An Outbreak of Shiga Toxin-Positive Enteroaggregative Escherichia coli 0104:H4 Related Hemolytic Uremic Syndrome in Turkey: A Multicenter Study.

INTRODUCTION: Serious outbreaks related to Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) have been reported globally. In 2011, Germany experienced a significant outbreak of HUS caused by enteroaggregative Escherichia coli (EAEC) O104:H4 strain. Since then, no other outbreaks of this strain have been reported. This study aims to evaluate pediatric patients affected by the second documented worldwide outbreak of STEC-HUS (EAEC O104:H4 serotype) contaminating local drinking water. METHODS: Medical records of patients hospitalized in five pediatric intensive care units (PICU) diagnosed with STEC-HUS between July and September 2022 were evaluated retrospectively. RESULTS: Eighteen patients (14 girls, and 4 boys) were enrolled in the study. The median age was 7.4 [Intetquartile range (IQ) 1.3-17] years. Abdominal pain was the most common symptom (100%). The mean duration between symptom onset and development of STEC-HUS was 3 days (IQ 1-9). EAEC O104:H4 serotype was detected in the stool samples of eight patients. Neurological involvement was observed in three patients, cardiac involvement in two patients, and both in one patient. Two patients required respiratory support and dialysis was performed in 16 (88.8%) patients. Plasmapheresis was administered to two patients, and eculizumab was given to four. No mortality was reported during follow-up; the mean durations of PICU and hospital stays were 11.3 and 31.6 days, respectively. CONCLUSION: Outbreaks of HUS can have severe implications on mortality and morbidity. However, timely diagnosis and implementation of appropriate supportive care, including dialysis, respiratory support, and suitable medical treatment for eligible patients, can lead to favorable outcomes.

Evaluation of paediatric herpes zoster cases: Comparison of herpes zoster attacks in children with and without underlying conditions.

AIM: Herpes zoster is rarely seen in children, but is more common and more severe in those with underlying medical conditions. The purpose of this study was to comprehensively evaluate cases of herpes zoster in all paediatric patients and to detail the clinical course and complications of this disease in children with and without underlying health problems in terms of similarities and differences. METHODS: The course of paediatric patients diagnosed with herpes zoster in a tertiary university hospital over a 19-year period was evaluated from the time of diagnosis, divided into groups with and without underlying disease. RESULTS: In our study, where we evaluated 150 herpes zoster attacks in 143 children, 79.3% of the patients (n = 119) had underlying diseases, while 20.7% (n = 31) were healthy children. The age at the time of primary varicella-zoster virus and herpes zoster was significantly younger in the group without an underlying disease compared to the group with an underlying disease. Pain was reported more in the healthy group, and the duration of symptoms was longer. Ophthalmic nerve involvement was significantly higher in the group without a known disease. Treatment was administered in 90% of all attacks. In the group with underlying diseases, the duration of intravenous treatment and hospital stay were significantly higher as expected. CONCLUSIONS: This study shows that herpes zoster attacks in healthy children can also progress with severe symptoms and complications. Approaches to reduce the burden of herpes zoster should be adopted and developed for all paediatric patients.

Super Learner Algorithm for Carotid Artery Disease Diagnosis: A Machine Learning Approach Leveraging Craniocervical CT Angiography.

This study introduces a machine learning (ML) approach to diagnosing carotid artery diseases, including stenosis, aneurysm, and dissection, by leveraging craniocervical computed tomography angiography (CTA) data. A meticulously curated, balanced dataset of 122 patient cases was used, ensuring reproducibility and data quality, and this is publicly accessible at (insert dataset location). The proposed method integrates a super learner model which combines adaptive boosting, gradient boosting, and random forests algorithms, achieving an accuracy of 90%. To enhance model robustness and generalization, techniques such as k-fold cross-validation, bootstrapping, data augmentation, and the synthetic minority oversampling technique (SMOTE) were applied, expanding the dataset to 1000 instances and significantly improving performance for minority classes like aneurysm and dissection. The results highlight the pivotal role of blood vessel structural analysis in diagnosing carotid artery diseases and demonstrate the superior performance of the super learner model in comparison with state-of-the-art (SOTA) methods in terms of both accuracy and robustness. This manuscript outlines the methodology, compares the results with state-of-the-art approaches, and provides insights for future research directions in applying machine learning to medical diagnostics.

