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.

Evaluation of 601 children with multisystem inflammatory syndrome (Turk MISC study).

PURPOSE: Due to its link with the 2019 coronavirus, the multisystem inflammatory syndrome in children (MISC) has garnered considerable international interest. The aim of this study, in which MISC patients were evaluated multicenter, and the data of the third period of the Turk-MISC study group, to compare the clinical and laboratory characteristics and outcomes of MISC patients who did and did not require admission to an intensive care unit (ICU). METHODS: This retrospective multicenter observational study was carried out between June 11, 2021, and January 01, 2022. The demographics, complaints, laboratory results, system involvements, and outcomes of the patients were documented. RESULTS: A total of 601 patients were enrolled; 157 patients (26.1%) required hospitalization in the intensive care unit (ICU). Median age was 8 years (interquartile range (IQR) 4.5-11.3 years. The proportion of Kawasaki disease-like features in the ICU group was significantly higher than in the non-ICU group (56.1% vs. 43.2% p = 0.006). The ICU group had considerably lower counts of both lymphocytes and platelets (lymphocyte count 900 vs. 1280 cells × µL, platelet count 153 vs. 212 cells × 103/ µL, all for p< 0.001). C-reactive protein, procalcitonin, and ferritin levels were significantly higher in the ICU group (CRP 164 vs. 129 mg/L, procalcitonin 9.2 vs. 2.2 µg/L, ferritin 644 vs. 334 µg/L, all for p< 0.001). Being between ages 5-12 and older than 12 increased the likelihood of hospitalization in the ICU by four [95% confidence intervals (CI)1.971-8.627] and six times (95% CI 2.575-14.654), respectively, compared to being between the ages 0-5. A one-unit increase in log D-dimer (µg/L) and log troponin (ng/L) was also demonstrated to increase the need for intensive care by 1.8 (95% CI 1.079-3.233) and 1.4 times (95% CI 1.133-1.789), respectively.     Conclusion: By comparing this study to our other studies, we found that the median age of MISC patients has been rising. Patients requiring an ICU stay had considerably higher levels of procalcitonin, CRP, and ferritin but significantly lower levels of lymphocyte and thrombocyte. In particular, high levels of procalcitonin in the serum might serve as a valuable laboratory marker for anticipating the need for intensive care. WHAT IS KNOWN: • Lymphopenia and thrombocytopenia were an independent predictor factors in patients with MISC who needed to stay in intensive care unit. • The possibility of the need to stay in the intensive care unit in patients with MISC who had Kawasaki disease-like findings was controversial compared with those who did not. WHAT IS NEW: • A one-unit increase log D dimer and log troponin was demonstrated to require for intensive care unit by 1.8 and 1.4 times, respectively. • Serum procalcitonin levels had the best performance to predict stay in the intensive care unit stay.

Zonulin and claudin-5 levels in multisystem inflammatory syndrome and SARS-CoV-2 infection in children.

AIM: SARS-CoV-2 infection in children is generally asymptomatic or mild; however, it can lead to a life-threatening clinical condition, multisystem inflammatory syndrome in children (MIS-C), days or weeks after the infection. Increased intestinal permeability isa possible triggering factor at the onset of the hyperinflammation associated with MIS-C. Zonulin and claudin-5 are involved in intestinal permeability. In this study, we aimed to investigate serum zonulin and claudin-5 levels in SARS-CoV-2 infection and MIS-C disease. METHODS: The study group consisted of children diagnosed with MIS-C or SARS-CoV-2 infection who presented to a university hospital paediatric emergency or infectious diseases departments. The control group included well patients seen at the General Pediatrics units for routine follow-up. Serum zonulin and claudin-5 levels were measured at the time of diagnosis. RESULTS: Fifteen patients were included in the MIS-C group, 19 in the SARS-CoV-2 infection group and 21 in the control group. The mean zonulin level in the MIS-C group was significantly higher than in the control group (P < 0.001). Mean Claudin-5 levels were Psignificantly lower in the SARS-CoV-2 infection group than in the control group (P < 0.001). CONCLUSION: These results indicate that increased intestinal permeability may be involved in the pathogenesis of SARS-CoV-2 infection and MIS-C disease. Larger clinical trials are needed to clarify the role of serum zonulin and claudin-5 on intestinal permeability in MIS-C and SARS-CoV-2 infection in children.

