Emerging trends in pediatric candidemia: mapping the rise in Candida parapsilosis incidence and antifungal resistance in Turkey.

Candidemia is emerging as a significant concern in children, particularly among those with underlying conditions like malignancies or prematurity. The interpretation of epidemiological data on candidemias and their antifungal resistance plays a vital role in aiding diagnosis and guiding clinicians in treatment decisions. From 2014 to 2021, a retrospective analysis was conducted in Istanbul, Turkey; comparing Candida albicans and non-albicans (NAC) spp in both surviving and deceased groups. Furthermore, an examination of Candida parapsilosis and other species was performed, assessing various clinical and laboratory parameters. Among 93 patients, with a median age of 17 months, C. parapsilosis emerged as the predominant isolated species (44%), followed by C. albicans (34.4%). Resistance to fluconazole, voricanozole, and echinocandins, along with a history of broad-spectrum antibiotic use were found to be significantly higher in the non-albicans Candida group compared to C. albicans group. In the C. parapsilosis group, statistically lower age was identified in comparison to the other groups (P = .018). In addition, high fluconazole and voriconazole resistance was detected in Candida parapsilosis spp. Our study highlights a notable prevalence of C. parapsilosis, particularly in younger children, which is different from similar studies in childhood. This trend may be attributed to the common use of total parenteral nutrition and central venous catheter in gastrointestinal disorders and metabolic diseases. Furthermore, as anticipated, high azole resistance is noted in C. parapsilosis and other non-albicans Candida species. Interestingly, resistance to both amphotericin B and echinocandins within this group has been notably high. It is crucial to emphasize the considerable antifungal resistance seen in C. parapsilosis isolates.

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.

COVID-19 associated thrombotic microangiopathy.

A limited number of cases of thrombotic microangiopathy (TMA) have previously been reported in association with COVID-19. Our report describes two cases of TMA associated with COVID-19, one of which was successfully treated with eculizumab. The first case was a 23-month-old girl, and the second case was a 9-month-old boy. PCR tests for SARS-CoV-2 were positive in both cases, and laboratory results showed microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. No known aetiology for TMA was found in either case. Stool tests for Shigatoxin-producing Escherichia coli were negative. Coagulation tests, ADAMTS13 activity, serum complement levels, and homocysteine levels were all within the normal range. No known genetic mutation was found, including mutations of complement, diacylglycerol kinase epsilon, and cobalamin C. In the first case, eculizumab was administered due to persistent haemolysis and prolonged anuria. In conclusion, TMA may be associated with COVID-19 infection. Treatment with eculizumab may be beneficial in selected patients because of the potential activation of the complement system.

New approach in stage 1 surgery for hypoplastic left heart syndrome: preliminary outcomes.

OBJECTIVES: We present the short-term results of an alternative method in stage 1 surgery for hypoplastic left heart syndrome. METHODS: Data of 16 consecutive patients who were treated with the novel method in our clinic between February 2019 and March 2021 were analysed retrospectively. Preoperative data and postoperative follow-up were recorded. RESULTS: Of the 16 operated patients, 12 were diagnosed with hypoplastic left heart syndrome, while four were diagnosed with hypoplastic left heart syndrome variants. Seven patients died during early postoperative period. One patient died at home waiting stage 2 surgery. Three patient underwent stage 2 surgery. Pulmonary artery reconstruction was performed in one patient due to left pulmonary artery distortion. CONCLUSIONS: We believe that our method can be an effective alternative in the surgery of hypoplastic left heart syndrome and its variants. It is hoped that with increasing number of studies and more experience better outcome will be achieved.

A case of severe DRESS syndrome treated with therapeutic plasma exchange and intravenous immunoglobulin therapy.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in children is a rare adverse drug reaction with skin rash, fever, hematologic abnormalities, and multiorgan involvement. The diagnosis is difficult because of its various clinical presentations, nonetheless is extremely important due to the mortality rate. We describe a 14-year-old boy who developed hypersensitivity to either teicoplanin or meropenem therapy. After failing to improve with corticosteroids, he was successfully treated with therapeutic plasma exchange (TPE). TPE should be considered in the treatment with corticosteroid-resistant DRESS syndrome.

Diagnostic and Prognostic Biomarkers of Coronavirus Disease 2019 in Children.