Pediatric Varicella-related Hospitalization in Turkey Between 2008 and 2018: Impact of Universal Single Dose Varicella Vaccine (VARICOMP Study).

BACKGROUND: A single-dose varicella vaccine at 12 months of age was introduced to the National Immunization Program in February 2013 in Turkey. This study aimed to evaluate varicella-related hospitalization in children and the impact of a single-dose live attenuated varicella vaccine over the first 5.5 years of introducing a universal varicella vaccination. METHODS: We analyzed data collected from the medical records of children <18 years old who required hospitalization due to varicella in 17 cities representing 50% of the childhood population in Turkey between 2008 and 2018. We calculated the rate of hospitalization for varicella per 100,000 children during the study period. The main objective of this study was to determine the yearly rate of hospitalization due to varicella and to compare these rates in the pre-vaccine and post-vaccine periods. The secondary objective was to compare demographic features, varicella-related complications, and outcomes between the pre-vaccine and post-vaccine periods. RESULTS: A total of 4373 children (2458 boys and 1915 girls; 72.3% previously healthy) were hospitalized for varicella over a 10-year period, including 2139 children during the pre-vaccine period and 2234 children during the post-vaccine period. Overall, varicella hospitalization rates decreased significantly after the introduction of varicella vaccination [pre-vaccine vs. post-vaccine period; 3.79 vs. 2.87 per 100,000 per year; P < 0.001; odds ratio 0.75; 95% confidence interval 0.64-0.88]. The incidence of varicella-related hospitalization among children between 1 and 5 years of age was significantly lower in the post-vaccine era than in the pre-vaccine era, with a 60.2% decrease in hospitalizations (2.43 vs. 6.12 per 100,000 children; P < 0.001, odds ratio 0.39; 95% confidence interval 0.34-0.46). In both the <1-year and 6- to 10-year age groups, the incidence of varicella-related hospitalizations was similar in the pre-vaccine and post-vaccine periods. The incidence of varicella-related hospitalization was higher in the post-vaccine era among 11-15 years and >15-year-old groups (P < 0.01 and P < 0.05). The mean age was higher during the post-vaccine period than during the pre-vaccine period (P < 0.001). The absolute number of secondary bacterial infections (P < 0.01), respiratory complications (P < 0.01), and neurological complications (P < 0.001) was significantly lower during the post-vaccine period. The incidence of severe varicella was lower during the post-vaccine period than during the pre-vaccine period (P < 0.001). CONCLUSIONS: After 5.5 years of routine single-dose varicella vaccine use, we observed the impact of varicella vaccination on the incidence of varicella-related hospitalizations, especially in the target age group. However, we did not observe herd protection in the other age groups. The implementation of a second dose of the varicella vaccine in the National Immunization Program would help control disease activity.

Changes in blood biochemistry thrombosis parameters 24 hours after stent-assisted endovascular treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: This study aims to elucidate the early changes in blood biochemistry thrombosis parameters following stent-assisted endovascular treatment of intracranial aneurysms. METHODS: Consecutive patients with unruptured aneurysms undergoing stent implantation during endovascular treatment were included in this prospective study with approval from the local ethics committee. Blood samples were collected immediately before and 24 h after the procedure for biochemical analysis, including basic thrombosis indicators, bleeding tests, and a complete blood count. RESULTS: The study included 80 patients (60 women, 20 men) with 134 aneurysms. A total of 135 stents (110 flow-diverting, 25 standard) were used. Additionally, intrasaccular coiling was utilized in 28 aneurysms among 27 patients. Following the procedure, there was a significant decrease in activated partial thromboplastin time, fibrinogen, hemoglobin, and platelet levels, and a significant increase in prothrombin time, D-dimer, von Willebrand factor (vWF) activity/antigen ratio, and leukocyte levels in all patients. Correlation analyses revealed significant positive associations between platelet and fibrinogen levels, and a negative association between D-dimer and fibrinogen levels in the coil (-) group. Additionally, there was a significant negative correlation between aneurysm volume and vWF activity/antigen ratio, and procedure duration and thrombocyte count, while a positive association was found between aneurysm number and leukocyte count in the coil (-) group. CONCLUSIONS: Analysis of blood chemistry alterations indicates that intravascular thrombosis occurs in the intracranial circulation following stent-assisted endovascular treatment of intracranial aneurysms. This thrombotic process is more pronounced in patients whose aneurysms were left open (i.e. flow-diverting stent alone).

