Mortality risk factors among critically ill children with MIS-C in PICUs: a multicenter study.

BACKGROUND: This study evaluated of clinical characteristics, outcomes, and mortality risk factors of a severe multisystem inflammatory syndrome in children admitted to a the pediatric intensive care unit. METHODS: A retrospective multicenter cohort study was conducted between March 2020 and April 2021 at 41 PICUs in Turkey. The study population comprised 322 children diagnosed with multisystem inflammatory syndrome. RESULTS: The organ systems most commonly involved were the cardiovascular and hematological systems. Intravenous immunoglobulin was used in 294 (91.3%) patients and corticosteroids in 266 (82.6%). Seventy-five (23.3%) children received therapeutic plasma exchange treatment. Patients with a longer duration of the PICU stay had more frequent respiratory, hematological, or renal involvement, and also had higher D-dimer, CK-MB, and procalcitonin levels. A total of 16 patients died, with mortality higher in patients with renal, respiratory, or neurological involvement, with severe cardiac impairment or shock. The non-surviving group also had higher leukocyte counts, lactate and ferritin levels, and a need for mechanical ventilation. CONCLUSIONS: In cases of MIS-C, high levels of D-dimer and CK-MB are associated with a longer duration of PICU stay. Non-survival correlates with elevated leukocyte counts and lactate and ferritin levels. We were unable to show any positive effect of therapeutic plasma exchange therapy on mortality. IMPACT: MIS-C is a life-threatening condition. Patients need to be followed up in the intensive care unit. Early detection of factors associated with mortality can improve outcomes. Determining the factors associated with mortality and length of stay will help clinicians in patient management. High D-dimer and CK-MB levels were associated with longer PICU stay, and higher leukocyte counts, ferritin and lactate levels, and mechanical ventilation were associated with mortality in MIS-C patients. We were unable to show any positive effect of therapeutic plasma exchange therapy on mortality.

A Report of 7-Year Experience on Pediatric Continuous Renal Replacement Therapy.

BACKGROUND: Continuous renal replacement therapies (CRRTs) either as continuous venovenous hemofiltration (CVVH) or hemodiafiltration (CVVHD) are used frequently in critically ill children. Many clinical variables and technical issues are known to affect the result. The factors that could be modified to increase the survival of renal replacement are sought. As a contribution, we present the data on 104 patients who underwent CRRT within a 7-year period. MATERIALS AND METHOD: A total of 104 patients admitted between 2009 and 2016 were included in the study. The demographic information, admittance pediatric risk of mortality (PRISM) scores, indication for CRRT, presence of fluid overload, CRRT modality, durations of CRRT, and pediatric intensive care unit (PICU) stay were compared between survivors and nonsurvivors. RESULTS: The overall rate of survival was 51%. Patients with fluid overload had significantly increased rate of death, CRRT duration, and PICU stay. Multiorgan dysfunction syndrome as the indication for CRRT was significantly related to decreased survival when compared to acute renal failure and acute attacks of metabolic diseases. The CRRT modality was not different between survivors and nonsurvivors. Standardized mortality ratio of the group was calculated to be 0.8. CONCLUSION: The CRRT in critically ill patients is successful in achieving fluid removal and correction of metabolic imbalances caused by organ failures or attacks of inborn errors of metabolism. It has a positive effect on expected mortality in high-risk PICU patients. To affect the outcome, follow-up should be focused on starting therapy in early stages of fluid overload. Prospective studies defining relative importance of risk factors causing mortality can assist in building up guidelines to affect the outcome.

Continuous Renal Replacement Therapy Applications on Extracorporeal Membrane Oxygenation Circuit.