Predictors of early diagnosis and severe infection in children with coronavirus disease 2019 (COVID-19), which has killed more than 4 million people worldwide, have not been identified. However, some biomarkers, including cytokines and chemokines, are associated with the diagnosis, pathogenesis and severity of COVID-19 in adults. We examined whether such biomarkers can be used to predict the diagnosis and prognosis of COVID-19 in pediatric patients. Eighty-nine children were included in the study, comprising three patient groups of 69 patients (6 severe, 36 moderate and 27 mild) diagnosed with COVID-19 by real-time polymerase chain reaction observed for 2-216 months and clinical findings and 20 healthy children in the same age group. Hemogram, coagulation, inflammatory parameters and serum levels of 16 cytokines and chemokines were measured in blood samples and were analyzed and compared with clinical data. Interleukin 1-beta (IL-1ß), interleukin-12 (IL-12) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in the COVID-19 patients (p = 0.035, p = 0.006 and p < 0.001). Additionally, D-dimer and IP-10 levels were higher in the severe group (p = 0.043 for D-dimer, area under the curve = 0.743, p = 0.027 for IP-10). Lymphocytes, C-reactive protein and procalcitonin levels were not diagnostic or prognostic factors in pediatric patients (p = 0.304, p = 0.144 and p = 0.67). Increased IL-1ß, IL-12 and IP-10 levels in children with COVID-19 are indicators for early diagnosis, and D-dimer and IP-10 levels are predictive of disease severity. In children with COVID-19, these biomarkers can provide information on prognosis and enable early treatment.

COVID-19 in Turkey: A tertiary center experience.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a serious epidemic in our country and all over the world since December 2019 and has become a global health problem. The disease caused by the SARS-CoV-2 virus has been named as coronavirus disease 19 (COVID-19). METHODS: We report on the epidemiological and clinical features of 37 children diagnosed with COVID-19. RESULTS: The median age was of the children was 10 years and 57.1% were male. In addition, 78.3% of the children had a history of contact with adult patients who had been diagnosed with COVID-19, and 27.0% had coexisting medical conditions. We found that 40.5% of our patients had mild infection, while 32.4% had moderate infection, and 27.1% had developed severe or critical illness. The most common abnormal laboratory findings in our patients were decreased lymphocytes (45.9%) and increased D-dimer values (43.2%), while abnormal radiological findings were detected in 56.7% of the children. In addition, 64.8% of the children had received azithromycin, 59.4% had received oseltamivir, and hydroxychloroquine was used in combination with azithromycin in 35.1% of the children. Non-invasive mechanical ventilation was required in 27.0% of the children. CONCLUSIONS: Although COVID-19 infection is usually mild in children, severe illness can be seen in children with comorbidities, or even in children who were previously healthy.

Sternotomy with electrocautery and sternal wound infection in congenital heart surgery in patients under 1 year of age.

OBJECTIVE: The present study aimed to compare the rate of wound site infection in patients <1 year of age who underwent sternotomy using electrocautery, a routinely performed procedure in our clinic, with those reported in the literature. METHODS: This double-center study included patients <1 year of age who underwent cardiac surgery via sternotomy performed with electrocautery for congenital heart disease between January 2017 and June 2019. Patient's data were retrospectively obtained from the hospital records. RESULTS: In our study, seven patients developed SSI, which was superficial in six (1.3%) patients and in the form of mediastinitis in one (0.2%) patient. CONCLUSION: Sternotomy with electrocautery, which we consider an easy and safe method, was also not found to be statistically different from the other methods in terms of SWI.

Daily Practice of Mechanical Ventilation and Weaning in Turkish PICUs: A Multicenter Prospective Survey.

OBJECTIVES: To investigate conventional mechanical ventilation weaning characteristics of patients requiring conventional mechanical ventilation support for greater than 48 hours within the PICU. DESIGN: The prospective observational multicenter cohort study was conducted at 15 hospitals. Data were being collected from November 2013 to June 2014, with two designated researchers from each center responsible for follow-up and data entry. SETTING: Fifteen tertiary PICUs in Turkey. PATIENTS: Patients between 1 month and 18 years old requiring conventional mechanical ventilation for greater than 48 hours were included. A single-center was not permitted to surpass 20% of the total sample size. Patients with no plans for conventional mechanical ventilation weaning were excluded. INTERVENTIONS: Conventional mechanical ventilation MEASUREMENTS AND MAIN RESULTS:: Pertinent variables included PICU and patient demographics, including clinical data, chronic diseases, comorbid conditions, and reasons for intubation. Conventional mechanical ventilation mode and weaning data were characterized by daily ventilator parameters and blood gases. Patients were monitored until hospital discharge. Of the 410 recruited patients, 320 were included for analyses. A diagnosis of sepsis requiring intubation and high initial peak inspiratory pressures correlated with a longer weaning period (mean, 3.65 vs 1.05-2.17 d; p < 0.001). Conversely, age, admission Pediatric Risk of Mortality III scores, days of conventional mechanical ventilation before weaning, ventilator mode, and chronic disease were not related to weaning duration. CONCLUSIONS: Pediatric patients requiring conventional mechanical ventilation with a diagnosis of sepsis and high initial peak inspiratory pressures may require longer conventional mechanical ventilation weaning prior to extubation. Causative factors and optimal weaning for this cohort needs further consideration.