Varicella-Zoster Virus Reactivation After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation, Single-Center Experience of Acyclovir Prophylaxis.

BACKGROUND: Varicella-zoster virus (VZV) reactivation is the most common infectious complication in the late posthematopoietic stem cell transplantation (HSCT) period and is reported as 16%-41%. Acyclovir prophylaxis is recommended for at least 1 year after HSCT to prevent VZV infections. However, studies on the most appropriate prophylaxis are ongoing in pediatric patients. METHODS: Patients who underwent allogeneic HSCT between January 1, 1996 and January 1, 2020 were retrospectively analyzed to outline the characteristics of VZV reactivation after allogeneic HSCT in pediatric patients using 6 months acyclovir prophylaxis. RESULTS: There were 260 patients and 273 HSCTs. Median age was 10.43 (0.47-18.38), and 56% was male. Median follow-up was 2325 days (18-7579 days). VZV reactivation occurred in 21.2% (n = 58) at a median of 354 (55-3433) days post-HSCT. The peak incidence was 6-12 months post-HSCT (43.1%). Older age at HSCT, female gender, history of varicella infection, lack of varicella vaccination, low lymphocyte, CD4 count, and CD4/CD8 ratio at 9 and 12 months post-HSCT was found as a significant risk for herpes zoster (HZ) in univariate analysis, whereas history of varicella infection and low CD4/CD8 ratio at 12 months post-HSCT was an independent risk factor in multivariate analysis. CONCLUSIONS: Tailoring acyclovir prophylaxis according to pre-HCT varicella history, posttransplant CD4 T lymphocyte counts and functions, and ongoing immunosuppression may help to reduce HZ-related morbidity and mortality.

Very-early-onset Inflammatory Bowel Disease in an Infant with a Partial RIPK1 Deletion.

The monogenic causes of very-early-onset inflammatory bowel disease (VEO-IBD) have been defined by genetic studies, which were usually related to primary immunodeficiencies. Receptor-interacting serine/threonine-protein kinase-1 (RIPK1) protein is an important signalling molecule in inflammation and cell death pathways. Its deficiency may lead to various clinical features linked to immunodeficiency and/or inflammation, including IBD. Here, we discuss an infant with malnutrition, VEO-IBD, recurrent infections and polyathritis who has a homozygous partial deletion in RIPK1 gene.

Cardiovascular manifestations and cardiac magnetic resonance follow-up of multisystem inflammatory syndrome in children (MIS-C).

OBJECTIVE: This study aimed to evaluate the cardiovascular manifestations and surveillance of multisystem inflammatory syndrome in children (MIS-C) and to determine the correlation of echocardiographic findings with cardiac magnetic resonance imaging findings. METHODS: Forty-four children diagnosed as MIS-C with cardiac involvement were enrolled in this observational descriptive study. The diagnosis of MIS-C was made according to the criteria of Centers for Disease Control and Prevention. Clinical findings, laboratory parameters, and electrocardiographic and echocardiographic findings at the time of diagnosis and during follow-up were evaluated. Cardiac magnetic resonance was performed on 28 (64%) cases. The 1-year follow-up imaging was performed in all cases with abnormal initial cardiac magnetic resonance findings. RESULTS: Forty-four patients (56.8% male) with a mean age of 8.5 ± 4.8 years were enrolled in this study. There was a significant positive correlation between high-sensitivity cardiac troponin T (mean: 162 ± 444.4 pg/ml) and N-terminal pro b-type natriuretic peptide (mean: 10,054 ± 11,604 pg/ml) (p < 0.01). Number of cases with an electrocardiographic and echocardiographic abnormality was 34 (77%) and 31 (70%), respectively. Twelve cases (45%) had left ventricular systolic dysfunction and 14 (32%) cases had pericardial effusion on admission. Three cases (11%) had cardiac magnetic resonance findings that may be attributed to the presence of myocardial inflammation, and pericardial effusion was present in seven (25%) cases. Follow-up cardiac magnetic resonances of all cases were normal. Cardiac abnormalities were completely resolved in all except two cases. CONCLUSIONS: Myocardial involvement can be seen during acute disease, but MIS-C generally does not lead to prominent damage during a year of surveillance. Cardiac magnetic resonance is a valuable tool to evaluate the degree of myocardial involvement in cases with MIS-C.