Serum B12, homocysteine, and anti-parietal cell antibody levels in children with autism.

AIMS: To compare vitamin B12, homocysteine, and anti-parietal cell antibody (APCA) levels between children with ASD and controls, paired in terms of age, sex, and socioeconomic level. METHODS: The research group consisted of 69 children, 36 with ASD and 33 controls. The severity of ASD was determined using the Childhood Autism Rating Scale (CARS). Serum vitamin B12, homocysteine and human anti-parietal cell levels were analysed using enzyme-linked immunosorbent assay. RESULTS: The serum vitamin B12 and homocysteine levels in children with ASD were lower than in the control group, but there was no significant difference in terms of APCA levels. CONCLUSIONS: Deficiencies in micronutrients, such as B12, may play a role in the pathogenesis and clinical symptoms of autism. However, it is believed that these parameters should be analysed in a wider population to clarify their effect on the aetiology of ASD.KEY POINTWe hypothesised that low levels of vitamin B12 and homocysteine levels reported in previous studies might be associated with APCA levels.The homocysteine and B12 levels were found to be significantly lower in children with ASD. There was no significant difference in serum APCA levels.No significant relationship was found between B12 levels and APCA.Given all these findings, it can be stated that vitamin B12 deficiency is not associated with an absorption-related mechanism due to the presence of APCA.Deficiencies in micronutrients, such as B12, may play a role in the pathogenesis and clinical symptoms of autism.In future studies, it will be beneficial to investigate other mechanisms that may cause vitamin B12 deficiency.

Early kidney injury in immunoglobulin A vasculitis: Role of renal biomarkers.

BACKGROUND: We aimed to determine whether urine kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) can be used as early noninvasive biomarkers of kidney injury in immunoglobulin A vasculitis. METHODS: Patients who were diagnosed with immunoglobulin A vasculitis were included in the study. Urine samples were collected for determination of urine KIM-1 and NGAL levels. The control group consisted of age-matched healthy children. RESULTS: Sixty-one patients who were diagnosed with immunoglobulin A vasculitis were included in the study; 37.7% of these patients were determined to have renal involvement. Median KIM-1 was found to be significantly higher in the patient group (69.59 pg/mL) than the control group (40.84 pg/mL) (P = 0.001). Median NGAL was determined to be statistically significantly higher in the patient group (59.87 ng/mL) compared with the control group (44.87 ng/mL) (P = 0.013). In 23.6% of the patients without renal involvement at admission renal involvement developed within the following 6 months. When median KIM-1 and NGAL at admission of these patients were compared with the control group, they were determined to be statistically significantly higher (P = 0.001, P = 0.003). CONCLUSIONS: The fact that our patients with late-term nephropathy had no hematuria and / or proteinuria and that KIM-1 and NGAL levels were determined to be high indicates that these biomarkers might be potentially reliable, noninvasive and early determinants of kidney injury.

Paediatric systemic lupus erythematosus: A single referral centre experience.