P-Wave Changes Associated with Chiari Network in the Right Atrium.

The Chiari network (CN) is a mobile, net-like structure occasionally present in the right atrium, near the opening of the inferior vena cava and coronary sinus. While typically asymptomatic, it may contribute to thromboembolism or right atrial pathologies. Here, we hypothesized that existing differences in P-wave morphology on electrocardiograms (ECG) may be associated with atrial conduction changes. Seventy-one children with a CN were recruited and matched to 60 healthy controls. P-wave duration, P-wave amplitude, P dispersion (Pd), QRS, PR, QT, and QTc (calculated with Bazett formula) intervals were measured and compared. Between the control and the patient groups, the mean P-wave duration was 78.1 ms and 88.7 ms, P amplitude was 1.3 mm and 1.1 mm, and Pd was 18.9 and 35.5 ms, respectively. These differences were statistically significant across all measurements (p < 0.05). Atrial conduction may be affected in patients with CN, and these patients may then develop atrial arrhythmia.

Aetiological evaluation of chest pain in childhood and adolescence.

BACKGROUND: Chest pain, as a common cause of hospital admissions in childhood, necessitates detailed investigations due to a wide range of differential diagnoses. In this study, we aimed to determine the distribution of diseases causing chest pain in children and investigate the clinical characteristics of children with chest pain. METHODS: This study included 782 patients aged between 3 and 18 years who presented to a paediatric cardiology outpatient clinic with chest pain between April 2017 and March 2018. Aetiological causes and demographic features of the patients were analysed. RESULTS: Most prevalent causes of chest pain were musculoskeletal system (33%) and psychogenic (28.4%) causes. Chest pain due to cardiac reasons was seen in eight patients (1%). Diseases of musculoskeletal and gastrointestinal systems and psychogenic disorders were significantly more common in male and female patients, respectively (p < 0.001 for all). In winter, patients' age and the number of patients with ≥12 years were higher than those in other seasons (p < 0.001). Most of the parents (70.8%) and patients (90.2%) thought that chest pain in their children was caused by cardiac causes. CONCLUSION: Most of the diagnoses for chest pain in childhood period are benign and include the musculoskeletal system and psychogenic diseases. Although chest pain due to cardiac diseases is rare, a comprehensive analysis of medical history, detailed physical examination and cardiac imaging with echocardiography is needed to reach more accurate diagnoses.

Evaluation of Continuous Renal Replacement Therapy and Therapeutic Plasma Exchange, in Severe Sepsis or Septic Shock in Critically Ill Children.

Background and objective: Severe sepsis and septic shock are life-threatening organ dysfunctions and causes of death in critically ill patients. The therapeutic goal of the management of sepsis is restoring balance to the immune system and fluid balance. Continuous renal replacement therapy (CRRT) is recommended in septic patients, and it may improve outcomes in patients with severe sepsis or septic shock. Therapeutic plasma exchange (TPE) is another extracorporeal procedure that can improve organ function by decreasing inflammatory and anti-fibrinolytic mediators and correcting haemostasis by replenishing anticoagulant proteins. However, research about sepsis and CRRT and TPE in children has been insufficient and incomplete. Therefore, we investigated the reliability and efficacy of extracorporeal therapies in paediatric patients with severe sepsis or septic shock. Materials and methods: We performed a multicentre retrospective study using data from all patients aged <18 years who were admitted to two paediatric intensive care units. Demographic data and reason for hospitalization were recorded. In addition, vital signs, haemogram parameters, and biochemistry results were recorded at 0 h and after 24 h of CRRT. Patients were compared according to whether they underwent CRRT or TPE; mortality between the two treatment groups was also compared. Results: Between January 2014 and April 2019, 168 septic patients were enrolled in the present study. Of them, 47 (27.9%) patients underwent CRRT and 24 underwent TPE. In patients with severe sepsis, the requirement for CRRT was statistically associated with mortality (p < 0.001). In contrast, the requirement for TPE was not associated with mortality (p = 0.124). Conclusion: Our findings revealed that the requirement for CRRT in patients with severe sepsis is predictive of increased mortality. CRRT and TPE can be useful techniques in critically ill children with severe sepsis. However, our results did not show a decrease of mortality with CRRT and TPE.

