomes. OBJECTIVES: This study aimed to determine the association between hyperchloremia and in-hospital mortality in pediatric patients with major trauma. DESIGN AND SETTING: This retrospective cohort study was conducted at a tertiary university hospital in Turkey. METHODS: Data were collected between March 2020 and April 2022. Patients aged 1 month to 18 years with major trauma who received intravenous fluids with a concentration > 0.9% sodium chloride were enrolled. Hyperchloremia was defined as a serum chloride level > 110 mmol/L. Clinical and laboratory data were compared between the survivors and nonsurvivors. RESULTS: The mortality rate was 23% (n = 20). The incidence of hyperchloremia was significantly higher in nonsurvivors than in survivors (P = 0.05). In multivariate logistic analysis, hyperchloremia at 48 h was found to be an independent risk factor for mortality in pediatric patients with major trauma. CONCLUSIONS: In pediatric patients with major trauma, hyperchloremia at 48-h postadmission was associated with 28-day mortality. This parameter might be a beneficial prognostic indicator.

Pediatric kidney care experience after the 2023 Turkey/Syria earthquake.

BACKGROUND/AIMS: Two earthquakes on February 6th, 2023 destroyed ten cities in Türkiye. We report our experience with pediatric victims during these catastrophes, with a focus on crush syndrome related-acute kidney injury (Crush-AKI) and death. METHOD: A web-based software was prepared. Patient demographics, time under rubble (TUR), admission laboratory data, dialysis, and kidney and overall outcomes were asked. RESULTS: 903 injured children (median age: 11.62 years) were evaluated. Mean TUR was 13 h (Interquartile range-IQR: 32.5), max 240 h). 31 of 32 patients with a TUR of >120 h survived. The patient who rescued after ten days survived.Two-thirds of the patients were given 50 mEq/L sodium-bicarbonate in 0.45% sodium-chloride solution on admission day. 58% of patients were given intravenous fluid (IVF) at a volume of 2000-3000 mL/m2 body surface area (BSA), 40% of 3000-4000 mL/m2 BSA, and only 2% of >4000 mL/m2 BSA. 425 patients had surgeries, 48 suffered from major bleeding. Amputations were recorded in 96 patients. Eighty-two and 66 patients required ventilator and inotropic support, respectively.Crush-AKI developed in 314 patients (36% of all patients). 189 patients were dialyzed. Age > 15 years, creatine phosphokinase (CK)≥20 950 U/L, TUR≥10 h, and the first-day IVF volume < 3000-4000 mL/m2 BSA were associated with Crush-AKI development. 22 deaths were recorded, 20 of 22 occurred in patients with Crush-AKI and within the first 4 days of admission. All patients admitted after 7 days survived. CONCLUSIONS: This is the most extensive pediatric kidney disaster data after an earthquake. Serum CK level was significantly associated with Crush-AKI at the levels of >20 950 U/L, but not with death. Adolescent age and initial IVF of less than 3000-4000 mL/m2 BSA were also asscoiated with Crush-AKI. Given that mildly injured victims can survive longer periods in the disaster field, we suggest uninterrupted rescue activity for at least 10 days.

A retrospective analysis: the outcome of renal replacement therapies in critically ill children.

OBJECTIVE: A few pediatric studies were present which focused on renal replacement therapy used for critically ill children. This research aimed to determine the ratio of utilization of intermittent hemodialysis, continuous renal replacement therapy, and peritoneal dialysis, and to study the properties and outcomes of critically ill pediatric patients who underwent renal replacement therapy. METHODS: Critically ill children admitted to the intensive care unit and received renal replacement therapy from February 2020 to May 2022 were included. The children were divided into three groups: hemodialysis, continuous renal replacement therapy, and peritoneal dialysis. RESULTS: A total of 37 patients (22 boys and 15 girls) who received renal replacement therapy met the criteria for this study. Continuous renal replacement therapy was used in 43%, hemodialysis in 38%, and peritoneal dialysis in 19%. In all, 28 (73%) children survived and 9 (27%) died in intensive care unit. The mean systolic blood pressure was significantly lower among children who received continuous renal replacement therapy (p<0.001). The need for inotropic medications and a higher PRISM III score were found to be the greatest indicators of mortality. CONCLUSION: The outcome of children receiving renal replacement therapy seems to be related to their needs for vasoactive drugs and the severity of the underlying disease in the continuous renal replacement therapy group relative to the other groups.

