Israel Medical Association Journal

Background: Enterovirus meningitis (EM) is a common central nervous system (CNS) infection with a seasonal peak in summer and fall.

Objective: To describe the epidemiologic and clinical patterns of EM in children before (2017–2019 years) and during the coronavirus disease 2019 (COVID-19) pandemic (2020–2022).

Methods: This retrospective study included children (age 0–16 years) hospitalized in a pediatric department in Israel diagnosed with EM: January 2017–December 2019 and January 2020–December 2022. The seasonal peak for each period was defined as the maximal incidence in particular months. EM was diagnosed by reverse transcription polymerase chain reaction of cerebrospinal fluid (CSF) for enteroviruses.

Results: During the study period, EM was diagnosed in 134 cases (median age 5 months [1–51], 76 [57%] males); 72 during 2017–2019 and 62 during 2020–2022. The most common presentation was fever. C-reactive protein (CRP) was elevated in 57 cases (43%). CSF profile showed pleocytosis in 130 cases (97%) and elevated protein in 80 (60%). In the 2020–2022 group, fewer patients were febrile, CRP was higher, and CSF profile showed a higher glucose level compared to the 2017–2019 group. Seasonal peaks in 2017–2019 occurred June–August, and in 2020–2022 February–April.

Conclusions: The COVID-19 pandemic altered the clinical characteristics of EM and its seasonal peak. Clinicians should be aware of changes in epidemiological patterns of EM to make appropriate diagnoses in viral infection in order to avoid unnecessary antibiotic treatment.

Background: Hyponatremia is common among hospitalized children, including those with community acquired pneumonia. The prevalence and severity of hyponatremia were reported to correlate with disease. However, data regarding the association between hyponatremia and causative infectious pathogens are limited and results are inconsistent.

Objectives: To investigate the associations between sodium levels, severity and causative pathogen in children with pneumonia.

Methods: A retrospective study of all children (< 18 years) hospitalized with pneumonia from 1 January 2018 to 31 December 2020. Admission sodium levels were compared to the presumed etiological pathogens, clinical parameters, and inflammatory markers.

Results: Among 751 (52% males) children, 10 (1%) had sodium levels < 130 mEq/L, 187 (25%) had mildly decreased levels 130–134 mEq/L, and the remaining 554 (74%) had normal levels 135–145 mEq/L. Sodium levels < 130 mEq/L were found in 7/236 (3%) of the patients with presumed bacterial pneumonia, in 0/20 of patients with presumed atypical-bacterial, and in only 3/495 (0.6%) of the patients with a presumed viral infection, P < 0.001. Sodium levels < 135 mEq/L conferred an odds ratio of 3.1 (95% confidence interval [95%CI] 2.1–4.3) and levels < 130 mEq/L an odds ratio of 6.8 (95%CI 1.8–33.0) for bacterial infection, P < 0.001 for both. Hyponatremia was also inversely associated with high white blood cell counts, absolute neutrophil cell counts, and C-reactive protein levels.

Conclusions: Hyponatremia was common among children hospitalized with pneumonia and was associated with elevated inflammatory markers and presumed bacterial pneumonia.

Background: Understanding medical guidelines can be challenging for patients and their families, leading to incorrect use or dosages due to inadequate or unclear explanations. Graphic organizers are tools that can help improve comprehension of medical guidelines.

Objectives: To assess the effectiveness of using designed graphic organizers to enhance comprehension of medical guidelines.

Methods: A prospective randomized controlled study was conducted at Soroka University Medical Center between 2015 and 2017. Parents of children aged 1–7 years, admitted for asthma exacerbation requiring the use of an inhaler with a spacer or for febrile convulsion requiring rectal diazepam, were enrolled. Participants were randomly assigned to receive instructions through a graphic organizer (intervention group) or plain text (control group). An assessment form was administered to evaluate the understanding of the correct steps for using the inhaler with a spacer or administering rectal diazepam. A follow-up telephone assessment was conducted after 30–60 days to evaluate recollection.