Investigation of relation between visceral and subcutaneous abdominal fat volumes and calcified aortic plaques via multislice computed tomography.

OBJECTIVE: The present study investigated effect of subcutaneous fat volume and abdominal visceral fat volume on aortic atherosclerosis via multislice computed tomography. MATERIALS AND METHODS: The present study comprised 424 subjects who underwent non-contrast-enhanced abdominal CT in our clinic between June 2012 and June 2013. Using dedicated software visceral fat volume was calculated for each individual and then subcutaneous fat volume was calculated by subtracting visceral fat volume from total fat volume. By dividing visceral fat volume/subcutaneous fat volume participants were assigned to three groups according to their mean visceral fat volume/subcutaneous fat volume: Group 1 consisted of subjects with visceral fat volume/subcutaneous fat volume lower than 0.48 (Group 1 < 0.48); Group 2 consisted of subjects with visceral fat volume/subcutaneous fat volume equal to or higher than 0.48 and lower than 0.69 (0.48 ≤ Group 2 < 0.69); and Group 3 consisted of subjects with visceral fat volume/subcutaneous fat volume equal to or higher than 0.69 (Group 3 ≥ 0.69). RESULTS: The mean abdominal aortic calcium scores according to Agatston scoring (au) were 136.8 ± 418.7 au in Group 1, 179.9 ± 463 au in Group 2 and 212.2 ± 486.9 in Group 3, respectively. CONCLUSIONS: We have demonstrated a significant correlation between visceral fat volume and abdominal aorta atherosclerosis, while there was absence of significant correlation between subcutaneous fat volume and abdominal atherosclerosis.

Can Complete Blood Count Parameters and Serum Electrolyte Levels Have a Predictive Role in Differential Diagnosis of Tuberculosis from Community-acquired Pneumonia in Children?

The complete blood count (CBC) parameters and the ratios regarding these parameters have been demonstrated to be useful diagnostic biomarkers for many infectious diseases. Herein, we aimed to evaluate and compare the usefulness of the predictive role of the CBC in the differential diagnosis of pulmonary tuberculosis (TB) from community-acquired pneumonia (CAP) in children. We also compared serum electrolyte levels between the 2 diseases. In this retrospective study, we analyzed the efficacy of CBC parameters and neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), plateletto-lymphocyte ratio (PLR), neutrophil-to-monocyte-plus-lymphocyte ratio (NMLR), and serum electrolyte levels in the differential diagnosis of pulmonary TB from CAP in children. We also classified patients with TB into 2 groups according to the microbiologic confirmation. We investigated whether there is any difference regarding these parameters in patients with positive microbiologic results. A total of 163 patients diagnosed with TB and CAP were included in this study. The WBC, neutrophil and monocyte counts, NLR, MLR, NMLR, mean platelet volume (MPV), and C-reactive protein (CRP) values were higher in CAP. There was statistical significance among serum sodium and phosphorus (P) levels between the 2 groups. Microbiologic confirmation was determined in 37 (35.5%) patients with the diagnosis of TB. The NLR, MLR, NMLR, CRP, and P values were significantly higher in patients with microbiologic confirmation. The results of the present study suggest that complete blood count parameters, NLR, MLR, NMLR, and CRP can be useful and cost-effective markers in differentiating pulmonary TB from CAP in the early stages of diagnosis.

Treatment with enhanced external counterpulsation improves cognitive functions in chronic heart failure patients.

OBJECTIVES: Chronic heart failure (CHF) has been associated with an increased risk of poorer cognitive performance in older adults. Reversibility of cognitive impairment after medical treatment has been reported, although the restorative effects of enhanced external counterpulsation (EECP) on cognitive performance have not been studied. We investigated the effect of EECP on cognitive functions in CHF patients. STUDY DESIGN: Thirty-six individuals (mean age: 66±8 years) who were diagnosed with CHF and were New York Heart Association (NYHA) Class II-III and Canadian Cardiovascular Society (CCS) Class II-III participated in this study. Neuropsychological assessment was performed in these patients. RESULTS: Patients in the EECP treatment group showed a statistically significant improvement in spontaneous naming (p=0.011) and forward row score of the attention subset among domains of cognition (p=0.020) and interference time of executive function (p=0.012). CONCLUSION: Enhanced external counter pulsation resulted in improvement in all domains of cognitive functions except verbal and visual memory tests.

