Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency.

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52LOF/IκBδGOF). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52LOF/IκBδLOF) or gain-of-function of p52 (hereafter, p52GOF/IκBδLOF). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.

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.

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.

A novel double hemizygous BTK mutation in a boy presenting with Pseudomonas skin abscesses.

Skin manifestations can serve as critical clues for early diagnosis of inborn errors of immunity. We report a patient with a double novel mutation in the BTK gene, who presented with skin abscesses caused by Pseudomonas aeruginosa. This case illustrates the importance of immune evaluation in patients with therapy-resistant skin lesions.

Incidence of primary vesicoureteral reflux in patients with febrile convulsions.

The aim of this study is to evaluate the incidence of vesicoureteral reflux (VUR) in patients with febrile convulsion (FC). For this, patients that were diagnosed with FC in 2018 were retrospectively reviewed. Those with epilepsy, motor/mental retardation, or spina bifida were excluded. Mid-stream urine samples were collected in children who were toilet trained while sterile bags were used in the smaller. Urinary tract infection (UTI) was defined as ˃ 5 leucocytes/HPF in urinalysis and a subsequent positive urine culture (≥ 10.000 CFU/ml). Children with UTI were further investigated via voiding cystourethrogram (VCUG) and dimercaptosuccinic acid (DMSA) scintigraphy for VUR. Urinalysis was present in 79 among a total of 181 patients (43.6%). Forty-five of the patients were male (57%). Mean age was 2.6 ± 1.4 years. UTI was diagnosed in 6 (7.6%) patients (5 females, 1 male). Three of the girls had recurrent febrile UTI and subsequently, VUR was diagnosed in two of them. VUR is found in 2.5% of the FC cases with urine sampling. Urinalysis should not be ignored in patients with FC as it may lead to diagnosis of VUR.

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.

Abducens nerve palsy in a girl with incomplete Kawasaki disease.

Kawasaki disease (KD) is a systemic vasculitis that can involve the nervous system, including the cranial nerves. Central nervous system findings, especially irritability, lethargy, and aseptic meningitis, occur in 1-30 % of KD patients (1). Cranial nerve palsies are seen rarely, and abducens nerve palsy has been reported in only three children. We describe a 2.5-year-old girl with incomplete KD who developed transient abducens nerve palsy after intravenous immunoglobulin (IVIG) treatment.

Toxic epidermal necrolysis treated with N-acetylcysteine.

Adverse drug reactions are the major cause of morbidity and mortality worldwide. Cutaneous drug reaction is the most common type of adverse reaction. Toxic epidermal necrolysis (TEN) is a rare, life-threatening mucocutaneous disease, usually attributable to drugs. There is no proven therapy for TEN. The mainstay of therapy is immediate withdrawal of the culprit drug, using disease-modifying agents, and meticulous supportive care. Several disease-modifying agents have been used such as steroid, i.v. human immunoglobulin (IVIg), plasmapheresis. A 10-year-old epileptic girl was admitted with lamotrigine-induced TEN. She was unresponsive to steroid. Her condition deteriorated despite IVIg treatment. She was treated with N-acetylcysteine (NAC). To our knowledge this is the first report of a child with TEN, a potentially lethal disorder, treated with NAC. NAC may be effective for children with TEN.

Pathogens in Pediatric Septic Arthritis: A Multi-Center Study in Turkiye (PEDSART Study).