Results: Seventy-four parents with similar demographic characteristics were enrolled (intervention group [38], control group [36]). There was no significant difference in comprehension between the two groups when using medical guidelines for the two interventions. However, there was a correlation between maternal education level and long-term recollection, with an average score of 24%, 42%, and 48% among mothers with less than 8 years, 8–12 years, and over 12 years of education, respectively (P = 0.004).

Conclusions: The use of graphic organizers did not improve parent comprehension of pediatric medical guidelines. However, long-term recollection was positively correlated with maternal education level.

Background: Wilson disease (WD) is an autosomal recessive disease characterized by a defect in hepatocellular copper transport with a wide spectrum of clinical manifestations and reported prevalence.

Objectives: To study the epidemiology and clinical manifestations of WD between two ethnic groups, Jewish and Bedouins, with different marriage patterns, in southern Israel.

Methods: We conducted a retrospective study investigating the clinical course and laboratory characteristics of children diagnosed with WD who were treated at Soroka University Medical Center.

Results: Sixteen patients were diagnosed between 2000 and 2021 (8 males, 50%), 14 were of Bedouins origin. The total cohort prevalence was 1:19,258 while the prevalence of the disease was significantly higher among Bedouins compared to Jews (1:10,828 vs.1:78,270, P-value = 0.004). The median age at diagnosis was 10.2 years, without a significant difference between the groups. The most common presenting symptom was hepatic manifestations: 81.2% had elevated transaminases, 12.5% had jaundice, 25% had neurological symptoms, one had a Kayser-Fleischer ring, and one had psychosis. The mean ceruloplasmin level was 3.0 mg/dl. During follow-up, nine patients normalized transaminases with treatment, while three required liver transplantation. There was no significant difference in the clinical presentation and disease course between the two ethnic groups.

Conclusions: Our cohort showed a high prevalence of WD compared to previous studies, especially among the Bedouin population, which has a high consanguinity rate. The prognosis of WD in our population is similar to other studies and depends mainly on treatment compliance.

Background: Acute bronchiolitis, primarily caused by respiratory syncytial virus (RSV), is the leading cause of hospitalization in young children. Despite international guidelines supporting clinical diagnosis, laboratory evaluations are often conducted with limited validity.

Objectives: To evaluate the association between C-reactive protein (CRP) serum levels on admission and disease severity in children hospitalized due to RSV bronchiolitis.

Methods: This retrospective cohort study included children (0–24 months old) who were hospitalized due to RSV bronchiolitis (2018–2022), CRP levels taken at admission.

Results: We included 1874 children (mean age of 6.7 months, 59% males); median CRP level 1.92 mg/dl. Children with elevated CRP (> 1.92 mg/dl) were significantly older (5.1 vs. 3.8 months, P < 0.001) and had higher rates of pneumonia (9.4% vs. 4.3%, P < 0.001), urinary tract infection (UTI), (2.2% vs. 0.2%, P < 0.001), acute otitis media (AOM) (1.7% vs. 0.2%, P < 0.001), admissions to the pediatric intensive care unit (PICU) (7.4% vs. 3.7%, P < 0.001), antibiotic treatment (49.8% vs. 37.2%, P < 0.001), and longer hospitalizations (3.83 vs. 3.31 days, P < 0.001). Multivariable analysis predicted increased risk for UTI, PICU admission, pneumonia, and longer hospitalization (relative risk 11.6, 2.25, 1.98, 1.44, respectively, P < 0.001). CRP thresholds of 3.51, 1.9, and 2.81 mg/dl for PICU admission, UTI, and pneumonia, were calculated using Youden's index with AUC 0.72, 0.62, and 0.61, respectively.

Conclusions: Elevated CRP levels at admission are associated with increased disease severity and higher complication rates in children hospitalized with RSV bronchiolitis.