COVID-19 in hospitalized infants aged under 3 months: multi-center experiences across Turkey.

To investigate coronavirus disease 2019 (COVID-19) in infants aged 0 to 3 months because there is currently a significant gap in the literature on the subject. A cross-sectional study was conducted with the involvement of 19 medical centers across Turkey and 570 infants. The majority of the patients were male (58.2%), and the three most common symptoms were fever (78.2%), cough (44.6%), and feeding intolerance (39.9%). The results showed that a small percentage of infants had positive blood (0.9%) or urine cultures (10.2%). Most infants presented with fever (78.2%). Children without underlying conditions (UCs) had mostly a complicated respiratory course and a normal chest radiography. Significant more positive urine culture rates were observed in infants with fever. A higher incidence of respiratory support requirements and abnormal chest findings were seen in infants with chronic conditions. These infants also had a longer hospital stay than those without chronic conditions.  Conclusions: Our study discloses the clinical observations and accompanying bacterial infections found in infants aged under 3 months with COVID-19. These findings can shed light on COVID-19 in infancy for physicians because there is limited clinical evidence available. What is Known: • COVID-19 in infants and older children has been seen more mildly than in adults. • The most common symptoms of COVID-19 in infants are fever and cough, as in older children and adults. COVID-19 should be one of the differential diagnoses in infants with fever. What is New: • Although most infants under three months had fever, the clinical course was uneventful and respiratory complications were rarely observed in healthy children. • Infants with underlying conditions had more frequent respiratory support and abnormal chest radiography and stayed longer in the hospital.

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.

Community-acquired S. aureus infection in childhood: a multi-center study.

BACKGROUND: The prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA) has been increasing worldwide. We aimed to investigate the prevalence of MRSA in community-acquired S. aureus infections, the risk factors for CA-MRSA infection and the clinical features of CA-MRSA. METHODS: A multi-center study with prospective and retrospective sections was conducted. Patients ≥ 3 months old and ≤18 years of age who were diagnosed with community-acquired S. aureus infections were included in this study and the patients` information were reviewed from the medical and microbiological database of the hospital. A standard question form about living conditions and exposure risk factors was administered to the parents of patients. The CA-MRSA infections were compared with the methicillin-susceptible S. aureus (CAMSSA) infections in terms of the queried risk factors and clinical variables. RESULTS: We identified 334 pediatric patients with S. aureus infection, 58 (17.4%) had an infection with CAMRSA. The refugee rate was higher in the CA-MRSA group. There was no significant difference regarding the exposure risk. The treatment modalities and outcomes were similar. CONCLUSIONS: The study was not able to show reliable clinical variables or epidemiological risk factors except for being a refugee for CA-MRSA infections. Empirical antibiotic treatment should therefore be determined according to the local CA-MRSA prevalence in patients presenting with a possible staphylococcus infection.

Antibiotic associated diarrhea in outpatient pediatric antibiotic therapy.

BACKGROUND: Antibiotic-associated diarrhea is one of the most frequent side effects of antimicrobial therapy. We assessed the epidemiological data of antibiotic-associated diarrhea in pediatric patients in our region. METHODS: The prospective multi-center study included pediatric patients who were initiated an oral antibiotic course in outpatient clinics and followed in a well-established surveillance system. This follow-up system constituded inclusion of patient by the primary physician, supply of family follow-up charts to the family, passing the demographics and clinical information of patient to the Primary Investigator Centre, and a close telephone follow-up of patients for a period of eight weeks by the Primary Investigator Centre. RESULTS: A result of 758 cases were recruited in the analysis which had a frequency of 10.4% antibiotic-associated diarrhea. Among the cases treated with amoxicillin-clavulanate 10.4%, and cephalosporins 14.4% presented with antibiotic-associated diarrhea. In the analysis of antibiotic-associated diarrhea occurrence according to different geographical regions of Turkey, antibiotic-associated diarrhea episodes differed significantly (p = 0.014), particularly higher in The Eastern Anatolia and Southeastern Anatolia. Though most commonly encountered with cephalosporin use, antibiotic-associated diarrhea is not a frequent side effect. CONCLUSION: This study on pediatric antibiotic-associated diarrhea displayed epidemiological data and the differences geographically in our region.

