The Safety of Pediatric Bedside Tracheostomy.

OBJECTIVE: Traditionally, pediatric tracheostomy has been viewed as a technically demanding procedure with a high complication rate, requiring the routine use of a formal operating room. Pediatric bedside tracheostomy in an intensive care unit (ICU) setting has not been widely reported, in contrast to the widespread adult bedside ICU tracheostomy. Transport of these critically ill, multiple life support systems dependent patients can be technically difficult, labor intensive, and potentially risky for these patients. Our study aimed to demonstrate the safety and efficacy of bedside tracheostomy in the pediatric ICU. MATERIALS AND METHODS: A retrospective analysis of all pediatric patients undergoing tracheostomy at a tertiary care center, between 1st of January 2013 and 31st of December 2019. RESULTS: During the study period, 117 pediatric patients underwent tracheostomy, 57 (48.7%) were performed bedside while 60 (51.3%) were performed in the operating room. Patients' ages ranged from 2 weeks to 17 years of age, with a median age of 16 months. No case of bedside tracheostomy necessitated a shift to the operating room. There was no difference in 30-day morbidity and mortality between the 2 groups. CONCLUSIONS: Our results suggest that pediatric open bedside tracheostomy in an ICU setting is a safe procedure, with similar complications and outcomes compared to tracheostomy performed in the operating room.

Thrombocytopenia and Bloodstream Infection: Incidence and Implication on Length of Stay in the Pediatric Intensive Care Unit.

The incidence and prognosis of thrombocytopenia in critically ill patients with bloodstream infection (BSI) is not well delineated in the pediatric intensive care unit (PICU) setting. We assessed these variables in our PICU and sought to determine whether thrombocytopenia could serve as a prognostic marker for length of stay (LOS). The study was conducted at the medical PICU of a university hospital, on all critically ill pediatric patients consecutively admitted during a 3-year period. Patient surveillance and data collection have been used to identify the risk factors during the study period. The main outcomes were BSI incidence and implication on morbidity and LOS. Data from 2,349 PICU patients was analyzed. The overall incidence of BSI was 3.9% (93/2,349). Overall, 85 of 93 patients (91.4%) with BSI survived and 8 patients died (8.6% mortality rate). The overall incidence of thrombocytopenia among these 93 patients was 54.8% (51/93) and 100% (8/8) for the nonsurvivors. Out of the 85 survivors, 27 thrombocytopenic patients were hospitalized for >14 days versus 14 of nonthrombocytopenic patients ( p = 0.007). Thrombocytopenia was associated with borderline significance with an increased LOS (adjusted odds ratio = 3.00, 95% confidence interval: 0.93-9.71, p = 0.066). Thrombocytopenia is common in critically ill pediatric patients with BSI and constitutes a simple and readily available risk marker for PICU LOS.

Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass support-A pilot study.

OBJECTIVE: The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients. Our goal was to assess whether serum Klotho levels can be used to predict outcomes in children undergoing cardiac surgery with CPB due to congenital heart defects (CHDs). METHODS: This prospective study was conducted on pediatric patients admitted to two Pediatric Cardiac Intensive Care Units, between 2012 and 2018. All patients were born with CHD and underwent corrective surgery with CPB. Sequential blood samples were analyzed by enzyme-linked immunosorbent assay for soluble Klotho levels at baseline, 2, 6, and 24 h after surgery. The association between Klotho levels and several demographic, intraoperative, and postoperative clinical and laboratory parameters was studied. RESULTS: Twenty-nine children undergoing cardiac surgery with CPB support were included. Serum Klotho levels were shown to significantly decrease 2 h after surgery and increase to baseline levels after 6 h (p < .001 and p < .05, respectively). Patients with low Klotho levels 2 h after surgery were at a 32-fold higher risk for developing postoperative complications (p = .015, odds ratio < 0.03). Moreover, Klotho levels at each of the four time points were lower in patients who developed postoperative complications. CONCLUSIONS: Cardiac surgery with CPB results in a significant decrease of serum Klotho levels 2 h after surgery in pediatric patients with CHDs, which can be used to predict development of postoperative complications in this patient population.