BACKGROUND AND AIMS: Continuous venovenous hemofiltration or hemodiafiltration is used frequently in pediatric patients, but experience of continuous renal replacement therapy (CRRT) application on extracorporeal membrane oxygenation (ECMO) circuit is still limited. Among several methods used for applying CRRT on ECMO patients, we aim to share our experience on inclusion of a CRRT device in the ECMO circuit which we believe is easier and safer to apply. MATERIALS AND METHODS: The data were collected on demographics, outcomes, and details of the treatment of ECMO patients who had CRRT. During the study period of 3 years, venous cannula of ECMO circuit before pump was used for CRRT access for both the filter inlet and outlet of CRRT machine to minimize the thromboembolic complications. The common indication for CRRT was fluid overload. RESULTS: CRRT was used in 3.68% of a total number of patients admitted and 43% of patients on ECMO. The patients have undergone renal replacement therapy for periods of time ranging between 24 h and 25 days (260 h mean). The survival rate of this group of patients with multiorgan failure was 33%. Renal recovery occurred in all of the survivors. Complications such as electrolyte imbalance, hypothermia, and bradykinin syndrome were easily managed. CONCLUSIONS: Adding a CRRT device on ECMO circuit is a safe and effective technique. The major advantages of this technique are easy to access, applying CRRT without extra anticoagulation process, preventing potential hemodynamic disturbances, and increased clearance of solutes and fluid overload using larger hemofilter.

Comparison of tissue Doppler imaging with MRI t2* and 24-hour rhythm holter heart rate variability for diagnosing early cardiac impairment in thalassemia major patients.

OBJECTIVES: Cardiology follow up is important in thalassemia major patients. The object of this study is to define parameters which can be used in the early detection of cardiac impairment. MATERIAL AND METHODS: Forty seven beta thalassemia major patients (mean age 16.3 ± 4.47 years; 22 boys, 25 girls) whose left ventricular systolic functions were normal and a healthy control group of fifty age and gender matched children were included in the study. M-mode echocardiographic measurements, systolic and diastolic functions with PW and tissue Doppler and heart rate variabilities (HRVs) were compared between the two groups. The patients were also grouped according to MRT2*, ferritin and left ventricular diastolic diameters (LVDds) to compare the echocardiographic and Holter parameters among them. RESULTS: None of the children in the study group had symptomatic congestive heart failure. PW Doppler late diastolic forward flow in pulmonary artery was higher in the thalassemia group when compared with the control group (P = 0.01) indicating decreased compliance of the right ventricle. While the systolic and diastolic functions were normal, all the HRV parameters in the thalassemia group were significantly lower than the control group (P = 0.005). CONCLUSIONS: Significant decrease in HRV and increase in PW late diastolic forward flow in pulmonary artery in the absence of systolic or diastolic dysfunction, points out that these parameters can be useful in detection of early cardiac impairment.

Effect of cardiopulmonary bypass on thiol/disulfide homeostasis in congenital heart surgery.

Background: This study aims to investigate whether thiol/disulfide homeostasis parameters measurements could be used as a new biomarker to predict the pre- and post-cardiopulmonary bypass oxidative status of pediatric patients undergoing congenital heart surgery. Methods: A total of 40 children with congenital heart disease (17 males, 23 females; mean age: 39.6±40.0 months; range, 2 to 216 months) who underwent open-heart surgery were included. The control group consisted of 40 age- and sex-matched healthy children (18 males, 22 females; mean age: 42.8±46.6 months; range, 12 to 156 months). The patients with congenital heart disease were divided into two groups as cyanotic patients (n=18) and acyanotic patients (n=22). Thiol/disulfide parameters were compared among the cyanotic, acyanotic congenital heart disease patients, and control group preoperatively (pre-CPB). The effects of cardiopulmonary bypass on thiol/disulfide parameters, pre-CBP, immediately after cardiopulmonary bypass (post-CPB0), and 24 h after cardiopulmonary bypass (post-CPB24) were investigated. Results: The mean native and total thiol levels in the cyanotic patients were significantly lower than those in the acyanotic patients and control group (p<0.0001). The cyanotic group exhibited higher disulfide levels than the acyanotic group (p<0.01). The mean native thiol and total thiol levels significantly decreased in the post-CPB0 (p<0.0001). The mean disulfide levels significantly increased in the post-CPB0 than the pre-CPB values (p<0.001). Post-CPB24 native and total thiol levels were elevated compared to post-CPB0 (p<0.0001). The mean disulfide levels significantly increased in the post-CPB24 period than the post-CPB0 values (p<0.001). The survivor patients responded better to oxidative stress than non-survivor patients. Conclusion: Thiol/disulfide measurement is a promising biomarker in determining the pre- and post-cardiopulmonary bypass oxidative status of pediatric patients undergoing congenital heart surgery. The interpretation of thiol/disulfide levels, pre- and postoperatively, may be used in predicting mortality and outcomes of these patients earlier.

