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.

A snapshot of pediatric inpatients and outpatients with COVID-19: a point prevalence study from Turkey.

This multi-center point prevalence study evaluated children who were diagnosed as having coronavirus disease 2019 (COVID-19). On February 2nd, 2022, inpatients and outpatients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included in the study from 12 cities and 24 centers in Turkey. Of 8605 patients on February 2nd, 2022, in participating centers, 706 (8.2%) had COVID-19. The median age of the 706 patients was 92.50 months, 53.4% were female, and 76.7% were inpatients. The three most common symptoms of the patients with COVID-19 were fever (56.6%), cough (41.3%), and fatigue (27.5%). The three most common underlying chronic diseases (UCDs) were asthma (3.4%), neurologic disorders (3.3%), and obesity (2.6%). The SARS-CoV-2-related pneumoniae rate was 10.7%. The COVID-19 vaccination rate was 12.5% in all patients. Among patients aged over 12 years with access to the vaccine given by the Republic of Turkey Ministry of Health, the vaccination rate was 38.7%. Patients with UCDs presented with dyspnea and pneumoniae more frequently than those without UCDs (p < 0.001 for both). The rates of fever, diarrhea, and pneumoniae were higher in patients without COVID-19 vaccinations (p = 0.001, p = 0.012, and p = 0.027).  Conclusion: To lessen the effects of the disease, all eligible children should receive the COVID-19 vaccine. The illness may specifically endanger children with UCDs. What is Known: • Children with COVID-19 mainly present with fever and cough, as in adults. • COVID-19 may specifically threaten children with underlying chronic diseases. What is New: • Children with obesity have a higher vaccination rate against COVID-19 than children without obesity. • Among unvaccinated children, fever and pneumoniae might be seen at a higher ratio than among vaccinated children.

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

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

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

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

Is Posaconazole Really Effective in Adolescent patients as a Prophylactic Agent: Experience of a Tertiary Care Center.

BACKGROUND: Invasive fungal infections (IFIs) are a leading cause of morbidity and death in immunocompromised patients. Data on efficacy and pharmacokinetics of posaconazole in pediatric patients are rare (1 to 5). Herein, we retrospectively analyzed adolescent patients who had received posaconazole as antifungal prophylaxis. METHODS: We retrospectively analyzed patients who received posaconazole as primary or secondary antifungal prophylaxis. RESULTS: A total of 34 adolescent patients, 19 men (55.9%) and 15 women (44.1%) with a mean age of 15.8±2.1 years were included. Twenty-five of 34 (73.5%) patients were on primary and nine of 34 (26.5%) patients were on secondary antifungal prophylaxis. Diagnosis of the patients receiving posaconazole as primary antifungal prophylaxis were acute myeloid leukemia (n=12, 48%), hematopoietic stem cell transplantation (n=7, 28%), acute lymphoblastic leukemia (n=5, 20%), and Fanconi aplastic anemia (n=1, 4%). Five patients (55.6%) with hematopoietic stem cell transplantation, 1 patient with acute myeloid leukemia (11.1%), 1 patient with Fanconi aplastic anemia (11.1%), and 2 (22.2%) patients with chronic granulomatous disease received posaconazole as secondary antifungal prophylaxis. Twelve of 25 (48%) patients receiving posaconazole as primary antifungal prophylaxis were complicated by IFI; 4 of them were proven, 6 probable, and 2 with possible IFI. Three of 9 patients (33.3%) receiving posaconazole as secondary antifungal prophylaxis was complicated by IFI (P=0.29), 2 of them were probable and 1 was possible IFI. Five of 25 patients (20%) receiving posaconazole as primary prophylaxis died because of IFI. CONCLUSION: Improvement of antifungal prophylaxis in patients with high risk of invasive infections seems clearly necessary, and analyzing serum posaconazole levels and individualizing dosing may be 1 approach to improve outcomes.

A case of Raoultella ornithinolytica urinary tract infection in a pediatric patient.

Raoultella ornithinolytica is a Gram-negative, non-motile, encapsulated, biofilm producing, facultative aerobic bacillus and is found in natural environment. Human infections with R.ornithinolytica is rare in children with only five cases having been reported previously. The present case report describes an urinary tract infection caused by R. ornithinolytica that was identified by MALDI-TOF MS and successfully treated with antibiotic therapy in a 6.5-year-old female child.

Hand, foot, and mouth disease: could EPs® 7630 be a treatment option? A prospective randomized open-label multicenter clinical study.

Purpose: Hand, foot and mouth disease (HFMD) is a viral contagious disease of children caused by human enteroviruses (EVs) and coxsackieviruses (CVs). There is no specific treatment option for HFMD. EPs® 7630's anti-infective and immunomodulatory properties have previously been demonstrated in several in vitro and in vivo studies; however, the use of this herbal medicine in children with HFMD has not previously been investigated. Methods: This prospective randomized multicenter clinical study included 208 children with HFMD. The diagnosis was made by pediatricians. The patients who were within the first 48 h of symptom onset (according to the first onset of fever and skin findings) were enrolled. The study participants were assigned into 2 groups as EPs® 7630 and control groups. All patients were followed up twice more, 48 h after the first admission and on the 5th-7th day. Another phone evaluation was conducted for those with continued complaints from the previous visit. Results: The median age was 27 (12-112) months. The male-female ratio was 0.98. One hundred thirty one (63%) of 190 patients had no history of household contact. EPs® 7630 group included 94 and control group included 96 patients. A significant difference was found between the groups in terms of complaint scores at the visits made at the 48th h of the treatment and on days 5-7 (p < 0.001). The mean ± SD disease duration of EPs® 7630 users was significantly shorter 6.07 ± 0.70 days (95% CI: 5.92-6.21)] than the control group [8.58 ± 0.94 days (95% CI: 8.39-8.77)] (p < 0.001). Besides, the hospitalization rate among the EPs® 7630 users were significantly lower (p = 0.019). No side effects were observed, except for unpleasant taste, which was reported in 5 patients (EPs® 7630 group). Conclusion: Considering its efficacy and safety profile EPs® 7630 may represent a feasible herbal-based treatment option for children with HFMD. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT06353477).