OBJECTIVES: Septic arthritis (SA) is a serious bacterial infection that must be treated efficiently and timely. The large number of culture-negative cases makes local epidemiological data important. Accordingly, this study aimed to evaluate the etiology, clinical characteristics, and therapeutic approach of SA in children in Turkiye, emphasizing the role of real-time polymerase chain reaction (PCR) techniques in the diagnosis. METHODS: In this multi-center, prospective study, children hospitalized due to SA between February 2018 and July 2020 in 23 hospitals in 14 cities in Turkiye were included. Clinical, demographic, laboratory, and radiological findings were assessed, and real-time PCR was performed using synovial fluid samples. RESULTS: Seventy-five children aged between 3 and 204 months diagnosed with acute SA were enrolled. Joint pain was the main complaint at admission, and the most commonly involved joints were the knees in 58 patients (77.4%). The combination of synovial fluid culture and real-time PCR detected causative bacteria in 33 patients (44%). In 14 (18.7%) patients, the etiological agent was demonstrated using only PCR. The most commonly isolated etiologic agent was Staphylococcus aureus, which was detected in 22 (29.3%) patients, while Streptococcus pyogenes was found in 4 (5.3%) patients and Kingella kingae in 3 (4%) patients. Streptococcus pyogenes and Kingella kingae were detected using only PCR. Most patients (81.3%) received combination therapy with multiple agents, and the most commonly used combination was glycopeptides plus third-generation cephalosporin. CONCLUSIONS: Staphylococcus aureus is the main pathogen in pediatric SA, and with the use of advanced diagnostic approaches, such as real-time PCR, the chance of diagnosis increases, especially in cases due to Kingella kingae and Streptococcus pyogenes.

Evaluation of pneumococcal PCR and urinary antigen detection in children.

BACKGROUND: The rapid detection of Streptococcus pneumoniae could assist in the management of pneumococcal infections. The Binax NOW S. pneumoniae test is a rapid immunochromatographic test for this purpose. METHODS: Multiplex PCR in parapneumonic pleural effusion fluid (PPEF) and cerebrospinal fluid (CSF) with Binax NOW urinary pneumococcal antigen test (PAT) from 80 children was compared in this study. RESULTS: PAT had a sensitivity of 36.4%, specificity of 97.3%, in CSF. PAT had a sensitivity of 50%, specificity of 81% for parapneumonic pleural effusion fluid. CONCLUSIONS: When rapid management of a serious infection is needed the Binax NOW test could be a reliable method for the exclusion of S. pneumoniae infection.

Diagnosis of Immunoglobulin G4-related disease in a child with ligneous conjunctivitis: a novel mutation in plasminogen gene and plasminogen activator inhibitor-1 polymorphism.

OBJECTIVES: Ligneous conjunctivitis (LC) is a chronic conjunctivitis characterized by recurrent, firm, fibrin-rich, woody pseudomembranes on the palpebral conjunctiva. It is an ultrarare autosomal recessive disease associated with congenital plasminogen (PLG) deficiency due to mutations in the PLG gene (6q26). Immunoglobulin G4-related disease (IgG4-RD) is an idiopathic, systemic fibroinflammatory disease characterized by elevated serum IgG4 concentration and tissue infiltration of IgG4-positive plasma cells leading to organ enlargement, fibrosis and damage. CASE REPORT: A 7-year-old girl with LC was hospitalized for recurrent pancreatitis and diagnosed as IgG4-RD. PLG activity level was 15% (normal range 55-145%). Co-segregation analysis indicated that the patient was homozygous for the c. NG_016200.1(NM_000301.5):c.1465 T>C mutation in PLG gene. c. NG_016200.1(NM_000301.5):c.1465 T>C PLG variant was found to be heterozygous by NGS analysis in both parents. She also had plasminogen activator inhibitor - 1 (PAI-1) NG_013213.1(NM_000602.5):c.-816A>G (4G/4G) homozygous polymorphism and a heterozygote NG_001333.2 (NM_002769.5):c.292_293insC mutation in the serine protease 1 (PRSS-1) gene. However, heterozygous PRSS-1NG_001333.2 (NM_002769.5):c.292_293insC variant was found in the mother of the patient. All detected variants are currently considered as a variant of uncertain (or unknown) significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) classification. Oral steroid, oral azathioprine, topical fresh frozen plasma, topical heparin, topical steroid and topical cyclosporine were given. After 3 years of follow-up, IgG4-RD is under partial remission and no pseudomembranes. CONCLUSION: She is the second case had both LC and IgG4-RD. We identified a NG_016200.1(NM_000301.5):c.1465 T>C novel homozygous mutation in PLG gene and a PAI-1 NG_016200.1(NM_000301.5):c.1465 T>C (4G/4G) homozygous polymorphism, which has been reported as a risk factor for thrombotic events.

Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis.

Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αß T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αß and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αß T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in response to TCR crosslinking, mitogens, or forced synapse formation with autologous B lymphocytes. Finally, the patients' total lymphocytes secrete small amounts of IFN-γ, and CD4+, CD8+, DN αß T, Vδ2+ γδ T, and MAIT cells display impaired IFN-γ production in response to BCG. Inherited ITK deficiency undermines the development and function of various IFN-γ-producing T cell subsets, thereby underlying TB.

The epidemiology and economic impact of varicella-related hospitalizations in Turkey from 2008 to 2010: a nationwide survey during the pre-vaccine era (VARICOMP study).

Varicella can cause complications that are potentially serious and require hospitalization. Our current understanding of the causes and incidence of varicella-related hospitalization in Turkey is limited and sufficiently accurate epidemiological and economical information is lacking. The aim of this study was to estimate the annual incidence of varicella-related hospitalizations, describe the complications, and estimate the annual mortality and cost of varicella in children. VARICOMP is a multi-center study that was performed to provide epidemiological and economic data on hospitalization for varicella in children between 0 and 15 years of age from October 2008 to September 2010 in Turkey. According to medical records from 27 health care centers in 14 cities (representing 49.3% of the childhood population in Turkey), 824 children (73% previously healthy) were hospitalized for varicella over the 2-year period. Most cases occurred in the spring and early summer months. Most cases were in children under 5 years of age, and 29.5% were in children under 1 year of age. The estimated incidence of varicella-related hospitalization was 5.29-6.89 per 100,000 in all children between 0-15 years of age in Turkey, 21.7 to 28 per 100,000 children under 1 year of age, 9.8-13.8 per 100,000 children under 5 years of age, 3.96-6.52 per 100,000 children between 5 and 10 years of age and 0.42 to 0.71 per 100,000 children between 10 and 15 years of age. Among the 824 children, 212 (25.7%) were hospitalized because of primary varicella infection. The most common complications in children were secondary bacterial infection (23%), neurological (19.1%), and respiratory (17.5%) complications. Secondary bacterial infections (p < 0.001) and neurological complications (p < 0.001) were significantly more common in previously healthy children, whereas hematological complications (p < 0.001) were more commonly observed in children with underlying conditions. The median length of the hospital stay was 6 days, and it was longer in children with underlying conditions (<0.001). The median cost of hospitalization per patient was $338 and was significantly higher in children with underlying conditions (p < 0.001). The estimated direct annual cost (not including the loss of parental work time and school absence) of varicella-related hospitalization in children under the age of 15 years in Turkey was $856,190 to $1,407,006. According to our estimates, 882 to 1,450 children are hospitalized for varicella each year, reflecting a population-wide occurrence of 466-768 varicella cases per 100,000 children. In conclusion, this study confirms that varicella-related hospitalizations are not uncommon in children, and two thirds of these children are otherwise healthy. The annual cost of hospitalization for varicella reflects only a small part of the overall cost of this disease, as only a very few cases require hospital admission. The incidence of this disease was higher in children <1 year of age, and there are no prevention strategies for these children other than population-wide vaccination. Universal vaccination is therefore the only realistic option for the prevention of severe complications and deaths. The surveillance of varicella-associated complications is essential for monitoring of the impact of varicella immunization.

The relationship between helicobacter pylori infection and nodular antral gastritis in pediatric patients.