A case of adrenal insufficiency during multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a disease related to coronavirus disease 2019 (COVID-19). Although the effects of COVID-19 on many systems are known, there is limited data regarding its effects on the endocrine system. This study aimed to discuss the effect of COVID-19 on cortisol dynamics in a patient who developed adrenal insufficiency after COVID-19 infection. An 11-yr-old boy with polymerase chain reaction-proven COVID-19 one month previously was referred with a five-day history of fever, vomiting, and rash. On admission, he had hypotension, tachycardia, and severe hyponatremia. After the evaluation, he was diagnosed with MIS-C and glucocorticoid therapy was initiated. During follow-up, the patient experienced adrenal insufficiency, and hydrocortisone treatment was initiated at a crisis dose. Four months later, the adrenal axis function had not recovered. The adrenocortical response in COVID-19 patients may be significantly impaired, resulting in increased mortality or morbidity.

CXCL10/IP10 as a Biomarker Linking Multisystem Inflammatory Syndrome and Left Ventricular Dysfunction in Children with SARS-CoV-2.

BACKGROUND: To investigate the diagnostic accuracy of CXCL10/IP10 for left ventricular (LV) dysfunction in multisystemic inflammatory syndrome (MIS-C). METHODS: This cross-sectional, longitudinal study included 36 patients with MIS-C. Patients were classified as follows: (1) patients presenting with Kawasaki-like features (group I = 11); (2) patients presenting with LV systolic dysfunction (group II = 9); and (3) other presentations (group III = 3). CXCL10/IP10 levels were measured upon admission and on days 3 and 7 of treatment. RESULTS: Twenty patients were male and 16 were female. The median age of patients at diagnosis was 7.5 (1.5-17) years. All patients had a fever lasting for a median of 4 (2-7) days. Ten patients had LV systolic dysfunction. The duration of hospitalization was longer in group II. Lymphocyte and platelet counts were lower, whereas NT-pro-BNP, troponin-I, D-dimer, and CXCL10/IP10 levels were higher in group II. Baseline levels of CXCL10/IP10 were weakly negatively correlated with ejection fraction (r = -0.387, p = 0.022). Receiver operator characteristic curve analysis yielded a cutoff value of CXCL10/IP10 to discriminate patients with LV dysfunction was 1839 pg/mL with sensitivity 88% and specificity 68% (Area under curve (AUC) = 0.827, 95% CI 0.682-0.972, p = 0.003). CONCLUSION: Having a good correlation with cardiac function, CXCL10/IP10 is a potential biomarker to predict LV dysfunction in MIS-C patients.

Increased Severe Cases and New-Onset Type 1 Diabetes Among Children Presenting With Diabetic Ketoacidosis During First Year of COVID-19 Pandemic in Turkey.

Introduction: There have been some significant changes regarding healthcare utilization during the COVID-19 pandemic. Majority of the reports about the impact of the COVID-19 pandemic on diabetes care are from the first wave of the pandemic. We aim to evaluate the potential effects of the COVID-19 pandemic on the severity of diabetic ketoacidosis (DKA) and new onset Type 1 diabetes presenting with DKA, and also evaluate children with DKA and acute COVID-19 infection. Methods: This is a retrospective multi-center study among 997 children and adolescents with type 1 diabetes who were admitted with DKA to 27 pediatric intensive care units in Turkey between the first year of pandemic and pre-pandemic year. Results: The percentage of children with new-onset Type 1 diabetes presenting with DKA was higher during the COVID-19 pandemic (p < 0.0001). The incidence of severe DKA was also higher during the COVID-19 pandemic (p < 0.0001) and also higher among children with new onset Type 1 diabetes (p < 0.0001). HbA1c levels, duration of insulin infusion, and length of PICU stay were significantly higher/longer during the pandemic period. Eleven patients tested positive for SARS-CoV-2, eight were positive for new onset Type 1 diabetes, and nine tested positive for severe DKA at admission. Discussion: The frequency of new onset of Type 1 diabetes and severe cases among children with DKA during the first year of the COVID-19 pandemic. Furthermore, the cause of the increased severe presentation might be related to restrictions related to the pandemic; however, need to evaluate the potential effects of SARS-CoV-2 on the increased percentage of new onset Type 1 diabetes.