In this study, the clinical and laboratory findings, management and follow-up of 32 children with paediatric systemic lupus erythematosus (pSLE) were evaluated to determine the prognostic factors in pSLE. Of the 32 patients, 25 (78.1%) were females. Age at onset of symptoms and diagnosis in the patients were 147.6 ± 49 months and 154.3 ± 48 months, respectively. The most common symptom on admission were joint problems, seen in 25 (78.1%) patients. Haematological alterations were seen in 25 (78.1%) cases during follow-up. Lupus nephritis was diagnosed in 10 (31.2%) patients. Malar rash was seen in a total of 12 (37.5%) patients during follow up, however it had been noted in five (15.6%) patients on admission. Antinuclear antibody and anti-dsDNA were positive in all patients and 31 (96.8%) patients, respectively. Decreased complement 3 and 4 levels were noted in 23 (71.8%) patients. Antiphospholipid antibody was studied in 27 patients and it was found to be positive in 13 (48.1%) patients. In conclusion, based on our findings, we would like to emphasize that pSLE has a large and remarkable clinical and laboratory findings.

The effect of attention deficit/hyperactivity disorder and other psychiatric disorders on the treatment of pediatric diabetes mellitus.

OBJECTIVE: Psychiatric diagnoses of patients with type 1 diabetes mellitus (T1DM), the severity of attention deficit/hyperactivity disorder (ADHD) symptoms of the patients and their primary caregivers, and the effects of these factors on treatment were investigated. METHODS: Sixty-one patients with T1DM were included in the study along with their parents. Psychiatric diagnoses of the patients were determined using a semistructured psychiatric interview, and their depression and ADHD symptom severities were evaluated with self-report scales. The ADHD symptom severities of the parents were evaluated using self-report scales. The relationships among the psychiatric symptoms and the hemoglobin A1c (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) levels of the patients were investigated. RESULTS: HbA1c levels were found to correlate with the hyperactivity levels of children and the number of diagnoses they had. FBG and PBG values of patients diagnosed with ADHD were found to be higher than in those who did not have ADHD. HbA1c, FBG, and PBG values of the patients who had any disruptive behavior disorder were found to be higher than in those who did not. ADHD total scores, gender (being female), having diagnoses of ADHD or depression were found to be predictive of HbA1c levels according to the regression analyses. No relationship between the clinical findings of the children and their parents' ADHD levels was found. CONCLUSIONS: The findings of this study implicate that children with T1DM should be evaluated in terms of ADHD which could have negative effects on the treatment.

Is Asymmetric Dimethylarginine a Useful Biomarker in Children With Carbon Monoxide Poisoning?

OBJECTIVE: Carbon monoxide poisoning (COP) is the leading cause of mortality and morbidity due to poisoning worldwide. Because children are affected more quick and severely from COP, they may require a longer treatment period, even if carboxyhemoglobin (CO-Hb) and/or lactate levels return to normal. Therefore, a new marker that predicts the duration of treatment and the final outcomes of COP is needed. METHODS: This case control study was conducted on 32 carbon monoxide-poisoned patients younger than 18 years who had been admitted to pediatric emergency department. The control group included age- and sex-matched 30 healthy children. Blood samples were obtained for analysis of arterial blood gases, CO-Hb percent, methemoglobine, lactate, and asymmetric dimethylarginine (ADMA). RESULTS: Asymmetric dimethylarginine levels were significantly increased (P < 0.05) in patients with COP on admission and after the treatment when compared with controls (1.36 [0.89-6.94], 1.69 [0.76-7.81], 1.21 [0.73-3.18] nmol/L, respectively). There was no positive correlation between CO-Hb and ADMA levels on admission and at 6 hours (P = 0.903, r = 0.218, P = 0.231, r = 0.022, respectively). Positive correlation was found between lactate and CO-Hb levels on admission (P = 0.018, r = 0.423). CONCLUSIONS: This study showed that ADMA levels were still high after 6 hours of 100% oxygen therapy in children with COP, even CO-Hb and/or lactate levels return to normal range. On the basis of these results, we consider that ADMA may be a useful biomarker in patient with COP.