Invasive Group A Streptococcus Infection in Children in Central Israel in 2012-2019.

BACKGROUND: Group A Streptococcus can cause serious and sometimes life-threatening disease in children. The past few years have witnessed a rise in invasive group A Streptococcus infection (iGASi) for unclear reasons. This study attempted to describe the epidemiology, the clinical and demographic characteristics and the outcomes associated with iGASi in hospitalized children in central Israel. METHODS: We retrospectively analyzed the medical records of children <18 years old discharged with a diagnosis of iGASi between January 2012 and December 2019. Clinical, laboratory and microbiologic data, and immunization status were retrieved. The patients were divided into severe and nonsevere groups based on their clinical presentation. The emm type was determined at the national reference center. RESULTS: A total of 167 patients with 206 positive cultures for group A Streptococcus were identified. Hospitalizations for iGASi increased from 701 to 958 per 100,000 admissions between 2012-2015 and 2016-2019, respectively, representing an increase of 37%. The majority of the isolates were from the otolaryngologic system followed by blood, deep soft tissue and respiratory sites. Uncomplicated mastoiditis was the most common diagnosis, followed by bacteremia. Pneumonia was the main diagnosis in the severe group (39.4%). CONCLUSIONS: The admissions because of iGASi in children <18 years old increased during the last 8 years. Surveillance systems and prospective studies should be conducted to expend our understanding of the epidemiology of iGASi in children, better assess the pathogenesis and specific risk factors and monitor changes in emm-type distribution.

MiRNA-124a: a Potential Biomarker for Neurological Deficits Following Cardiac Surgery in Pediatric Patients.

Brain injury is a major source of patient morbidity after cardiac surgery in children. New early accurate biomarkers are needed for the diagnosis of patients at risk for cerebral postoperative damage. Specific circulating miRNAs have been found as suitable biomarkers for many diseases. We tested whether miRNA-124a reflects neurological injury in pediatric patients following heart surgery. Serum samples were obtained from 34 patients before and six hours after heart surgery. MiRNAs-124a was quantified by RQ-PCR. MiRNA-124a levels six hours after heart surgery correlated with the neurological outcome of the patients. In children with neurological deficits, miRNA-124a levels increased while in those with no neurological deficits the levels decreased. MiRNA-124a was able, at six hours after the operation, to identify patients who are at risk for the appearance of neurological deficits. Circulating miRNA-124a is a potential biomarker for the appearance of neurological deficits in pediatric patients following heart surgery. Graphical Abstract.

Impact of rotavirus vaccine on admissions due to acute gastroenteritis and rotavirus gastroenteritis in Israel.

AIM: We examined the impact of insertion of the Rotavirus vaccine (RVV) into the Israeli National Immunisation Programme (NIP) on hospitalisations due to both acute gastroenteritis (AGE) and Rotavirus gastroenteritis (RVGE) in children. METHODS: We retrospectively analysed the medical records of children aged <5 years admitted with a diagnosis of AGE between 2008 and 2016 in two children's hospitals in central Israel. Clinical, laboratory, microbiological data and RV immunisation status were retrieved. Data were compared before and after the introduction of the RVV into the NIP. RESULTS: A total of 2042 children were admitted with AGE. Hospitalisations due to AGE and RVGE decreased from 3310 to 1950 and from 1027 to 585 per 100 000 admissions, respectively, after the RVV (relative risk reduction (RRR) of 41% and 43%, respectively). RV remained the most common pathogen in both study periods. There was no significant difference in the clinical course between immunised and non-immunised children admitted with RVGE. CONCLUSION: The introduction of the RVV to the NIP significantly reduced the admissions due to both AGE and RVGE in children <5 years. However, RV is still the most common agent for admissions due to AGE in this age group.

STAT3 isoforms differentially affect ACE2 expression: A potential target for COVID-19 therapy.