Clinical Management of a Pandrug-Resistant OXA-48 Klebsiella pneumoniae Infection in the Pediatric Intensive Care Unit.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the serious forms of health care-associated infection. Pan-drug resistant (PDR) CRKP infections can cause severe infections. Mortality and treatment costs in the pediatric intensive care unit (PICU) are high. This study aims to share our experience regarding the treatment of oxacillinase (OXA)-48-positive PDR-CRKP infection in our 20-bed tertiary PICU with isolated rooms and 1 nurse for every 2-3 patients. Methods: Patient demographic characteristics, underlying diseases, previous infections, source of infection PDR-CRKP, treatment modalities, measures used, and outcomes were recorded. Findings: Eleven patients (eight men and three women) were found to have PDR OXA-48-positive CRKP. Because of the simultaneous detection of PDR-CRKP in three patients and the rapid spread of the disease, it was classified as a clinical outbreak, and strict infection control measures were taken. Combination therapy with double carbapenemase (meropenem and imipenem), amikacin, colistin, and tigecycline was used for treatment. The mean duration of treatment and isolation was 15.7 and 65.4 days, respectively. No treatment-related complication was observed, only one patient died, and the mortality rate was 9%. Conclusions: This severe clinical outbreak can be successfully treated with effective treatment with combined antibiotics and strict adherence to infection control measures. ClinicalTrial.gov ID: 28/01/2022 - 1/5.

Multisystem Inflammatory Syndrome in Children Admitted to a Tertiary Pediatric Intensive Care Unit.

Background Multisystem inflammatory syndrome in children (MIS-C) is characterized by persistent fever, abdominal pain, vomiting, diarrhea, rash, conjunctivitis, headaches, and mucocutaneous manifestations and it can cause circulatory dysfunction, resulting in hypotension, shock, and end-organ injury in the heart and other organs and possibly death. In this study, we aimed to analyze the clinical spectrum, treatment options and outcomes of children with MIS-C who were admitted to our pediatric intensive care (PICU). Materials and Methods Clinical and laboratory findings and treatment of the patients admitted to the PICU with MIS-C between April 2020 and January 2021 were recorded, and their outcomes were evaluated. Results Nineteen patients with a median age of 12.5 years (interquartile range (IQR): 5.8-14.0 years) were admitted. Eleven (57.8%) were males. The most frequent clinical and laboratory features were fever (100%), abdominal pain (94.7%), rash (63.1%), headache (68.4%), diarrhea (47.3%), seizure (10.5%), cardiac dysfunction (52.6%), acute kidney injury (26.3%), lymphopenia (84.2%), and thrombocytopenia (36.8%). However, 8 patients needed mechanical respiratory support, 11 patients needed inotropes, 2 patients needed plasma exchange, and 1 patient needed continuous renal replacement therapy. All patients received corticosteroids, 17 patients (89.2%) received intravenous immunoglobulin, 2 patients received anakinra, 10 patients received acetylsalicylic acid, and 6 patients received enoxaparin. Median PICU length of stay was 3 days (IQR: 2-5) and only one patient died. Conclusion In conclusion, MIS-C may present with a variety of clinical manifestations, and it can lead to life-threatening critical illness. Most children need intensive care and the response to immunomodulation is usually favorable.

[Evaluation of the Epidemiological, Clinical and Radiological Features of Pneumonia Cases Caused by Mycoplasma pneumoniae in Childhood]. / Çocukluk Çaginda Mycoplasma pneumoniae'nin Etken Olarak Saptandigi Pnömoni Olgularinin Epidemiyolojik, Klinik ve Radyolojik Özelliklerinin Degerlendirilmesi.