Investigation of the Relation between Epithelial Barrier Function and Autism Symptom Severity in Children with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by limitations in mutual communication and social interaction as well as restricted, repetitive patterns of behaviors, interests, or activities. The possible role of biological abnormalities in the etiopathogenesis of this disorder arouses research interest in this area. This is a case-control study evaluating epithelial barrier function by comparing serum concentrations of occludin and zonulin in children with ASD (n = 60) and controls (n = 30). The Childhood Autism Rating Scale (CARS) was used to evaluate autism symptom levels in all children. Serum occludin and zonulin levels were analyzed using an enzyme-linked immunosorbent assay. Serum occludin was significantly lower in children with ASD than in control subjects. In children with ASD, a decrease in occludin level was significantly associated with the disorder symptom levels items mean score (CARS total scores). Our findings showed that children with ASD had alterations in epithelial barrier function compared to the control group. The investigation of the mechanism underlying the different levels of occludin between ASD and controls may be of importance in clarifying the etiopathogenesis of ASD, as well as its follow-up and treatment.

Outcomes of COVID-19 Infections in children: A single-center retrospective study.

The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. Our aim was to describe clinical findings and outcomes of severe acute respiratory syndrome (SARS)-CoV-2 viral infection and COVID-19 cared for at a large pediatric tertiary care hospital during the first year of the pandemic. Patients aged 1 month to 18 years who were diagnosed as having COVID-19 between March 2020 and April 2021 were included. The files of patients diagnosed with COVID-19 were reviewed retrospectively. Results: Four hundred sixty seven children were included in the study. There were 34 (7.3%) patients under 1 year of age, 111 (23.8%) between 1 and 5 years, 98 (30.4%) between 5 and 10 years, 142 (30.4%) between 11 and 15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and shortness of breath (17.1%) in those aged over 15 years were found to be significantly more common in comparison with the other age groups (p < 0.05). Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Three patients died during the study period (0.64%). While SARS-CoV-2 infection may be asymptomatic and COVID-19 usually has a mild clinical course, some children have severe disease or mortality.

An unusual cause of fever in a neonate: influenza A (H1N1) virus pneumonia.

The 2009 flu outbreak in humans, known as H1N1 influenza A, refers to influenza A due to a new H1N1 strain called swine-origin influenza virus A. The signs and symptoms of novel influenza A (H1N1) virus infection are similar to those of seasonal influenza, and specific diagnostic testing is required to distinguish novel influenza A (H1N1) virus from seasonal influenza virus. It results in various degrees of infection, ranging from mild to severe to fatal. For the treatment of swine-origin influenza virus A oseltamivir and zanamivir are effective in most cases. Influenza A (H1N1) pneumonia in the newborn has not been yet reported in the literature. To our knowledge, this is the first report of a neonate of pneumonia in which influenza A (H1N1) virus was isolated.

Cerebral venous sinus thrombosis in an adolescent with Ewing sarcoma.

BACKGROUND: Although thromboembolic complications are common in adult patients with malignant diseases, cerebral venous sinus thrombosis has been rarely described in cancer afflicted pediatric and adolescent population. CASE HISTORY: A 16-year-old adolescent girl referred for complaints of pain and swelling on her left leg. On physical examination, a solid tibial mass was discovered. After the diagnosis of Ewing sarcoma with a tru-cut biopsy, chemotherapy protocol consisting of cisplatin, ifosfamide, adriamycine, and vincristine was started. During the first course of the treatment, the patient expressed headache, diplopia, and ptosis. Contrast-enhanced magnetic resonance (MR) images and MR angiography showed superior sagittal and transverse sinus thromboses. After anticoagulant therapy, the thromboses disappeared within 1.5 months. She received her chemotherapy protocol with the anticoagulant prophylaxis. After a follow-up period of 12 months, she is still in a good neurological recovery without any sequel. CONCLUSION: Children and adolescents with cancer should be monitored closely for thrombotic complications. We discuss this uncommon case to draw attention to the importance of early diagnosis and adequate treatment of intracranial thrombosis in childhood cancer, and we review the relevant literature.