The SARS-coronavirus 2 is the aetiologic agent COVID-19. ACE2 has been identified as a cell entry receptor for the virus. Therefore, trying to understand how the gene is controlled has become a major goal. We silenced the expression of STAT3α and STAT3ß, and found that while silencing STAT3α causes an increase in ACE2 expression, silencing STAT3ß causes the opposite effect. Studying the role of STAT3 in ACE2 expression will shed light on the molecular events that contribute to the progression of the disease and that the different roles of STAT3α and STAT3ß in that context must be taken in consideration. Our results place STAT3 in line with additional potential therapeutic targets for treating COVID-19 patients.

Predictors for plication performance following diaphragmatic paralysis in children.

INTRODUCTION AND OBJECTIVES: Diaphragmatic paralysis (DP) in children can result from various etiologies. Guidelines for patient selection for diaphragmatic plication (DPL) are lacking. Our objectives were to describe the etiologies of DP and to determine the risk factors and predictors for DPL in the pediatric population. METHODS: Retrospective data were retrieved from departmental databases on patients with DP from the pediatric, cardiac, and neonatal intensive care departments of Safra Children's Hospital from 2010 to 2017. RESULTS: DP was diagnosed in 88 patients, 29 with noncardiac surgery-related etiologies, for example, congenital, surgery, trauma, and shock and 59 with cardiac surgery-related etiologies. In total, 27 (31%) patients underwent DPL, and they had significant comorbidities involving respiratory, central nervous, and cardiovascular systems, higher lung injury scores, and lower weight compared with the patients who did not undergo DPL (P = .002, P = .002, P < .001, P = .012, and P = .013, respectively). A multivariate regression model revealed significant independent predictors for DPL, including morbidities of central nervous (odds ratio [OR = 9.651, P = .005), respiratory (OR = 4.875, P = .039), and cardiovascular systems (OR = 23.938, P = .001). CONCLUSIONS: Etiologies of DP are very diverse in the pediatric population. Comorbidities of respiratory, central nervous, and cardiovascular systems are risk factors for plication requirement in respiratory support-dependent pediatric patients with DP. Early DPL should be considered in these patients.

[POSTGRADUATE TRAINING IS OUR SPECIALTY].

BACKGROUND: In recent years, following public expectations for high quality medical care and a teaching system that can adapt to public needs, changes are being implemented in medical education. The Scientific Council of the Israeli Medical Association (IMA) is responsible, under the Physicians Ordinance, for the planning and supervision of the physicians' specialization system in Israel and promotes post graduate medical education of the highest quality for the advancement of medicine in Israel. In this issue, we highlight the key goals of medical education: knowledge acquisition, skills imparting and application of professional values, as well as the different tasks the Scientific Council has undertaken in order to advance them. This issue includes reports discussing amendments to specialization programs, creation of new specialties, changes to board certification examinations and accrediting and overseeing professional training. In addition, the issue will emphasize the significant changes being made in medical education in Israel while implementing Competency Based Medical Education (CBME).

[POSTGRADUATE MEDICAL EDUCATION ACCREDITATION IN ISRAEL].

INTRODUCTION: Accreditation of Post-Graduate Medical Education permits medical institutions to train residents, allowing them to achieve specialist certification. An accreditation system usually employs several tools such as site-visits, information gathering and occasionally self-evaluation, to determine adherence to pre-defined standards. The Scientific Council of the Israeli Medical Association is entrusted by law on this accreditation system in Israel. In our article, we briefly review the Post-Graduate Medical Education accreditation system in Israel and a number of pivotal challenges faced by the Scientific Council in this field in the 21st century. These challenges include the adaptation to different medical settings such as community based clinics and medical arrays, the adaptation of tools used for accreditation, new methods for up to date information gathering and updated structure of site-visit teams. A significant future challenge will be adapting the accreditation system to the new Competency Based Medical Education model of residency promoted in Israel by the Scientific Council.

Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies.