A Retrospective Analysis of Risk Factors and Impact of Acute Kidney Injury in Critically Ill Children.

BACKGROUND: Acute kidney injury (AKI) is a serious clinical condition in critically ill children and is associated with worse outcomes. A few pediatric studies focused on the risk factors of AKI. We aimed to identify the incidence, risk factors, and outcomes of AKI in the pediatric intensive care unit (PICU). PATIENTS AND METHODS: All the patients admitted to PICU over a period of 20 months were included. We compared both groups the risk factors between AKI and non-AKI. RESULTS: A total of 63 patients (17.5%) of the 360 patients developed AKI during PICU stay. The presence of comorbidity, diagnosis of sepsis, increased PRISM III score, and positive renal angina index were found to be risk factors for AKI on admission. Thrombocytopenia, multiple organ failure syndrome, the requirement of mechanical ventilation, use of inotropic drugs, intravenous iodinated contrast media, and exposure to an increased number of nephrotoxic drugs were independent risk factors during the hospital stay. The patients with AKI had a lower renal function on discharge and had worse overall survival. CONCLUSIONS: AKI is prevalent and multifactorial in critically sick children. The risk factors of AKI may be present on admission and during the hospital stay. AKI is related to prolonged mechanical ventilation days, longer PICU stays, and a higher mortality rate. Based on the presented results early prediction of AKI and consequent modification of nephrotoxic medication may generate positive effects on the outcome of critically ill children.

Lactate Clearance as an Early Prognostic Marker of Mortality for Pediatric Trauma.

Background While lactate clearance (LC) has already been shown as a prognostic indicator in clinical studies, its certain character needs to be defined in pediatric trauma. This research aimed to evaluate the correlation between early lactate clearance and mortality in pediatric trauma.Patients and methods A retrospective cohort study was conducted in a university hospital. Repeated LC was measured at admission, at the 2nd, 6th, and 12th hours post-admission. The association of lactate clearance with mortality was analyzed and using receiver operating characteristic (ROC) to determine the threshold levels of lactate clearance and also logistic regression analysis was performed to determine whether LC was an independent risk factor.Results Seventy-eight patients were included and overall mortality was 13%. LC values of the non-survivors was significantly lower than survivors for LC0-2 h (28.60±14.26 vs 4.64±15.90), LC0-6 h (46.63±15.23 vs 3.33±18.07), LC0-12 h (56.97±15.53 vs 4.82±22.59) (p:<0.001, p:<0.001 and p:<0.001, respectively). Areas under the curve of lactate clearance at the 2nd, 6th, and 12th hours after therapy start were a significant predictor for mortality (p:<0.001, p:<0.001, and p:<0.001, respectively). Threshold values of LC were 12.9, 19.5 and 29.3%, respectively.Conclusion Lactate clearance was a beneficial tool to estimate outcomes of pediatric trauma. Poor lactate clearance was a significant marker for poor prognosis.

Management of thrombocytopenia-associated multiple organ failure: plasma infusion vs plasma exchange.

BACKGROUND: Thrombocytopenia-associated multiple organ failure (TAMOF) causes a high ratio of mortality in pediatric patients. Only anticoagulants and profibrinolytic molecules can be replaced with plasma infusion (PI), while therapeutic plasma exchange (TPE) eliminates antifibrinolytic and thrombogenic molecules and charges inadequate anticoagulants and profibrinolytic molecules. This study aims to compare the efficacy of plasma exchange to plasma infusion in pediatric TAMOF patients. METHODS: Twenty-seven patients with TAMOF were included and the efficacy of PI and TPE was compared. The demographic data, admission laboratory values, Pediatric Logistic Organ Dysfunction (PELOD) scores before the beginning of treatment and PELOD at the end of treatment, and outcomes of groups were compared. RESULTS: Sixteen children were in the plasma infusion group, eleven children were in the plasma exchange group. The total mortality rate of all patients was 37%. The PELOD scores were significantly reduced on the 5th day of treatment in both groups and also PELOD scores were significantly higher on the 5th day of study in the non-survivor group (p: < 0.001). The fifth day of PELOD scores and ferritin had a significant effect on mortality (OR: 1.85, 95% CI: 1.02-2.69; p: 0.04, OR: 1.43, 95% CI: 0.97-2.03; p: 0.05). The overall mortality ratio was not different between TPE and PI groups (p: 0.12). CONCLUSIONS: Although there was no difference in mortality rates in children who received plasma exchange compared to children who received plasma infusion, mechanical ventilation and length of pediatric intensive care unit (PICU) day were shorter in the TPE group. The small patient population may be the major cause for the lack of significant statistical difference.