A full-term 1-month-old female was brought to our pediatric emergency department (ED) due to 3 days of increasing respiratory distress. She was born at term to healthy, consanguineous (2nd degree) Bedouin parents after a pregnancy that lacked adequate monitoring. At birth, a physical examination revealed an imperforate anus and a recto-vestibular fistula, left hydronephrosis, large patent ductus arteriosus (PDA), and an atrial septal defect (ASD). The diagnosis of VACTER association was made. Importantly, she had no respiratory difficulties, nor hemivertebra or tethered cord.

On admission to the ED, she presented with severe respiratory distress, tachypnea, dyspnea, and hypoxemia without evidence of upper airway obstruction or stridor. Due to impending respiratory failure, she was transferred to the pediatric intensive care unit and started on non-invasive respiratory support through a high-flow nasal cannula (HFNC), which partially relieved her work of breathing. The nasal swab for respiratory viruses was positive for enterovirus, and her urine culture grew Escherichia coli. She was transferred to the pediatric ward after clinical improvement on day 3. Echocardiography performed for evaluation of pulmonary hypertension estimated normal pressures but revealed a vascular ring anomaly. A computed tomography (CT) angiography performed confirmed the presence of an aberrant left pulmonary artery also referred to as a left pulmonary artery sling (LPAS) [Figure 1A].

Gaucher disease (GD) is an inherited autosomal recessive genetic disorder caused by mutations in the glucocerebroside (GBA1) gene [1]. These variants result in decreased activity of the lysosomal enzyme β-glucocerebrosidase (GCase), which is essential for breaking down glucocerebroside into glucose and ceramide. Consequently, activated macrophages, known as Gaucher cells, accumulate undegraded glucocerebroside. The phagocytic role and naturally high-level GCase activity of macrophages may partly explain why these cells are particularly affected in GD. The accumulation of glucocerebroside in macrophages causes an expansion in the population of these cells, leading to symptoms like hepatosplenomegaly, thrombocytopenia, anemia, bleeding tendency, growth retardation, and bone issues. Bone marrow infiltration may result in bone infarction, episodes of bone crises, and osteonecrosis, mainly of large joints and less commonly as pathological fractures. These latter skeletal complications are the most critical irreversible consequence of untreated GD, significantly impacting the quality of life of patients, and hence should be avoided by early administration of specific therapy. The accumulation of glucocerebroside in lysosomes has been linked to a pro-inflammatory state [2]. In addition, the misfolding and retention of mutant GCase within the endoplasmic reticulum (ER) has been associated with ER stress and activation of the unfolded protein response, contributing to GD phenotypic heterogeneity, inflammation, and immune dysregulation [3].

One of the most wonderful things in the practice of medicine is the endless opportunities to learn new things and encounter novel medical conditions and their manifestations. However, not all new experiences are necessarily welcomed. As we recently discovered, there are some medical encounters that no physician should ever face, because no patient should have to endure these encounters. That is, no person, and certainly no child, should ever go through the kind of cruel captivity we recently encountered following the horrific events of 7 October 2023 in Israel.

We read with interest the retrospective study by Ohana Sarna and colleagues [1] titled Clinical Characteristics, Etiology, and Outcomes of Hypothermia in Well-appearing Children Referred to the Emergency Department. The study comprised 99 children younger than 16 years of age who presented to pediatric emergency department (PED) with hypothermia (temperature of < 36.5°C). The authors evaluated the incidence of serious bacterial infection (SBI) in 15 infants aged 0–3 months, 71 children aged 3–36 months, and 13 children older than 36 months. They concluded that the incidence of SBI in infants younger than 3 months of age was low and the older children had a benign course and outcome. As pediatric endocrinologists, we would like to mention another important cause of hypothermia, especially in infants but also in children: congenital and acquired hypothyroidism.

Background: Pseudomonas aeruginosa (PSA) is an infectious pathogen associated with acute appendicitis; however, it is not consistently addressed by empirical antibiotic therapy, despite potential complications.