BACKGROUND: Systemic lupus erythematosus (SLE) comprise a diverse range of clinical manifestations. To date, more than 30 single gene causes of lupus/lupus like syndromes in humans have been identified. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to phenotypic and genetic heterogeneity. METHODS: We employed whole exome sequencing (WES) in patients presenting with childhood-onset lupus with severe and/or atypical presentations to identify cases that are explained by a single-gene (monogenic) cause. RESULTS: From January 2015 to June 2018 15 new cases of childhood-onset SLE were diagnosed in Edmond and Lily Safra Children's Hospital. By WES we identified causative mutations in four subjects in five different genes: C1QC, SLC7A7, MAN2B1, PTEN and STAT1. No molecular diagnoses were established on clinical grounds prior to genetic testing. CONCLUSIONS: We identified a significant fraction of monogenic SLE etiologies using WES and confirm the genetic locus heterogeneity in childhood-onset lupus. These results highlight the importance of establishing a genetic diagnosis for children with severe or atypical lupus by providing accurate and early etiology-based diagnoses and improving subsequent clinical management.

Treatment Outcomes of Stenotrophomonas maltophilia Bacteremia in Critically Ill Children: A Multicenter Experience.

OBJECTIVES: Stenotrophomonas maltophilia is a gram-negative opportunistic bacterium that may cause a myriad of clinical diseases in immunocompromised individuals. We aimed to describe the clinical characteristics, risk factors, mortality, and treatment of S. maltophilia bacteremia in critically ill children, a topic on which data are sparse. DESIGN: A multicenter observational retrospective study in which medical charts of critically ill children with S. maltophilia bacteremia were reviewed between 2012 and 2017. SETTING: Data were collected from each of the four largest PICUs nationwide, allocated in tertiary medical centers to which children with complex conditions are referred regularly. PATIENTS: A total of 68 suitable cases of S. maltophilia bacteremia were retrieved and reviewed. MEASUREMENTS AND MAIN RESULTS: The total occurrence rate of S. maltophilia isolation had increased significantly during the study period (r = 0.65; p = 0.02). The crude mortality was 42%, and the attributed mortality was 18%. Significant risk factors for mortality were a longer length of hospital stay prior to infection (33 d in nonsurvivors vs 28 in survivors; p = 0.03), a nosocomial source of infection (p = 0.02), presentation with septic shock (p < 0.001), and treatment with chemotherapy (p = 0.007) or carbapenem antibiotics (p = 0.05) prior to culture retrieval. On multivariate analysis, septic shock (odds ratio, 14.6; 95% CI, 1.45-147.05; p = 0.023) and being treated with chemotherapy prior to infection (odds ratio, 5.2; 95% CI, 1.59-17.19; p = 0.006)] were associated with mortality. The combination of ciprofloxacin, trimethoprim-sulfamethoxazole, and minocycline resulted in the longest survival time (p < 0.01). CONCLUSIONS: The significant attributed mortality associated with S. maltophilia bacteremia in critically ill children calls for an aggressive therapeutic approach. The findings of this investigation favor a combination of trimethoprim-sulfamethoxazole, ciprofloxacin, and minocycline.

Circulating MicroRNAs: a Potential Biomarker for Cardiac Damage, Inflammatory Response, and Left Ventricular Function Recovery in Pediatric Viral Myocarditis.

Viral myocarditis (VM) can be a life-threatening event resulting in cardiac failure, chronic cardiomyopathy, and death. VM typically includes three phases, i.e., acute, subacute, and resolution/chronic. We prospectively investigated cardiac- and inflammatory-associated plasma-circulating miRNA levels in eight pediatric patients with VM during the three stages of the disease. The level of cardiac-associated miR-208a was significantly elevated during the acute phase compared with the subacute and resolution/chronic phases. The level of cardiac- and inflammatory-associated miR-21 was significantly elevated during the acute phase compared to the resolution/chronic phase. Moreover, cardiac-associated miR-208b levels during the subacute phase correlated with systolic left ventricular function recovery as measured during the resolution/chronic phase. The findings of our study demonstrate an association between cardiac damage and the inflammatory response and the expression of miR-208a and miR-21 during the pathological progression of myocarditis. We also found that miR-208b levels exhibit a prognostic significance for left ventricular functional recovery.

Management of Stenotrophomonas maltophilia Infections in Critically Ill Children.