Comparison of Surgical Techniques Used in Ventricular Septal Defect Closure.

INTRODUCTION: We compared transatrial closure, tricuspid valve septal detachment, and tricuspid valve chordal detachment techniques for ventricular septal defect (VSD) closure. METHODS: Patients who had VSD closure with three different techniques in our clinic between September 2016 and December 2020 were retrospectively reviewed. A total of 117 patients were included in the study. The patients were divided into three groups: group 1, classical transatrial closure; group 2, closure with tricuspid valve septal detachment; and group 3, closure with tricuspid valve chordal detachment. The groups were evaluated by serial transthoracic echocardiography (preoperative, postoperative 1st day, postoperative 1st month). Cardiac rhythm checks and recordings were performed. RESULTS: No residual VSD was observed in early or late periods in any of the groups whose VSD closure was performed with the three different techniques. No severe tricuspid regurgitation (TR) was detected during the early and late postoperative periods of all operating procedures. When the groups were compared in terms of early/late TR after the operation (without TR+trace amount of TR and mild TR+moderate TR were compared), no statistically significant difference was found (P>0,05; P=0,969 and P>0,05; P=0,502). CONCLUSION: In this study, we found no statistically significant difference between three VSD closure techniques in terms of early TR, late TR, residual VSD, and permanent atrioventricular complete block during postoperative period. We hope that our results will be supported by the results of researches that are being made about this subject in large series.

The Notch1/CD22 signaling axis disrupts Treg function in SARS-CoV-2-associated multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcomes were previously correlated with Notch4 expression on Tregs, here, we show that Tregs in MIS-C were destabilized through a Notch1-dependent mechanism. Genetic analysis revealed that patients with MIS-C had enrichment of rare deleterious variants affecting inflammation and autoimmunity pathways, including dominant-negative mutations in the Notch1 regulators NUMB and NUMBL leading to Notch1 upregulation. Notch1 signaling in Tregs induced CD22, leading to their destabilization in a mTORC1-dependent manner and to the promotion of systemic inflammation. These results identify a Notch1/CD22 signaling axis that disrupts Treg function in MIS-C and point to distinct immune checkpoints controlled by individual Treg Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.

Thyroid hormones in children on antiepileptic therapy.

The aim of this study was to evaluate the thyroid function alterations in a group of epileptic children taking antiepileptic drugs (AEDs). Patients demographic data and the free throxine (fT4) and thyroid-stimulating hormone (TSH) levels at the beginning of the treatment and at the third, sixth and ninth months of AED treatment were recorded retrospectively. A total of 106 children, 59 males and 47 females, were enrolled in the study. Mean patient age was 3.7 years, ranging between 3 months and 14 years. In total, 54% of patients were on valproic acid (VPA), 16% phenobarbital (PB), 14% were on carbamazepine (CBZ), 6% were on oxcarbazepine (OXC), 5% were on levetiracetam, and 5% were on topiramate therapy. There were no significant differences in average fT4 values between the drug groups. But the mean fT4 levels of the patients on VPA therapy showed a clear decrease within the observation period. No significant difference in average TSH values between the groups was detected in the beginning and in the third and sixth month. However, in the ninth month, a significant increase in TSH values was found in the VPA group (p = 0.007). In the patients taking VPA, average TSH values rose progressively while staying within normal limits. During follow-up, thyroid dysfunction were found in 21 patients (19.6%). A statistically significant relationship was found between severe electroencephalography (EEG) findings and thyroid dysfunction (p = 0.041). It was concluded that epileptic children with severe EEG findings and using VPA could have thyroid dysfunction. These patients should be followed up closely by thyroid function tests during treatment.

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.

Notch1-CD22-Dependent Immune Dysregulation in the SARS-CoV2-Associated Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcome were previously correlated with Notch4 expression on regulatory T (Treg) cells, here we show that the Treg cells in MIS-C are destabilized in association with increased Notch1 expression. Genetic analysis revealed that MIS-C patients were enriched in rare deleterious variant impacting inflammation and autoimmunity pathways, including dominant negative mutations in the Notch1 regulators NUMB and NUMBL. Notch1 signaling in Treg cells induced CD22, leading to their destabilization in an mTORC1 dependent manner and to the promotion of systemic inflammation. These results establish a Notch1-CD22 signaling axis that disrupts Treg cell function in MIS-C and point to distinct immune checkpoints controlled by individual Treg cell Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.