BACKGROUND: Helicobacter pylori (H. pylori) is a spiral-shaped gram-negative bacterium that colonizes the gastric mucosa. It is a common infectious agent in children. In this study, we aim to evaluate the demographic data, and the clinical and histopathological findings of pediatric patients that underwent upper gastrointestinal endoscopy (UGSE) in our clinic. METHODS: Between July 2017 and February 2019, 636 patients applied to the Selcuk University Faculty of Medicine, Pediatric Gastroenterology outpatient clinic with complaints of epigastric abdominal pain and/or dyspeptic complaints. Patients who underwent upper gastrointestinal endoscopy were evaluated retrospectively. Data on age, gender, family history of peptic ulcer disease, and family history of H. pylori were recorded. Endoscopic and histopathological findings were collected from medical records. RESULTS: 235 (36.9%) of the patients participating in the study were male, and 401 (63.1%) were female. H. pylori infection was detected in 277 (43.6%) patients as a result of histopathological examination of H. Pylori, urea breath tests and H. Pylori antigen tests in the stools of patients are included in the study. Nodular antral gastritis was detected in 282 (44.3%) of our patients endoscopically. H. pylori was detected in 83.7% (n: 236) of the 282 patients with nodular antral gastritis. Nodular antral gastritis was observed to be significantly higher in H. pylori-positive patients than in H. pylori-negative cases (odds ratio (OR), 39.16; 95% confidence interval (CI), 24.88-61.64; p: <0.001). CONCLUSION: Nodular antral gastritis is caused by chronic H. pylori infection. It is predicted that early detection of H. pylori infection in children is important and may decrease complications later in life. Our study shows that all the markers evaluated are very good predictors of H. pylori infection. Positive significant association was found between the prevalence of H. pylori infection and nodular antral gastritis.

Evaluation of hematological parameters and inflammatory markers in children with COVID-19.

BACKGROUND: The aim of this study was to evaluate hematological parameters in children with COVID-19 and determine the effects of inflammatory biomarkers on the assessment of hospitalization. METHODS: This retrospective single-center study was performed on 633 children with COVID-19 between March 2020 and January 2021. The study population was separated into two groups: inpatients (n = 83) and outpatients (n = 550). Univariate and multivariate logistic regression was applied to identify risk factors for hospitalization. RESULTS: Lymphopenia (n = 228, 36%) was found mainly to be a hematological abnormality in all cases. Compared with outpatients, inpatients had significantly higher white blood cell (WBC) (p = 0.005), lymphocyte (p < 0.001), and platelet counts (p = 0.036), and significantly higher red cell distribution width (p = 0.001), C-reactive protein (CRP) (p = 0.003), procalcitonin (p = 0.001), D-dimer (p < 0.001), and lymphocyte to monocyte ratio values (p = 0.004). On the other hand, they had significantly lower values of hemoglobin (p < 0.001), neutrophil to lymphocyte ratio (p = 0.024), platelet lymphocyte ratio (p = 0.001), derivated neutrophil to lymphocyte ratio (p = 0.037), and mean platelet volume to lymphocyte ratio (p < 0.001). ROC analysis showed that WBC, CRP, and procalcitonin cutoff values were the best discriminated between inpatients and outpatients. The results for the areas under the curve of WBC, CRP, and procalcitonin used to assess patients' hospitalization were 0.595 (95% CI 0.519-0.670, p = 0.005), 0.599 (95% CI 0.527-0.672, p = 0.003), and 0.599 (95% CI 0.525-0.673, p = 0.004), respectively. CONCLUSION: We suggest that high WBC and procalcitonin levels can be used as independent predictors of hospitalization in children with COVID-19.

Gastrointestinal and Liver Manifestations in Children with COVID-19 and Their Relationship to Clinical Course.