BACKGROUND: Stenotrophomonas maltophilia is a life-threatening nosocomial pathogen with profound multidrug-resistant attributes. It is associated with high mortality, particularly in immunocompromised patients. Data on therapy for S. maltophilia infections are scarce, especially in children hospitalized in intensive care settings (pediatric intensive care unit). METHODS: A retrospective chart review of pediatric patients with isolates of S. maltophilia hospitalized over a 5-year period in 2 pediatric intensive care units. RESULTS: Thirty-one patients and 91 isolates from blood, respiratory secretions and soft tissues were identified and reviewed. The overall incidence of S. maltophilia infections increased during the study period (P = 0.003). The all-cause crude mortality was 61%, and the attributed mortality was approximately 16%. Risk factors associated with mortality included longer hospitalization before infection (P = 0.002), septic shock (P = 0.003), mechanical ventilation (P = 0.004), an indwelling central vein catheter (P = 0.03) and prior use of steroids (P = 0.04) and carbapenems (P = 0.004). On multivariate analysis, mortality was associated with mechanical ventilation (P = 0.02) and preinfection hospitalization days (P = 0.01). Combination treatment of trimethoprim and sulfamethoxazole, ciprofloxacin and/or minocycline significantly extended survival time (P < 0.001). The method of treatment did not significantly affect the interval between S. maltophilia isolation to resolution of infection (P = 0.200). CONCLUSIONS: Combinations of trimethoprim and sulfamethoxazole, ciprofloxacin and minocycline are proposed for pediatric intensive care unit patients harboring S. maltophilia. Meticulous evaluation of central vascular access and prior treatment with carbapenems are indicated, especially for mechanically ventilated and septic children.

Dehydration as a Rare Cause of Pulmonary Artery Thrombosis in a 2-Week-Old Term Neonate.

Pulmonary arterial thrombosis is an extremely rare occurrence in the neonatal population. We describe a 2-week-old female neonate who presented in critical condition with severe cyanosis and dehydration and was found to have a large thrombus in the main branches of the pulmonary arteries. She was successfully treated with surgical embolectomy. Pulmonary arterial thrombosis should always be considered in the differential diagnosis of a dehydrated neonate presenting with severe cyanosis and evidence of pulmonary hypertension.

Lobectomy on ECMO as a Life-Saving Procedure following Necrotizing Pneumonia in a Toddler: A Case Study.

Necrotizing pneumonia is a severe form of pneumonia that is mainly treated with conservative treatment, including antibiotics. We report a unique case of necrotizing pneumonia due to group A streptococcus infection in an 18-month-old boy who required extracorporeal membrane oxygenation (ECMO) support. Following surgical lobectomy, the child was weaned off ECMO and recovered uneventfully.

Elevated Baseline Cortisol Levels Are Predictive of Bad Outcomes in Critically Ill Children.

OBJECTIVE: The definition of an adequate adrenal response in critically ill children continues to be controversial. We aimed to evaluate the cortisol levels at baseline and after adrenocorticotropin (ACTH) stimulation and determine their association to clinical outcome of critically ill children. METHODS: All children who underwent an ACTH test in the pediatric intensive care unit (PICU) in a tertiary medical center between 2006 and 2013 were included in the study. Data on age, sex, diagnosis, vasoactive-inotropic score, length of pediatric intensive care unit stay, and mortality were obtained. Laboratory variables included hematologic and chemistry data, arterial lactate, and total plasma cortisol levels at baseline and after ACTH stimulation. RESULTS: Ninety-nine patients (61 males; median [range] age, 2 [0-204] months) were enrolled. The mortality rate of children with a baseline cortisol level of 600 nmol/L or greater was 36% (12/33 patients) versus 18% (12/66 patients) for children with a baseline cortisol level of less than 600 nmol/L (odds ratio, 2.6 [95% confidence interval, 1-6.6]; P = 0.05). There was a positive correlation between baseline cortisol and lactate levels (r = 0.40, P < 0.0001), vasoactive-inotropic scores (r = 0.24, P = 0.02), and mortality (P = 0.05). There was no correlation between peak cortisol measured at the ACTH test or the delta increment of cortisol from baseline and mortality. CONCLUSIONS: A high baseline cortisol level in critically ill children was associated with more severe illness, higher lactate level, and a higher mortality rate. Routine baseline cortisol assessment is recommended to identify patients at high mortality risk.