[A unique population in today's paediatric intensive care unit: Immigrant children presenting with infectious diseases]. / Una población única en la Unidad de Cuidados Intensivos Pediátricos de la actualidad: niños inmigrantes que presentan enfermedades infecciosas.

INTRODUCTION: Despite similar disease severity scores; we found a higher crude death rate in the group of immigrant children compared to the group of native children in a paediatric intensive care unit. Our study aimed to compare descriptive data and standardised mortality ratios (SMR) in order to analyse differences in mortality. MATERIAL AND METHODS: We conducted a retrospective study comparing demographic characteristics, diagnostic data, disease severity scores and mortality in immigrant children of Syrian descent and children of Turkish descent. We included data for the medical and surgical patients admitted in 1 year. The sample included 1283 patients. RESULTS: We compared the age and sex distribution, presence of underlying disease, frequency of community-acquired infectious diseases, length of say, PRISM scores, SMR and crude death rates in the 2 groups. There were 1077 patients in the Turkish group and 206 patients in the immigrant group. The proportion of patients with underlying disease was greater in the Turkish group (42% vs. 37.4%). The proportion of patients with a community-acquired infectious disease as the presenting complaint was similar in both groups (52.9% vs. 47.4%). The mortality in patients with infectious disease was higher in the immigrant group (19.3% vs. 9.8%). There was not significant difference in the mean PRISM score between the 2 groups. We found a higher mortality in the immigrant group (16% vs. 11%). The standardised mortality ratio was 0.32 in the total sample group; 0.4 in the immigrant group and 0.24 in the Turkish group. CONCLUSIONS: In our study, we found an association between community-acquired infectious disease and increased mortality in the immigrant group. The underlying mechanism for this increase remains to be explained and further research is required to determine whether parameters related to infection should be added to this severity score for its use in this specific population.

Clinical and Laboratory Findings of 12 Children with Invasive Meningococcal Disease in Pediatric Intensive Care Unit.

INTRODUCTION: Invasive meningococcal disease (IMD) is a serious infectious disease requiring stay in a pediatric intensive care unit (PICU) that continues to be associated with high morbidity and mortality rates. Prompt recognition, early antibiotic therapy, and aggressive supportive therapies can reduce mortality. We aimed to assess the clinical and laboratory characteristics of children with IMD. Patients and Methods. We retrospectively evaluated the medical records of 12 children with IMD requiring PICU stay between January 2018 and July 2019. RESULTS: We followed up 12 patients (five girls and seven boys, 5-168 months of age, and four below one year of age) with IMD (nine patients have meningococcemia with meningitis, and three patients have meningococcemia) in PICU. All children were previously healthy and have not received meningococcal vaccines. Their pediatric risk of mortality (PRISM) scores varies between 5 and 37, four of the patients required mechanical ventilation, and the predicted mortality was 39% at admission. Seven patients had catecholamine refractory septic shock and disseminated intravascular coagulation (DIC). Three of the patients required extracorporeal treatment. The predominant serogroup is Men B (5/12). The mortality rate was 16.6% with early use of antibiotics, fluids, and other interventions. CONCLUSION: Mortality related to IMD is higher among children with severe meningococcemia despite early interventions in PICU. Routine use of meningococcal vaccines during childhood would be a better strategy for controlling IMD in both developing and developed countries.

Multisystemic inflammatory syndrome in children associated with COVID-19: a single center experience in Turkey.

OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with the coronavirus disease 2019 (COVID-19) is a new concern emerging as a severe presentation of COVID-19 in children. We aimed to describe the characteristics and short-term outcomes of children diagnosed with MIS-C. MATERIAL AND METHODS: A retrospective study was conducted on 24 patients who were diagnosed with MIS-C between June 1, 2020 and December 1, 2020. A total of 24 (14 male and 10 female) patients were included in the study. RESULTS: The median age at the diagnosis was 111 (10-180) months. A total of 17 patients had a history of contact with a patient with COVID-19. Among the 24 patients, the most common findings were gastrointestinal involvement (n=20), followed by conjunctivitis (n=12), erythematous rash (n=11), and oral changes (n=10). Cardiovascular involvement was detected in 12 patients, of whom six had systolic dysfunction, four had mild coronary artery involvement, four had pericardial effusion, and three had mitral insufficiency. All patients received intravenous immunoglobulin, and 14 patients were treated with methylprednisolone in addition. Anti-interleukin-1 was given to two patients. The median duration of hospitalization was 8 (5-15) days. A total of 23 patients were discharged and evaluated on the median of 68.5 (52-140) days after discharge. The remaining one patient with dilated cardiomyopathy died after 2 months in the intensive care unit. CONCLUSION: Increasing the knowledge on MIS-C will provide clinicians with information on early recognition, evaluation, and management of these patients.

Predicting Outcome in Mechanically Ventilated Pediatric Patients.

To apply and determine whether standardized mortality scores are appropriate to predict the risk of mortality in mechanically ventilated pediatric patients, 150 patients were retrospectively evaluated. Pediatric risk of mortality (PRISM) III-24 and pediatric index of mortality (PIM)-2 scores were unable to discriminate survivors and nonsurvivors; the observed mortality rate was lower than expected mortality rates. Oxygenation index (OI) was calculated at 0, 12, 24, and 72 hours of ventilation. OI-12 and OI-72 were found to be higher in nonsurvivors. PRISM III-24 and PIM-2 scores failed to predict mortality risk in mechanically ventilated pediatric patients. OI can be used to predict degree of respiratory failure and mortality risk.

Continuous Renal Replacement Therapy for Treatment of Severe Attacks of Inborn Errors of Metabolism.

Severe metabolic crises in children with inborn errors of metabolism can result in mortality or severe morbidities where continuous renal replacement therapy (CRRT) can be lifesaving . Clinical data, the pediatric risk of mortality (PRISM) scores calculated in the first 24 hours, and pediatric logistic organ dysfunction (PELOD) scores calculated in the last 24 hours before CRRT, were studied . Overall, CRRT was successful in restoring metabolic balance in 72% of patients. PELOD scores before CRRT were lower in survivors ( p = 0.02). Despite numerous comorbid factors, CRRT can be used effectively in management of metabolic crises. Early intervention with this therapy before occurrence of complications must be targeted.

BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immuneosseous- dysplasia.

Düzova A, Gülhan B, Topaloglu R, Özaltin F, Cengiz AB, Yetimakman AF, Dogru D, Güçer S, Besbas N. BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immune-osseous-dysplasia. Turk J Pediatr 2019; 61: 111-116. Patients with juvenile onset Schimke immune-osseous-dysplasia (SIOD) have less severe symptoms and can survive in the second and third decade of life. We present an 18 year-old adolescent with juvenile onset SIOD who was diagnosed after renal transplantation and developed BK virus associated nephropathy (BKVAN) and severe pneumonia during follow-up. The patient developed nephrotic syndrome, unresponsive to immunosuppressives, at the age of 8 years. He had a history of meningitis, short stature, microcephaly, prominent ears, and bilateral cryptorchidism. A renal transplantation was performed at the age of 15 years. During follow-up, he suffered from leucopenia, urinary tract infections, herpes labialis, and candida esophagitis. Sanger sequencing of SMARCAL1 revealed a missense mutation on exon 11 (R586W). A renal biopsy performed after a sharp increase in serum creatinine (without significant viremia) revealed BKVAN which responded to sirolimus monotherapy and cidofovir. Three months later, he suffered from productive cough and dyspnea with diffuse ground glass pulmonary infiltrates. His clinical situation deteriorated and non-invasive mechanical ventilation was started. Cidofovir (2 mg/kg) was re-started weekly for a possible BKV pneumonia with intravenous immunoglobulin. After 5 doses of cidofovir and intense antibiotic regime, his dyspnea resolved with stable graft functions. In our case; BKVAN, which developed without significant viremia, and possibly associated pneumonia were treated successfully with cidofovir and sirolimus monotherapy.