Myoclonic seizure due to cyclopentolate eye drop in a preterm infant.

Cyclopentolate is widely used in ophthalmology for its intense mydriatic and cycloplegic activity. Systemic side effects have been described in both adults and children. Myoclonic seizure is a rare side effect of eye drops that are used in eye examinations. We report herein a case of convulsion in a three month- old girl following cyclopentolate hydrochloride and phenylephrine hydrochloride eye drops, which were used in advance of ophthalmoscopy for examination of retinopathy of prematurity (ROP). Physicians should be aware of the uncommon systemic side effects of cyclopentolate, and drops should be used in appropriate dosages.

COVID-19 associated lower urinary tract symptoms in children.

INTRODUCTION: SARS-COV-2 is associated with unexpected symptoms. Several studies in adults reported urinary frequency with COVID-19. The aim of this study is to reveal lower urinary tract symptoms associated with COVID-19 (CALUTS) in children. PATIENTS-METHODS: All children diagnosed with COVID-19 and associated multisystem inflammatory syndrome in children (MIS-C) between November 2020-June 2021 in our hospital were reviewed and asked for urinary symptoms at the time of or following their disease. The ones reporting symptoms were invited for further evaluation. Parents were inquired for their child's former bladder and bowel function, their symptoms after the diagnosis of COVID-19 or MIS-C, onset and duration of the symptoms, and their current state. They were questioned for the frequency of voiding as well as dysuria, odor, and the presence of incontinence as well as other symptoms of COVID-19. The patients who reported symptoms at the time of inquiry were followed for cessation of symptoms. The parameters age, sex, need for hospitalization and admission to ICU were also compared to the whole group to evaluate the main characteristics of patients with lower urinary tract symptoms. RESULTS: In total 20 patients (18/216 with acute disease and 2/36 with MIS-C) reported CALUTS (figure). Age and sex distribution were not significantly different from the patients without urinary symptoms (p = 0.777 and p = 0.141 respectively). All were otherwise healthy children with no concomitant chronic diseases other than overactive bladder in two. There were 13 girls and 7 boys. Mean age was 11 years (±5 years). Thirteen of the patients were older than 10 years; however, there were also 3 children under 5 years of age. All parents described a sudden onset of extremely increased urinary frequency and urgency lasting for weeks which disappeared gradually. Median bladder and bowel dysfunction questionnaire (BBDQ) score before COVID-19 was 2.5 (1-18) which increased to a median of 22 (15-29) at the time of the symptoms (p < 0.001). The timing of onset and duration of symptoms were variable and not associated with symptom severity (p = 0.306 and p = 0.450 respectively). Eight patients (40%) reported diarrhea. The duration of diarrhea was limited to less than one week in all. CONCLUSIONS: Our study revealed that SARS-COV-2 can be associated with lower urinary tract symptoms also in children both during the acute phase and MIS-C. Further studies are necessary to understand the etiopathogenesis and prevalence of this unexpected aspect of COVID-19.

A new use of Lactobacillus rhamnosus GG administration in the NICU: colonized vancomycin-resistant enterococcus eradication in the gastrointestinal system.

INTRODUCTION: Enterococci are microbiota microorganisms that normally have low virulence; however, under some conditions they may cause community-acquired urinary tract and even hospital-acquired serious infections. Vancomycin-resistant enterococci (VRE) can cause aggressive infections in immunosuppressive patients; especially in newborns in intensive care units. Asymptomatic gastrointestinal system carriers are important sources of VRE. Asymptomatic patients colonized by VRE can infect both other patients and the environment. Prevention of gastrointestinal colonization of VRE is an important issue to prevent VRE infection, and for rational use of hospital source. METHOD: This study was carried out at Hacettepe University, Faculty of Medicine in Newborn Intensive Care Unit between November 2015 and March 2017. The newborn infants who were find as colonized by VRE during weekly surveillance VRE rectal stool culture screening were taken into the study. A single dose of one million colonies of Lactobacillus rhamnosus GG (LGG®) was given to the study group daily. The probiotic supplement continued until consecutive three negative cultures were detected or maximum 6 months. Control group received conventional treatment. RESULTS: In the study group, VRE eradication was successful in 21 patients out of 22 within 6 months and 1 patient was still VRE positive at 6 months. In the control group, VRE was eradicated in 12 patients out of 23 and 11 patients continued to be colonized by VRE at 6 months. There was a statistically significant difference between the groups (p <.05). CONCLUSION: Lactobacillus rhamnosus GG use is associated with early clearance of vancomycin-resistant enterococcus in newborn patients.