The current study aimed to investigate the clinical, laboratory and radiological findings of the pneumonia cases in children that were confirmed as M.pneumoniae by polymerase chain reaction (PCR) testing and to reveal the factors that can be decisive in the diagnosis. Seventy-seven children were included in this study. The median age of the patients was 31 months (1 month-17 years 4 months). The 63.6% of the patients were younger than five years of age, 53.2% were girls and 46.8% were boys. During the eight-year research period, the frequency of M.pneumoniae in the patients hospitalized with the diagnosis of pneumonia was found to be 3.1%. The rate of M.pneumoniae as the underlying factor of pneumonia was found to be statistically significantly lower in patients aged 0-60 months compared to the patients aged 61-216 months. In patients with M.pneumoniae accompanied by viruses, the age group was more likely to between 0-60 months. The most common symptoms were cough (96.1%) and fever (74%). Physical examinations revealed that 70.1% of the patients had rales, 63.6% had tachypnea, 45.5% had oropharyngeal hyperaemia, 35.1% had subcostal-intercostal retraction, 31.2% had long expiration period, 26% had rhonchus, 24.7% had decrease in breath sounds, 15.6% had cervical lymphadenopathy, 13% had tachycardia, 3.9% had otitis media, 3.9% had tonsil hypertrophy and 2.6% had a maculopapular rash. The rate of hypoxemia was found to be 42.2%. When the physical examination findings of patients with only M.pneumoniae detected in multiplex PCR analysis and those with accompanying viruses in M.pneumoniae were compared, tachypnea, oropharyngeal hyperemia and decreased breath sounds were found to be statistically significantly higher in patients with M.pneumoniae only. Retraction was detected more frequently in patients with accompanying viruses. When the laboratory results of the patients were evaluated according to age, leukocytosis was detected in only 18.2% of the patients, while the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were found to be high in 75% and 85.7% of the patients, respectively. In the multiplex PCR analysis, the CRP values of the patients with only M.pneumoniae were found to be higher than the patients with accompanying viruses. M.pneumoniae was accompanied by viruses at the rate of 40.3%. The most common accompanying viruses were rhinovirus, adenovirus, bocavirus and metapneumovirus. The 55.8% of the patients had lobar-segmental consolidation, 46.8% had parahilar-peribronchial thickening, 18.2% had atelectasis, 11.7% had pleural effusion, 9.1% had increase in reticulonodular density, 6.5% had lymphadenopathy whereas no abnormality was observed in 5.2% of them. No diffuse interstitial involvement was recorded. The CRP value of the patients who had lobar segmental consolidation which was detected through chest X-rays were statistically higher than those without consolidation. In multiplex PCR analysis, the rate of parahilar-peribronchial thickening detected in chest X-ray findings was found to be higher in patients with M.pneumoniae accompanied by viruses compared to those with only M.pneumoniae. The rate of the patients who were given empirical antibiotics against atypical agents was 45.5%. The rate of empirically administered antibiotic treatment for atypical agents after being hospitalization was higher in patients diagnosed with only M.pneumoniae compared to patients with M.pneumoniae and viruses. One patient (1.3%) died. As there are no typical clinical, laboratory or radiological findings specific to M.pneumoniae pneumonia, all of the findings should be assessed as a whole to establish a diagnosis. Besides, for the detection of M.pneumoniae, diagnostic tests which are cost effective, with rapid results and are capable of distinguishing colonisation from active infection should be developed.

Pediatric Invasive Aspergillosis: a Retrospective Review of 59 Cases.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality. This study aimed to present our 10-year IA experience at a single center. Fifty-nine pediatric patients with IA were included in this study. The male-to-female ratio was 42/17. The median age was 8.75 years. Hematologic malignancy was present in the majority of the patients (40/59, 68%). The mean neutropenia duration was 18.5 days. Cytosine arabinoside was the most common immunosuppressive therapy directed at T cells during IA diagnosis. IA cases were categorized as proven (27%), probable (51%), or possible (22%) according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. The lungs (78%) were the most common site of IA, and nodules were the most frequent radiological findings (75.5%). In 38 patients (64.4%) receiving antifungal prophylaxis, prophylactic agents included fluconazole (30.5%), liposomal amphotericin B (23.7%), posaconazole (8.5%), and voriconazole (1.7%). Initial treatment was most commonly administered as monotherapy (69.5%). The median antifungal treatment duration was 67 days. Eleven deaths (18.6%) were due to aspergillosis. With the increased use of corticosteroids, biological agents, and intensive immunosuppressive chemotherapy, IA will most likely continue to occur frequently in pediatric patients.

Epistatic Effects Between Amino Acid Insertions and Substitutions Mediate Toxin resistance of Vertebrate Na+,K+-ATPases.