Is vasoactive-inotropic score associated with early lactate clearance a predictive outcome of children with septic shock?

BACKGROUND: The main goal of septic shock therapy is to keep hemodynamic parameters in the normal range for adequate tissue perfusion. Persistent lactic acidemia has increased mortality. We evaluate the association between vasoactive-inotropic score (VIS) and lactate clearance (LC) to predict mortality of septic shock in children. METHODS: This is a retrospective study of consecutive septic shock in children admitted to the pediatric intensive care unit. Vital signs, laboratory values, and VIS were obtained at admission and the 6th hour of hospitalization. LC was calculated at the 6th hour. The associations between LC and VIS were evaluated using univariate and multivariate analysis. Receiver operating characteristic analysis was used to describe the cutoff values of LC and VIS. RESULTS: Eighty-two children, age 82.3 ± 59.8 months, were included, with an overall lactate clearance of 29 ± 26%, and a mortality rate of 25.6%. The optimal cutoff value of LC was 20%. Children with LC ≥ 20% compared with LC < 20% had a lower VIS [(21.41 ± 8.36) vs. (27.48 ± 10.11) (p: 0.009)]. In multivariate comparison, PELOD score and VIS were significantly associated with 6-hour lactate clearance < 20% but VIS at 6 hours had a significant inverse relationship with LC < 20%. The cutoff for VIS was ≥ 16.2 for prognosticating the 6-hour LC and the high VIS group had a significantly lower LC and higher mortality ratio than the low VIS group. CONCLUSIONS: High VIS was associated with lower lactate clearance and has been described as a predictor of greater mortality among septic shock in children.

Are platelet indices promising ratios for predicting pediatric septic shock prognosis?

OBJECTIVES: The aim of the present study was to determine the prognostic value of thrombocytopenia, platelet indices (MPV/PLT and PDW/PLT) in children with septic shock. BACKGROUND: Septic shock is one of the major causes of mortality among children worldwide. METHODS: A retrospective analysis was made of children admitted to the pediatric intensive care unit between November 2010 and December 2019. Two hundred four children were included; they were diagnosed with septic shock according to the international pediatric sepsis consensus conference criteria. The MPV/platelet ratio and PDW/platelet ratios were estimated as the MPV and PDW values divided by the platelet count on the first three days of hospitalization. The clinical outcome was 28-day mortality. RESULTS: MPV/PLT and PDW/PLT ratios were found to be significantly higher in the non-survivors than survivor (p≤0.001). In the multivariate logistic regression analysis, higher MPV/platelet ratios at 72h (OR: 7.41; 95% CI: 1.25-43.7; p=0.027) and PDW/platelet ratios at 72h (OR: 2.9; 95% CI: 1.13-7.50; p=0.027) were significant risk factors for mortality. CONCLUSIONS: Platelet indices are useful laboratory parameters in septic shock. MPV/PLT and PDW/PLT ratios can be promising reliable markers for 28-day mortality in children with septic shock (Tab. 4, Fig. 1, Ref. 29).

Long-term renal survival of paediatric patients with lupus nephritis.