Objectives: To investigate the incidence, predictors, and outcomes of PSA-associated acute appendicitis in children.

Methods: We conducted a retrospective analysis involving pediatric patients who underwent acute appendicitis surgery and had positive peritoneal cultures. Clinical, microbiological, and intraoperative data were extracted from medical records.

Results: Among 2523 children with acute appendicitis, 798 (31.6%) underwent peritoneal cultures, revealing 338 positive cases (42.3%), with PSA detected in 77 cases (22.8%). Children with PSA were three times more likely to exhibit high intraoperative grading ≥ 3 (93.4% vs. 76.8%, 95% confidence interval [95%CI] 1.2–8.3, P = 0.023) and nearly four times more likely to have polymicrobial cultures (88.3% vs. 62.1%, 95%CI 1.8–8.0, P < 0.001) than those without PSA in peritoneal cultures. Duration of symptoms did not predict PSA isolation (P = 0.827). Patients with PSA had longer median hospital stays (8 days, interquartile range [IQR] 7–10) than those with other pathogens (7 days, IQR 5–9) (P = 0.004). Antibiotic treatment duration, intensive care unit admission rates, readmission, and mortality were similar between the two groups (P = 0.893, 0.197, 0.760, and 0.761, respectively).

Conclusions: PSA is a common pathogen in children diagnosed with acute appendicitis and positive peritoneal cultures. The likelihood of isolating PSA increases with high-grade intraoperative assessment and in the presence of multiple pathogens in peritoneal cultures, suggests antipseudomonal treatment.

Background: Hypothermia, as a sign of serious bacterial infection (SBI) in children and infants older than 90 days is poorly characterized, especially in the post-pneumococcal vaccine era.

Objectives: To assess the prevalence of SBI in children and infants presenting to the pediatric emergency department (PED) with reported or documented hypothermia.

Methods: Retrospective data analysis was conducted of all well-appearing children aged 0–16 years who presented with a diagnosis of hypothermia at two tertiary PEDs from 2010 to 2019.

Results: The study comprised 99 children, 15 (15.2%) age 0–3 months, 71 (71.7%) 3–36 months, and 13 (13.1%) > 36 months. The youngest age group had increased length of stay in the hospital (P < 0.001) and increased rates of pediatric intensive care unit admissions (P < 0.001). Empirical antibiotic coverage was initiated in 80% of the children in the 0–3 months group, 21.1% in the 3–36 months group, and 15.4% in > 36 months (P < 0.001). Only one case of SBI was recorded and no bacteremia or meningitis. Hypothermia of unknown origin was the most common diagnosis in all age groups (34%, 42%, 46%), respectively, followed by bronchiolitis (26%) and hypoglycemia (13.3%) for 0–3 month-old children, unspecified viral infection (20%) and otitis media (7%) for 3–36-month old, and unspecified viral infection (23%) and alcohol intoxication (15.2%) in > 36 months.

Conclusion: There is a low incidence of SBI in well-appearing children presenting to the PED with hypothermia and a benign course and outcome in those older than 3 months.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused significant global turmoil, including changes in social and societal conduct such as lockdowns, social isolation, and extensive regulations. These changes can be major sources of stress. The first wave of the pandemic (April–May 2020) was a time of global uncertainty. We evaluated symptom severity among 29 Israeli children and adolescents with obsessive-compulsive disorder (OCD). Our previous study found that most of these participants did not experience an exacerbation of symptoms.

Objective: To re-evaluate the OCD symptoms of 18 participants from the original group of 29 children and adolescents during three time points: before the pandemic, during the first wave, and 2 years later.

Methods: Obsessive-compulsive symptoms (OCS) were assessed using the Clinical Global Impression Scale (CGI), a functional questionnaire, and the Obsessive-Compulsive Inventory-child version (OCI-CV).