The recurrent evolution of resistance to cardiotonic steroids (CTS) across diverse animals most frequently involves convergent amino acid substitutions in the H1-H2 extracellular loop of Na+,K+-ATPase (NKA). Previous work revealed that hystricognath rodents (e.g., chinchilla) and pterocliform birds (sandgrouse) have convergently evolved amino acid insertions in the H1-H2 loop, but their functional significance was not known. Using protein engineering, we show that these insertions have distinct effects on CTS resistance in homologs of each of the two species that strongly depend on intramolecular interactions with other residues. Removing the insertion in the chinchilla NKA unexpectedly increases CTS resistance and decreases NKA activity. In the sandgrouse NKA, the amino acid insertion and substitution Q111R both contribute to an augmented CTS resistance without compromising ATPase activity levels. Molecular docking simulations provide additional insight into the biophysical mechanisms responsible for the context-specific mutational effects on CTS insensitivity of the enzyme. Our results highlight the diversity of genetic substrates that underlie CTS insensitivity in vertebrate NKA and reveal how amino acid insertions can alter the phenotypic effects of point mutations at key sites in the same protein domain.

[Effect of the Pneumococcal Conjugated Vaccines on Burden of all Cause Pneumonia, Bacterial Pneumonia and Empyema in Children]. / ÜKonjuge Pnömokok Asilarinin Çocuklarda Tüm Nedenli Pnömoniler, Bakteriyel Pnömoni ve Ampiyem Hastalik Yükü Üzerine Etkisinin Arastirilmasi.

The aim of this single-center retrospective study was to determine the changes in the burden of allcause pneumonia, bacterial pneumonia and empyema in children aged 0-18 years after the availability of 7-valent pneumococcal conjugated vaccine (PCV7) and 13-valent pneumococcal conjugated vaccine (PCV13) in our country. Children aged 0-18 years who were hospitalized with the diagnosis of pneumonia and treated in Ankara between January 1, 2006 and December 30, 2019 were included in the study. The burden of disease according to the years was calculated as follows: after determining the number of patients with all-cause pneumonia, bacterial pneumonia and the empyema who were admitted to the pediatric infectious diseases service, we divided those numbers to admission numbers to all outpatient clinics in that year as the ratio in 100 000. The years 2006-2007 were accepted as pre-vaccine period, 2009-2010 as PCV7 period and 2012-2019 as PCV13 period. As 2008 and 2011 were the years when PCV7 and PCV13 vaccines implemented into the routine vaccination schedule, they were accepted as transition years and the patient data from these years were not used. All of the patients data were obtained from the patient files. There was a significant decrease in the disease burden of all-cause pneumonia in 0-18 years age and 0-24 months age group after PCV13 period compared to PCV7 period (p<0.001 and p<0.001). A statistically significant decrease was found in all-cause pneumonia among children older than 60 months after PCV13 period compared to PCV7 period and pre-vaccine period (p<0.05 and p<0.01, respectively). When pre-PCV13 (PCV7 and pre-vaccine periods together) and post-PCV13 periods were compared; in 0-18 years age, 0-24 months age and 24-60 months age groups, there was a significant decrease in the burden of disease due to all-cause pneumonia after PCV13 (p<0.001, p<0.001 and p<0.05) period. When the bacterial pneumonia disease burden in PCV13 period was evaluated, bacterial pneumonia disease burden in 0-18 years and 0-24 months age group was found to be significantly lower than in both pre-vaccine and PCV7 periods (p<0.001 and p<0.001). After PCV13 vaccine, the disease burden due to bacterial pneumonia was found to be significantly lower in 0-18 years age, 0-24 months age and older than 60 months age groups compared to pre-PCV13 period (p<0.001, p<0.001 and p<0.01). When PCV7 and PCV13 periods were compared in 0-18 years age group, a significant decrease was found in hospitalizations due to empyema after PCV13 (p<0.05). In conclusion, PCV7 and PCV13 led to a significant reduction in the incidence of all-cause pneumonia and bacterial pneumonia in children.

SARS-CoV-2 infection showing signs of cerebral sinus vein thrombosis in the infantile period.

The clinical manifestations of SARS-CoV-2 infection mainly involve the respiratory system. However, there is increasing evidence that this virus can affect other organs, causing a wide range of clinical symptoms. This is the report of a 40-day-old patient who presented with sepsis and had no risk factors other than SARS-CoV-2 infection, whose radiological findings were compatible with cerebral sinus vein thrombosis.