BACKGROUND: Childhood-onset systemic lupus erythematosus (SLE) is more severe than adult-onset disease, including more frequent kidney involvement. This study aimed to investigate baseline clinical features, treatment modalities and short- and long-term renal outcomes of paediatric patients with lupus nephritis (LN). MATERIALS AND METHODS: This study enrolled 53 LN patients out of 102 childhood-onset SLE patients followed at Hacettepe University between 2000 and 2020. The demographic and clinical data were reviewed retrospectively from the medical charts and electronic records. All SLE patients with renal involvement underwent renal biopsy either at the time of diagnosis or during follow-up. RESULTS: The median age at onset of SLE was 13.3 years [interquartile range (IQR) 10.4-15.8]. The median follow-up duration was 43.1 months (IQR 24.3-69.3). Of the 102 SLE patients, 53 (52%) had LN. The most frequent histopathological class was Class IV LN (54.7%), followed by Class III (22.6%). The proportion of patients who achieved either complete or partial remission was 77.3% and 73% at 6 and 12 months, respectively. In the overall LN cohort, 5- and 10-year renal survival rates were 92% and 85.7%, respectively. The remission rate at Month 6 was significantly higher in mycophenolate mofetil (MMF)- and cyclophosphamide (CYC)-treated groups than other combination therapies (P = 0.02). Although no difference was found between the CYC and MMF response rates (P = 0.57) in proliferative LN (Classes III and IV), the majority of Class IV patients (79%) received CYC as induction therapy. There was no difference between the response rates in any treatment regimens at Month 12 (P = 0.56). In the multivariate analysis, male gender, requiring dialysis at the time of LN diagnosis and failure to achieve remission at 6 and 12 months were found to be associated with poor renal outcome. CONCLUSIONS: Our study demonstrated that male gender, failure to achieve remission at 6 and 12 months and requiring dialysis at the time of diagnosis were the best predictors of poor renal outcome. Therefore appropriate and aggressive management of paediatric LN is essential to achieve and maintain remission.

Rituximab for Children With Difficult-to-Treat Nephrotic Syndrome: Its Effects on Disease Progression and Growth.

Background: Since the early 2000s rituximab (RTX) has been thought of as an alternative treatment for steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS). Objective: This study aimed to determine the effects of RTX treatment on disease outcome and growth in pediatric SSNS and SRNS patients. Materials and Methods: The medical records of pediatric SSNS and SRNS patients that began RTX treatment at the mean age of 10.8 ± 5.1 years between 2009 and 2017 were retrospectively reviewed. Additionally, the effect of RTX on growth was evaluated based on patient height, weight, and BMI z scores. Results: The study included 41 children, of which 21 had SSNS and 20 had SRNS. Mean age at diagnosis of NS was 5.8 ± 4.7 years. Mean duration of post-RTX treatment follow-up was 2.3 ± 1.6 years. Among the SSNS patients, 6 and 11 patients were steroid free and calcineurin inhibitor free at the last follow-up visit, respectively. The 1-year cumulative steroid and calcineurin inhibitor doses both decreased after RTX treatment, as compared to before RTX (P = 0.001 and P = 0.015, respectively). The median height z-score at the time of RTX initiation was -1.2 and the median height z-score at the last follow-up visit was -0.6 (P = 0.044). The median BMI z-score decreased from 1.6 (IQR; 0.9-3.0) at the time RTX was initiated to 1.1 IQR; [(-0.7)-2.5] at the last follow-up visit (P = 0.007). At the last follow-up visit 4 SRNS patients had complete remission and 4 had partial remission. The 1-year cumulative steroid dosage in the SRNS patients decreased significantly after RTX, as compared to before RTX (P = 0.001). The median height z-score at the time of RTX initiation was -0.8 and the median height z-score at the last follow-up visit was -0.7 (P = 0.81). The median BMI z-score decreased from 0.3 at the time RTX was initiated to -0.1 at the last follow-up visit (P = 0.11). Conclusion: RTX has a more positive effect on disease outcome and growth in SSNS patients than in those with SRNS.

The Short-Term Effects of Ketogenic Diet on Cardiac Ventricular Functions in Epileptic Children.

OBJECTIVE: Our primary aim was to determine the short-term effects of a ketogenic diet on cardiac ventricular function in patients with refractory epilepsy. METHODS: Thirty-eight drug-resistant epileptic patients who were treated with a ketogenic diet were enrolled in this prospective study. Echocardiography was performed on all patients before beginning the ketogenic diet and after the sixth month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and pulsed-wave tissue Doppler imaging measurements were performed on all patients. RESULTS: The median age of the 32 patients was 45.5 months, and 22 (57.8%) of them were male. Body weight, height, and body mass index increased significantly at the sixth month of therapy when compared with baseline values (P < 0.05). Baseline variables assessed by conventional M-mode echocardiography showed no significant difference at month 6 (P > 0.05). Doppler flow indices of mitral annulus and tricuspid annulus velocity of patients at baseline and month 6 showed no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at month 6 (P < 0.05). Although mitral annulus tissue Doppler imaging studies showed no significant difference (P > 0.05), there was a decrease in Ea velocity and Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P < 0.05). CONCLUSION: A 6-month duration ketogenic diet does not impair left ventricular functions in children with refractory epilepsy; however, it may be associated with a right ventricular diastolic dysfunction.