Results: OCS in patients did not change significantly during the three time points. Participants reported minimal changes in their general functioning 2 years after the outbreak of COVID-19 and showed minimal change in OCI-CV scale scores.

Conclusions: Our results indicated clinical stability of OCD symptoms among most of the participants.

Background: Pediatric patients with newly diagnosed type 1 diabetes mellitus (T1DM) are commonly treated with daily multiple insulin injections or an insulin pump. They tend to have higher body mass index-standard deviation scores (BMI-SDS) than non-diabetic children.

Objectives: To identify patterns in the changes in BMI in the 3 years after T1DM diagnosis, and to discover factors that relate to excessive weight gain.

Methods: This retrospective study included clinical and laboratory data for 194 boys and girls aged 2–18 years at the time of diagnosis and at 1, 2, and 3 years after. Their BMI values were compared to non-diabetic children using BMI percentile and z-score (standard deviation) based on the U.S. Centers for Disease Control and Prevention (CDC) growth charts.

Results: Both males and females had low mean BMI-SDS at diagnosis (-0.4499 ± 1.38743 male, 0.3050 ± 1.29887 female) that increased after 1 year (-0.0449 ± 1.14772 male, 0.1451 ± 0.98893 female). Lower glycated hemoglobin (HbA1c) at 1 year correlated with higher BMI-SDS (r = -0.215, P = 0.011). No such correlation was found in the following 2 years. The daily dose of basal insulin correlated with higher BMI-SDS at 1 year (r = 0.183, P = 0.026) and 3 years (r = 0.297, P < 0.01). No association was found between the use of an insulin pump or continuous glucose monitoring and higher BMI-SDS.

Conclusions: BMI-SDS of children with T1DM was lower than average at the time of diagnosis and rose higher than average in the 3 years following. Higher BMI-SDS was not significantly associated with sex or ethnicity. The most prominent increase happened in the first year.

Background: School closures due to the coronavirus disease 2019 (COVID-19) outbreak affected students physically, socially, and psychologically with an increase in the number of children and adolescent presenting with anxiety, depression, and drug abuse.

Objectives: To examine the impact of COVID-19 and lockdown on the mental health of minors during the pandemic period and to characterize the type and number of referrals to a regional psychiatric outpatient clinic.

Methods: This study included 380 children evaluated in an outpatient child psychiatric clinic. They were divided into two groups: before the lockdowns (BLD) (n=248), from January 2019 to February 2020, and during the lockdowns (LD) (n=132), from March 2020 to April 2021.

Results: When comparing the LD to BLD, there was increase in suicide attempts (9.8% vs. 2.8%) and in the use of psychotherapy (81% vs. 56%). There was a decrease in the diagnoses of behavior disorders (29.5% vs. 44.8%) and ADHD (29.5% vs. 50%); as well as a decrease in stimulant usage (22.7% vs. 38%). There was a statistically non-significant increase in the number of children with depression, anxiety, and drug-use disorder.

Conclusions: Many children developed educational, social, emotional, and behavioral gaps during LD, and they lost skills to deal with everyday problems due to social isolation. It is important to follow the long-term impact of the lockdowns and social isolation.

Background: Blood pressure (BP) is routinely measured while triaging children presenting to the pediatric emergency department (PED).

Objectives: To determine whether a medical clown shortens the time to acquire a BP measurement among children undergoing triage in the PED.

Methods: The study comprised 133 children. Patients were assigned to one of two groups: with a medical clown or without a medical clown.

Results: The presence of a medical clown led to a significantly shorter time to acquire a blood pressure measurement (60 ± 23 seconds vs. 81 ± 43.5 seconds, P < 0.001. Clowns had a significant effect on shortening total triage length among children of Jewish ethnicity compared to Arab ethnicity (113 ± 353.6 seconds vs. 154 ± 418 seconds, P = 0.012).

Conclusions: Using medical clowns while measuring BP during triage when used in a culturally appropriate manner shortens time.