OBJECTIVE: Coronavirus disease 2019 is a major health problem in all age groups. Although most clinical symptoms are respiratory, gastrointestinal symptoms are often reported. This is a major concern for children and has limited research coverage. In this study, we evaluated the frequencies of gastrointestinal symptoms and liver biochemical findings in children with coronavirus disease 2019 and their relationship with clinical course and length of hospital stay. MATERIALS AND METHODS: Demographic data, clinical, and laboratory findings of children with Coronavirus disease 2019 who were followed up by the Department of Pediatric Infectious Diseases between March 2020 and August 2020 were recorded. They were classified accord- ing to age groups as <5 years, 5-10 years, and >10 years. Laboratory findings were analyzed according to age groups. Demographic, clinical, and laboratory findings were compared in both situations, the presence of gastrointestinal symptoms and the presence of elevated liver enzymes. It was considered statistically significant if it was <.05. RESULTS: A total of 294 patients (median age 10 years [14 days to 18 years]) were enrolled in this study. Although fever is the most common symptom of coronavirus disease 2019, 15.6% of patients presented with acute gastroenteritis. Most patients with liver involvement (n = 130, 44.2%) were under 5 years of age (n = 74, 56.9%, P <.001). The patterns of abnormal liver test results were cholestatic (71.5%), hepatocellular (18.4%), and mixed (10%) types. Severe or mas- sive elevation of aminotransferase or liver failure was not observed. No statistically significant difference was noted in outcomes, including length of stay, for patients with gastrointestinal symptoms (P = .178) or liver involvement (P = .146). CONCLUSION: The presence of gastrointestinal symptoms or elevated liver enzymes does not affect the course of the disease in children with coronavirus disease 2019.

Evaluation of vaccination status of health care workers for recommended vaccines and their acceptance of SARS-CoV-2 vaccines.

INTRODUCTION: Health care workers (HCWs) are disproportionately exposed to infectious diseases and play a role in nosocomial transmission, making them a key demographic for vaccination. HCW vaccination rates are not optimal in many countries; hence, compulsory vaccination policies have been implemented in some countries. Although these policies are effective and necessary under certain conditions, resolving HCWs' hesitancies and misconceptions about vaccines is crucial. HCWs have the advantage of direct contact with patients; hence, they can respond to safety concerns, explain the benefits of vaccination, and counter antivaccine campaigns that escalate during pandemics, as has been observed with COVID-19. METHOD: A short survey was carried out in May-June 2020 on the vaccination status of HCWs working with pediatric patients with COVID-19. The survey inquired about their vaccination status (mumps/measles/rubella [MMR], varicella, influenza, and diphtheria/tetanus [dT]) and willingness to receive hypothetical future COVID-19 vaccines. The respondents were grouped according to gender, age, occupation, and region. RESULTS: In total, 4927 HCWs responded to the survey. Most were young, healthy adults. The overall vaccination rates were 57.8% for dT in the past 10 years, 44.5% for MMR, 33.2% for varicella, and 13.5% for influenza. Vaccination rates were the highest among physicians. The majority of HCWs (81%) stated that they would be willing to receive COVID-19 vaccines. CONCLUSION: Although vaccination rates for well-established vaccines were low, a majority of HCWs were willing to receive COVID-19 vaccines when available. Education and administrative trust should be enhanced to increase vaccination rates among HCWs.

A novel homozygous COL11A2 deletion causes a C-terminal protein truncation with incomplete mRNA decay in a Turkish patient.

Recessive mutations in COL11A2 (collagen, type XI, alpha 2), are responsible for otospondylomegaepiphyseal dysplasia (OSMED) and non-syndromic hearing loss while dominant mutations are associated with Stickler type III, isolated cleft palate, Robin sequence, non-ophthalmic Stickler syndrome, early onset osteoarthritis and autosomal dominant hearing loss. We describe here the clinical findings of two Turkish cousins with OSMED carrying a novel homozygous truncating mutation in exon 38 of COL11A2 gene, c.2763delT, identified on cDNA and confirmed at gDNA. This mutation is located on triple helix repeat domain of the collagen alpha-2(XI) chain, where the majority of the previously identified mutations are located. Real-time RT-PCR experiment provided that mutated transcript does not decay completely. Although our analysis displays the partial survival of the mutant transcript from blood tissue, not from cartilage, we propose that this mechanism may play an important role on the variable expressivity of the heterozygous COL11A2 gene mutations.