The Short-Term Effect of Ketogenic Diet on Carotid Intima-Media Thickness and Elastic Properties of the Carotid Artery and the Aorta in Epileptic Children.

The aim of this prospective study is to investigate the effect of a 6-month-long ketogenic diet on carotid intima-media thickness, carotid artery, and aortic vascular functions. Thirty-eight drug-resistant epileptic patients who were being treated with ketogenic diet were enrolled. Fasting total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and glucose concentrations were measured and echocardiography was performed in all patients before the beginning of ketogenic diet and at the sixth month of treatment. The body weight, height, body mass index, serum levels of triglyceride, total cholesterol, and low-density lipoprotein increased significantly at month 6 when compared to baseline values (P < .05). Carotid intima-media thickness, elastic properties of the aorta, and carotid artery did not change at the sixth month of therapy compared to baseline values. A 6-month-long ketogenic diet has no effect on carotid intima-media thickness and elastic properties of the carotid artery and the aorta.

Usefulness of Neutrophil to Lymphocyte Ratio in Prediction of Coronary Artery Lesions in Patients with Kawasaki Disease.

BACKGROUND: Kawasaki disease is an inflammatory condition. Neutrophil to lymphocyte ratio is a marker reflecting inflammation. AIMS: The aim of the study is to evaluate usefulness of neutrophil to lymphocyte ratio in diagnosis of Kawasaki disease and in prediction of coronary artery lesions. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Seventy-five children with Kawasaki disease and 66 controls were retrospectively enrolled. Their leukocyte, neutrophil, and lymphocyte counts were recorded. Abnormally distributed data were shown as median (interquartile range). Cases having coronary artery diameter two standard deviation above mean were diagnosed to have coronary artery lesions. RESULTS: Median age of Kawasaki disease patients was 34 months. Twentyfive of those (33.33%) had incomplete Kawasaki disease and twenty-six (34.66%) had coronary artery lesions. Leukocyte [12.61 (6.09)×10(3)/µL vs. 8.48 (5.58)×10(3)/µL], neutrophil [6.73 (4.10) ×10(3)/µL vs. 4.62 (5.47)×10(3)/µL], and lymphocyte [4.04 (2.91)×10(3)/µL vs. 3.02 (2.57) ×10(3)/µL] counts were significantly higher in Kawasaki disease patients compared to controls (all p values <0.01). However, there was not significant difference between patients and controls regarding neutrophil to lymphocyte ratio [1.72 (1.22) vs. 1.71 (1.88)]. Findings of Kawasaki disease and incomplete Kawasaki disease cases did not differ, while comparison of patients with and without coronary artery lesions revealed significantly higher neutrophil to lymphocyte ratio values in former group [2.02 (1.63) vs. 1.50 (1.28), p=0.01]. The cut-off neutrophil to lymphocyte ratio value for prediction of coronary artery lesions was determined as 1.32. CONCLUSION: Neutrophil to lymphocyte ratio values in Kawasaki patients with coronary lesions were significantly higher than the ones without and values greater than 1.32 were useful in prediction of coronary lesions.

Dispersion durations of P-wave and QT interval in children treated with a ketogenic diet.

BACKGROUND: Limited data are available on the effects of a ketogenic diet on dispersion duration of P-wave and QT-interval measures in children. We searched for the changes in these measures with serial electrocardiograms in patients treated with a ketogenic diet. METHODS: Twenty-five drug-resistant patients with epilepsy treated with a ketogenic diet were enrolled in this study. Electrocardiography was performed in all patients before the beginning and at the sixth month after implementation of the ketogenic diet. Heart rate, maximum and minimum P-wave duration, P-wave dispersion, and maximum and minimum corrected QT interval and QT dispersion were manually measured from the 12-lead surface electrocardiogram. RESULTS: Minimum and maximum corrected QT and QT dispersion measurements showed nonsignificant increase at month 6 compared with baseline values. Other previously mentioned electrocardiogram parameters also showed no significant changes. CONCLUSIONS: A ketogenic diet of 6 months' duration has no significant effect on electrocardiogram parameters in children. Further studies with larger samples and longer duration of follow-up are needed to clarify the effects of ketogenic diet on P-wave dispersion and corrected QT and QT dispersion.